- Email: [email protected]
Enantioselective synthesis of the tricyclic core of (+)-strigol
Tetrahedron 72 (2016) 6634e6639
Contents lists available at ScienceDirect
Tetrahedron journal homepage: www.elsevier.com/locate/tet
Enantioselective synthesis of the tricyclic core of (þ)-strigol Aiko Takahashi, Yusuke Ogura, Masaru Enomoto, Shigefumi Kuwahara * Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 30 July 2016 Received in revised form 25 August 2016 Accepted 29 August 2016 Available online 31 August 2016
An enantioselective synthesis of the tricyclic core structure of (þ)-strigol, a potent seed germination stimulant for root parasitic weeds, has been achieved from 2-iodo-4,4-dimethyl-2-cyclohexen-1-one in 14 steps. The key steps include a CBS reduction of an iodo enone to obtain a cyclohexenol derivative of high enantiomeric excess, regioselective epoxide ring opening with a Grignard reagent in a low-polarity solvent, highly diastereoselective addition of vinyllithium to a ketone, and Lewis acid-promoted installation an acetate unit onto a bicyclic allylic acetate intermediate. Ó 2016 Elsevier Ltd. All rights reserved.
Keywords: Strigol Strigolactone Plant hormone Epoxide Total synthesis
1. Introduction (þ)-Strigol (1) is the first member of the strigolactone family of natural products discovered in 1966 as a potent seed germination stimulant for the root parasitic weed Striga lutea (syn. Striga asiatica) which causes significant damage to crops of gramineous and leguminous plants mainly in the tropical and subtropical areas of Africa and Asia (Fig. 1).1,2 It was originally isolated from the root exudates of cotton (a non-host plant for the weed),1a and later from those of its genuine hosts of economical importance (maize, proso millet, and sorghum).3 Strigolactones are now known to be produced also by a wide range of plants other than host plants for parasitic weeds and consist of 15 members.4 This family of natural products are structurally characterized by a fused tricyclic g-lactone core (ABC scaffold) connected through an enol ether linkage to an a,b-unsaturated g-lactone unit (D ring). They all have the same C/D ring structure as 1, while their A/B ring portions show some structural diversity.4 Besides the seed germination stimulatory activity toward parasitic weeds,5 strigolactones have been elucidated to possess some additional functions of enormous biological importance, especially: (1) induction of hyphal branching in arbuscular mycorrhizal fungi that enables the fungi to establish their symbiosis with plants;6 and (2) activity as a plant hormone to suppress the growth of preformed axillary shoot buds and thereby inhibit shoot branching.7 These plant physiologically and
* Corresponding author. Fax: þ81 22 717 8783; e-mail address: skuwahar@biochem. tohoku.ac.jp (S. Kuwahara). http://dx.doi.org/10.1016/j.tet.2016.08.078 0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
agriculturally important functions of strigolactones prompted a great deal of studies from various aspects such as isolation of new members, mode of action, biosynthesis, and identification of receptor.4,8
Fig. 1. Structures of (þ)-strigol (1) and its tricyclic core (2).
Synthetic studies on strigolactones and their analogs for structureeactivity relationship investigations have also been actively conducted by many research groups and numerous publications have appeared since the first total synthesis of ()-strigol by Sih and co-workers in 19749e11 As for the synthesis of optically active forms of naturally occurring strigolactones, four types of synthetic strategies have been adopted with the exception of direct resolution of their synthetic racemates: (1) preparation of an optically active ABC scaffold via optical resolution (including enzymatic or chiral HPLC separation) and its non-diastereoselective connection to a racemic D ring unit followed by chromatographic separation of the resulting diastereomeric mixture;12 (2) preparation of an optically active ABC scaffold from the chiral pool followed by the same
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
6635
sequence as described in (1);13 (3) preparation of a racemic ABC scaffold and its connection to an optically active D ring unit followed by chromatographic separation of the resulting diastereomeric mixture;14 and (4) asymmetric synthesis of an ABC scaffold and its connection to a racemic D ring unit followed by diastereomeric separation.15 However, the strategy composed of asymmetric synthesis of an ABC scaffold and its diastereoselective unification with a D ring moiety has never been reported so far. As part of our efforts toward such a totally stereoselective synthesis of strigolactones, we describe herein a synthetic approach to the tricyclic ABC core (2) of (þ)-strigol. To the best of our knowledge, this is the first example of the synthesis of 2 that uses neither optical resolution nor naturally occurring chiral starting materials.12aec,13a Scheme 2. Enantioselective preparation of 7 and its conversion into siloxy epoxide 13.
2. Results and discussion Scheme 1 outlines our retrosynthetic analysis of 2. Compound 2 was traced back to olefinic carboxylate 3 with the intention of installing the g-lactone and the double bond in 2 by halolactonization of 3 and subsequent dehydrohalogenation. The g,d-unsaturated carboxylate 3 would be obtainable by SN20 -type introduction of an acetate unit into 4. For the construction of the bicyclic allylic alcohol 4, we envisaged a two-step sequence comprising the addition of a vinyl group to ketone 5 from its bottom face and ring-closing metathesis (RCM) of the resulting diene product. The ketone 5 would be prepared by regioselective ring opening of epoxide 6, which in turn should be derived from optically active cyclohexenol derivative 7 by hydroxyl-directed epoxidation.
allylmagnesium bromide in refluxing ether,22 gave a 1.1:1 mixture of 14 and its regioisomer 140 ,23 changing the solvent from ether to toluene/hexane (1:1) significantly increased the ratio to 3.2:1, providing the desired isomer 14 in 73% isolated yield.24,25 To obtain bicyclic intermediate 18, the alcohol 14 was first oxidized to olefinic ketone 15, the ozonolysis of which afforded 16. Z-Selective iodomethylenation of the aldehyde 16 followed by intramolecular NozakieHiyamaeKishi coupling of the resulting iodo ketone 17 furnished 18.26,27 Compound 18 was also prepared much more efficiently in two steps from 15 by its exposure to vinyllithium in THF at 78 C to form allylic alcohol 19 as the exclusive diastereomer and subsequent ring-closing metathesis of the diene product 19.28 It is worth mentioning that the reaction of 15 with vinylmagnesium chloride (instead of vinyllithium) in THF was very sluggish at low temperatures (78 to 50 C) presumably due to steric congestion around the ketone functionality, and a substantial amount of the corresponding epimeric alcohol (1-epi-19) was also produced when the reaction temperature was raised to room temperature.
Scheme 1. Retrosynthetic analysis of 2.
Our first task for the synthesis of 2 was the preparation of 7 in high enantiomeric purity (Scheme 2). Although compound 7 was known to be preparable by a Noyori asymmetric reduction of the corresponding enone, the enantiomeric excess (ee) of the alcoholic product 7 was reported to be only 47%.16,17 We, therefore, adopted an alternative route via iodine-substituted cyclohexenol derivative 11, the (R)-enantiomer of which had previously been synthesized in 98% ee by a modified CoreyeBakshieShibata (CBS) reduction using diethylaniline$BH3 and a catalytic amount of (S)-2-methoxy-CBSoxazaborolidine.18 The reduction of 9 using (R)-2-methoxy-CBS oxazaborolidine as catalyst proceeded smoothly, providing 11 in 92% yield;18c,19 the iodo enone 9 in turn was readily prepared from enone 8 almost quantitatively according to the literature (I2, DMAP, K2CO3, THFeH2O).20 Hydrogenolytic removal of the iodine atom in 11 was best performed with 5% Pd/C in MeOH in the presence of Et3N as catalyst poison,21 furnishing 7 in a satisfactory overall yield of 76% from 8. Diastereoselective epoxidation of 12 with MCPBA in the presence of solid NaHCO3 afforded 12 as an inseparable 93:7 cis/ trans mixture. Finally, protection of the alcohol as its TBS ether provided 13. With the protected cis-epoxy alcohol 13 in hand, we next proceeded to its epoxide ring opening with allylmagnesium bromide (Scheme 3). Although the epoxide 13, upon exposure to
Scheme 3. Preparation of bicyclic allylic alcohol 18.
The installation of an acetate unit at the C2 position of 18 was first attempted by applying the JohnsoneClaisen rearrangement to the cyclic allylic alcohol (Scheme 5, a). Treatment of 18 with triethyl or trimethyl orthoacetate in the presence of an acid catalyst (propionic acid, p-anisic acid, or o-nitrophenol) at high temperatures ranging from 135 to 180 C, however, gave no desired product 20,
6636
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
resulting in the formation of complex mixtures.29 The EschenmosereClaisen rearrangement of 18 to 21 was also unsuccessful (b). The IrelandeClaisen rearrangement of acetate 22, obtained by acetylation of 18, was also attempted by treating 22 with a base (MNR0 2¼LDA or KHMDS) and a silylating agent (TMSCl or TBSCl) in THF, THF/HMPA, or toluene, and then stirring the mixture at temperatures ranging from 78 to 110 C (c). However, neither the desired product 23 nor the corresponding carboxylic acid was detected in the reaction mixture. The introduction of a malonate unit into 22 by the TsujieTrost reaction was next examined (d).30 Although the reaction of 22 with dimethyl malonate was conducted under various conditions (base: NaH, K2CO3, or Cs2CO3; Pd(0) species: Pd(PPh3)3 or Pd2(dba)3; ligand: Ph3P, n-Bu3P, or dppe), none of the conditions gave the desired product 24, resulting in the recovery of the starting material 22 in most cases. The installation of an acetate unit onto 22 was eventually achieved by modification of the procedure developed by Mukaiyama and coworkers which had rarely been documented in the literature.31 When a mixture of 22 and silyl ketene acetal 25 in CH2Cl2 was treated with BF3$OEt2 at 78 C, a quick reaction took place to give an inseparable mixture of 26 and 260 in 86% yield, albeit with a modest selectivity of 2:1. The stereochemistry of each epimer was assigned later at the stage of 29/290 (see Scheme 5) on the basis of their NOESY spectra (vide infra).
Scheme 5. Completion of the synthesis of 2.
stereochemistries as depicted in Scheme 5 (see Supplementary data). The mixture of 29 and 290 was treated with DBU in toluene to afford, after silica gel column chromatographic separation, olefinic lactone 31 together with recovered 290 ; the recovery of 290 supported our stereochemical assignment to the tricyclic g-lactones in light of the anti elimination mechanism in E2 reactions.34 Finally, removal of the TBS group in 31 furnished the target molecule 2, the 1 H and 13C NMR spectra of which showed good agreement with those reported.12a,b,35 The melting point and the specific rotation of 2 [mp¼104e106 C, [a]25 D ¼ þ8.24 (c¼1.25, CHCl3)] were also virtually identical with authentic data [mp¼103e104 C, [a]25 D ¼ þ8.28 (c¼1.3, CHCl3)].12a Since compound 2 was previously transformed into (þ)-strigol (1), albeit in non-diastereoselective manner,12aec the present synthesis constitutes a formal total synthesis of 1.36 3. Conclusion
Scheme 4. Installation of an acetate unit onto 18.
