- Email: [email protected]
Synthetic studies on taxanes: construction of the tricyclic skeleton on the basis of a [6+2] cycloaddition reaction
Tetrahedron Letters 55 (2014) 1097–1099
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Synthetic studies on taxanes: construction of the tricyclic skeleton on the basis of a [6+2] cycloaddition reaction Ryosuke Hanada a, Katsuhiko Mitachi b, Keiji Tanino b,⇑ a b
Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
a r t i c l e
i n f o
Article history: Received 11 November 2013 Revised 19 December 2013 Accepted 25 December 2013 Available online 4 January 2014 Keywords: Taxanes Total synthesis Cycloaddition reaction Acetylene dicobalt complex Epoxy nitrile
a b s t r a c t The stereoselective synthesis of a tricyclic model compound of taxane diterpenes was achieved. The eight-membered B ring was constructed on the basis of a [6+2] cycloaddition reaction of a dicobalt acetylene complex with an enol silyl ether of cyclohexanone. After conversion of the cobalt complex moiety to an epoxide and introduction of a 3-cyanopropyl group, the A ring was formed via an intramolecular cyclization reaction under basic conditions. Ó 2014 Elsevier Ltd. All rights reserved.
The taxane diterpenoids, hundreds of which were isolated and characterized from yew trees (the genus Taxus), have been of great interest to organic and medicinal chemists because of the important activities of taxol and its derivatives in cancer chemotherapy.1 These compounds possess the characteristic 6-8-6 tricyclic skeleton involving a highly strained ‘anti-Bredt rule’ olefin at the bridge-head position of the AB-ring system, which makes taxoids as one of the most challenging synthetic targets. There have been reported a number of synthetic studies of taxoids involving the total synthesis of taxol,2,3 taxusin,4 and taxadiene5 (Fig. 1). It should be noted that how to construct the eight-membered Bring with many substituents is another serious problem in total synthesis of taxoids. We herein report a new method for constructing the tricyclic taxane skeleton through a higher-order cycloaddition reaction affording an eight-membered ring. Recently, we reported a novel method for the stereoselective synthesis of cyclooctanones via the formal intermolecular [6+2] cycloaddition reaction using dicobalt acetylene complex 2 as a six-carbon unit (Scheme 1).6 The reaction proceeds through intermolecular addition of enol triisopropylsilyl (TIPS) ether 1 with dicobalt propargyl cation A generated from 2, giving rise to silyloxonium ion B that in turn undergoes an intramolecular addition reaction. While concerted cycloaddition like the Diels–Alder reaction usually affords a
cis-fused bicyclic compound from a cycloalkene derivative,7 the stepwise mechanism of the [6+2] cycloaddition reaction allowed the formation of a trans-fused bicyclic compound 3 from enol silyl ether 1. These results led us to design a new route for constructing the taxane skeleton as shown in Scheme 2. From the retrosynthetic perspective, we envisioned a tricyclic compound 4 to be obtained from cyano alcohol 5 which would arise from epoxy nitrile 6 exploiting the intramolecular cyclization reaction under basic conditions.8 The cyclization precursor 6 would be obtained from bicyclic ketone 8 via conversion of the cobalt complex moiety to an olefin followed by introduction of the side chain through a stereoselective addition reaction.
⇑ Corresponding author. E-mail address: [email protected] (K. Tanino). 0040-4039/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2013.12.096
Figure 1. Structure of taxane diterpenoids.
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R. Hanada et al. / Tetrahedron Letters 55 (2014) 1097–1099
Scheme 1. Synthesis of cyclooctanone derivative 2 via a [6+2] cycloaddition reaction.
Scheme 4. Construction of the BC-ring system via the [6+2] cycloaddition reaction. Scheme 2. Retrosynthetic analysis of the taxane skeleton.
Scheme 3. Preparation of six-carbon unit 9.
