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Base- and acid-catalyzed intramolecular oxy-Michael reaction for the synthesis of tetrahydrofuran ring
Tetrahedron 72 (2016) 4962e4967
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Base- and acid-catalyzed intramolecular oxy-Michael reaction for the synthesis of tetrahydrofuran ring Yuki Murata, Jun’ichi Uenishi * Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8412, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 3 June 2016 Received in revised form 25 June 2016 Accepted 30 June 2016 Available online 1 July 2016
Base- and acid-catalyzed intramolecular oxy-Michael reactions are reported. Three ε-hydroxy a,b-unsaturated ketones 1, 2, and 3 and one ester 4 were cyclized in 5-exo-trigonal fashion to afford 2,5disubstituted tetrahydrofurans in good yields. The substituent at the g-hydroxy group and its stereochemistry influenced the stereoselectivity of the THF products. The precursor 2 bearing an (R)-g-hydroxy group gave 2,5-trans-6 exclusively. In contrast, 3, bearing an (S)-g-hydroxy group, gave only 2,5-cis-7 under acidic conditions but gave a mixture of 2,5-trans and 2,5-cis isomers of 7 under basic conditions. On the other hand, in the absence of a hydroxyl group at the g-position, the cyclization conducted under both basic and acidic reaction conditions provided a mixture of 2,5-trans- and 2,5-cis isomers of 5 and 8. Ó 2016 Published by Elsevier Ltd.
On the celebration of Tetrahedron Prize 2014, this paper is dedicated to Professor Jiro Tsuji for his great contribution on Pdchemistry
Keywords: Oxy-Michael reaction Stereochemistry THF ring Facial selectivity Catalytic reaction
1. Introduction Oxa-heterocycles are an important unit in heterocyclic chemistry and the synthesis of oxa-cyclic ring has been well investigated.1 Tetrahydrofuran (THF) rings exist widely as a core component in natural products2 as well as in biologically active compounds3 including C-nucleosides. A number of synthetic methods for 2,5substituted THF compounds by ring forming reactions have been reported, e.g., cascade reaction of epoxides,4aec oxidative ring formation to alkenes,4d,e halolactonization,4f,g radical cyclization,4hej CH-insertion,4k and oxy-palladation.4l The oxy-Michael reaction is a powerful method to form oxa-heterocycles not only for tetrahydropyran (THP) rings5 but also for THF rings. In fact, the 2,5substituted THF ring unit has been synthesized by this method.6 However the method has been employed mainly for a,b-unsaturated esters but poorly for a,b-unsaturated ketones. The reaction has been used limitedly for the g-substituted a,b-unsaturated esters,7 and only a few reaction for the g-hydroxy a,b-unsaturated ester have been reported so far.7h We have been interested in the oxy-Michael reaction with ε-hydroxy-a,b-unsaturated ketones
* Corresponding author. Tel.: þ81 75 595 4665; fax: þ81 75 595 4763; e-mail address: [email protected] (J. Uenishi). http://dx.doi.org/10.1016/j.tet.2016.06.081 0040-4020/Ó 2016 Published by Elsevier Ltd.
including g-hydroxy derivatives for the synthesis of the 5-acetonylTHF ring and its stereochemical course of the reactions. In this paper, we report the oxy-Michael reaction of four substrates 1e4 and the investigation of their stereochemistry (Scheme 1).
Scheme 1. Precursors of oxy-Michael reaction and synthesis of 2,5-disubstituted THF compounds.
2. Results and discussion The precursors of the oxy-Michael reaction 1, 2, 3 and 4 were prepared from 2-deoxy-D-ribose, D-arabinose and D-ribose in 2 steps.8 First, we treated compound 1 with 20 mol % of t-BuOK in THF at room temperature. The two diastereomeric isomers of 2,5trans-5 and 2,5-cis-5 were obtained with 82% yield in a ratio of 2:3
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(Scheme 2). Unfortunately they were not separable by chromatography. They were derivatized to a mixture of di-O-toluoyl derivatives 2,5-trans-9 and 2,5-cis-9 with 47% yield in two steps i) removal of cyclic silyl ether with TBAF and ii) toluoylation with toluoyl chloride. After this conversion, they were separable by HPLC to give the polar 2,5-trans-9 and the less polar 2,5-cis-9. The major isomer was identified to be 2,5-cis-9 and the minor isomer 2,5trans-9 determined by the NOESY experiments.9 When the reaction was conducted at e78 C, a mixture of 2,5-trans-5 and 2,5-cis-5 was obtained in 80% yield and the selectivity of cis isomer increased little to be 1:2.
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79% yield. Their stereochemistries were determined after the conversion to the corresponding benzoates. A 1:2 mixture of 2,5-trans-7 and 2,5-cis-7 was acylated with benzoyl chloride to give a mixture of 2,5-trans-10 and 2,5-cis-10 in the same ratio. They were separable and their NOESY spectra supported their relative structures.9 According to the oxy-Michael reactions for a,b-unsaturated esters in literature,6 the 2,5-trans isomer was usually formed predominantly. However the reaction of the a,b-unsaturated ketone in the present cases, favored the production of the 2,5-cis isomer as opposed to the 2,5-trans isomer. When the g-substituent was
Scheme 2. Oxy-Michael reaction of 1, 2, 3 and transformation to 9 and 10.
Interestingly, the reaction of 2 under the same conditions afforded a single stereoisomer either at room temperature or at 78 C, which was assigned to be 2,5-trans-6.9 These chemical yields were excellent in 85% and 83%, respectively. On the other hand, the reaction of 3 gave a mixture of 2,5trans-7 and 2,5-cis-7 in a ratio of 1:0.8 at room temperature in 80% yield. However, when the reaction was conducted at 78 C, 2,5-cis-7 produced favorably in a ratio of 1:2.0 with
present, the stereochemistry of the product was not simple. We examined other reaction conditions using either basic or acidic catalysts. The results are shown in Table 1. The effect of temperature on the reaction rate was evaluated but little difference in the selectivity was observed (entries 1e3) except the case at 78 C (entry 4). The chemical yields were not much affected by the nature of the solvent (t-BuOH and toluene) used in the reaction (entries 5 and 6). The reactions in DMSO and
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Table 1 PdII-catalyzed cyclization of 1e3
Entry
Precursor
Base or acid (mol %)
Solvent
Temp ( C)
Time (min)
Product
Yielda (%)
2,5-trans: 2,5-cisb
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
1 1 1 1 1 1 1 1 1 2 2 2 2 3 3 3 3
t-BuOK (20) t-BuOK (20) t-BuOK (20) t-BuOK (20) t-BuOK (20) t-BuOK (20) DBU (50) DBU (50) CSA (30) t-BuOK (20) t-BuOK (20) DBU (20) CSA (30) t-BuOK (20) t-BuOK (20) DBU (20) CSA (30)
THF THF THF THF t-BuOH Toluene THF Benzene CH2Cl2 THF THF THF CH2Cl2 THF THF THF CH2Cl
Reflux rt 0 78 rt rt Reflux Reflux rt rt 78 Reflux rt rt 78 Reflux rt
5 5 15 60 10 10 60 60 180 5 10 5 20 5 10 40 40
5 5 5 5 5 5 5 5 5 6 6 6 6 7 7 7 7
80 82 84 80 82 70 67 64 75 85 83 71 69 80 79 80 71
1:1.5 1:1.5 1:1.4 1:2.0 1:1.4 1:1.4 1:1.4 1:1.4 1:1.3 trans only trans only trans only trans only 1:0.8 1:2.2 1:0.9 cis only
a b
Isolated yield. Ratio was calculated by the integration value of 1H NMR spectrum.
acetonitrile did not provide any of 5 (not in Table). Although an amine base (DBU) slowly promoted the reaction at room temperature in THF, the reaction was accelerated either in refluxing THF or benzene in a ratio of 1:1.4 of the trans and cis isomers with moderate yields (entries 7 and 8). Treatment of 1 with 30 mol % of dlcamphorsulfonic acid in CH2Cl2 provided compounds 5 in 75% yield with a 1:1.3 ratio (entry 9). In contrast to the substrate 1, it is quite interesting that the substrate 2 gave a trans stereoisomer 6 exclusively, even under the basic (t-BuOK or DBU, entries 10e12) or acidic (CSA, entry 13) conditions. On the other hand, the substrate 3 was cyclized with t-BuOK to give a mixture of 2,5-trans and 2,5-cis products depending on the conditions and the trans and cis isomers were formed in a 1:0.8 ratio at room temperature and in a 1:2.2 ratio at 78 C (entries 14 and 15). The reaction of 3 with DBU base gave 7 with a 1:0.9 ratio in THF at refluxing temperature similarly (entry 16). However, it is surprising that the CSA-catalyzed reaction of 3 in CH2Cl2 at room temperature afforded 2,5-cis-7 as a single product in 71% yield (entry 17). Michael reaction is known to be equilibrium in its process. A 4:3 mixture of 2,5-trans-7 and 2,5-cis-7 was treated with t-BuOK in THF at both room temperature and 78 C. Though some loss was observed, the ratio did not change at all in both reactions. On the other hand, upon exposure of the mixtures in CH2Cl2 containing 0.3 equiv of CSA at room temperature for 1 h, the ratio of the recovered products was changed to be the only 2,5-cis-7 isomer. The mixtures would equilibrate to be the thermodynamically more stable 2,5-cisisomer by retro-Michael and Michael processes under the acidic conditions but not under the basic conditions. It is known that the a-glycoside of D-ribose analogues is less stable than that of the bglycoside due to the consecutive substituents at the a,b,g-positions on the furan ring. Similarly, 2,5-trans-7 could be expected to be less stable rather than 2,5-cis-7. We have also examined a,b-unsaturated ester 4. The reaction with 5 mol % of t-BuOK gave 2,5-trans-8 and 2,5-cis-8 with no selectively (Scheme 3). However the trans isomer was formed favorably at 78 C in a ratio of 1:0.3. This trend of stereochemistry has been observed previously in the g-nonsubstituted ε-hydroxy-a,bunsaturated esters.6 These structures were confirmed by NOESY
spectra after conversion to their toluoyl esters 11. While, the reaction under the acidic conditions with 30 mol % of CSA in CH2Cl2 at room temperature gave a recovery of starting material even after 24 h.
Scheme 3. Oxy-Michael reaction of 4 and transformation to 11.