The final stage of our synthesis of 2 is shown in Scheme 5. The 2:1 mixture of 26 and 260 obtained in Scheme 4 was subjected to alkaline hydrolysis to afford carboxylic acid 27 (dr¼2:1), which was then exposed to NBS in CHCl3 in the presence of guanidine derivative 28.32 This bromolactonization reaction provided a mixture containing diastereomeric g-lactones 29 and 290 , and d-lactone 30 in a ratio of ca. 1:1:1, which was easily separated by silica gel column chromatography into a mixture of 29 and 290 , and 30. By repeating the separation of the mixture (29/290 ), each diastereomer could be isolated in a pure state,33 and the analysis of the NOESY spectra of 29 and 290 enabled the determination of their
In conclusion, an enantioselective synthesis of the tricyclic core structure (2) of (þ)-strigol (1) has been achieved from 2-iodo-4,4dimethyl-2-cyclohexen-1-one 9 by a 14-step sequence that features: (1) preparation of cyclohexenol derivative 7 of high enantiomeric excess (98% ee) by a modified CBS reduction of 9 coupled with hydrogenolysis of the resulting allylic alcohol 11; (2) regioselective epoxide ring opening of intermediate 13 with allylmagnesium bromide in a solvent of low polarity (13/14); (3) highly diastereoselective formation of bicyclic allylic alcohol 18 in two steps (15/19/18); and (4) Lewis acid-promoted introduction of an acetate unit into allyl acetate 22 (22/26). Efforts to improve the efficiency of the transformation of 22 into 2 are now in progress and will be reported in due course along with diastereoselective conversion of 2 into (þ)-strigol (1). 4. Experimental section 4.1. General IR spectra were recorded by a Jasco FT/IR-4100 spectrometer using an ATR (ZnSe) attachment. NMR spectra were recorded with TMS as an internal standard in CDCl3 by a Varian 400-MRTT spectrometer (400 MHz for 1H and 100 MHz for 13C) unless otherwise stated. Optical rotation values were measured with a Jasco P-2200
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
polarimeter, and mass spectra were obtained with Jeol JMS-700 spectrometer operated in the EI or FAB mode. Melting points were determined with a Yanaco MP-J3 apparatus and are uncorrected. Merck silica gel 60 (70e230 mesh) was used for column chromatography. Analytical thin-layer chromatography was performed using Merck silica gel 60 F254 plates (0.25 mm thick). Solvents for reactions were distilled prior to use: THF from Na and benzophenone; CH2Cl2 and DMF from CaH2; toluene, hexane, and ether from LiAlH4. All air- or moisture-sensitive reactions were conducted under a nitrogen atmosphere unless otherwise stated. 4.1.1. (S)-2-Iodo-4,4-dimethylcyclohex-2-en-1-ol (11). To a stirred solution of 10 (203 mg, 0.801 mmol) in THF (12 mL) was added B(OMe)3 (89 mL, 0.80 mmol) at room temperature. After 1 h of stirring, PhNMe2$BH3 (1.6 mL, 9.0 mmol) and a solution of 9 (2.00 g, 8.00 mmol) in THF (15 mL) were successively added, and the stirring was continued for 1 h. The mixture was quenched with MeOH, diluted with saturated aqueous NH4Cl, and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 30:1) to give 11 (1.85 g, 92%) as a colorless oil. [a]17 D ¼ 42.5 (c¼0.900, CH2Cl2). IR: n¼3446 (br w), 1669 (w) cm1. 1H NMR: d¼1.00 (s, 3H), 1.04 (s, 3H), 1.50 (ddd, J¼13.6, 8.4, 3.2 Hz, 1H), 1.63 (ddd, J¼13.6, 9.8, 3.2 Hz, 1H), 1.82e1.91 (m, 1H), 2.01 (d, J¼4.8 Hz, 1H, OH), 2.02e2.10 (m, 1H), 4.13 (br q, J¼5.0 Hz, 1H), 6.24 (s, 1H) ppm. 13C NMR: d¼28.0, 28.8 (2C), 32.2, 37.4, 72.0, 102.5, 150.3 ppm. HRMS (EI): calcd for C8H13OI [M]þ 252.0011; found 252.0010. 4.1.2. (S)-4,4-Dimethylcyclohex-2-en-1-ol (7). A mixture of 11 (8.95 g, 35.5 mmol), Et3N (5.90 mL, 42.3 mmol), and 5% Pd/C (4.88 g) in MeOH (170 mL) was stirred at room temperature for 1 h under a hydrogen atmosphere. The mixture was filtered through a pad of Celite, and the filtrate was concentrated in vacuo. The residue was diluted with water and extracted with EtOAc. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo to give 7 (3.87 g, 86%) as a colorless oil, which was pure enough to be used for the next step. [a]21 D ¼ 104 (c¼0.700, CHCl3). IR: n¼3346 (m), 3020 (w), 1056 (s), 746 (m) cm1. 1 H NMR: d¼0.97 (s, 3H), 1.02 (s, 3H), 1.39e1.47 (m, 2H), 1.54e1.67 (m, 2H), 1.87e1.96 (m, 1H), 4.15 (br s, 1H), 5.53 (d, J¼10.0 Hz, 1H), 5.60 (dd, J¼10.0, 2.8 Hz, 1H) ppm. 13C NMR: d¼29.0, 29.1, 29.2, 31.9, 33.6, 65.9, 127.3, 140.7 ppm. HRMS (EI): calcd for C8H14O [M]þ 126.1045; found 126.1043. 4.1.3. (1S,2S,6R)-5,5-Dimethyl-7-oxabicyclo[4.1.0]heptan-2-ol (12). To a stirred mixture of 7 (1.01 g, 8.00 mmol) and NaHCO3 (739 mg, 8.80 mmol) in CH2Cl2 (50 mL) was added MCPBA (70% purity, 2.17 g, 8.80 mmol) at 0 C. After 6 h, the mixture was concentrated in vacuo to a half of its original volume and filtered through a short column of alumina. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane/EtOAc, 2:1e1:1) to give 12 (cis/trans¼93:7, 1.13 g, 99%) as a colorless oil. [a]18 D ¼ 37.9 (c¼1.00, CHCl3). IR: n¼3420 (m), 1064 (w), 912 (w) cm1. 1H NMR: d¼1.02 (s, 3H), 1.06 (s, 1H, OH), 1.08 (s, 3H), 1.36 (ddd, J¼13.8, 9.2, 3.2 Hz, 1H), 1.42e1.51 (m, 1H), 1.53e1.62 (m, 1H), 1.99e2.04 (m, 1H), 2.93 (d, J¼3.6 Hz, 1H), 3.36 (t, J¼3.6 Hz, 1H), 3.97e4.04 (m, 1H) ppm. 13C NMR: d¼25.9, 26.3, 26.4, 29.1, 32.0, 56.4, 63.6, 66.3 ppm. HRMS (EI): calcd for C8H14O2 [M]þ 142.0994; found 142.0989. 4.1.4. tert-Butyl{[(1R,2S,6R)-5,5-dimethyl-7-oxabicyclo[4.1.0]heptan2-yl]oxy}dimethylsilane (13). To a stirred solution of 12 (2.00 g, 14.1 mmol) in DMF (45 mL) were added successively imidazole (2.80 g, 41.1 mmol) and TBSCl (4.10 g, 27.2 mmol) at 0 C. The mixture was gradually warmed to room temperature and stirred
6637
overnight. The mixture was quenched with saturated aqueous NaHCO3 at 0 C and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 20:1) to give 13 (3.32 g, 92%) as a colorless oil. [a]19 D ¼ 26.0 (c¼2.00, CHCl3). IR: n¼1110 (w), 913 (s), 744 (s) cm1. 1H NMR: d¼0.10 (s, 3H), 0.11 (s, 3H), 0.91 (s, 9H), 1.01 (s, 3H), 1.07 (s, 3H), 1.04e1.12 (m, 1H), 1.29e1.35 (m, 1H), 1.38e1.45 (m, 1H), 1.50e1.58 (m, 1H), 2.82 (dd, J¼4.0, 1.6 Hz, 1H), 3.16e3.18 (m, 1H), 4.00 (ddd, J¼9.6, 5.6, 2.0 Hz, 1H) ppm. 13C NMR: d¼4.6, e4.5, 18.3, 24.7, 25.7, 25.9 (3C), 28.6, 28.8, 35.7, 57.2, 62.6, 70.1 ppm. HRMS (EI): calcd for C14H28O2Si [M]þ 256.1858; found 256.1859. 4.1.5. (1S,5S,6S)-6-Allyl-5-[(tert-butyldimethylsilyl)oxy]-2,2dimethylcyclohexan-1-ol (14) and (1R,2S,6S)-2-Allyl-6-[(tert-butyldimethylsilyl)oxy]-3,3-dimethylcyclohexan-1-ol (140 ). A solution of allylmagnesium bromide in Et2O (1.0 m, 19.4 mL, 19.4 mmol) was placed in a flask. The solvent was removed in vacuo and then the residue was diluted with hexane (32 mL). To the resulting suspension was added a solution of 13 (3.32 g, 12.9 mmol) in toluene (32 mL) at room temperature. After 5 h of stirring at 40 C, the mixture was quenched with saturated aqueous NH4Cl at 0 C and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/ EtOAc, 50:1) to give 14 (2.83 g, 73%) as a colorless oil. Data for 14: Rf¼0.36 (hexane/EtOAc, 10:1; Merck silica gel 60 F254, 0.25 mm thick). [a]19 D ¼ þ29.7 (c¼2.00, CHCl3). IR: n¼3503 (m), 3075 (w), 1253 (m), 1100 (m), 837 (m) cm1. 1H NMR: d¼0.06 (s, 6H), 0.89 (s, 9H), 0.90 (s, 3H), 0.96 (s, 3H), 1.13 (ddd, J¼13.8, 13.8, 3.6 Hz, 1H), 1.35e1.72 (m, 5H), 2.28e2.37 (m, 1H), 2.48e2.56 (m, 1H), 3.06 (dd, J¼10.4, 5.2 Hz, 1H), 3.32 (ddd, J¼10.4, 10.4, 4.6 Hz, 1H), 5.05 (dm, J¼10.2 Hz, 1H), 5.15 (dm, J¼17.2 Hz, 1H), 5.95 (ddt, J¼17.2, 10.2, 7.2 Hz, 1H) ppm. 13C NMR: d¼4.7, e3.7, 18.1, 25.9 (4C), 28.9, 31.2, 32.6, 35.1, 35.2, 47.1, 72.3, 78.8, 116.4, 137.4 ppm. HRMS (FAB): calcd for C17H35O2Si [MþH]þ 299.2506; found 299.2409. Data for 140 : Rf¼0.53 (hexane/EtOAc, 10:1; Merck silica gel 60 F254, 0.25 mm thick). [a]18 D ¼ þ45.7 (c¼0.88, CHCl3). IR: n¼3575 (w), 3075 (w), 1637 (w), 1254 (m), 1083 (s), 837 (s), 775 (m) cm1. 1H NMR: d¼0.08 (s, 6H), 0.81 (s, 3H), 0.92 (s, 9H), 0.95 (s, 3H), 1.01e1.10 (m, 1H), 1.50 (dt, J¼10.4, 5.2 Hz, 1H), 1.56e1.67 (m, 3H), 1.76 (d, J¼10.4 Hz, 1H, OH), 2.15e2.28 (m, 2H), 3.34 (ddd, J¼10.4, 10.4, 2.8 Hz, 1H), 3.92e3.95 (m, 1H), 4.91 (dm, J¼10.4 Hz, 1H), 5.01 (dq, J¼16.8, 1.9 Hz, 1H), 5.97 (ddt, J¼16.8, 10.4, 6.8 Hz, 1H) ppm. 13C NMR: d¼4.9, e4.4, 18.1, 25.8 (4C), 28.1, 30.6, 32.5, 34.7, 34.8, 47.4, 71.0, 74.1, 113.7, 141.2 ppm. HRMS (FAB): calcd for C17H35O2Si [MþH]þ 299.2506; found 299.2405. 4.1.6. (5S,6R)-6-Allyl-5-[(tert-butyldimethylsilyl)oxy]-2,2dimethylcyclohexan-1-one (15). To a stirred solution of 14 (80.0 mg, 0.268 mmol) in CH2Cl2 (1.0 mL) were added successively iPr2NEt (233 mL, 1.34 mmol), DMSO (95 mL, 1.1234 mmol), and SO3$Py (128 mg, 0.804 mmol) at 0 C. After 3 h of stirring at ambient temperature, the mixture was quenched with water and extracted with CH2Cl2. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 50:1) to give 15 (73.0 mg, 92%) as a colorless oil. [a]19 D ¼ 2.9 (c¼2.00, CHCl3). IR: n¼3080 (w), 1711 (vs), 1254 (m), 1097 (s), 838 (s) cm1. 1 H NMR: d¼0.06 (s, 3H), 0.07 (s, 3H), 0.91 (s, 9H), 1.03 (s, 3H), 1.18 (s, 3H), 1.37 (ddd, J¼14.0, 12.0, 5.6 Hz, 1H), 1.67 (dt, J¼14.0, 3.8 Hz, 1H), 1.82e1.95 (m, 2H), 2.32e2.44 (m, 2H), 2.68 (ddd, J¼10.0, 7.6, 4.0 Hz, 1H), 3.47 (ddd, J¼10.0, 10.0, 5.2 Hz, 1H), 4.95 (dm, J¼10.0 Hz, 1H), 5.02 (dm, J¼17.2 Hz, 1H), 5.82 (ddt, J¼17.2, 10.0, 6.8 Hz, 1H) ppm. 13C NMR: d¼4.8, e4.0, 18.0, 24.9, 25.1, 25.8 (3C), 29.8, 31.3, 35.0, 44.3,
6638
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
55.5, 74.6, 115.6, 137.3, 213.6 ppm. HRMS (EI): calcd for C17H32O2Si [M]þ 296.2172; found 296.2172.
33.6, 36.3, 38.3, 49.6, 79.1, 79.4, 119.1, 160.3, 171.2 ppm. HRMS (EI): calcd for C19H34O3Si [M]þ 338.2277; found 338.2279.
4.1.7. (1S,5S,6R)-6-Allyl-5-((tert-butyldimethylsilyl)oxy)-2,2dimethyl-1-vinylcyclohexan-1-ol (19). To a stirred solution of tetravinyltin (1.7 mL, 9.34 mmol) in THF (40 mL) was added a solution of nBuLi (1.6 m in hexane, 23 mL, 36.8 mmol) at 78 C. After 30 min of stirring at the same temperature, the mixture was further stirred at ambient temperature for 15 min. To the resulting mixture was added a solution of 15 (6.95 g, 23.4 mmol) in THF (60 mL) while stirring at 78 C. After 40 min, the mixture was quenched with saturated aqueous NH4Cl and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (SiO2 containing 10 w/w % K2CO3; hexane/EtOAc, 70:1) to give 19 (7.52 g, 99%) as a colorless oil. [a]24 D ¼ 1.5 (c¼2.00, CHCl3). IR: n¼3566 (m), 3070 (w), 1254 (m), 1077 (m), 837 (m) cm1. 1 H NMR (600 MHz, DMSO-d6): d¼0.00 (s, 3H), 0.02 (s, 3H), 0.69 (s, 3H), 0.83 (s, 9H), 0.93 (s, 3H), 1.20e1.27 (m, 1H), 1.39e1.48 (m, 2H), 1.60 (dt, J¼10.3, 5.2 Hz, 1H), 1.65e1.69 (m, 1H), 1.79e1.85 (m, 1H), 2.13e2.19 (m, 1H), 3.42e3.47 (m, 1H), 3.94 (s, 1H, OH), 4.74 (dm, J¼10.2 Hz, 1H), 4.81 (dm, J¼17.1 Hz, 1H), 5.12 (dd, J¼10.9, 2.5 Hz, 1H), 5.26 (dd, J¼16.9, 2.5 Hz, 1H), 5.90e5.98 (m, 2H) ppm. 13C NMR (150 MHz, DMSO-d6): d¼4.3, e3.5, 18.1, 22.6, 26.26 (3C), 26.32, 32.1, 32.8, 34.7, 37.8, 49.9, 74.5, 79.3, 113.4, 114.9, 139.4, 142.1 ppm. HRMS (EI): calcd for C19H36O2Si [M]þ 324.2485; found 324.2488.
4.1.10. (3aR,5S,8bS)-5-[(tert-Butyldimethylsilyl)oxy]-8,8-dimethyl3,3a,4,5,6,7,8,8b-octahydro-2H-indeno[1,2-b]furan-2-one (31). To a stirred solution of 22 (115 mg, 0.340 mmol) in CH2Cl2 (3.4 mL) were successively added 25 (148 mL, 0.678 mmol) and BF3$OEt2 (51 mL, 0.41 mmol) at 78 C. After 1 h, the mixture was quenched with saturated aqueous NaHCO3 and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 70:1) to give a 2:1 mixture of 26 and 260 (103 mg, 86%) as a colorless oil. To a stirred solution of the mixture (100 mg, 0.284 mmol) in MeOH/hexane (1:1, 1.3 mL) was added 5 m aqueous NaOH (630 mL, 3.15 mmol) at room temperature. After 2 h, the mixture was neutralized with 2 m aqueous HCl at 0 C and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 8:1) to give 27 (91 mg, 95%, dr 2:1) as a colorless oil. To a stirred solution of 27 (95.0 mg, 0.281 mmol) in CHCl3 (1.4 mL) were successively added NBS (50.0 mg, 0.281 mmol) and 28 (4.0 mL, 0.032 mmol) at room temperature. After 5 min, the mixture was quenched with saturated aqueous Na2S2O3 and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 30:1) to give a mixture of 29, 290 , and 30 which was taken up in toluene (2.7 mL). To the solution was added DBU (61 mL, 0.41 mmol) and the resulting solution was stirred at 80 C for 26 h. The mixture was cooled to room temperature and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 30:1) to give 31 (24.0 mg, 25% from 27) as a colorless oil. [a]24 D ¼ 11 (c¼0.520, CHCl3). IR: n¼1776 (s), 1254 (m), 1167 (m), 1090 (m), 839 (m) cm1. 1H NMR: d¼0.068 (s, 3H), 0.074 (s, 3H), 0.90 (s, 9H), 1.08 (s, 3H), 1.15 (s, 3H), 1.42 (ddd, J¼13.0, 13.0, 3.0 Hz, 1H), 1.54 (ddd, J¼13.0, 5.6, 3.0 Hz, 1H), 1.70 (dddd, J¼13.0, 13.0, 9.0, 3.0 Hz, 1H), 1.82e1.90 (m, 1H), 2.35 (dd, J¼18.4, 5.8 Hz, 1H), 2.43 (br d, J¼16.8 Hz, 1H), 2.51 (dd, J¼16.8, 8.0 Hz, 1H), 2.79 (dd, J¼18.4, 10.4 Hz, 1H), 2.98e3.08 (m, 1H), 4.12 (br t, J¼7.0 Hz, 1H), 5.46 (dt, J¼7.6, 2.0 Hz, 1H) ppm. 13C NMR: d¼4.9, e4.3, 18.1, 25.8 (3C), 27.3, 27.9, 30.0, 32.2, 34.4, 36.0, 37.6, 38.8, 68.3, 89.9, 141.4, 143.5, 177.4 ppm. HRMS (EI): calcd for C19H32O3Si [M]þ 336.2121; found 336.2119. The intermediates 29 and 290 could be separated by repeated silica gel column chromatography (hexane/EtOAc, 30:1) and exhibited the following physicochemical properties. Data for 29: mp 107e109 C. [a]23 D ¼ þ8.4 (c¼0.500, CHCl3). IR: n¼1789 (vs), 1157 (m), 1100 (m) cm1. 1H NMR: d¼0.05 (s, 3H), 0.06 (s, 3H), 0.88 (s, 9H), 1.26 (s, 3H), 1.36 (s, 3H), 1.29e1.36 (m, 1H), 1.48e1.60 (m, 1H), 1.69e1.78 (m, 2H), 1.99e2.09 (m, 2H), 2.20 (dt, J¼13.2, 10.6 Hz, 1H), 2.36 (dd, J¼18.4, 1.8 Hz, 1H), 2.80 (dd, J¼18.4, 10.0 Hz, 1H), 3.17e3.26 (m, 1H), 3.87 (ddd, J¼10.6, 9.0, 5.2 Hz, 1H), 5.19 (d, J¼5.6 Hz, 1H) ppm. 13C NMR: d¼4.7, e4.2, 18.0, 24.9, 25.8 (3C), 28.7, 31.9, 35.7, 36.2, 36.7, 39.0, 39.2, 47.6, 74.5, 89.8, 95.9, 176.8 ppm. HRMS (EI): calcd for C19H33O3BrSi [M]þ 416.1383; found 416.1382. Data for 290 : mp 70e72 C. [a]23 D ¼ 7.1 (c¼0.500, CHCl3). IR: n¼1787 (s), 1253 (m), 1155 (m), 1092 (m), 836 (m) cm1. 1H NMR (600 MHz): d¼0.04 (s, 3H), 0.05 (s, 3H), 0.87 (s, 9H), 1.20 (s, 3H), 1.36 (s, 3H), 1.51e1.61 (m, 2H), 1.66 (dd, J¼14.4, 3.2 Hz, 1H), 1.69e1.74 (m, 1H), 2.00e2.07 (m, 1H), 2.38 (d, J¼18.4 Hz, 1H), 2.48 (br t, J¼8.9 Hz, 1H), 2.74 (ddd, J¼14.4, 11.3, 7.7 Hz, 1H), 2.85 (dd, J¼18.4, 10.2 Hz, 1H), 3.28 (ddd, J¼10.6, 10.6, 4.7 Hz, 1H), 3.31e3.37 (m, 1H), 5.12 (d, J¼6.0 Hz, 1H) ppm. 13C NMR: d¼4.7, e3.8, 17.9, 25.5, 25.8 (3C), 30.5, 31.1, 35.5, 36.3, 37.0, 37.3, 37.7, 55.1,
4.1.8. (3aS,7S,7aR)-7-[(tert-Butyldimethylsilyl)oxy]-4,4-dimethyl1,4,5,6,7,7a-hexahydro-3aH-inden-3a-ol (18). A mixture of 19 (400 mg, 1.23 mmol) and the second generation Grubbs catalyst (104 mg, 0.123 mmol) in CH2Cl2 (12 mL) was heated under reflux for 1.5 h and then cooled to room temperature. To the mixture was added DMSO (438 mL, 6.17 mmol) and the resulting mixture was stirred overnight. The mixture was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane/ EtOAc, 30:1) to give 18 (358 mg, 98%) as a colorless oil. [a]24 D ¼ þ75.8 (c¼0.515, CHCl3). IR: n¼3480 (br w), 3046 (w), 1255 (m), 1094 (s), 1005 (m) cm1. 1H NMR: d¼0.03 (s, 6H), 0.88 (s, 9H), 1.01 (s, 3H), 1.06 (s, 3H), 1.11 (ddd, J¼14.0, 8.8, 7.6 Hz, 1H), 1.24e1.32 (br s, 1H, OH), 1.40 (dt, J¼14.0, 4.0 Hz, 1H), 1.53e1.62 (m, 2H), 2.04 (dd, J¼8.4, 5.2 Hz, 1H), 2.21 (d, J¼16.8 Hz, 1H), 2.66 (dd, J¼16.8, 5.2 Hz, 1H), 3.12 (ddd, J¼8.4, 8.4, 7.2 Hz, 1H), 5.98e6.02 (m, 2H) ppm. 13C NMR: d¼4.6, e3.8, 18.0, 24.0, 25.8, 25.9 (3C), 29.7, 35.1, 35.3, 35.7, 53.0, 75.3, 88.3, 135.7, 136.1 ppm. HRMS (EI): calcd for C17H32O2Si [M]þ 296.2171; found 296.2173. 4.1.9. (3aS,7S,7aR)-7-[(tert-Butyldimethylsilyl)oxy]-4,4-dimethyl1,4,5,6,7,7a-hexahydro-3aH-inden-3a-yl acetate (22). To a stirred solution of 18 (350 mg, 1.18 mmol) in toluene (14 mL) were successively added Et3N (1.60 mL, 11.5 mmol), DMAP (29 mg, 0.24 mmol) and Ac2O (1.10 mL, 11.6 mmol) at room temperature. The mixture was heated under reflux for 33 h and then cooled to room temperature before being quenched with water and extracted with ether. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 50:1) to give 22 (291 mg, 73%) as a colorless oil. [a]23 D ¼ 89.9 (c¼1.50, CHCl3). IR: n¼1733 (s), 1245 (s), 1095 (m), 838 (m) cm1. 1H NMR: d¼0.05 (s, 6H), 0.89 (s, 9H), 1.09 (s, 3H), 1.13 (s, 3H), 1.19 (ddd, J¼13.6, 13.6, 4.4 Hz, 1H), 1.46 (dt, J¼13.6, 3.4 Hz, 1H), 1.58e1.64 (m, 1H), 1.65e1.73 (m, 1H), 1.97 (ddd, J¼15.0, 7.6, 5.2 Hz, 1H), 2.01 (s, 3H), 2.10 (ddd, J¼15.0, 7.6, 2.0 Hz, 1H), 2.74e2.82 (m, 1H), 3.05 (ddd, J¼10.4, 10.4, 4.8 Hz, 1H), 5.42 (t, J¼2.4 Hz, 1H), 5.57e5.61 (m, 1H) ppm. 13C NMR: d¼4.6, e3.9, 18.0, 21.4, 25.75, 25.82 (3C), 28.2, 31.8,
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