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2.1. Reaction mechanism Based on the above results, we considered the stereochemical course of the reactions. An attack of the oxygen nucleophile on the alkene face of the a,b-unsaturated carbonyl group could occur in two rotational isomers for conformers I and II (Scheme 4). An a,bunsaturated ketone could assume an extended form in the conformer I with the OeC bond formation leading to the 2,5-trans isomer. On the other hand, the a,b-unsaturated ketone could be arranged in a bent form in the conformer II that could lead to the 2,5-cis isomer. (i) When X is a hydrogen (compound 2), the conformer I would escape from a 1,3-allylic strain and that would give a single stereoisomer 2,5-trans-6. The experimental results supported this stereochemical course of the reactions for 2. (ii) When X is not a hydrogen (compound 3), an allylic strain appears in its conformer I. The product from the conformer I would be the 2,5trans-7 that is a rather sterically strained isomer, because of the presence of three consecutive substituents located on the a-face of the THF ring. Therefore, another conformer II would be possible and an interaction of a metal alkoxide with the carbonyl might be expected to stabilize the conformer II. Although we are not able to estimate its strength of the allylic strain in this case (X¼OH for the conformer I), the total effects could influence the formation of 2,5trans-7 and 2,5-cis-7. Equilibrium between trans and cis isomers may exist under the acidic conditions converting the 2,5-trans isomer to a single thermodynamically favored 2,5-cis-isomer.
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the synthesis of 2,5-disubstituted THF compounds and the stereochemical results are valuable for further consideration of intramolecular oxy-Michael reactions in the formation of 5membered heterocycles.
4. Experimental 4.1. General information All reactions were run under an atmosphere of nitrogen. Solvents and reagents were dried prior to use. Et2O and THF were distilled from sodium benzophenone ketyl. CH2Cl2 was distilled from P2O5 and toluene was distilled from CaH2. 1H NMR spectra were recorded on JEOLJNM-ECS-400 (400 MHz). Proton chemical shifts were internally referenced to the residual proton resonance in CDCl3 (d 7.26) and CD2Cl2 (d 5.32). 13C NMR spectra were recorded on JEOLJNM-ECS-400 (100 MHz) and JEOLECA-600 (150 MHz). Carbon chemical shifts were internally referenced to the deuterated solvent signals in CDCl3 (d 77.00). Mass spectra (MS) were recorded on JEOL JMC-GC MATE. Electron impact (EI) spectra were performed at 70 eV for low and high resolution mass spectra. Optical rotations were recorded on a JASCO P-2200. HPLC analyses were performed on a Shimazu using UV-2075 detector. Analytical thin layer chromatography (TLC) was performed on Merck silica gel 60F254 plates. Flash column chromatography was performed with Merck silica gel 60 (40e63 mm pore size).
4.2. Experimental procedures and characterization data 4.2.1. Typical procedure of t-BuOK catalyzed oxy-Michael reaction of 1e4. To a mixture of alkene (0.15 mmol) in THF (0.6 mL) was added potassium tert-butoxide (3.4 mg, 0.03 mmol) at room temperature and the mixture was stirred for 5 min. Satd ammonium chloride was added and the mixture was extracted with 30% EtOAc in hexane. Organic extract was washed with water and brine and dried over MgSO4. Solvent was removed and the residue was purified with 10% EtOAc in hexane for compounds 5 and 8 and 20% EtOAc in hexane for compounds 6 and 7.
Scheme 4. Facial selection in oxy-Michael reaction for 1, 2 and 3.
The difference of stereoselectivity observed in a,b-unsaturated ketone 1 and a,b-unsaturated ester 4 is not clear. It is assumed that the conformer II of 1 would be more favorable than that of 4.10 3. Conclusion In summary, we have disclosed the stereochemistry of the oxyMichael reaction for the chiral 3-hydroxy a,b-unsaturated ketones 1e3 and ester 4. This reaction proceeded via a 5-exo-trigonal fashion and effectively provided 2,5-disubstituted tetrahydrofurans. In the absence of a g-hydroxy group a mixture of 2,5disubstituted tetrahydrofurans was obtained. The 2,5-cis product is favorably produced in the case of a,b-unsaturated ketone which differs from the product of the a,b-unsaturated ester. In the presence of an (R)-hydroxy group at the g-position, the 2,5-trans isomer, 2,5-trans-6, was produced exclusively. In the presence of an (S)-g-hydroxy group both 2,5-trans and 2,5-cis isomers, 2,5trans-7 and 2,5-cis-7, were formed under the basic conditions. However, the thermodynamically stable cis-isomer was only produced under the acidic conditions. These findings will be useful for
4.2.2. 2,5-trans-5 and 2,5-cis-5 (2:3). Colorless oil; Colorless oil; Rf¼0.31 (10% EtOAc in hexane); 1H NMR (400 MHz, CDCl3) d 4.47e4.35 (m, 2H), 4.03e3.92 (m, 1H), 3.77e3.67 (m, 2H), 2.87 (dd, J¼16.4, 7.2 Hz, 2/5H), 2.74 (dd, J¼16.0, 6.8 Hz, 3/5H), 2.63 (dd, J¼16.5, 5.9 Hz, 2/5H), 2.55 (dd, J¼16.0, 5.9 Hz, 3/5H), 2.46e2.37 (m, 2/5H), 2.18 (s, 6/5H), 2.17 (s, 9/5H), 2.15 (ddd, J¼12.8, 6.4, 4.6 Hz, 3/ 5H), 1.89e1.67 (m, 1H), 1.09e0.97 (m, 28H); 13C NMR (100 MHz, CDCl3) d 207.2 (2/5C), 206.9 (3/5C), 86.2 (3/5C), 83.5 (2/5C), 73.7 (2/5C) 73.6 (2/5C), 73.53 (3/5C), 73.50 (3/5C), 63.8 (3/5C), 63.5 (2/ 5C), 49.8 (2/5C), 49.5 (3/5C), 40.7 (2/5C), 40.6 (3/5C), 30.97 (3/5C), 30.93 (2/5C), 17.7 (3C), 17.6 (4C), 17.5 (1C), 17.47 (2C), 17.43 (2C), 17.3 (3C), 17.2 (2C), 17.1 (1C), 13.6 (3/5C), 13.58 (2/5C), 13.52 (3/5C), 13.4 (2/5C), 13.1 (3/5C), 13.0 (2/5C), 12.7 (1C); MS (CI): m/z¼417 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C20H41O5Si2: 417.2493; Found. 4.2.3. 2,5-trans-6. Colorless oil; Rf¼0.23 (20% EtOAc in hexane); 1 [a]20 D 25.7 (c 0.39, CHCl3), H NMR (400 MHz, CDCl3) d 4.28 (t, J¼7.3 Hz, 1H), 4.10 (ddd, J¼8.2, 6.4, 5.4 Hz, 1H), 3.99 (br t, J¼6.4 Hz, 1H), 3.93 (dd, J¼12.4, 3.2 Hz, 1H), 3.85 (dd, J¼12.4, 5.2 Hz, 1H), 3.75 (ddd, J¼7.3, 5.2, 3.2 Hz, 1H), 3.29 (br s, 1H), 3.00 (dd, J¼17.9, 5.4 Hz, 1H), 2.77 (dd, J¼17.4, 8.2 Hz, 1H), 2.20 (s, 3H), 1.10e0.97 (m, 28H); 13 C NMR (100 MHz, CDCl3) d 208.7, 81.5, 81.2, 77.9, 77.7, 62.7, 48.3, 30.6, 17.5, 17.3 (3C), 17.07, 17.02 (3C), 13.5, 13.2, 12.8, 12.5; MS (CI): m/
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z¼433 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C20H41O6Si2: 433.2442; Found 433.2449. 4.2.4. 2,5-trans-7 and 2,5-cis-7 (1:0.8). Colorless oil; Rf¼0.18 (20% EtOAc in hexane); 1H NMR (400 MHz, CDCl3) d 4.44 (td, J¼6.9, 3.2 Hz, 5/9H), 4.36 (dd, J¼7.2, 4.8 Hz, 5/9H), 4.23 (t, J¼5.9 Hz, 4/9H), 4.19 (t, J¼4.1 Hz, 5/9H), 4.11 (dt, J¼8.0, 4.8 Hz, 4/9H), 4.02e3.94 (m, 1H), 3.88e3.75 (m, 22/9H), 2.96 (dd, J¼17.4, 7.8 Hz, 4/9H), 2.79 (dd, J¼16.4, 4.8 Hz, 5/9H), 2.75 (dd, J¼17.4, 6.0 Hz, 4/9H), 2.66 (dd, J¼16.4, 7.2 Hz, 5/9H), 2.20 (s, 3H), 1.08e0.97 (m, 28H); 13C NMR (100 MHz, CDCl3) d 207.7 (4/9C), 207.5 (5/9C), 83.2 (4/9C), 80.2 (4/ 9C), 79.9 (5/9C), 76.6 (5/9C), 74.7 (4/9C), 74.3 (5/9C), 72.4 (4/9C), 72.2 (5/9C), 63.1 (4/9C), 62.9 (5/9C), 47.3 (5/9C), 43.4 (4/9C), 31.3 (4/ 9C), 30.9 (5/9C), 17.6 (2C), 17.59 (1C), 17.51 (4C), 17.4 (2C), 17.39 (2C), 17.35 (1C), 17.2 (2C), 17.19 (1C), 17.15 (1C), 13.6 (4/9C), 13.5 (5/9C), 13.4 (4/9C), 13.3 (5/9C), 13.0 (4/9C), 12.9 (5/9C), 12.7 (1C); MS (CI): m/z¼433 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C20H41O6Si2: 433.2442; Found 433.2436. 4.2.5. 2,5-trans-8 and 2,5-cis-8 (3:2). Colorless oil; Rf¼0.32 (20% EtOAc in hexane); 1H NMR (400 MHz, CDCl3) d 4.48e4.37 (m, 2H), 4.06e3.96 (m, 1H), 3.79e3.63 (m, 2H), 3.69 (s, 6/5H), 3.68 (s, 3/5H), 2.75 (dd, J¼15.1, 7.8 Hz, 3/5H), 2.57 (dd, J¼15.6, 6.9 Hz, 2/ 5H), 2.41 (dd, J¼15.1, 5.9 Hz, 3/5H), 2.35 (dd, J¼15.6, 5.9 Hz, 2/ 5H), 2.26 (ddd, J¼15.1, 7.3, 2.3 Hz, 3/5H), 2.14 (ddd, J¼13.2, 6.4, 3.7 Hz, 2/5H), 1.84 (m, 1H), 1.27e0.99 (m, 28H); 13C NMR (100 MHz, CDCl3) d 171.6 (3/5C), 171.5 (2/5C), 86.3 (2/5C), 83.6 (3/ 5C), 73.9 (2/5C), 73.8 (3/5C), 73.58 (2/5C), 73.55 (3/5C), 63.9 (2/ 5C), 63.4 (3/5C), 51.92 (2/5C), 51.90 (3/5C), 40.9 (3/5C), 40.5 (2/ 5C), 40.4 (2/5C), 40.3 (3/5C), 17.7 (2C), 17.58 (3C), 17.57 (3C), 17.4 (2C), 17.3 (2C), 17.2 (2C), 17.1 (2C), 13.7 (3/5C), 13.6 (2/5C), 13.5 (2/ 5C), 13.4 (3/5C), 13.1 (2/5C), 13.0 (3/5C), 12.7 (1C); MS (CI): m/ z¼433 [MþH]þ; HRMS (EI): m/z [MþH]þ calcd for C20H41O6Si2: 433.2442; Found 433.2436. 