73.6, 91.2, 91.6, 176.8 ppm. HRMS (EI): calcd for C19H33O3BrSi [M]þ 416.1383; found 416.1382. 4.1.11. (3aR,5S,8bS)-5-Hydroxy-8,8-dimethyl-3,3a,4,5,6,7,8,8b-octahydro-2H-indeno[1,2-b]furan-2-one (2). To a solution of 31 (20.0 mg, 0.0594 mmol) in THF (110 mL) was added a solution of TBAF (1.0 m in THF, 118 mL, 0.12 mmol) at room temperature. After 10 min, the mixture was quenched with saturated aqueous NaHCO3 and extracted with EtOAc. The extract was successively washed with saturated water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 5:1e2:1) and recrystallization (hexane/ CH2Cl2) to give 2 (10.0 mg, 76%) as a white solid. Mp 104e106 C 11a (lit.11a mp 103e106 C). [a]25 [a]25 D ¼ þ8.24 (c¼1.25, CHCl3) [lit. D ¼ þ8.28 (c¼1.3, CHCl3)]. IR: n¼3445 (m), 1769 (s), 1168 (m), 913 (m), 743 (m) cm1. 1H NMR: d¼1.09 (s, 3H), 1.16 (s. 3H), 1.43 (d, J¼6.4 Hz, 1H, OH), 1.46 (ddd, J¼13.6, 11.2, 3.0 Hz, 1H), 1.59 (ddd, J¼13.6, 6.8, 2.8 Hz, 1H), 1.66e1.76 (m, 1H), 1.95e2.04 (m, 1H), 2.37 (dd, J¼18.4, 5.0 Hz, 1H), 2.50 (br d, J¼16.8 Hz, 1H), 2.63 (dd, J¼16.8, 8.0 Hz, 1H), 2.82 (dd, J¼18.4, 10.4 Hz, 1H), 3.03e3.13 (m, 1H), 4.14 (q, J¼6.4 Hz, 1H), 5.47 (d, J¼7.6 Hz, 1H) ppm. 13C NMR: d¼27.4, 27.5, 29.6, 32.3, 34.5, 35.9, 36.8, 38.6, 67.1, 89.7, 142.4, 142.7, 177.3 ppm. HRMS (EI): calcd for C13H18O3 [M]þ 222.1256; found 222.1256. Acknowledgements We are grateful to Ms. Yuka Taguchi (Tohoku University) for her help in NMR and MS measurements. Supplementary data Supplementary data (NMR spectra of 2 and key synthetic intermediates) associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.tet.2016.08.078. References and notes 1. (a) Cook, C. E.; Whichard, L. P.; Turner, B.; Wall, M. E. Science 1966, 154, 1189e1190; (b) Cook, C. E.; Whichard, L. P.; Wall, M. E.; Egley, G. H.; Coggon, P.; Luhan, P. A.; McPhail, A. T. J. Am. Chem. Soc. 1972, 94, 6198e6199; (c) Brooks, D. W.; Bevinakatti, H. S.; Powell, D. R. J. Org. Chem. 1985, 50, 3779e3781. 2. Parker, C. Weed Sci. 2012, 60, 269e276. 3. Siame, B. A.; Weerasuriya, Y.; Wood, K.; Ejeta, G.; Butler, L. G. J. Agric. Food Chem. 1993, 41, 1486e1491. 4. For a review, see Cavar, S.; Zwanenburg, B.; Tarkowski, P. Phytochem. Rev. 2015, 14, 691e711. 5. It was reported that synthetic strigolactone analogs could also induce seed germination of non-parasitic plants. For details, see: (a) Bradow, J. M.; Connick, W. J., Jr.; Papperman, A. B.; Wartelle, L. H. J. Plant Growth Regul. 1990, 9, 35e41; (b) -Pfister, R.; Villedieu-Percherron, E.; Lachia, M.; Jung, P. M. J.; Screpanti, C.; Fonne Wendeborn, S.; Zurwerra, D.; De Mesmaeker, A. Chimia 2014, 68, 654e663. 6. Akiyama, K.; Matsuzaki, K.; Hayashi, H. Nature 435, 824e827. s, V.; Dun, E. A.; 7. (a) Gomez-Roldan, V.; Fermas, S.; Brewer, P. B.; Puech-Page Pillot, J.-P.; Letisse, F.; Matusova, R.; Danoun, S.; Portais, J.-C.; Bouwmeester, H.; card, G.; Beveridge, C. A.; Rameau, C.; Rochange, S. F. Nature 2008, 455, Be 189e194; (b) Umehara, M.; Hanada, A.; Yoshida, S.; Akiyama, K.; Arite, T.; Takeda-Kamiya, N.; Magome, H.; Kamiya, Y.; Shirasu, K.; Yoneyama, K.; Kyozuka, J.; Yamaguchi, S. Nature 2008, 455, 195e200. 8. For reviews, see: (a) Seto, Y.; Kameoka, H.; Yamaguchi, S.; Kyozuka, J. Plant Cell Physiol. 2012, 53, 1843e1853; (b) Zwanenburg, B.; Pospísil, T. Mol. Plant 2013, 6, 38e62; (c) Zwanenburg, B.; Pospísil, T.; Zeljkovic, S. C. Planta 2016, 243, 1311e1326; (d) Flematti, G. R.; Scaffidi, A.; Waters, M. T.; Smith, S. M. Planta 2016, -Pfister, R.; Lumbroso, A.; Rendine, S.; 243, 1361e1373; (e) Screpanti, C.; Fonne Lachia, M.; De Mesmaeker, A. Bioorg. Med. Chem. Lett. 2016, 26, 2392e2400.
6639
9. Heather, J. B.; Mittal, R. S. D.; Sih, C. J. J. Am. Chem. Soc. 1974, 96, 1976e1977. 10. (a) Boyer, F.-D.; de Saint Germain, A.; Pillot, J.-P.; Pouvreau, J.-B.; Chen, V. X.; venin, A.; Simier, P.; Delavault, P.; Beau, J.-M.; Rameau, C. Plant Ramos, S.; Ste Physiol. 2012, 159, 1524e1544; (b) Lachia, M.; Wolf, H. C.; Jung, P. J. M.; Screpanti, C.; De Mesmaeker, A. Bioorg. Med. Chem. Lett. 2015, 25, 2184e2188; (c) Zwanenburg, B.; Regeling, H.; van Tilburg-Joukema, C. W.; van Oss, B.; Molenveld, P.; de Gelder, R.; Tinnemans, P. Eur. J. Org. Chem. 2016, 2163e2169; (d) Takahashi, I.; Fukui, K.; Asami, T. Pest Manag. Sci. [Online early access]. doi: 10. 1002/ps.4265. 11. For a review, see Zwanenburg, B.; Zeljkovic, S. C.; Pospísil, T. Pest Manag. Sci. 2016, 72, 15e29. 12. (a) Heather, J. B.; Mittal, R. S. D.; Sih, C. J. J. Am. Chem. Soc. 1976, 98, 3661e3669; (b) Samson, E.; Frischmuth, K.; Berlage, U.; Heinz, U.; Hobert, K.; Welzel, P. Tetrahedron 1991, 47, 1411e1416; (c) Hirayama, K.; Mori, K. Eur. J. Org. Chem. 1999, 2211e2217; (d) Chen, V. X.; Boyer, F.-D.; Rameau, C.; Retailleau, P.; Vors, J.-P.; Beau, J.-M. Chem.dEur. J. 2010, 16, 13941e13945. 13. (a) Berlage, U.; Schmidt, J.; Milkova, Z.; Welzel, P. Tetrahedron Lett. 1987, 28, 3095e3098; (b) Matsui, J.; Bando, M.; Kido, M.; Takeuchi, Y.; Mori, K. Eur. J. Org. Chem. 1999, 2183e2194. 14. Sugimoto, Y.; Wigchert, S. C. M.; Thuring, J. W. J. F.; Zwanenburg, B. J. Org. Chem. 1998, 63, 1259e1267. 15. Lachia, M.; Dakas, P. Y.; De Mesmaeker, A. Tetrahedron Lett. 2014, 55, 6577e6581. 16. Ohkuma, T.; Ikehira, H.; Ikariya, T.; Noyori, R. Synlett 1997, 467e468. 17. For an alternative method to obtain 7 (96% ee) from rac-7 via multiple enzymatic treatments, see Winska, K.; Grudniewska, A.; Chojnacka, A.; Biolonska, A.; Wawrzenczyk, C. Tetrahedron: Asymmetry 2010, 21, 670e678. 18. (a) Masui, M.; Shioiri, T. Synlett 1997, 273e274; (b) Salunkhe, S. M.; Burkhardt, E. R. Tetrahedron Lett. 1997, 38, 1523e1526; (c) Soorukram, D.; Knochel, P. Org. Lett. 2004, 6, 2409e2411; (d) Fujioka, H.; Matsuda, S.; Horai, M.; Fujii, E.; Morishita, M.; Nishiguchi, N.; Hara, K.; Kita, Y. Chem.dEur. J. 2007, 13, 5238e5248. 19. The enantiomeric excess of 11 (98% ee) was determined by analyzing the 1H NMR spectra of the corresponding (R)- and (S)-MTPA esters. 20. Liu, H.; Yan, P.; Li, Y.; Liu, J.; Sun, Q.; Wang, X.; Wang, C. Monatsh. Chem. 2012, 143, 1055e1059. 21. Boyd, D. R.; Sharma, N. D.; Malone, J. F.; Allen, C. C. R. Chem. Commun. 2009, 3633e3635. 22. Nicolai, S.; Swallow, P.; Waser, J. Tetrahedron 2015, 71, 5959e5964. 23. The ratio of 14 and 140 was determined by 1H NMR analysis of the crude reaction product. 24. When the reaction was conducted at 40 C in ether/hexane (1:1), the 14/140 ratio was 1.8:1, while in toluene the ratio was 2.2:1. 25. For related studies, see: (a) Chini, M.; Crotti, P.; Flippin, L. A.; Gardelli, C.; Macchia, F. J. Org. Chem. 1992, 57, 1713e1718; (b) Cainelli, G.; Giacomini, D.; , A. Tetrahedron: Asymmetry 1994, 5, 1913e1916. Perciaccante, F.; Trere 26. Stork, G.; Zhao, K. Tetrahedron Lett. 1989, 30, 2173e2174. 27. Jin, H.; Uenishi, J.; Christ, W. J.; Kishi, Y. J. Am. Chem. Soc. 1986, 108, 5644e5646. 28. Ahn, Y. M.; Yang, K.; Georg, G. I. Org. Lett. 2001, 3, 1411e1413. 29. For a review of Claisen-type rearrangements, see Castro, A. M. M. Chem. Rev. 2004, 104, 2939e3002. 30. Trost, B. M.; Vranken, D. L. V. Chem. Rev. 1996, 96, 395e422 and references cited therein. 31. (a) Mukaiyama, T.; Nagaoka, H.; Ohshima, M.; Murakami, M. Chem. Lett. 1986, 1009e1012; (b) Musacchio, A. J.; Nguyen, L. Q.; Beard, G. H.; Knowles, R. R. J. Am. Chem. Soc. 2014, 136, 12217e12220. 32. Ahmad, S. M.; Braddock, D. C.; Cansell, G.; Hermitage, S. A. Tetrahedron Lett. 2007, 48, 915e918. 33. Although the d-lactone 30 was not fully purified, the structure could be deduced from its MS, IR and 1H NMR data including NOE correlations. MS (EI): m/ z 416 [C19H3379BrO3Si (Mþ)] and 418 [C19H3381BrO3Si (Mþ)]; IR: nmax 1739 (vs); 1 H NMR (600 MHz, CDCl3): d 0.07 (3H, s), 0.08 (3H, s), 0.88 (9H, s), 1.17 (3H, s), 1. 18 (3H, s), 1.35 (1H, dt, J¼14.4, 3.6 Hz), 1.59e1.64 (1H, m), 1.65e1.70 (1H, m), 2. 09 (1H, dd, J¼14.2, 8.9 Hz), 2.17e2.26 (2H, m), 2.34e2.39 (1H, m), 2.60 (1H, dd, J¼18.4, 2.1 Hz), 2.69e2.72 (1H, m), 2.90 (1H, ddd, J¼18.4, 4.8, 2.6 Hz), 3.99 (1H, ddd, J¼11.5, 9.6, 5.3 Hz), 4.22 (1H, br s). 34. It should be noted that the d-lactone 30 was also recovered without any change when exposed to DBU in toluene at 80 C. 35. Brooks, D. W.; Bevinakatti, H. S.; Kennedy, E.; Hathaway, J. J. Org. Chem. 1985, 50, 628e632. 36. For studies on diastereoselective connection of an ABC scaffold to a D-ring unit, €hrig, S.; Milkova, Z. Chem. Commun. 1999, 2017e2022; (b) see: (a) Welzel, P.; Ro Reizelman, A.; Zwanenburg, B. Eur. J. Org. Chem. 2002, 810e814; (c) Bromhead, L. J.; Visser, J.; McErlean, C. S. P. J. Org. Chem. 2014, 79, 1516e1520; (d) Ref. 11 and references cited therein.