4.2.6. 2,5-cis-7. Acid catalyzed cyclization of 3; A mixture of alkene 3 (34.2 mg, 0.08 mmol) and CSA (5.5 mg, 0.024 mmol) was stirred at room temperature for 40 min. Water was added and the mixture was extracted with 30% EtOAc in hexane. The extract was washed with 5% NaHCO3, brine and dried over MgSO4. Solvent was removed and the residue was purified by silica gel column chromatography eluted with 20% EtOAc in hexane to give 2,5-cis-7 (24.3 mg) in 71% yield. Colorless oil; Rf¼0.18 (20% EtOAc in hexane); 1 [a]20 D 12.6 (c 0.22, CHCl3); H NMR (400 MHz, CDCl3) d 4.24 (t, J¼6.4 Hz, 1H), 4.11 (td, J¼7.8, 5.0 Hz, 1H), 3.99 (dd, J¼10.5, 2.3 Hz. 1H), 3.86e3.76 (m, 3H), 2.75 (dd, J¼16.5, 5.0 Hz, 1H), 2.66 (dd, J¼16.5, 7.8 Hz, 1H), 2.19 (s, 3H), 1.14e0.82 (m, 28H); 13C NMR (100 MHz, CDCl3) d 207.7, 83.3, 79.9, 74.3, 72.2, 63.0, 47.2, 31.3, 17.7, 17.6, 17.5, 17.4, 17.3, 17.24, 17.22, 13.6, 13.4, 13.0, 12.9; MS (CI): m/ z¼433 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C20H41O6Si2: 433.2442; Found 433.2436. 4.3. Determination of the stereochemistry of the products: typical procedure A mixture of 2,5-trans-5 and 2,5-cis-5 (103 mg; 2:3 ratio) in THF (1.2 mL) and TBAF (0.74 mL, 1.0 M in THF solution) was stirred for 30 min at 0 C. Then, solvent was removed and the residue was purified by column chromatography on silica gel eluted with 60% acetone in hexane to give diol. The product was then dissolved in CH2Cl2 and triethylamine (439 mL, 3.15 mmol), DMAP (1 mg, 0.008 mmol) were added. To this mixture, p-toluoyl chloride (209 mL, 1.58 mmol) was added and the mixture was stirred for 6 h at room temperature. The mixture was diluted with CH2Cl2 and washed with water and brine. CH2Cl2 layer was dried over MgSO4 and evaporated. Residual oil was purified by flash chromatography
on silica gel eluted with 30% EtOAc in hexane to give a mixture of isomers (49.7 mg) in 49% yield. A part of the product was purified by HPLC under the following conditions; column (ChemcoPak NUCLEOSIL 100-10), column size (20x250 mm), eluent (30% AcOEt in hexane), flow rate (10 mL/min), detection (254 nm), retention time (t2,5-cis-9¼18.75, t2,5-trans-9¼24.10). 4.3.1. 2,5-cis-9. Colorless oil; Rf¼0.17 (20% EtOAc in hexane); [a]20 D þ25.6 (c 0.34, CHCl3), 1H NMR (400 MHz, CDCl3) d 7.93e7.90 (m, 4H), 7.25e7.23 (m, 4H), 5.48 (dt, J¼6.4, 2.3 Hz, 1H), 4.61 (dtd, J¼10.5, 6.9, 5.4 Hz, 1H), 4.52 (dd, J¼11.4, 4.1 Hz, 1H), 4.46 (dd, J¼11.4, 4.1 Hz, 1H), 4.36 (td, J¼4.1, 2.3 Hz, 1H), 2.86 (dd, J¼16.5, 6.9 Hz, 1H), 2.64 (dd, J¼16.5, 5.5 Hz, 1H), 2.42 (s, 3H), 2.41 (s, 3H), 2.39 (dt, J¼13.7, 6.9 Hz, 1H), 2.18 (s, 3H), 1.92 (ddd, J¼13.7, 10.5, 6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 206.8, 166.5, 166.3, 144.3, 144.1, 129.89, 129.84, 129.4, 129.3, 127.3, 127.0, 82.7, 76.9, 75.2, 64.7, 48.9, 38.8, 31.1, 21.89, 21.87; MS (EI): m/z¼410 [M]þ; HRMS (EI): m/z [M]þ calcd for C24H26O6: 410.1727; Found 410.1729. 4.3.2. 2,5-trans-9. Colorless oil; Rf¼0.17 (20% EtOAc in hexane); 1 [a]20 D þ38.4 (c 0.20, CHCl3), H NMR (400 MHz, CDCl3); d 7.93e7.90 (m, 4H), 7.24e7.21 (m, 4H), 5.49 (dt, J¼5.9, 3.2 Hz, 1H), 4.71 (ddt, J¼7.3, 6.6, 5.5 Hz, 1H), 4.52e4.41 (m, 3H), 2.97 (dd, J¼16.5, 6.9 Hz, 1H), 2.74 (ddd, J¼14.2, 7.3, 5.9 Hz, 1H), 2.72 (dd, J¼16.5, 6.4 Hz, 1H), 2.42 (s, 3H), 2.40 (s, 3H), 2.20 (s, 3H), 1.95 (ddd, J¼14.2, 5.5, 3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 206.8, 166.5, 166.3, 144.3, 144.0, 129.87, 129.81, 129.4, 129.3, 127.2, 127.0, 81.8, 76.7, 75.3, 64.7, 49.9, 37.9, 30.8, 21.89, 21.86; MS (CI): m/z¼411 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C24H27O6: 411.1810; Found 411.1808. 4.3.3. A mixture of 2,5-trans-8 and 2,5-cis-8. A mixture of 2,5-trans8 and 2,5-cis-8 (103 mg, 0.16 mmol; 2:1 ratio) was desilylated and p-toluoylated by the same method for the preparation of 2,5-trans9 and 2,5-cis-9 to give a mixture of 2,5-trans-11 and 2,5-cis-11 (35.8 mg) in 53% yield. A part of the mixture was separated by HPLC under the following conditions; column (ChemcoPak NUCLEOSIL 100-10), column size (20x250 mm), eluent (20% AcOEt in hexane), flow rate (10 mL/min), detection (254 nm), retention time (t2,5-cis11¼22.11 min, t2,5-trans-11¼24.82 min). 4.3.4. 2,5-cis-11. Colorless oil; Rf¼0.32 (20% EtOAc in hexane); [a]20 D þ28.4 (c 0.26, CHCl3), 1H NMR (400 MHz, CDCl3) d 7.95e7.93 (m, 4H), 7.24e7.22 (m, 4H), 5.51 (dt, J¼6.4, 1.8 Hz, 1H), 4.63 (ddt, J¼10.9, 7.1, 5.8 Hz, 1H), 4.49 (d, J¼4.1 Hz, 2H), 4.39 (td, J¼4.1, 1.8 Hz, 1H), 3.70 (s, 3H), 2.74 (dd, J¼15.8, 7.1 Hz, 1H), 2.60 (dd, J¼15.8, 5.8 Hz, 1H), 2.42 (s, 3H), 2.41 (s, 3H), 2.37 (ddd, J¼13.7, 5.8, 1.8 Hz, 1H), 2.03 (ddd, J¼13.7, 10.5, 6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 171.4, 166.5, 166.3, 144.3, 144.0, 129.91, 129.86, 129.3 (2C), 127.2, 127.1, 82.8, 76.9, 75.5, 64.7, 52.0, 40.1, 38.6, 21.89, 21.88; MS (EI): m/z¼426 [M]þ; HRMS (EI): m/z [M]þ calcd for C24H26O7: 426.1676; Found 426.1679. 4.3.5. 2,5-trans-11. Colorless oil; Rf¼0.32 (20% EtOAc in hexane); 1 [a]20 D þ44.5 (c 0.60, CHCl3), H NMR (400 MHz, CDCl3) d 7.93e7.90 (m, 4H), 7.24e7.21 (m, 4H), 5.51 (dt, J¼6.4, 2.7 Hz, 1H), 4.74 (tdd, J¼7.3, 6.4, 4.5 Hz, 1H), 4.53e4.43 (m, 3H), 3.70 (s, 3H), 2.84 (dd, J¼15.1, 7.3 Hz, 1H), 2.71 (ddd, J¼14.2, 7.3, 6.9 Hz, 1H), 2.64 (dd, J¼15.1, 6.4 Hz, 1H), 2.42 (s, 3H), 2.40 (s, 3H), 2.04 (ddd, J¼14.2, 4.5, 3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 171.4, 166.5, 166.3, 144.3, 144.0, 129.89, 129.84, 129.4, 129.3, 127.2, 126.9, 82.1, 76.7, 75.8, 64.7, 52.0, 41.0, 37.7, 21.89, 21.86; MS (EI): m/z¼426 [M]þ; HRMS (EI): m/z [M]þ calcd for C24H26O7: 426.1676; Found 426.1679. 4.3.6. A mixture of 2,5-trans-7 and 2,5-cis-7. (60.2 mg, 0.25 mmol, 1:0.8 ratio) and benzoyl chloride (65 mL, 76 mg, 0.56 mmol) in pyridine (1 mL) was stirred for 12 h at room temperature. The mixture was diluted with CH2Cl2 (30 mL) and washed with water
Y. Murata, J. Uenishi / Tetrahedron 72 (2016) 4962e4967
(5 mL 2) and brine. The extract was dried over MgSO4 and solvent was removed. The residue was purified by flash column chromatography on silica gel eluted with 10% EtOAc in hexane to give a mixture of 2,5-trans-10 (37 mg) in 50% yield and 2,5-cis-10 (29 mg) in 39% yield. 4.3.7. 2,5-cis-10. Colorless oil; Rf¼0.23 (10% EtOAc in hexane); 1 [a]20 D þ25.6 (c 0.34, CHCl3), H NMR (400 MHz, CDCl3) d 7.93e7.90 (m, 4H), 7.25e7.23 (m, 4H), 5.48 (dt, J¼6.4, 2.3 Hz, 1H), 4.61 (dtd, J¼10.5, 6.9, 5.4 Hz, 1H), 4.52 (dd, J¼11.4, 4.1 Hz, 1H), 4.46 (dd, J¼11.4, 4.1 Hz, 1H), 4.36 (td, J¼4.1, 2.3 Hz, 1H), 2.86 (dd, J¼16.5, 6.9 Hz, 1H), 2.64 (dd, J¼16.5, 5.5 Hz, 1H), 2.42 (s, 3H), 2.41 (s, 3H), 2.39 (dt, J¼13.7, 6.9 Hz, 1H), 2.18 (s, 3H), 1.92 (ddd, J¼13.7, 10.5, 6.4 Hz, 1H); 13 C NMR (100 MHz, CDCl3) d 206.8, 166.5, 166.3, 144.3, 144.1, 129.89, 129.84, 129.4, 129.3, 127.3, 127.0, 82.7, 76.9, 75.2, 64.7, 48.9, 38.8, 31.1, 21.89, 21.87; MS (EI): m/z¼410 [M]þ; HRMS (EI): m/z [M]þ calcd for C24H26O6: 410.1727; Found 410.1729. 4.3.8. 2,5-trans-10. Colorless oil; Rf¼0.16 (10% EtOAc in hexane); 1 [a]20 D þ38.4 (c 0.20, CHCl3), H NMR (400 MHz, CDCl3); d 7.93e7.90 (m, 4H), 7.24e7.21 (m, 4H), 5.49 (dt, J¼5.9, 3.2 Hz, 1H), 4.71 (ddt, J¼7.3, 6.6, 5.5 Hz, 1H), 4.52e4.41 (m, 3H), 2.97 (dd, J¼16.5, 6.9 Hz, 1H), 2.74 (ddd, J¼14.2, 7.3, 5.9 Hz, 1H), 2.72 (dd, J¼16.5, 6.4 Hz, 1H), 2.42 (s, 3H), 2.40 (s, 3H), 2.20 (s, 3H), 1.95 (ddd, J¼14.2, 5.5, 3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 206.8, 166.5, 166.3, 144.3, 144.0, 129.87, 129.81, 129.4, 129.3, 127.2, 127.0, 81.8, 76.7, 75.3, 64.7, 49.9, 37.9, 30.8, 21.89, 21.86; MS (CI): m/z¼411 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C24H27O6: 411.1810; Found 411.1808.
4.4. Isomerization of a mixture of 2,5-trans-7 and 2,5-cis-7 A mixture of 2,5-trans-7 and 2,5-cis-7 (21.4 mg, 0.049 mmol) with a 5:4 ratio and CSA (3.5 mg, 0.015 mmol) in CH2Cl2 (0.6 mL) was stirred at room temperature for 60 min. Purification by silica gel column chromatography described for the preparation of 2,5trans-7 and 2,5-cis-7 provided 2,5-cis-7 (13.3 mg) with the same ratio.
Acknowledgements The authors acknowledge financial support by the Minister of Education Science and Culture Japan.
Supplementary data Supplementary data associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.tet.2016.06.081.
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References and notes 1. Recent reviews (a) Nasir, N. M.; Ermanis, K.; Clarke, P. A. Org. Biomol. Chem. 2014, 12, 3323e3335; (b) Cornil, J.; Gonnard, L.; Bensoussan, C.; Serra-Muns, A.; Gnamm, C.; Commandeur, C.; Commandeur, M.; Reymond, S.; Guerinot, A.; Cossy, J. Acc. Chem. Res. 2014, 48, 761e773; (c) Dohanosova, J.; Gracza, T. Molecules 2013, 18, 6173e6192; (d) Lorente, A.; Lamariano-Merketegi, J.; Albericio, F.; Alvarez, M. Chem. Rev. 2013, 113, 4567e4610; (e) Wolfe, J. P.; Hay, M. B. Tetrahedron 2007, 63, 261e290; (f) Muzart, J. Tetrahedron 2005, 61, 5955e6008. 2. (a) Malmstrom, J.; Christophersen, C.; Brrrero, A. F.; Oltra, J. E.; Justicia, J.; Rosales, A. J. Nat. Prod. 2002, 65, 364; (b) Liaw, C.-C.; Wu, T.-Y.; Chang, F.-R.; Wu, Y.C. Planta Med. 2010, 75, 1390e1404; (c) Keller-Schierlein, W.; Gerlach, H. Fortschr. Chem. Org. Naturst. 1968, 26, 161e189; (d) Kobayashi, J.; Tsuda, M. Nat. Prod. Rep. 2004, 21, 77e93; (e) Murakami, M.; Matsuda, H.; Makabe, K.; Yamaguchi, K. Tetrahedron Lett. 1991, 32, 2391e2394. 3. (a) De Clercq, E. J. Med. Chem. 2016, 59, 2301e2311; (b) Boutureira, O.; Metheu, M. I.; Diaz, Y.; Castillon, S. Synthesis of C-nucleoside In Chemical Synthesis of Nucleoside Analogues; Merino, P., Ed.; John Wiley & Sons: Hoboken USA, 2013; pp 263e316; (c) Stambasky, J.; Hocek, M.; Kocovsly, P. Chem. Rev. 2009, 109, 6729e6764. 4. Cascade reaction (a) Hu, L.; Lu, X.; Deng, L. J. Am. Chem. Soc. 2015, 137, 8400e8403; (b) Veidenberg, I.; Toom, L.; Villo, P.; Vares, L. Tetrahedron Lett. 2014, 55, 3569e3571; (c) Morimoto, Y.; Iwai, T.; Nishikawa, Y.; Kinoshita, T. Tetrahedron: Asymmetry 2002, 13, 2641e2647 Oxidative ring formation; (d) Sheikh, N. S. Org. Biomol. Chem. 2014, 12, 9492e9504; (e) Sheikh, N. S. Nat. Prod. Rep. 2014, 31, 1088e1100 Halo ether formation; (f) White, J. D.; Quaranta, L.; Wang, G. J. Org. Chem. 2007, 72, 1717e1728; (g) Kang, S. H.; Lee, S. B. Tetrahedron Lett. 1993, 34, 7579e75892 Radical Cyclization formation; (h) Berlin, S.; Ericsson, C.; Engman, L. J. Org. Chem. 2003, 68, 8386e8396; (i) Jeong, E. J.; Kang, E. J.; Sung, L. T.; Hong, S. K.; Lee, E. J. Am. Chem. Soc. 2002, 124, 14655e14662; (j) Evans, P. A.; Roseman, J. D. Tetrahedron Lett. 1995, 36, 31e34 CH-insertion; (k) Clark, J. S. Tetrahedron Lett. 1992, 33, 6193e6196 Oxy-palladation; (l) Uenishi, J.; Fujikura, Y.; Kawai, N. Org. Lett. 2011, 13, 2350e2353. 5. (a) Fuwa, H. Heterocycles 2012, 85, 1255e1298; (b) Nising, C. F.; Brase, S. Chem. Soc. Rev. 2012, 41, 988e999; (c) Nising, C. F.; Brase, S. Chem. Soc. Rev. 2008, 37, 1218e1228. 6. Oxy-Michael reaction for 1,5-disubstituted THF compounds (a) Lorente, A.; Gil, A.; Fernandez, R.; Cuevas, C.; Albericio, F.; Alvarez, M. Chem.dEur. J. 2015, 21, 150e156; (b) Krishna, P. R.; Anitha, K.; Raju, G. Tetrahedron 2013, 69, 1649e1657; (c) Lu, Y.; Zou, G.; Zhao, G. ACS Catal. 2013, 3, 1356e1359; (d) Armstrong, A.; Pyrkotis, C. Tetrahedron Lett. 2009, 50, 3325e3328; (e) Abbineni, C.; Sasmal, P. K.; Mullanti, K.; Iqbal, J. Tetrahedron Lett. 2007, 48, 4259e4262; (f) Zakrzewski, P.; Lau, C. K. Synlett 2003, 215e218; (g) Kubota, T.; Tsuda, M.; Kobayashi, J. Tetrahedron 2003, 59, 1613e1625; (h) Guindon, Y.; Delorme, D.; Lau, C. K.; Zamboni, R. J. Org. Chem. 1988, 53, 267e275. 7. Reaction of g-substituted a,b-unsaturated esters (a) Valot, G.; Mailhol, D.; Rehens, C. S.; O’Malley, D. P.; Godineau, E.; Takigawa, H.; Philipps, P.; Furstner, A. Chem.dEur. J. 2015, 21, 2398e2408; (b) Sabitha, G.; Chandrashekhar, G.; Yadav, J. S.; Rachineni, K.; Jagadeesh, B. RSC Adv. 2012, 2, 10157e10159; (c) Fries, P.; Halter, D.; Kleinschek, A.; Hartung, J. J. Am. Chem. Soc. 2011, 133, 3906e3912; (d) Paudyal, M. P.; Rath, N. P.; Spilling, C. D. Org. Lett. 2010, 12, 2954e2957; (e) Ghosh, A. K.; Shurrush, K.; Kulkarni, S. J. Org. Chem. 2009, 74, 4508e4518; (f) Bates, R. H.; Shotwell, J. B.; Roush, W. R. Org. Lett. 2008, 10, 4343e4346; (g) Kubota, T.; Tsuda, M.; Kobayashi, J. Org. Lett. 2001, 3, 1363e1366; (h) Harusawa, S.; Fujii, K.; Nishiura, M.; Araki, L.; Usami, Y.; Zhao, Z.; Lilly, D. M. J. Heterocycles 2011, 83, 2041e2055; (i) Bull. Korean Chem. Soc. 1992, 13, 222e223; (j) Ohrui, H.; Jones, G. H.; Moffatt, J. G.; Maddox, M. L.; Christensen, A. T.; Byram, S. K. J. Am. Chem. Soc. 1975, 97, 4602e4613. 8. Preparation of 1e4: cyclic bis-silyl ether formation and successive Wittig reaction. Murata, Y.; Uenishi, J. submitted in J. Org. Chem. 9. See the Supplementary data. 10. Similar selectivity was observed for the C-1 allylation and glycosidation in the case of 2-deoxy-D-ribose.