Contents lists available at ScienceDirect
Tetrahedron journal homepage: www.elsevier.com/locate/tet
Enantioselective synthesis of the tricyclic core of (þ)-strigol Aiko Takahashi, Yusuke Ogura, Masaru Enomoto, Shigefumi Kuwahara * Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 30 July 2016 Received in revised form 25 August 2016 Accepted 29 August 2016 Available online 31 August 2016
An enantioselective synthesis of the tricyclic core structure of (þ)-strigol, a potent seed germination stimulant for root parasitic weeds, has been achieved from 2-iodo-4,4-dimethyl-2-cyclohexen-1-one in 14 steps. The key steps include a CBS reduction of an iodo enone to obtain a cyclohexenol derivative of high enantiomeric excess, regioselective epoxide ring opening with a Grignard reagent in a low-polarity solvent, highly diastereoselective addition of vinyllithium to a ketone, and Lewis acid-promoted installation an acetate unit onto a bicyclic allylic acetate intermediate. Ó 2016 Elsevier Ltd. All rights reserved.
Keywords: Strigol Strigolactone Plant hormone Epoxide Total synthesis
1. Introduction (þ)-Strigol (1) is the first member of the strigolactone family of natural products discovered in 1966 as a potent seed germination stimulant for the root parasitic weed Striga lutea (syn. Striga asiatica) which causes significant damage to crops of gramineous and leguminous plants mainly in the tropical and subtropical areas of Africa and Asia (Fig. 1).1,2 It was originally isolated from the root exudates of cotton (a non-host plant for the weed),1a and later from those of its genuine hosts of economical importance (maize, proso millet, and sorghum).3 Strigolactones are now known to be produced also by a wide range of plants other than host plants for parasitic weeds and consist of 15 members.4 This family of natural products are structurally characterized by a fused tricyclic g-lactone core (ABC scaffold) connected through an enol ether linkage to an a,b-unsaturated g-lactone unit (D ring). They all have the same C/D ring structure as 1, while their A/B ring portions show some structural diversity.4 Besides the seed germination stimulatory activity toward parasitic weeds,5 strigolactones have been elucidated to possess some additional functions of enormous biological importance, especially: (1) induction of hyphal branching in arbuscular mycorrhizal fungi that enables the fungi to establish their symbiosis with plants;6 and (2) activity as a plant hormone to suppress the growth of preformed axillary shoot buds and thereby inhibit shoot branching.7 These plant physiologically and
* Corresponding author. Fax: þ81 22 717 8783; e-mail address: skuwahar@biochem. tohoku.ac.jp (S. Kuwahara). http://dx.doi.org/10.1016/j.tet.2016.08.078 0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
agriculturally important functions of strigolactones prompted a great deal of studies from various aspects such as isolation of new members, mode of action, biosynthesis, and identification of receptor.4,8
Fig. 1. Structures of (þ)-strigol (1) and its tricyclic core (2).
Synthetic studies on strigolactones and their analogs for structureeactivity relationship investigations have also been actively conducted by many research groups and numerous publications have appeared since the first total synthesis of ()-strigol by Sih and co-workers in 19749e11 As for the synthesis of optically active forms of naturally occurring strigolactones, four types of synthetic strategies have been adopted with the exception of direct resolution of their synthetic racemates: (1) preparation of an optically active ABC scaffold via optical resolution (including enzymatic or chiral HPLC separation) and its non-diastereoselective connection to a racemic D ring unit followed by chromatographic separation of the resulting diastereomeric mixture;12 (2) preparation of an optically active ABC scaffold from the chiral pool followed by the same
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
6635
sequence as described in (1);13 (3) preparation of a racemic ABC scaffold and its connection to an optically active D ring unit followed by chromatographic separation of the resulting diastereomeric mixture;14 and (4) asymmetric synthesis of an ABC scaffold and its connection to a racemic D ring unit followed by diastereomeric separation.15 However, the strategy composed of asymmetric synthesis of an ABC scaffold and its diastereoselective unification with a D ring moiety has never been reported so far. As part of our efforts toward such a totally stereoselective synthesis of strigolactones, we describe herein a synthetic approach to the tricyclic ABC core (2) of (þ)-strigol. To the best of our knowledge, this is the first example of the synthesis of 2 that uses neither optical resolution nor naturally occurring chiral starting materials.12aec,13a Scheme 2. Enantioselective preparation of 7 and its conversion into siloxy epoxide 13.
2. Results and discussion Scheme 1 outlines our retrosynthetic analysis of 2. Compound 2 was traced back to olefinic carboxylate 3 with the intention of installing the g-lactone and the double bond in 2 by halolactonization of 3 and subsequent dehydrohalogenation. The g,d-unsaturated carboxylate 3 would be obtainable by SN20 -type introduction of an acetate unit into 4. For the construction of the bicyclic allylic alcohol 4, we envisaged a two-step sequence comprising the addition of a vinyl group to ketone 5 from its bottom face and ring-closing metathesis (RCM) of the resulting diene product. The ketone 5 would be prepared by regioselective ring opening of epoxide 6, which in turn should be derived from optically active cyclohexenol derivative 7 by hydroxyl-directed epoxidation.
allylmagnesium bromide in refluxing ether,22 gave a 1.1:1 mixture of 14 and its regioisomer 140 ,23 changing the solvent from ether to toluene/hexane (1:1) significantly increased the ratio to 3.2:1, providing the desired isomer 14 in 73% isolated yield.24,25 To obtain bicyclic intermediate 18, the alcohol 14 was first oxidized to olefinic ketone 15, the ozonolysis of which afforded 16. Z-Selective iodomethylenation of the aldehyde 16 followed by intramolecular NozakieHiyamaeKishi coupling of the resulting iodo ketone 17 furnished 18.26,27 Compound 18 was also prepared much more efficiently in two steps from 15 by its exposure to vinyllithium in THF at 78 C to form allylic alcohol 19 as the exclusive diastereomer and subsequent ring-closing metathesis of the diene product 19.28 It is worth mentioning that the reaction of 15 with vinylmagnesium chloride (instead of vinyllithium) in THF was very sluggish at low temperatures (78 to 50 C) presumably due to steric congestion around the ketone functionality, and a substantial amount of the corresponding epimeric alcohol (1-epi-19) was also produced when the reaction temperature was raised to room temperature.
Scheme 1. Retrosynthetic analysis of 2.
Our first task for the synthesis of 2 was the preparation of 7 in high enantiomeric purity (Scheme 2). Although compound 7 was known to be preparable by a Noyori asymmetric reduction of the corresponding enone, the enantiomeric excess (ee) of the alcoholic product 7 was reported to be only 47%.16,17 We, therefore, adopted an alternative route via iodine-substituted cyclohexenol derivative 11, the (R)-enantiomer of which had previously been synthesized in 98% ee by a modified CoreyeBakshieShibata (CBS) reduction using diethylaniline$BH3 and a catalytic amount of (S)-2-methoxy-CBSoxazaborolidine.18 The reduction of 9 using (R)-2-methoxy-CBS oxazaborolidine as catalyst proceeded smoothly, providing 11 in 92% yield;18c,19 the iodo enone 9 in turn was readily prepared from enone 8 almost quantitatively according to the literature (I2, DMAP, K2CO3, THFeH2O).20 Hydrogenolytic removal of the iodine atom in 11 was best performed with 5% Pd/C in MeOH in the presence of Et3N as catalyst poison,21 furnishing 7 in a satisfactory overall yield of 76% from 8. Diastereoselective epoxidation of 12 with MCPBA in the presence of solid NaHCO3 afforded 12 as an inseparable 93:7 cis/ trans mixture. Finally, protection of the alcohol as its TBS ether provided 13. With the protected cis-epoxy alcohol 13 in hand, we next proceeded to its epoxide ring opening with allylmagnesium bromide (Scheme 3). Although the epoxide 13, upon exposure to
Scheme 3. Preparation of bicyclic allylic alcohol 18.
The installation of an acetate unit at the C2 position of 18 was first attempted by applying the JohnsoneClaisen rearrangement to the cyclic allylic alcohol (Scheme 5, a). Treatment of 18 with triethyl or trimethyl orthoacetate in the presence of an acid catalyst (propionic acid, p-anisic acid, or o-nitrophenol) at high temperatures ranging from 135 to 180 C, however, gave no desired product 20,
6636
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
resulting in the formation of complex mixtures.29 The EschenmosereClaisen rearrangement of 18 to 21 was also unsuccessful (b). The IrelandeClaisen rearrangement of acetate 22, obtained by acetylation of 18, was also attempted by treating 22 with a base (MNR0 2¼LDA or KHMDS) and a silylating agent (TMSCl or TBSCl) in THF, THF/HMPA, or toluene, and then stirring the mixture at temperatures ranging from 78 to 110 C (c). However, neither the desired product 23 nor the corresponding carboxylic acid was detected in the reaction mixture. The introduction of a malonate unit into 22 by the TsujieTrost reaction was next examined (d).30 Although the reaction of 22 with dimethyl malonate was conducted under various conditions (base: NaH, K2CO3, or Cs2CO3; Pd(0) species: Pd(PPh3)3 or Pd2(dba)3; ligand: Ph3P, n-Bu3P, or dppe), none of the conditions gave the desired product 24, resulting in the recovery of the starting material 22 in most cases. The installation of an acetate unit onto 22 was eventually achieved by modification of the procedure developed by Mukaiyama and coworkers which had rarely been documented in the literature.31 When a mixture of 22 and silyl ketene acetal 25 in CH2Cl2 was treated with BF3$OEt2 at 78 C, a quick reaction took place to give an inseparable mixture of 26 and 260 in 86% yield, albeit with a modest selectivity of 2:1. The stereochemistry of each epimer was assigned later at the stage of 29/290 (see Scheme 5) on the basis of their NOESY spectra (vide infra).
Scheme 5. Completion of the synthesis of 2.
stereochemistries as depicted in Scheme 5 (see Supplementary data). The mixture of 29 and 290 was treated with DBU in toluene to afford, after silica gel column chromatographic separation, olefinic lactone 31 together with recovered 290 ; the recovery of 290 supported our stereochemical assignment to the tricyclic g-lactones in light of the anti elimination mechanism in E2 reactions.34 Finally, removal of the TBS group in 31 furnished the target molecule 2, the 1 H and 13C NMR spectra of which showed good agreement with those reported.12a,b,35 The melting point and the specific rotation of 2 [mp¼104e106 C, [a]25 D ¼ þ8.24 (c¼1.25, CHCl3)] were also virtually identical with authentic data [mp¼103e104 C, [a]25 D ¼ þ8.28 (c¼1.3, CHCl3)].12a Since compound 2 was previously transformed into (þ)-strigol (1), albeit in non-diastereoselective manner,12aec the present synthesis constitutes a formal total synthesis of 1.36 3. Conclusion
Scheme 4. Installation of an acetate unit onto 18.