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Base- and acid-catalyzed intramolecular oxy-Michael reaction for the synthesis of tetrahydrofuran ring Yuki Murata, Jun’ichi Uenishi * Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8412, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 3 June 2016 Received in revised form 25 June 2016 Accepted 30 June 2016 Available online 1 July 2016
Base- and acid-catalyzed intramolecular oxy-Michael reactions are reported. Three ε-hydroxy a,b-unsaturated ketones 1, 2, and 3 and one ester 4 were cyclized in 5-exo-trigonal fashion to afford 2,5disubstituted tetrahydrofurans in good yields. The substituent at the g-hydroxy group and its stereochemistry influenced the stereoselectivity of the THF products. The precursor 2 bearing an (R)-g-hydroxy group gave 2,5-trans-6 exclusively. In contrast, 3, bearing an (S)-g-hydroxy group, gave only 2,5-cis-7 under acidic conditions but gave a mixture of 2,5-trans and 2,5-cis isomers of 7 under basic conditions. On the other hand, in the absence of a hydroxyl group at the g-position, the cyclization conducted under both basic and acidic reaction conditions provided a mixture of 2,5-trans- and 2,5-cis isomers of 5 and 8. Ó 2016 Published by Elsevier Ltd.
On the celebration of Tetrahedron Prize 2014, this paper is dedicated to Professor Jiro Tsuji for his great contribution on Pdchemistry
Keywords: Oxy-Michael reaction Stereochemistry THF ring Facial selectivity Catalytic reaction
1. Introduction Oxa-heterocycles are an important unit in heterocyclic chemistry and the synthesis of oxa-cyclic ring has been well investigated.1 Tetrahydrofuran (THF) rings exist widely as a core component in natural products2 as well as in biologically active compounds3 including C-nucleosides. A number of synthetic methods for 2,5substituted THF compounds by ring forming reactions have been reported, e.g., cascade reaction of epoxides,4aec oxidative ring formation to alkenes,4d,e halolactonization,4f,g radical cyclization,4hej CH-insertion,4k and oxy-palladation.4l The oxy-Michael reaction is a powerful method to form oxa-heterocycles not only for tetrahydropyran (THP) rings5 but also for THF rings. In fact, the 2,5substituted THF ring unit has been synthesized by this method.6 However the method has been employed mainly for a,b-unsaturated esters but poorly for a,b-unsaturated ketones. The reaction has been used limitedly for the g-substituted a,b-unsaturated esters,7 and only a few reaction for the g-hydroxy a,b-unsaturated ester have been reported so far.7h We have been interested in the oxy-Michael reaction with ε-hydroxy-a,b-unsaturated ketones
* Corresponding author. Tel.: þ81 75 595 4665; fax: þ81 75 595 4763; e-mail address: [email protected] (J. Uenishi). http://dx.doi.org/10.1016/j.tet.2016.06.081 0040-4020/Ó 2016 Published by Elsevier Ltd.
including g-hydroxy derivatives for the synthesis of the 5-acetonylTHF ring and its stereochemical course of the reactions. In this paper, we report the oxy-Michael reaction of four substrates 1e4 and the investigation of their stereochemistry (Scheme 1).
Scheme 1. Precursors of oxy-Michael reaction and synthesis of 2,5-disubstituted THF compounds.
2. Results and discussion The precursors of the oxy-Michael reaction 1, 2, 3 and 4 were prepared from 2-deoxy-D-ribose, D-arabinose and D-ribose in 2 steps.8 First, we treated compound 1 with 20 mol % of t-BuOK in THF at room temperature. The two diastereomeric isomers of 2,5trans-5 and 2,5-cis-5 were obtained with 82% yield in a ratio of 2:3
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(Scheme 2). Unfortunately they were not separable by chromatography. They were derivatized to a mixture of di-O-toluoyl derivatives 2,5-trans-9 and 2,5-cis-9 with 47% yield in two steps i) removal of cyclic silyl ether with TBAF and ii) toluoylation with toluoyl chloride. After this conversion, they were separable by HPLC to give the polar 2,5-trans-9 and the less polar 2,5-cis-9. The major isomer was identified to be 2,5-cis-9 and the minor isomer 2,5trans-9 determined by the NOESY experiments.9 When the reaction was conducted at e78 C, a mixture of 2,5-trans-5 and 2,5-cis-5 was obtained in 80% yield and the selectivity of cis isomer increased little to be 1:2.
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79% yield. Their stereochemistries were determined after the conversion to the corresponding benzoates. A 1:2 mixture of 2,5-trans-7 and 2,5-cis-7 was acylated with benzoyl chloride to give a mixture of 2,5-trans-10 and 2,5-cis-10 in the same ratio. They were separable and their NOESY spectra supported their relative structures.9 According to the oxy-Michael reactions for a,b-unsaturated esters in literature,6 the 2,5-trans isomer was usually formed predominantly. However the reaction of the a,b-unsaturated ketone in the present cases, favored the production of the 2,5-cis isomer as opposed to the 2,5-trans isomer. When the g-substituent was
Scheme 2. Oxy-Michael reaction of 1, 2, 3 and transformation to 9 and 10.
Interestingly, the reaction of 2 under the same conditions afforded a single stereoisomer either at room temperature or at 78 C, which was assigned to be 2,5-trans-6.9 These chemical yields were excellent in 85% and 83%, respectively. On the other hand, the reaction of 3 gave a mixture of 2,5trans-7 and 2,5-cis-7 in a ratio of 1:0.8 at room temperature in 80% yield. However, when the reaction was conducted at 78 C, 2,5-cis-7 produced favorably in a ratio of 1:2.0 with
present, the stereochemistry of the product was not simple. We examined other reaction conditions using either basic or acidic catalysts. The results are shown in Table 1. The effect of temperature on the reaction rate was evaluated but little difference in the selectivity was observed (entries 1e3) except the case at 78 C (entry 4). The chemical yields were not much affected by the nature of the solvent (t-BuOH and toluene) used in the reaction (entries 5 and 6). The reactions in DMSO and
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Table 1 PdII-catalyzed cyclization of 1e3
Entry
Precursor
Base or acid (mol %)
Solvent
Temp ( C)
Time (min)
Product
Yielda (%)
2,5-trans: 2,5-cisb
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
1 1 1 1 1 1 1 1 1 2 2 2 2 3 3 3 3
t-BuOK (20) t-BuOK (20) t-BuOK (20) t-BuOK (20) t-BuOK (20) t-BuOK (20) DBU (50) DBU (50) CSA (30) t-BuOK (20) t-BuOK (20) DBU (20) CSA (30) t-BuOK (20) t-BuOK (20) DBU (20) CSA (30)
THF THF THF THF t-BuOH Toluene THF Benzene CH2Cl2 THF THF THF CH2Cl2 THF THF THF CH2Cl
Reflux rt 0 78 rt rt Reflux Reflux rt rt 78 Reflux rt rt 78 Reflux rt
5 5 15 60 10 10 60 60 180 5 10 5 20 5 10 40 40
5 5 5 5 5 5 5 5 5 6 6 6 6 7 7 7 7
80 82 84 80 82 70 67 64 75 85 83 71 69 80 79 80 71
1:1.5 1:1.5 1:1.4 1:2.0 1:1.4 1:1.4 1:1.4 1:1.4 1:1.3 trans only trans only trans only trans only 1:0.8 1:2.2 1:0.9 cis only
a b
Isolated yield. Ratio was calculated by the integration value of 1H NMR spectrum.
acetonitrile did not provide any of 5 (not in Table). Although an amine base (DBU) slowly promoted the reaction at room temperature in THF, the reaction was accelerated either in refluxing THF or benzene in a ratio of 1:1.4 of the trans and cis isomers with moderate yields (entries 7 and 8). Treatment of 1 with 30 mol % of dlcamphorsulfonic acid in CH2Cl2 provided compounds 5 in 75% yield with a 1:1.3 ratio (entry 9). In contrast to the substrate 1, it is quite interesting that the substrate 2 gave a trans stereoisomer 6 exclusively, even under the basic (t-BuOK or DBU, entries 10e12) or acidic (CSA, entry 13) conditions. On the other hand, the substrate 3 was cyclized with t-BuOK to give a mixture of 2,5-trans and 2,5-cis products depending on the conditions and the trans and cis isomers were formed in a 1:0.8 ratio at room temperature and in a 1:2.2 ratio at 78 C (entries 14 and 15). The reaction of 3 with DBU base gave 7 with a 1:0.9 ratio in THF at refluxing temperature similarly (entry 16). However, it is surprising that the CSA-catalyzed reaction of 3 in CH2Cl2 at room temperature afforded 2,5-cis-7 as a single product in 71% yield (entry 17). Michael reaction is known to be equilibrium in its process. A 4:3 mixture of 2,5-trans-7 and 2,5-cis-7 was treated with t-BuOK in THF at both room temperature and 78 C. Though some loss was observed, the ratio did not change at all in both reactions. On the other hand, upon exposure of the mixtures in CH2Cl2 containing 0.3 equiv of CSA at room temperature for 1 h, the ratio of the recovered products was changed to be the only 2,5-cis-7 isomer. The mixtures would equilibrate to be the thermodynamically more stable 2,5-cisisomer by retro-Michael and Michael processes under the acidic conditions but not under the basic conditions. It is known that the a-glycoside of D-ribose analogues is less stable than that of the bglycoside due to the consecutive substituents at the a,b,g-positions on the furan ring. Similarly, 2,5-trans-7 could be expected to be less stable rather than 2,5-cis-7. We have also examined a,b-unsaturated ester 4. The reaction with 5 mol % of t-BuOK gave 2,5-trans-8 and 2,5-cis-8 with no selectively (Scheme 3). However the trans isomer was formed favorably at 78 C in a ratio of 1:0.3. This trend of stereochemistry has been observed previously in the g-nonsubstituted ε-hydroxy-a,bunsaturated esters.6 These structures were confirmed by NOESY
spectra after conversion to their toluoyl esters 11. While, the reaction under the acidic conditions with 30 mol % of CSA in CH2Cl2 at room temperature gave a recovery of starting material even after 24 h.
Scheme 3. Oxy-Michael reaction of 4 and transformation to 11.