The final stage of our synthesis of 2 is shown in Scheme 5. The 2:1 mixture of 26 and 260 obtained in Scheme 4 was subjected to alkaline hydrolysis to afford carboxylic acid 27 (dr¼2:1), which was then exposed to NBS in CHCl3 in the presence of guanidine derivative 28.32 This bromolactonization reaction provided a mixture containing diastereomeric g-lactones 29 and 290 , and d-lactone 30 in a ratio of ca. 1:1:1, which was easily separated by silica gel column chromatography into a mixture of 29 and 290 , and 30. By repeating the separation of the mixture (29/290 ), each diastereomer could be isolated in a pure state,33 and the analysis of the NOESY spectra of 29 and 290 enabled the determination of their
In conclusion, an enantioselective synthesis of the tricyclic core structure (2) of (þ)-strigol (1) has been achieved from 2-iodo-4,4dimethyl-2-cyclohexen-1-one 9 by a 14-step sequence that features: (1) preparation of cyclohexenol derivative 7 of high enantiomeric excess (98% ee) by a modified CBS reduction of 9 coupled with hydrogenolysis of the resulting allylic alcohol 11; (2) regioselective epoxide ring opening of intermediate 13 with allylmagnesium bromide in a solvent of low polarity (13/14); (3) highly diastereoselective formation of bicyclic allylic alcohol 18 in two steps (15/19/18); and (4) Lewis acid-promoted introduction of an acetate unit into allyl acetate 22 (22/26). Efforts to improve the efficiency of the transformation of 22 into 2 are now in progress and will be reported in due course along with diastereoselective conversion of 2 into (þ)-strigol (1). 4. Experimental section 4.1. General IR spectra were recorded by a Jasco FT/IR-4100 spectrometer using an ATR (ZnSe) attachment. NMR spectra were recorded with TMS as an internal standard in CDCl3 by a Varian 400-MRTT spectrometer (400 MHz for 1H and 100 MHz for 13C) unless otherwise stated. Optical rotation values were measured with a Jasco P-2200
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
polarimeter, and mass spectra were obtained with Jeol JMS-700 spectrometer operated in the EI or FAB mode. Melting points were determined with a Yanaco MP-J3 apparatus and are uncorrected. Merck silica gel 60 (70e230 mesh) was used for column chromatography. Analytical thin-layer chromatography was performed using Merck silica gel 60 F254 plates (0.25 mm thick). Solvents for reactions were distilled prior to use: THF from Na and benzophenone; CH2Cl2 and DMF from CaH2; toluene, hexane, and ether from LiAlH4. All air- or moisture-sensitive reactions were conducted under a nitrogen atmosphere unless otherwise stated. 4.1.1. (S)-2-Iodo-4,4-dimethylcyclohex-2-en-1-ol (11). To a stirred solution of 10 (203 mg, 0.801 mmol) in THF (12 mL) was added B(OMe)3 (89 mL, 0.80 mmol) at room temperature. After 1 h of stirring, PhNMe2$BH3 (1.6 mL, 9.0 mmol) and a solution of 9 (2.00 g, 8.00 mmol) in THF (15 mL) were successively added, and the stirring was continued for 1 h. The mixture was quenched with MeOH, diluted with saturated aqueous NH4Cl, and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 30:1) to give 11 (1.85 g, 92%) as a colorless oil. [a]17 D ¼ 42.5 (c¼0.900, CH2Cl2). IR: n¼3446 (br w), 1669 (w) cm1. 1H NMR: d¼1.00 (s, 3H), 1.04 (s, 3H), 1.50 (ddd, J¼13.6, 8.4, 3.2 Hz, 1H), 1.63 (ddd, J¼13.6, 9.8, 3.2 Hz, 1H), 1.82e1.91 (m, 1H), 2.01 (d, J¼4.8 Hz, 1H, OH), 2.02e2.10 (m, 1H), 4.13 (br q, J¼5.0 Hz, 1H), 6.24 (s, 1H) ppm. 13C NMR: d¼28.0, 28.8 (2C), 32.2, 37.4, 72.0, 102.5, 150.3 ppm. HRMS (EI): calcd for C8H13OI [M]þ 252.0011; found 252.0010. 4.1.2. (S)-4,4-Dimethylcyclohex-2-en-1-ol (7). A mixture of 11 (8.95 g, 35.5 mmol), Et3N (5.90 mL, 42.3 mmol), and 5% Pd/C (4.88 g) in MeOH (170 mL) was stirred at room temperature for 1 h under a hydrogen atmosphere. The mixture was filtered through a pad of Celite, and the filtrate was concentrated in vacuo. The residue was diluted with water and extracted with EtOAc. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo to give 7 (3.87 g, 86%) as a colorless oil, which was pure enough to be used for the next step. [a]21 D ¼ 104 (c¼0.700, CHCl3). IR: n¼3346 (m), 3020 (w), 1056 (s), 746 (m) cm1. 1 H NMR: d¼0.97 (s, 3H), 1.02 (s, 3H), 1.39e1.47 (m, 2H), 1.54e1.67 (m, 2H), 1.87e1.96 (m, 1H), 4.15 (br s, 1H), 5.53 (d, J¼10.0 Hz, 1H), 5.60 (dd, J¼10.0, 2.8 Hz, 1H) ppm. 13C NMR: d¼29.0, 29.1, 29.2, 31.9, 33.6, 65.9, 127.3, 140.7 ppm. HRMS (EI): calcd for C8H14O [M]þ 126.1045; found 126.1043. 4.1.3. (1S,2S,6R)-5,5-Dimethyl-7-oxabicyclo[4.1.0]heptan-2-ol (12). To a stirred mixture of 7 (1.01 g, 8.00 mmol) and NaHCO3 (739 mg, 8.80 mmol) in CH2Cl2 (50 mL) was added MCPBA (70% purity, 2.17 g, 8.80 mmol) at 0 C. After 6 h, the mixture was concentrated in vacuo to a half of its original volume and filtered through a short column of alumina. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane/EtOAc, 2:1e1:1) to give 12 (cis/trans¼93:7, 1.13 g, 99%) as a colorless oil. [a]18 D ¼ 37.9 (c¼1.00, CHCl3). IR: n¼3420 (m), 1064 (w), 912 (w) cm1. 1H NMR: d¼1.02 (s, 3H), 1.06 (s, 1H, OH), 1.08 (s, 3H), 1.36 (ddd, J¼13.8, 9.2, 3.2 Hz, 1H), 1.42e1.51 (m, 1H), 1.53e1.62 (m, 1H), 1.99e2.04 (m, 1H), 2.93 (d, J¼3.6 Hz, 1H), 3.36 (t, J¼3.6 Hz, 1H), 3.97e4.04 (m, 1H) ppm. 13C NMR: d¼25.9, 26.3, 26.4, 29.1, 32.0, 56.4, 63.6, 66.3 ppm. HRMS (EI): calcd for C8H14O2 [M]þ 142.0994; found 142.0989. 4.1.4. tert-Butyl{[(1R,2S,6R)-5,5-dimethyl-7-oxabicyclo[4.1.0]heptan2-yl]oxy}dimethylsilane (13). To a stirred solution of 12 (2.00 g, 14.1 mmol) in DMF (45 mL) were added successively imidazole (2.80 g, 41.1 mmol) and TBSCl (4.10 g, 27.2 mmol) at 0 C. The mixture was gradually warmed to room temperature and stirred
6637
overnight. The mixture was quenched with saturated aqueous NaHCO3 at 0 C and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 20:1) to give 13 (3.32 g, 92%) as a colorless oil. [a]19 D ¼ 26.0 (c¼2.00, CHCl3). IR: n¼1110 (w), 913 (s), 744 (s) cm1. 1H NMR: d¼0.10 (s, 3H), 0.11 (s, 3H), 0.91 (s, 9H), 1.01 (s, 3H), 1.07 (s, 3H), 1.04e1.12 (m, 1H), 1.29e1.35 (m, 1H), 1.38e1.45 (m, 1H), 1.50e1.58 (m, 1H), 2.82 (dd, J¼4.0, 1.6 Hz, 1H), 3.16e3.18 (m, 1H), 4.00 (ddd, J¼9.6, 5.6, 2.0 Hz, 1H) ppm. 13C NMR: d¼4.6, e4.5, 18.3, 24.7, 25.7, 25.9 (3C), 28.6, 28.8, 35.7, 57.2, 62.6, 70.1 ppm. HRMS (EI): calcd for C14H28O2Si [M]þ 256.1858; found 256.1859. 4.1.5. (1S,5S,6S)-6-Allyl-5-[(tert-butyldimethylsilyl)oxy]-2,2dimethylcyclohexan-1-ol (14) and (1R,2S,6S)-2-Allyl-6-[(tert-butyldimethylsilyl)oxy]-3,3-dimethylcyclohexan-1-ol (140 ). A solution of allylmagnesium bromide in Et2O (1.0 m, 19.4 mL, 19.4 mmol) was placed in a flask. The solvent was removed in vacuo and then the residue was diluted with hexane (32 mL). To the resulting suspension was added a solution of 13 (3.32 g, 12.9 mmol) in toluene (32 mL) at room temperature. After 5 h of stirring at 40 C, the mixture was quenched with saturated aqueous NH4Cl at 0 C and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/ EtOAc, 50:1) to give 14 (2.83 g, 73%) as a colorless oil. Data for 14: Rf¼0.36 (hexane/EtOAc, 10:1; Merck silica gel 60 F254, 0.25 mm thick). [a]19 D ¼ þ29.7 (c¼2.00, CHCl3). IR: n¼3503 (m), 3075 (w), 1253 (m), 1100 (m), 837 (m) cm1. 1H NMR: d¼0.06 (s, 6H), 0.89 (s, 9H), 0.90 (s, 3H), 0.96 (s, 3H), 1.13 (ddd, J¼13.8, 13.8, 3.6 Hz, 1H), 1.35e1.72 (m, 5H), 2.28e2.37 (m, 1H), 2.48e2.56 (m, 1H), 3.06 (dd, J¼10.4, 5.2 Hz, 1H), 3.32 (ddd, J¼10.4, 10.4, 4.6 Hz, 1H), 5.05 (dm, J¼10.2 Hz, 1H), 5.15 (dm, J¼17.2 Hz, 1H), 5.95 (ddt, J¼17.2, 10.2, 7.2 Hz, 1H) ppm. 13C NMR: d¼4.7, e3.7, 18.1, 25.9 (4C), 28.9, 31.2, 32.6, 35.1, 35.2, 47.1, 72.3, 78.8, 116.4, 137.4 ppm. HRMS (FAB): calcd for C17H35O2Si [MþH]þ 299.2506; found 299.2409. Data for 140 : Rf¼0.53 (hexane/EtOAc, 10:1; Merck silica gel 60 F254, 0.25 mm thick). [a]18 D ¼ þ45.7 (c¼0.88, CHCl3). IR: n¼3575 (w), 3075 (w), 1637 (w), 1254 (m), 1083 (s), 837 (s), 775 (m) cm1. 1H NMR: d¼0.08 (s, 6H), 0.81 (s, 3H), 0.92 (s, 9H), 0.95 (s, 3H), 1.01e1.10 (m, 1H), 1.50 (dt, J¼10.4, 5.2 Hz, 1H), 1.56e1.67 (m, 3H), 1.76 (d, J¼10.4 Hz, 1H, OH), 2.15e2.28 (m, 2H), 3.34 (ddd, J¼10.4, 10.4, 2.8 Hz, 1H), 3.92e3.95 (m, 1H), 4.91 (dm, J¼10.4 Hz, 1H), 5.01 (dq, J¼16.8, 1.9 Hz, 1H), 5.97 (ddt, J¼16.8, 10.4, 6.8 Hz, 1H) ppm. 13C NMR: d¼4.9, e4.4, 18.1, 25.8 (4C), 28.1, 30.6, 32.5, 34.7, 34.8, 47.4, 71.0, 74.1, 113.7, 141.2 ppm. HRMS (FAB): calcd for C17H35O2Si [MþH]þ 299.2506; found 299.2405. 4.1.6. (5S,6R)-6-Allyl-5-[(tert-butyldimethylsilyl)oxy]-2,2dimethylcyclohexan-1-one (15). To a stirred solution of 14 (80.0 mg, 0.268 mmol) in CH2Cl2 (1.0 mL) were added successively iPr2NEt (233 mL, 1.34 mmol), DMSO (95 mL, 1.1234 mmol), and SO3$Py (128 mg, 0.804 mmol) at 0 C. After 3 h of stirring at ambient temperature, the mixture was quenched with water and extracted with CH2Cl2. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 50:1) to give 15 (73.0 mg, 92%) as a colorless oil. [a]19 D ¼ 2.9 (c¼2.00, CHCl3). IR: n¼3080 (w), 1711 (vs), 1254 (m), 1097 (s), 838 (s) cm1. 1 H NMR: d¼0.06 (s, 3H), 0.07 (s, 3H), 0.91 (s, 9H), 1.03 (s, 3H), 1.18 (s, 3H), 1.37 (ddd, J¼14.0, 12.0, 5.6 Hz, 1H), 1.67 (dt, J¼14.0, 3.8 Hz, 1H), 1.82e1.95 (m, 2H), 2.32e2.44 (m, 2H), 2.68 (ddd, J¼10.0, 7.6, 4.0 Hz, 1H), 3.47 (ddd, J¼10.0, 10.0, 5.2 Hz, 1H), 4.95 (dm, J¼10.0 Hz, 1H), 5.02 (dm, J¼17.2 Hz, 1H), 5.82 (ddt, J¼17.2, 10.0, 6.8 Hz, 1H) ppm. 13C NMR: d¼4.8, e4.0, 18.0, 24.9, 25.1, 25.8 (3C), 29.8, 31.3, 35.0, 44.3,
6638
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
55.5, 74.6, 115.6, 137.3, 213.6 ppm. HRMS (EI): calcd for C17H32O2Si [M]þ 296.2172; found 296.2172.
33.6, 36.3, 38.3, 49.6, 79.1, 79.4, 119.1, 160.3, 171.2 ppm. HRMS (EI): calcd for C19H34O3Si [M]þ 338.2277; found 338.2279.
4.1.7. (1S,5S,6R)-6-Allyl-5-((tert-butyldimethylsilyl)oxy)-2,2dimethyl-1-vinylcyclohexan-1-ol (19). To a stirred solution of tetravinyltin (1.7 mL, 9.34 mmol) in THF (40 mL) was added a solution of nBuLi (1.6 m in hexane, 23 mL, 36.8 mmol) at 78 C. After 30 min of stirring at the same temperature, the mixture was further stirred at ambient temperature for 15 min. To the resulting mixture was added a solution of 15 (6.95 g, 23.4 mmol) in THF (60 mL) while stirring at 78 C. After 40 min, the mixture was quenched with saturated aqueous NH4Cl and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (SiO2 containing 10 w/w % K2CO3; hexane/EtOAc, 70:1) to give 19 (7.52 g, 99%) as a colorless oil. [a]24 D ¼ 1.5 (c¼2.00, CHCl3). IR: n¼3566 (m), 3070 (w), 1254 (m), 1077 (m), 837 (m) cm1. 1 H NMR (600 MHz, DMSO-d6): d¼0.00 (s, 3H), 0.02 (s, 3H), 0.69 (s, 3H), 0.83 (s, 9H), 0.93 (s, 3H), 1.20e1.27 (m, 1H), 1.39e1.48 (m, 2H), 1.60 (dt, J¼10.3, 5.2 Hz, 1H), 1.65e1.69 (m, 1H), 1.79e1.85 (m, 1H), 2.13e2.19 (m, 1H), 3.42e3.47 (m, 1H), 3.94 (s, 1H, OH), 4.74 (dm, J¼10.2 Hz, 1H), 4.81 (dm, J¼17.1 Hz, 1H), 5.12 (dd, J¼10.9, 2.5 Hz, 1H), 5.26 (dd, J¼16.9, 2.5 Hz, 1H), 5.90e5.98 (m, 2H) ppm. 13C NMR (150 MHz, DMSO-d6): d¼4.3, e3.5, 18.1, 22.6, 26.26 (3C), 26.32, 32.1, 32.8, 34.7, 37.8, 49.9, 74.5, 79.3, 113.4, 114.9, 139.4, 142.1 ppm. HRMS (EI): calcd for C19H36O2Si [M]þ 324.2485; found 324.2488.
4.1.10. (3aR,5S,8bS)-5-[(tert-Butyldimethylsilyl)oxy]-8,8-dimethyl3,3a,4,5,6,7,8,8b-octahydro-2H-indeno[1,2-b]furan-2-one (31). To a stirred solution of 22 (115 mg, 0.340 mmol) in CH2Cl2 (3.4 mL) were successively added 25 (148 mL, 0.678 mmol) and BF3$OEt2 (51 mL, 0.41 mmol) at 78 C. After 1 h, the mixture was quenched with saturated aqueous NaHCO3 and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 70:1) to give a 2:1 mixture of 26 and 260 (103 mg, 86%) as a colorless oil. To a stirred solution of the mixture (100 mg, 0.284 mmol) in MeOH/hexane (1:1, 1.3 mL) was added 5 m aqueous NaOH (630 mL, 3.15 mmol) at room temperature. After 2 h, the mixture was neutralized with 2 m aqueous HCl at 0 C and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 8:1) to give 27 (91 mg, 95%, dr 2:1) as a colorless oil. To a stirred solution of 27 (95.0 mg, 0.281 mmol) in CHCl3 (1.4 mL) were successively added NBS (50.0 mg, 0.281 mmol) and 28 (4.0 mL, 0.032 mmol) at room temperature. After 5 min, the mixture was quenched with saturated aqueous Na2S2O3 and extracted with Et2O. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 30:1) to give a mixture of 29, 290 , and 30 which was taken up in toluene (2.7 mL). To the solution was added DBU (61 mL, 0.41 mmol) and the resulting solution was stirred at 80 C for 26 h. The mixture was cooled to room temperature and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 30:1) to give 31 (24.0 mg, 25% from 27) as a colorless oil. [a]24 D ¼ 11 (c¼0.520, CHCl3). IR: n¼1776 (s), 1254 (m), 1167 (m), 1090 (m), 839 (m) cm1. 1H NMR: d¼0.068 (s, 3H), 0.074 (s, 3H), 0.90 (s, 9H), 1.08 (s, 3H), 1.15 (s, 3H), 1.42 (ddd, J¼13.0, 13.0, 3.0 Hz, 1H), 1.54 (ddd, J¼13.0, 5.6, 3.0 Hz, 1H), 1.70 (dddd, J¼13.0, 13.0, 9.0, 3.0 Hz, 1H), 1.82e1.90 (m, 1H), 2.35 (dd, J¼18.4, 5.8 Hz, 1H), 2.43 (br d, J¼16.8 Hz, 1H), 2.51 (dd, J¼16.8, 8.0 Hz, 1H), 2.79 (dd, J¼18.4, 10.4 Hz, 1H), 2.98e3.08 (m, 1H), 4.12 (br t, J¼7.0 Hz, 1H), 5.46 (dt, J¼7.6, 2.0 Hz, 1H) ppm. 13C NMR: d¼4.9, e4.3, 18.1, 25.8 (3C), 27.3, 27.9, 30.0, 32.2, 34.4, 36.0, 37.6, 38.8, 68.3, 89.9, 141.4, 143.5, 177.4 ppm. HRMS (EI): calcd for C19H32O3Si [M]þ 336.2121; found 336.2119. The intermediates 29 and 290 could be separated by repeated silica gel column chromatography (hexane/EtOAc, 30:1) and exhibited the following physicochemical properties. Data for 29: mp 107e109 C. [a]23 D ¼ þ8.4 (c¼0.500, CHCl3). IR: n¼1789 (vs), 1157 (m), 1100 (m) cm1. 1H NMR: d¼0.05 (s, 3H), 0.06 (s, 3H), 0.88 (s, 9H), 1.26 (s, 3H), 1.36 (s, 3H), 1.29e1.36 (m, 1H), 1.48e1.60 (m, 1H), 1.69e1.78 (m, 2H), 1.99e2.09 (m, 2H), 2.20 (dt, J¼13.2, 10.6 Hz, 1H), 2.36 (dd, J¼18.4, 1.8 Hz, 1H), 2.80 (dd, J¼18.4, 10.0 Hz, 1H), 3.17e3.26 (m, 1H), 3.87 (ddd, J¼10.6, 9.0, 5.2 Hz, 1H), 5.19 (d, J¼5.6 Hz, 1H) ppm. 13C NMR: d¼4.7, e4.2, 18.0, 24.9, 25.8 (3C), 28.7, 31.9, 35.7, 36.2, 36.7, 39.0, 39.2, 47.6, 74.5, 89.8, 95.9, 176.8 ppm. HRMS (EI): calcd for C19H33O3BrSi [M]þ 416.1383; found 416.1382. Data for 290 : mp 70e72 C. [a]23 D ¼ 7.1 (c¼0.500, CHCl3). IR: n¼1787 (s), 1253 (m), 1155 (m), 1092 (m), 836 (m) cm1. 1H NMR (600 MHz): d¼0.04 (s, 3H), 0.05 (s, 3H), 0.87 (s, 9H), 1.20 (s, 3H), 1.36 (s, 3H), 1.51e1.61 (m, 2H), 1.66 (dd, J¼14.4, 3.2 Hz, 1H), 1.69e1.74 (m, 1H), 2.00e2.07 (m, 1H), 2.38 (d, J¼18.4 Hz, 1H), 2.48 (br t, J¼8.9 Hz, 1H), 2.74 (ddd, J¼14.4, 11.3, 7.7 Hz, 1H), 2.85 (dd, J¼18.4, 10.2 Hz, 1H), 3.28 (ddd, J¼10.6, 10.6, 4.7 Hz, 1H), 3.31e3.37 (m, 1H), 5.12 (d, J¼6.0 Hz, 1H) ppm. 13C NMR: d¼4.7, e3.8, 17.9, 25.5, 25.8 (3C), 30.5, 31.1, 35.5, 36.3, 37.0, 37.3, 37.7, 55.1,
4.1.8. (3aS,7S,7aR)-7-[(tert-Butyldimethylsilyl)oxy]-4,4-dimethyl1,4,5,6,7,7a-hexahydro-3aH-inden-3a-ol (18). A mixture of 19 (400 mg, 1.23 mmol) and the second generation Grubbs catalyst (104 mg, 0.123 mmol) in CH2Cl2 (12 mL) was heated under reflux for 1.5 h and then cooled to room temperature. To the mixture was added DMSO (438 mL, 6.17 mmol) and the resulting mixture was stirred overnight. The mixture was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane/ EtOAc, 30:1) to give 18 (358 mg, 98%) as a colorless oil. [a]24 D ¼ þ75.8 (c¼0.515, CHCl3). IR: n¼3480 (br w), 3046 (w), 1255 (m), 1094 (s), 1005 (m) cm1. 1H NMR: d¼0.03 (s, 6H), 0.88 (s, 9H), 1.01 (s, 3H), 1.06 (s, 3H), 1.11 (ddd, J¼14.0, 8.8, 7.6 Hz, 1H), 1.24e1.32 (br s, 1H, OH), 1.40 (dt, J¼14.0, 4.0 Hz, 1H), 1.53e1.62 (m, 2H), 2.04 (dd, J¼8.4, 5.2 Hz, 1H), 2.21 (d, J¼16.8 Hz, 1H), 2.66 (dd, J¼16.8, 5.2 Hz, 1H), 3.12 (ddd, J¼8.4, 8.4, 7.2 Hz, 1H), 5.98e6.02 (m, 2H) ppm. 13C NMR: d¼4.6, e3.8, 18.0, 24.0, 25.8, 25.9 (3C), 29.7, 35.1, 35.3, 35.7, 53.0, 75.3, 88.3, 135.7, 136.1 ppm. HRMS (EI): calcd for C17H32O2Si [M]þ 296.2171; found 296.2173. 4.1.9. (3aS,7S,7aR)-7-[(tert-Butyldimethylsilyl)oxy]-4,4-dimethyl1,4,5,6,7,7a-hexahydro-3aH-inden-3a-yl acetate (22). To a stirred solution of 18 (350 mg, 1.18 mmol) in toluene (14 mL) were successively added Et3N (1.60 mL, 11.5 mmol), DMAP (29 mg, 0.24 mmol) and Ac2O (1.10 mL, 11.6 mmol) at room temperature. The mixture was heated under reflux for 33 h and then cooled to room temperature before being quenched with water and extracted with ether. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 50:1) to give 22 (291 mg, 73%) as a colorless oil. [a]23 D ¼ 89.9 (c¼1.50, CHCl3). IR: n¼1733 (s), 1245 (s), 1095 (m), 838 (m) cm1. 1H NMR: d¼0.05 (s, 6H), 0.89 (s, 9H), 1.09 (s, 3H), 1.13 (s, 3H), 1.19 (ddd, J¼13.6, 13.6, 4.4 Hz, 1H), 1.46 (dt, J¼13.6, 3.4 Hz, 1H), 1.58e1.64 (m, 1H), 1.65e1.73 (m, 1H), 1.97 (ddd, J¼15.0, 7.6, 5.2 Hz, 1H), 2.01 (s, 3H), 2.10 (ddd, J¼15.0, 7.6, 2.0 Hz, 1H), 2.74e2.82 (m, 1H), 3.05 (ddd, J¼10.4, 10.4, 4.8 Hz, 1H), 5.42 (t, J¼2.4 Hz, 1H), 5.57e5.61 (m, 1H) ppm. 13C NMR: d¼4.6, e3.9, 18.0, 21.4, 25.75, 25.82 (3C), 28.2, 31.8,
A. Takahashi et al. / Tetrahedron 72 (2016) 6634e6639