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2.1. Reaction mechanism Based on the above results, we considered the stereochemical course of the reactions. An attack of the oxygen nucleophile on the alkene face of the a,b-unsaturated carbonyl group could occur in two rotational isomers for conformers I and II (Scheme 4). An a,bunsaturated ketone could assume an extended form in the conformer I with the OeC bond formation leading to the 2,5-trans isomer. On the other hand, the a,b-unsaturated ketone could be arranged in a bent form in the conformer II that could lead to the 2,5-cis isomer. (i) When X is a hydrogen (compound 2), the conformer I would escape from a 1,3-allylic strain and that would give a single stereoisomer 2,5-trans-6. The experimental results supported this stereochemical course of the reactions for 2. (ii) When X is not a hydrogen (compound 3), an allylic strain appears in its conformer I. The product from the conformer I would be the 2,5trans-7 that is a rather sterically strained isomer, because of the presence of three consecutive substituents located on the a-face of the THF ring. Therefore, another conformer II would be possible and an interaction of a metal alkoxide with the carbonyl might be expected to stabilize the conformer II. Although we are not able to estimate its strength of the allylic strain in this case (X¼OH for the conformer I), the total effects could influence the formation of 2,5trans-7 and 2,5-cis-7. Equilibrium between trans and cis isomers may exist under the acidic conditions converting the 2,5-trans isomer to a single thermodynamically favored 2,5-cis-isomer.
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the synthesis of 2,5-disubstituted THF compounds and the stereochemical results are valuable for further consideration of intramolecular oxy-Michael reactions in the formation of 5membered heterocycles.
4. Experimental 4.1. General information All reactions were run under an atmosphere of nitrogen. Solvents and reagents were dried prior to use. Et2O and THF were distilled from sodium benzophenone ketyl. CH2Cl2 was distilled from P2O5 and toluene was distilled from CaH2. 1H NMR spectra were recorded on JEOLJNM-ECS-400 (400 MHz). Proton chemical shifts were internally referenced to the residual proton resonance in CDCl3 (d 7.26) and CD2Cl2 (d 5.32). 13C NMR spectra were recorded on JEOLJNM-ECS-400 (100 MHz) and JEOLECA-600 (150 MHz). Carbon chemical shifts were internally referenced to the deuterated solvent signals in CDCl3 (d 77.00). Mass spectra (MS) were recorded on JEOL JMC-GC MATE. Electron impact (EI) spectra were performed at 70 eV for low and high resolution mass spectra. Optical rotations were recorded on a JASCO P-2200. HPLC analyses were performed on a Shimazu using UV-2075 detector. Analytical thin layer chromatography (TLC) was performed on Merck silica gel 60F254 plates. Flash column chromatography was performed with Merck silica gel 60 (40e63 mm pore size).
4.2. Experimental procedures and characterization data 4.2.1. Typical procedure of t-BuOK catalyzed oxy-Michael reaction of 1e4. To a mixture of alkene (0.15 mmol) in THF (0.6 mL) was added potassium tert-butoxide (3.4 mg, 0.03 mmol) at room temperature and the mixture was stirred for 5 min. Satd ammonium chloride was added and the mixture was extracted with 30% EtOAc in hexane. Organic extract was washed with water and brine and dried over MgSO4. Solvent was removed and the residue was purified with 10% EtOAc in hexane for compounds 5 and 8 and 20% EtOAc in hexane for compounds 6 and 7.
Scheme 4. Facial selection in oxy-Michael reaction for 1, 2 and 3.
The difference of stereoselectivity observed in a,b-unsaturated ketone 1 and a,b-unsaturated ester 4 is not clear. It is assumed that the conformer II of 1 would be more favorable than that of 4.10 3. Conclusion In summary, we have disclosed the stereochemistry of the oxyMichael reaction for the chiral 3-hydroxy a,b-unsaturated ketones 1e3 and ester 4. This reaction proceeded via a 5-exo-trigonal fashion and effectively provided 2,5-disubstituted tetrahydrofurans. In the absence of a g-hydroxy group a mixture of 2,5disubstituted tetrahydrofurans was obtained. The 2,5-cis product is favorably produced in the case of a,b-unsaturated ketone which differs from the product of the a,b-unsaturated ester. In the presence of an (R)-hydroxy group at the g-position, the 2,5-trans isomer, 2,5-trans-6, was produced exclusively. In the presence of an (S)-g-hydroxy group both 2,5-trans and 2,5-cis isomers, 2,5trans-7 and 2,5-cis-7, were formed under the basic conditions. However, the thermodynamically stable cis-isomer was only produced under the acidic conditions. These findings will be useful for
4.2.2. 2,5-trans-5 and 2,5-cis-5 (2:3). Colorless oil; Colorless oil; Rf¼0.31 (10% EtOAc in hexane); 1H NMR (400 MHz, CDCl3) d 4.47e4.35 (m, 2H), 4.03e3.92 (m, 1H), 3.77e3.67 (m, 2H), 2.87 (dd, J¼16.4, 7.2 Hz, 2/5H), 2.74 (dd, J¼16.0, 6.8 Hz, 3/5H), 2.63 (dd, J¼16.5, 5.9 Hz, 2/5H), 2.55 (dd, J¼16.0, 5.9 Hz, 3/5H), 2.46e2.37 (m, 2/5H), 2.18 (s, 6/5H), 2.17 (s, 9/5H), 2.15 (ddd, J¼12.8, 6.4, 4.6 Hz, 3/ 5H), 1.89e1.67 (m, 1H), 1.09e0.97 (m, 28H); 13C NMR (100 MHz, CDCl3) d 207.2 (2/5C), 206.9 (3/5C), 86.2 (3/5C), 83.5 (2/5C), 73.7 (2/5C) 73.6 (2/5C), 73.53 (3/5C), 73.50 (3/5C), 63.8 (3/5C), 63.5 (2/ 5C), 49.8 (2/5C), 49.5 (3/5C), 40.7 (2/5C), 40.6 (3/5C), 30.97 (3/5C), 30.93 (2/5C), 17.7 (3C), 17.6 (4C), 17.5 (1C), 17.47 (2C), 17.43 (2C), 17.3 (3C), 17.2 (2C), 17.1 (1C), 13.6 (3/5C), 13.58 (2/5C), 13.52 (3/5C), 13.4 (2/5C), 13.1 (3/5C), 13.0 (2/5C), 12.7 (1C); MS (CI): m/z¼417 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C20H41O5Si2: 417.2493; Found. 4.2.3. 2,5-trans-6. Colorless oil; Rf¼0.23 (20% EtOAc in hexane); 1 [a]20 D 25.7 (c 0.39, CHCl3), H NMR (400 MHz, CDCl3) d 4.28 (t, J¼7.3 Hz, 1H), 4.10 (ddd, J¼8.2, 6.4, 5.4 Hz, 1H), 3.99 (br t, J¼6.4 Hz, 1H), 3.93 (dd, J¼12.4, 3.2 Hz, 1H), 3.85 (dd, J¼12.4, 5.2 Hz, 1H), 3.75 (ddd, J¼7.3, 5.2, 3.2 Hz, 1H), 3.29 (br s, 1H), 3.00 (dd, J¼17.9, 5.4 Hz, 1H), 2.77 (dd, J¼17.4, 8.2 Hz, 1H), 2.20 (s, 3H), 1.10e0.97 (m, 28H); 13 C NMR (100 MHz, CDCl3) d 208.7, 81.5, 81.2, 77.9, 77.7, 62.7, 48.3, 30.6, 17.5, 17.3 (3C), 17.07, 17.02 (3C), 13.5, 13.2, 12.8, 12.5; MS (CI): m/
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z¼433 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C20H41O6Si2: 433.2442; Found 433.2449. 4.2.4. 2,5-trans-7 and 2,5-cis-7 (1:0.8). Colorless oil; Rf¼0.18 (20% EtOAc in hexane); 1H NMR (400 MHz, CDCl3) d 4.44 (td, J¼6.9, 3.2 Hz, 5/9H), 4.36 (dd, J¼7.2, 4.8 Hz, 5/9H), 4.23 (t, J¼5.9 Hz, 4/9H), 4.19 (t, J¼4.1 Hz, 5/9H), 4.11 (dt, J¼8.0, 4.8 Hz, 4/9H), 4.02e3.94 (m, 1H), 3.88e3.75 (m, 22/9H), 2.96 (dd, J¼17.4, 7.8 Hz, 4/9H), 2.79 (dd, J¼16.4, 4.8 Hz, 5/9H), 2.75 (dd, J¼17.4, 6.0 Hz, 4/9H), 2.66 (dd, J¼16.4, 7.2 Hz, 5/9H), 2.20 (s, 3H), 1.08e0.97 (m, 28H); 13C NMR (100 MHz, CDCl3) d 207.7 (4/9C), 207.5 (5/9C), 83.2 (4/9C), 80.2 (4/ 9C), 79.9 (5/9C), 76.6 (5/9C), 74.7 (4/9C), 74.3 (5/9C), 72.4 (4/9C), 72.2 (5/9C), 63.1 (4/9C), 62.9 (5/9C), 47.3 (5/9C), 43.4 (4/9C), 31.3 (4/ 9C), 30.9 (5/9C), 17.6 (2C), 17.59 (1C), 17.51 (4C), 17.4 (2C), 17.39 (2C), 17.35 (1C), 17.2 (2C), 17.19 (1C), 17.15 (1C), 13.6 (4/9C), 13.5 (5/9C), 13.4 (4/9C), 13.3 (5/9C), 13.0 (4/9C), 12.9 (5/9C), 12.7 (1C); MS (CI): m/z¼433 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C20H41O6Si2: 433.2442; Found 433.2436. 4.2.5. 2,5-trans-8 and 2,5-cis-8 (3:2). Colorless oil; Rf¼0.32 (20% EtOAc in hexane); 1H NMR (400 MHz, CDCl3) d 4.48e4.37 (m, 2H), 4.06e3.96 (m, 1H), 3.79e3.63 (m, 2H), 3.69 (s, 6/5H), 3.68 (s, 3/5H), 2.75 (dd, J¼15.1, 7.8 Hz, 3/5H), 2.57 (dd, J¼15.6, 6.9 Hz, 2/ 5H), 2.41 (dd, J¼15.1, 5.9 Hz, 3/5H), 2.35 (dd, J¼15.6, 5.9 Hz, 2/ 5H), 2.26 (ddd, J¼15.1, 7.3, 2.3 Hz, 3/5H), 2.14 (ddd, J¼13.2, 6.4, 3.7 Hz, 2/5H), 1.84 (m, 1H), 1.27e0.99 (m, 28H); 13C NMR (100 MHz, CDCl3) d 171.6 (3/5C), 171.5 (2/5C), 86.3 (2/5C), 83.6 (3/ 5C), 73.9 (2/5C), 73.8 (3/5C), 73.58 (2/5C), 73.55 (3/5C), 63.9 (2/ 5C), 63.4 (3/5C), 51.92 (2/5C), 51.90 (3/5C), 40.9 (3/5C), 40.5 (2/ 5C), 40.4 (2/5C), 40.3 (3/5C), 17.7 (2C), 17.58 (3C), 17.57 (3C), 17.4 (2C), 17.3 (2C), 17.2 (2C), 17.1 (2C), 13.7 (3/5C), 13.6 (2/5C), 13.5 (2/ 5C), 13.4 (3/5C), 13.1 (2/5C), 13.0 (3/5C), 12.7 (1C); MS (CI): m/ z¼433 [MþH]þ; HRMS (EI): m/z [MþH]þ calcd for C20H41O6Si2: 433.2442; Found 433.2436. 4.2.6. 2,5-cis-7. Acid catalyzed cyclization of 3; A mixture of alkene 3 (34.2 mg, 0.08 mmol) and CSA (5.5 mg, 0.024 mmol) was stirred at room temperature for 40 min. Water was added and the mixture was extracted with 30% EtOAc in hexane. The extract was washed with 5% NaHCO3, brine and dried over MgSO4. Solvent was removed and the residue was purified by silica gel column chromatography eluted with 20% EtOAc in hexane to give 2,5-cis-7 (24.3 mg) in 71% yield. Colorless oil; Rf¼0.18 (20% EtOAc in hexane); 1 [a]20 D 12.6 (c 0.22, CHCl3); H NMR (400 MHz, CDCl3) d 4.24 (t, J¼6.4 Hz, 1H), 4.11 (td, J¼7.8, 5.0 Hz, 1H), 3.99 (dd, J¼10.5, 2.3 Hz. 1H), 3.86e3.76 (m, 3H), 2.75 (dd, J¼16.5, 5.0 Hz, 1H), 2.66 (dd, J¼16.5, 7.8 Hz, 1H), 2.19 (s, 3H), 1.14e0.82 (m, 28H); 13C NMR (100 MHz, CDCl3) d 207.7, 83.3, 79.9, 74.3, 72.2, 63.0, 47.2, 31.3, 17.7, 17.6, 17.5, 17.4, 17.3, 17.24, 17.22, 13.6, 13.4, 13.0, 12.9; MS (CI): m/ z¼433 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C20H41O6Si2: 433.2442; Found 433.2436. 4.3. Determination of the stereochemistry of the products: typical procedure A mixture of 2,5-trans-5 and 2,5-cis-5 (103 mg; 2:3 ratio) in THF (1.2 mL) and TBAF (0.74 mL, 1.0 M in THF solution) was stirred for 30 min at 0 C. Then, solvent was removed and the residue was purified by column chromatography on silica gel eluted with 60% acetone in hexane to give diol. The product was then dissolved in CH2Cl2 and triethylamine (439 mL, 3.15 mmol), DMAP (1 mg, 0.008 mmol) were added. To this mixture, p-toluoyl chloride (209 mL, 1.58 mmol) was added and the mixture was stirred for 6 h at room temperature. The mixture was diluted with CH2Cl2 and washed with water and brine. CH2Cl2 layer was dried over MgSO4 and evaporated. Residual oil was purified by flash chromatography
on silica gel eluted with 30% EtOAc in hexane to give a mixture of isomers (49.7 mg) in 49% yield. A part of the product was purified by HPLC under the following conditions; column (ChemcoPak NUCLEOSIL 100-10), column size (20x250 mm), eluent (30% AcOEt in hexane), flow rate (10 mL/min), detection (254 nm), retention time (t2,5-cis-9¼18.75, t2,5-trans-9¼24.10). 4.3.1. 2,5-cis-9. Colorless oil; Rf¼0.17 (20% EtOAc in hexane); [a]20 D þ25.6 (c 0.34, CHCl3), 1H NMR (400 MHz, CDCl3) d 7.93e7.90 (m, 4H), 7.25e7.23 (m, 4H), 5.48 (dt, J¼6.4, 2.3 Hz, 1H), 4.61 (dtd, J¼10.5, 6.9, 5.4 Hz, 1H), 4.52 (dd, J¼11.4, 4.1 Hz, 1H), 4.46 (dd, J¼11.4, 4.1 Hz, 1H), 4.36 (td, J¼4.1, 2.3 Hz, 1H), 2.86 (dd, J¼16.5, 6.9 Hz, 1H), 2.64 (dd, J¼16.5, 5.5 Hz, 1H), 2.42 (s, 3H), 2.41 (s, 3H), 2.39 (dt, J¼13.7, 6.9 Hz, 1H), 2.18 (s, 3H), 1.92 (ddd, J¼13.7, 10.5, 6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 206.8, 166.5, 166.3, 144.3, 144.1, 129.89, 129.84, 129.4, 129.3, 127.3, 127.0, 82.7, 76.9, 75.2, 64.7, 48.9, 38.8, 31.1, 21.89, 21.87; MS (EI): m/z¼410 [M]þ; HRMS (EI): m/z [M]þ calcd for C24H26O6: 410.1727; Found 410.1729. 4.3.2. 2,5-trans-9. Colorless oil; Rf¼0.17 (20% EtOAc in hexane); 1 [a]20 D þ38.4 (c 0.20, CHCl3), H NMR (400 MHz, CDCl3); d 7.93e7.90 (m, 4H), 7.24e7.21 (m, 4H), 5.49 (dt, J¼5.9, 3.2 Hz, 1H), 4.71 (ddt, J¼7.3, 6.6, 5.5 Hz, 1H), 4.52e4.41 (m, 3H), 2.97 (dd, J¼16.5, 6.9 Hz, 1H), 2.74 (ddd, J¼14.2, 7.3, 5.9 Hz, 1H), 2.72 (dd, J¼16.5, 6.4 Hz, 1H), 2.42 (s, 3H), 2.40 (s, 3H), 2.20 (s, 3H), 1.95 (ddd, J¼14.2, 5.5, 3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 206.8, 166.5, 166.3, 144.3, 144.0, 129.87, 129.81, 129.4, 129.3, 127.2, 127.0, 81.8, 76.7, 75.3, 64.7, 49.9, 37.9, 30.8, 21.89, 21.86; MS (CI): m/z¼411 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C24H27O6: 411.1810; Found 411.1808. 4.3.3. A mixture of 2,5-trans-8 and 2,5-cis-8. A mixture of 2,5-trans8 and 2,5-cis-8 (103 mg, 0.16 mmol; 2:1 ratio) was desilylated and p-toluoylated by the same method for the preparation of 2,5-trans9 and 2,5-cis-9 to give a mixture of 2,5-trans-11 and 2,5-cis-11 (35.8 mg) in 53% yield. A part of the mixture was separated by HPLC under the following conditions; column (ChemcoPak NUCLEOSIL 100-10), column size (20x250 mm), eluent (20% AcOEt in hexane), flow rate (10 mL/min), detection (254 nm), retention time (t2,5-cis11¼22.11 min, t2,5-trans-11¼24.82 min). 4.3.4. 2,5-cis-11. Colorless oil; Rf¼0.32 (20% EtOAc in hexane); [a]20 D þ28.4 (c 0.26, CHCl3), 1H NMR (400 MHz, CDCl3) d 7.95e7.93 (m, 4H), 7.24e7.22 (m, 4H), 5.51 (dt, J¼6.4, 1.8 Hz, 1H), 4.63 (ddt, J¼10.9, 7.1, 5.8 Hz, 1H), 4.49 (d, J¼4.1 Hz, 2H), 4.39 (td, J¼4.1, 1.8 Hz, 1H), 3.70 (s, 3H), 2.74 (dd, J¼15.8, 7.1 Hz, 1H), 2.60 (dd, J¼15.8, 5.8 Hz, 1H), 2.42 (s, 3H), 2.41 (s, 3H), 2.37 (ddd, J¼13.7, 5.8, 1.8 Hz, 1H), 2.03 (ddd, J¼13.7, 10.5, 6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 171.4, 166.5, 166.3, 144.3, 144.0, 129.91, 129.86, 129.3 (2C), 127.2, 127.1, 82.8, 76.9, 75.5, 64.7, 52.0, 40.1, 38.6, 21.89, 21.88; MS (EI): m/z¼426 [M]þ; HRMS (EI): m/z [M]þ calcd for C24H26O7: 426.1676; Found 426.1679. 4.3.5. 2,5-trans-11. Colorless oil; Rf¼0.32 (20% EtOAc in hexane); 1 [a]20 D þ44.5 (c 0.60, CHCl3), H NMR (400 MHz, CDCl3) d 7.93e7.90 (m, 4H), 7.24e7.21 (m, 4H), 5.51 (dt, J¼6.4, 2.7 Hz, 1H), 4.74 (tdd, J¼7.3, 6.4, 4.5 Hz, 1H), 4.53e4.43 (m, 3H), 3.70 (s, 3H), 2.84 (dd, J¼15.1, 7.3 Hz, 1H), 2.71 (ddd, J¼14.2, 7.3, 6.9 Hz, 1H), 2.64 (dd, J¼15.1, 6.4 Hz, 1H), 2.42 (s, 3H), 2.40 (s, 3H), 2.04 (ddd, J¼14.2, 4.5, 3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 171.4, 166.5, 166.3, 144.3, 144.0, 129.89, 129.84, 129.4, 129.3, 127.2, 126.9, 82.1, 76.7, 75.8, 64.7, 52.0, 41.0, 37.7, 21.89, 21.86; MS (EI): m/z¼426 [M]þ; HRMS (EI): m/z [M]þ calcd for C24H26O7: 426.1676; Found 426.1679. 4.3.6. A mixture of 2,5-trans-7 and 2,5-cis-7. (60.2 mg, 0.25 mmol, 1:0.8 ratio) and benzoyl chloride (65 mL, 76 mg, 0.56 mmol) in pyridine (1 mL) was stirred for 12 h at room temperature. The mixture was diluted with CH2Cl2 (30 mL) and washed with water
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(5 mL 2) and brine. The extract was dried over MgSO4 and solvent was removed. The residue was purified by flash column chromatography on silica gel eluted with 10% EtOAc in hexane to give a mixture of 2,5-trans-10 (37 mg) in 50% yield and 2,5-cis-10 (29 mg) in 39% yield. 4.3.7. 2,5-cis-10. Colorless oil; Rf¼0.23 (10% EtOAc in hexane); 1 [a]20 D þ25.6 (c 0.34, CHCl3), H NMR (400 MHz, CDCl3) d 7.93e7.90 (m, 4H), 7.25e7.23 (m, 4H), 5.48 (dt, J¼6.4, 2.3 Hz, 1H), 4.61 (dtd, J¼10.5, 6.9, 5.4 Hz, 1H), 4.52 (dd, J¼11.4, 4.1 Hz, 1H), 4.46 (dd, J¼11.4, 4.1 Hz, 1H), 4.36 (td, J¼4.1, 2.3 Hz, 1H), 2.86 (dd, J¼16.5, 6.9 Hz, 1H), 2.64 (dd, J¼16.5, 5.5 Hz, 1H), 2.42 (s, 3H), 2.41 (s, 3H), 2.39 (dt, J¼13.7, 6.9 Hz, 1H), 2.18 (s, 3H), 1.92 (ddd, J¼13.7, 10.5, 6.4 Hz, 1H); 13 C NMR (100 MHz, CDCl3) d 206.8, 166.5, 166.3, 144.3, 144.1, 129.89, 129.84, 129.4, 129.3, 127.3, 127.0, 82.7, 76.9, 75.2, 64.7, 48.9, 38.8, 31.1, 21.89, 21.87; MS (EI): m/z¼410 [M]þ; HRMS (EI): m/z [M]þ calcd for C24H26O6: 410.1727; Found 410.1729. 4.3.8. 2,5-trans-10. Colorless oil; Rf¼0.16 (10% EtOAc in hexane); 1 [a]20 D þ38.4 (c 0.20, CHCl3), H NMR (400 MHz, CDCl3); d 7.93e7.90 (m, 4H), 7.24e7.21 (m, 4H), 5.49 (dt, J¼5.9, 3.2 Hz, 1H), 4.71 (ddt, J¼7.3, 6.6, 5.5 Hz, 1H), 4.52e4.41 (m, 3H), 2.97 (dd, J¼16.5, 6.9 Hz, 1H), 2.74 (ddd, J¼14.2, 7.3, 5.9 Hz, 1H), 2.72 (dd, J¼16.5, 6.4 Hz, 1H), 2.42 (s, 3H), 2.40 (s, 3H), 2.20 (s, 3H), 1.95 (ddd, J¼14.2, 5.5, 3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 206.8, 166.5, 166.3, 144.3, 144.0, 129.87, 129.81, 129.4, 129.3, 127.2, 127.0, 81.8, 76.7, 75.3, 64.7, 49.9, 37.9, 30.8, 21.89, 21.86; MS (CI): m/z¼411 [MþH]þ; HRMS (CI): m/z [MþH]þ calcd for C24H27O6: 411.1810; Found 411.1808.