73.6, 91.2, 91.6, 176.8 ppm. HRMS (EI): calcd for C19H33O3BrSi [M]þ 416.1383; found 416.1382. 4.1.11. (3aR,5S,8bS)-5-Hydroxy-8,8-dimethyl-3,3a,4,5,6,7,8,8b-octahydro-2H-indeno[1,2-b]furan-2-one (2). To a solution of 31 (20.0 mg, 0.0594 mmol) in THF (110 mL) was added a solution of TBAF (1.0 m in THF, 118 mL, 0.12 mmol) at room temperature. After 10 min, the mixture was quenched with saturated aqueous NaHCO3 and extracted with EtOAc. The extract was successively washed with saturated water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc, 5:1e2:1) and recrystallization (hexane/ CH2Cl2) to give 2 (10.0 mg, 76%) as a white solid. Mp 104e106 C 11a (lit.11a mp 103e106 C). [a]25 [a]25 D ¼ þ8.24 (c¼1.25, CHCl3) [lit. D ¼ þ8.28 (c¼1.3, CHCl3)]. IR: n¼3445 (m), 1769 (s), 1168 (m), 913 (m), 743 (m) cm1. 1H NMR: d¼1.09 (s, 3H), 1.16 (s. 3H), 1.43 (d, J¼6.4 Hz, 1H, OH), 1.46 (ddd, J¼13.6, 11.2, 3.0 Hz, 1H), 1.59 (ddd, J¼13.6, 6.8, 2.8 Hz, 1H), 1.66e1.76 (m, 1H), 1.95e2.04 (m, 1H), 2.37 (dd, J¼18.4, 5.0 Hz, 1H), 2.50 (br d, J¼16.8 Hz, 1H), 2.63 (dd, J¼16.8, 8.0 Hz, 1H), 2.82 (dd, J¼18.4, 10.4 Hz, 1H), 3.03e3.13 (m, 1H), 4.14 (q, J¼6.4 Hz, 1H), 5.47 (d, J¼7.6 Hz, 1H) ppm. 13C NMR: d¼27.4, 27.5, 29.6, 32.3, 34.5, 35.9, 36.8, 38.6, 67.1, 89.7, 142.4, 142.7, 177.3 ppm. HRMS (EI): calcd for C13H18O3 [M]þ 222.1256; found 222.1256. Acknowledgements We are grateful to Ms. Yuka Taguchi (Tohoku University) for her help in NMR and MS measurements. Supplementary data Supplementary data (NMR spectra of 2 and key synthetic intermediates) associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.tet.2016.08.078. References and notes 1. (a) Cook, C. E.; Whichard, L. P.; Turner, B.; Wall, M. E. Science 1966, 154, 1189e1190; (b) Cook, C. E.; Whichard, L. P.; Wall, M. E.; Egley, G. H.; Coggon, P.; Luhan, P. A.; McPhail, A. T. J. Am. Chem. Soc. 1972, 94, 6198e6199; (c) Brooks, D. W.; Bevinakatti, H. S.; Powell, D. R. J. Org. Chem. 1985, 50, 3779e3781. 2. Parker, C. Weed Sci. 2012, 60, 269e276. 3. Siame, B. A.; Weerasuriya, Y.; Wood, K.; Ejeta, G.; Butler, L. G. J. Agric. Food Chem. 1993, 41, 1486e1491. 4. For a review, see Cavar, S.; Zwanenburg, B.; Tarkowski, P. Phytochem. Rev. 2015, 14, 691e711. 5. It was reported that synthetic strigolactone analogs could also induce seed germination of non-parasitic plants. For details, see: (a) Bradow, J. M.; Connick, W. J., Jr.; Papperman, A. B.; Wartelle, L. H. J. Plant Growth Regul. 1990, 9, 35e41; (b) -Pfister, R.; Villedieu-Percherron, E.; Lachia, M.; Jung, P. M. J.; Screpanti, C.; Fonne Wendeborn, S.; Zurwerra, D.; De Mesmaeker, A. Chimia 2014, 68, 654e663. 6. Akiyama, K.; Matsuzaki, K.; Hayashi, H. Nature 435, 824e827. s, V.; Dun, E. A.; 7. (a) Gomez-Roldan, V.; Fermas, S.; Brewer, P. B.; Puech-Page Pillot, J.-P.; Letisse, F.; Matusova, R.; Danoun, S.; Portais, J.-C.; Bouwmeester, H.; card, G.; Beveridge, C. A.; Rameau, C.; Rochange, S. F. Nature 2008, 455, Be 189e194; (b) Umehara, M.; Hanada, A.; Yoshida, S.; Akiyama, K.; Arite, T.; Takeda-Kamiya, N.; Magome, H.; Kamiya, Y.; Shirasu, K.; Yoneyama, K.; Kyozuka, J.; Yamaguchi, S. Nature 2008, 455, 195e200. 8. For reviews, see: (a) Seto, Y.; Kameoka, H.; Yamaguchi, S.; Kyozuka, J. Plant Cell Physiol. 2012, 53, 1843e1853; (b) Zwanenburg, B.; Pospísil, T. Mol. Plant 2013, 6, 38e62; (c) Zwanenburg, B.; Pospísil, T.; Zeljkovic, S. C. Planta 2016, 243, 1311e1326; (d) Flematti, G. R.; Scaffidi, A.; Waters, M. T.; Smith, S. M. Planta 2016, -Pfister, R.; Lumbroso, A.; Rendine, S.; 243, 1361e1373; (e) Screpanti, C.; Fonne Lachia, M.; De Mesmaeker, A. Bioorg. Med. Chem. Lett. 2016, 26, 2392e2400.
6639
9. Heather, J. B.; Mittal, R. S. D.; Sih, C. J. J. Am. Chem. Soc. 1974, 96, 1976e1977. 10. (a) Boyer, F.-D.; de Saint Germain, A.; Pillot, J.-P.; Pouvreau, J.-B.; Chen, V. X.; venin, A.; Simier, P.; Delavault, P.; Beau, J.-M.; Rameau, C. Plant Ramos, S.; Ste Physiol. 2012, 159, 1524e1544; (b) Lachia, M.; Wolf, H. C.; Jung, P. J. M.; Screpanti, C.; De Mesmaeker, A. Bioorg. Med. Chem. Lett. 2015, 25, 2184e2188; (c) Zwanenburg, B.; Regeling, H.; van Tilburg-Joukema, C. W.; van Oss, B.; Molenveld, P.; de Gelder, R.; Tinnemans, P. Eur. J. Org. Chem. 2016, 2163e2169; (d) Takahashi, I.; Fukui, K.; Asami, T. Pest Manag. Sci. [Online early access]. doi: 10. 1002/ps.4265. 11. For a review, see Zwanenburg, B.; Zeljkovic, S. C.; Pospísil, T. Pest Manag. Sci. 2016, 72, 15e29. 12. (a) Heather, J. B.; Mittal, R. S. D.; Sih, C. J. J. Am. Chem. Soc. 1976, 98, 3661e3669; (b) Samson, E.; Frischmuth, K.; Berlage, U.; Heinz, U.; Hobert, K.; Welzel, P. Tetrahedron 1991, 47, 1411e1416; (c) Hirayama, K.; Mori, K. Eur. J. Org. Chem. 1999, 2211e2217; (d) Chen, V. X.; Boyer, F.-D.; Rameau, C.; Retailleau, P.; Vors, J.-P.; Beau, J.-M. Chem.dEur. J. 2010, 16, 13941e13945. 13. (a) Berlage, U.; Schmidt, J.; Milkova, Z.; Welzel, P. Tetrahedron Lett. 1987, 28, 3095e3098; (b) Matsui, J.; Bando, M.; Kido, M.; Takeuchi, Y.; Mori, K. Eur. J. Org. Chem. 1999, 2183e2194. 14. Sugimoto, Y.; Wigchert, S. C. M.; Thuring, J. W. J. F.; Zwanenburg, B. J. Org. Chem. 1998, 63, 1259e1267. 15. Lachia, M.; Dakas, P. Y.; De Mesmaeker, A. Tetrahedron Lett. 2014, 55, 6577e6581. 16. Ohkuma, T.; Ikehira, H.; Ikariya, T.; Noyori, R. Synlett 1997, 467e468. 17. For an alternative method to obtain 7 (96% ee) from rac-7 via multiple enzymatic treatments, see Winska, K.; Grudniewska, A.; Chojnacka, A.; Biolonska, A.; Wawrzenczyk, C. Tetrahedron: Asymmetry 2010, 21, 670e678. 18. (a) Masui, M.; Shioiri, T. Synlett 1997, 273e274; (b) Salunkhe, S. M.; Burkhardt, E. R. Tetrahedron Lett. 1997, 38, 1523e1526; (c) Soorukram, D.; Knochel, P. Org. Lett. 2004, 6, 2409e2411; (d) Fujioka, H.; Matsuda, S.; Horai, M.; Fujii, E.; Morishita, M.; Nishiguchi, N.; Hara, K.; Kita, Y. Chem.dEur. J. 2007, 13, 5238e5248. 19. The enantiomeric excess of 11 (98% ee) was determined by analyzing the 1H NMR spectra of the corresponding (R)- and (S)-MTPA esters. 20. Liu, H.; Yan, P.; Li, Y.; Liu, J.; Sun, Q.; Wang, X.; Wang, C. Monatsh. Chem. 2012, 143, 1055e1059. 21. Boyd, D. R.; Sharma, N. D.; Malone, J. F.; Allen, C. C. R. Chem. Commun. 2009, 3633e3635. 22. Nicolai, S.; Swallow, P.; Waser, J. Tetrahedron 2015, 71, 5959e5964. 23. The ratio of 14 and 140 was determined by 1H NMR analysis of the crude reaction product. 24. When the reaction was conducted at 40 C in ether/hexane (1:1), the 14/140 ratio was 1.8:1, while in toluene the ratio was 2.2:1. 25. For related studies, see: (a) Chini, M.; Crotti, P.; Flippin, L. A.; Gardelli, C.; Macchia, F. J. Org. Chem. 1992, 57, 1713e1718; (b) Cainelli, G.; Giacomini, D.; , A. Tetrahedron: Asymmetry 1994, 5, 1913e1916. Perciaccante, F.; Trere 26. Stork, G.; Zhao, K. Tetrahedron Lett. 1989, 30, 2173e2174. 27. Jin, H.; Uenishi, J.; Christ, W. J.; Kishi, Y. J. Am. Chem. Soc. 1986, 108, 5644e5646. 28. Ahn, Y. M.; Yang, K.; Georg, G. I. Org. Lett. 2001, 3, 1411e1413. 29. For a review of Claisen-type rearrangements, see Castro, A. M. M. Chem. Rev. 2004, 104, 2939e3002. 30. Trost, B. M.; Vranken, D. L. V. Chem. Rev. 1996, 96, 395e422 and references cited therein. 31. (a) Mukaiyama, T.; Nagaoka, H.; Ohshima, M.; Murakami, M. Chem. Lett. 1986, 1009e1012; (b) Musacchio, A. J.; Nguyen, L. Q.; Beard, G. H.; Knowles, R. R. J. Am. Chem. Soc. 2014, 136, 12217e12220. 32. Ahmad, S. M.; Braddock, D. C.; Cansell, G.; Hermitage, S. A. Tetrahedron Lett. 2007, 48, 915e918. 33. Although the d-lactone 30 was not fully purified, the structure could be deduced from its MS, IR and 1H NMR data including NOE correlations. MS (EI): m/ z 416 [C19H3379BrO3Si (Mþ)] and 418 [C19H3381BrO3Si (Mþ)]; IR: nmax 1739 (vs); 1 H NMR (600 MHz, CDCl3): d 0.07 (3H, s), 0.08 (3H, s), 0.88 (9H, s), 1.17 (3H, s), 1. 18 (3H, s), 1.35 (1H, dt, J¼14.4, 3.6 Hz), 1.59e1.64 (1H, m), 1.65e1.70 (1H, m), 2. 09 (1H, dd, J¼14.2, 8.9 Hz), 2.17e2.26 (2H, m), 2.34e2.39 (1H, m), 2.60 (1H, dd, J¼18.4, 2.1 Hz), 2.69e2.72 (1H, m), 2.90 (1H, ddd, J¼18.4, 4.8, 2.6 Hz), 3.99 (1H, ddd, J¼11.5, 9.6, 5.3 Hz), 4.22 (1H, br s). 34. It should be noted that the d-lactone 30 was also recovered without any change when exposed to DBU in toluene at 80 C. 35. Brooks, D. W.; Bevinakatti, H. S.; Kennedy, E.; Hathaway, J. J. Org. Chem. 1985, 50, 628e632. 36. For studies on diastereoselective connection of an ABC scaffold to a D-ring unit, €hrig, S.; Milkova, Z. Chem. Commun. 1999, 2017e2022; (b) see: (a) Welzel, P.; Ro Reizelman, A.; Zwanenburg, B. Eur. J. Org. Chem. 2002, 810e814; (c) Bromhead, L. J.; Visser, J.; McErlean, C. S. P. J. Org. Chem. 2014, 79, 1516e1520; (d) Ref. 11 and references cited therein.