4.4. Isomerization of a mixture of 2,5-trans-7 and 2,5-cis-7 A mixture of 2,5-trans-7 and 2,5-cis-7 (21.4 mg, 0.049 mmol) with a 5:4 ratio and CSA (3.5 mg, 0.015 mmol) in CH2Cl2 (0.6 mL) was stirred at room temperature for 60 min. Purification by silica gel column chromatography described for the preparation of 2,5trans-7 and 2,5-cis-7 provided 2,5-cis-7 (13.3 mg) with the same ratio.
Acknowledgements The authors acknowledge financial support by the Minister of Education Science and Culture Japan.
Supplementary data Supplementary data associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.tet.2016.06.081.
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References and notes 1. Recent reviews (a) Nasir, N. M.; Ermanis, K.; Clarke, P. A. Org. Biomol. Chem. 2014, 12, 3323e3335; (b) Cornil, J.; Gonnard, L.; Bensoussan, C.; Serra-Muns, A.; Gnamm, C.; Commandeur, C.; Commandeur, M.; Reymond, S.; Guerinot, A.; Cossy, J. Acc. Chem. Res. 2014, 48, 761e773; (c) Dohanosova, J.; Gracza, T. Molecules 2013, 18, 6173e6192; (d) Lorente, A.; Lamariano-Merketegi, J.; Albericio, F.; Alvarez, M. Chem. Rev. 2013, 113, 4567e4610; (e) Wolfe, J. P.; Hay, M. B. Tetrahedron 2007, 63, 261e290; (f) Muzart, J. Tetrahedron 2005, 61, 5955e6008. 2. (a) Malmstrom, J.; Christophersen, C.; Brrrero, A. F.; Oltra, J. E.; Justicia, J.; Rosales, A. J. Nat. Prod. 2002, 65, 364; (b) Liaw, C.-C.; Wu, T.-Y.; Chang, F.-R.; Wu, Y.C. Planta Med. 2010, 75, 1390e1404; (c) Keller-Schierlein, W.; Gerlach, H. Fortschr. Chem. Org. Naturst. 1968, 26, 161e189; (d) Kobayashi, J.; Tsuda, M. Nat. Prod. Rep. 2004, 21, 77e93; (e) Murakami, M.; Matsuda, H.; Makabe, K.; Yamaguchi, K. Tetrahedron Lett. 1991, 32, 2391e2394. 3. (a) De Clercq, E. J. Med. Chem. 2016, 59, 2301e2311; (b) Boutureira, O.; Metheu, M. I.; Diaz, Y.; Castillon, S. Synthesis of C-nucleoside In Chemical Synthesis of Nucleoside Analogues; Merino, P., Ed.; John Wiley & Sons: Hoboken USA, 2013; pp 263e316; (c) Stambasky, J.; Hocek, M.; Kocovsly, P. Chem. Rev. 2009, 109, 6729e6764. 4. Cascade reaction (a) Hu, L.; Lu, X.; Deng, L. J. Am. Chem. Soc. 2015, 137, 8400e8403; (b) Veidenberg, I.; Toom, L.; Villo, P.; Vares, L. Tetrahedron Lett. 2014, 55, 3569e3571; (c) Morimoto, Y.; Iwai, T.; Nishikawa, Y.; Kinoshita, T. Tetrahedron: Asymmetry 2002, 13, 2641e2647 Oxidative ring formation; (d) Sheikh, N. S. Org. Biomol. Chem. 2014, 12, 9492e9504; (e) Sheikh, N. S. Nat. Prod. Rep. 2014, 31, 1088e1100 Halo ether formation; (f) White, J. D.; Quaranta, L.; Wang, G. J. Org. Chem. 2007, 72, 1717e1728; (g) Kang, S. H.; Lee, S. B. Tetrahedron Lett. 1993, 34, 7579e75892 Radical Cyclization formation; (h) Berlin, S.; Ericsson, C.; Engman, L. J. Org. Chem. 2003, 68, 8386e8396; (i) Jeong, E. J.; Kang, E. J.; Sung, L. T.; Hong, S. K.; Lee, E. J. Am. Chem. Soc. 2002, 124, 14655e14662; (j) Evans, P. A.; Roseman, J. D. Tetrahedron Lett. 1995, 36, 31e34 CH-insertion; (k) Clark, J. S. Tetrahedron Lett. 1992, 33, 6193e6196 Oxy-palladation; (l) Uenishi, J.; Fujikura, Y.; Kawai, N. Org. Lett. 2011, 13, 2350e2353. 5. (a) Fuwa, H. Heterocycles 2012, 85, 1255e1298; (b) Nising, C. F.; Brase, S. Chem. Soc. Rev. 2012, 41, 988e999; (c) Nising, C. F.; Brase, S. Chem. Soc. Rev. 2008, 37, 1218e1228. 6. Oxy-Michael reaction for 1,5-disubstituted THF compounds (a) Lorente, A.; Gil, A.; Fernandez, R.; Cuevas, C.; Albericio, F.; Alvarez, M. Chem.dEur. J. 2015, 21, 150e156; (b) Krishna, P. R.; Anitha, K.; Raju, G. Tetrahedron 2013, 69, 1649e1657; (c) Lu, Y.; Zou, G.; Zhao, G. ACS Catal. 2013, 3, 1356e1359; (d) Armstrong, A.; Pyrkotis, C. Tetrahedron Lett. 2009, 50, 3325e3328; (e) Abbineni, C.; Sasmal, P. K.; Mullanti, K.; Iqbal, J. Tetrahedron Lett. 2007, 48, 4259e4262; (f) Zakrzewski, P.; Lau, C. K. Synlett 2003, 215e218; (g) Kubota, T.; Tsuda, M.; Kobayashi, J. Tetrahedron 2003, 59, 1613e1625; (h) Guindon, Y.; Delorme, D.; Lau, C. K.; Zamboni, R. J. Org. Chem. 1988, 53, 267e275. 7. Reaction of g-substituted a,b-unsaturated esters (a) Valot, G.; Mailhol, D.; Rehens, C. S.; O’Malley, D. P.; Godineau, E.; Takigawa, H.; Philipps, P.; Furstner, A. Chem.dEur. J. 2015, 21, 2398e2408; (b) Sabitha, G.; Chandrashekhar, G.; Yadav, J. S.; Rachineni, K.; Jagadeesh, B. RSC Adv. 2012, 2, 10157e10159; (c) Fries, P.; Halter, D.; Kleinschek, A.; Hartung, J. J. Am. Chem. Soc. 2011, 133, 3906e3912; (d) Paudyal, M. P.; Rath, N. P.; Spilling, C. D. Org. Lett. 2010, 12, 2954e2957; (e) Ghosh, A. K.; Shurrush, K.; Kulkarni, S. J. Org. Chem. 2009, 74, 4508e4518; (f) Bates, R. H.; Shotwell, J. B.; Roush, W. R. Org. Lett. 2008, 10, 4343e4346; (g) Kubota, T.; Tsuda, M.; Kobayashi, J. Org. Lett. 2001, 3, 1363e1366; (h) Harusawa, S.; Fujii, K.; Nishiura, M.; Araki, L.; Usami, Y.; Zhao, Z.; Lilly, D. M. J. Heterocycles 2011, 83, 2041e2055; (i) Bull. Korean Chem. Soc. 1992, 13, 222e223; (j) Ohrui, H.; Jones, G. H.; Moffatt, J. G.; Maddox, M. L.; Christensen, A. T.; Byram, S. K. J. Am. Chem. Soc. 1975, 97, 4602e4613. 8. Preparation of 1e4: cyclic bis-silyl ether formation and successive Wittig reaction. Murata, Y.; Uenishi, J. submitted in J. Org. Chem. 9. See the Supplementary data. 10. Similar selectivity was observed for the C-1 allylation and glycosidation in the case of 2-deoxy-D-ribose.