In order to prepare the key intermediate 8 through a [6+2] cycloaddition reaction, new six-carbon unit 9 having a quaternary carbon atom was synthesized as shown in Scheme 3. Diol 11, which was prepared from ketol 10 and methyl propargyl ether, was subjected to the pinacol rearrangement reaction promoted by trifluoromethanesulfonimide (Tf2NH) in 1,1,1,3,3,3hexafluoroisopropanol to afford ketone 12.9 Treatment of 12 with TIPSOTf and triethylamine yielded the corresponding enol silyl ether 13 that in turn was reacted with Co2(CO)8 to afford dicobalt acetylene complex 9.10 With the new six-carbon unit in hand, construction of the BC ring system through the [6+2] cycloaddition reaction was explored (Scheme 4). Under the influence of EtAlCl2, cobalt complex 9 underwent the cycloaddition reaction with enol silyl ether 1 to give the desired bicyclic ketone 8 as a single diastereomer in 72%
yield based on 9. Transformation of the cobalt complex 8 into olefin 7 was then examined by using the protocol of Isobe.11 However, heating of 8 simply with tributyltin hydride resulted in the formation of a 2.5:1 inseparable mixture of enone 7 and its isomer 70 through partial isomerization of the olefin moiety. Although the mechanism of the side reaction was not clear, we found that the reaction in the presence of an excess amount of 1,4-cyclohexadiene brought about an increase in the ratio of 7/70 to 5:1. The resulting mixture was reacted with 4-pentenyllithium, which was prepared from 5-bromo-1-pentene and tert-butyllithium, and introduction of the side chain was achieved in a stereoselective manner to afford the desired alcohol 14 as a single diastereomer. The reaction of diene 14 with m-chloroperbenzoic acid (mCPBA) occurred in regio- and stereoselective manner to afford epoxide 15 as a single isomer, and the impurities arising from 70 were removed at this stage. The stereoselection in the epoxidation of alcohol 14 may be attributable to the directing effect of the hydroxyl group, because oxidation of the corresponding TMS ether resulted in the formation of a 1:2 mixture of epoxide 16 and its diastereomer. Finally, olefin 16 was subjected to the hydrocyanation reaction catalyzed by a cobalt complex according to the Carreira’s protocol,12 giving rise to nitrile 17 as a mixture of diastereomers. The cyclization precursor in hand, the stage was set for construction of the A-ring (Scheme 5). Under the influence of lithium diethylamide, epoxy nitrile 17 underwent the cyclization reaction to afford the desired product 18 in high yield. The cyclization product was obtained as a 10:1 diastereomeric mixture at the a-carbon of the nitrile moiety, and the configuration of the major isomer was determined by the NOE experiment.13 The remaining problem in constructing the taxane skeleton was installation of the highly strained bridgehead olefin in the A-ring. With a view to utilize the cyano group as the precursor of a carbanion species, alcohol 18 was transformed into epoxide 20 through the Chugaev elimination of xanthate 1914 followed by mCPBA
R. Hanada et al. / Tetrahedron Letters 55 (2014) 1097–1099
1099
Scheme 5. Construction of the tricyclic skeleton from epoxy nitrile 17.
oxidation from the convex face. It is noteworthy that formation of the strained C10–C11 olefin was favored over the regio isomer with the C9–C10 double bond (D10,11:D9,10 = 5:1). Finally, epoxy nitrile 20 was reduced with Li metal in the presence of di(tertbutyl)bipheny to generate an anionic species which underwent b-elimination of the epoxide,15 and the desired allyl alcohol 2116 was obtained in excellent yield. In conclusion, we have achieved the stereoselective synthesis of a model compound of taxane diterpenoids. The BC-ring system was constructed on the basis of a [6+2] cycloaddition reaction of a dicobalt acetylene complex with a six-membered enol silyl ether. After conversion of the cobalt complex moiety to an epoxide and introduction of a 3-cyanobutyl group, the A-ring was formed via an intramolecular substitution reaction under basic conditions. Introduction of the highly strained ‘anti-Bredt rule’ olefin at the bridgehead position of the AB-ring system was achieved by reductive cleavage of an epoxy nitrile. The studies toward the total synthesis of taxane diterpenoids are now under progress. Acknowledgments This work was partially supported by the Grant-in-Aid for Scientific Research on Innovative Areas (Project No. 2105: Organic Synthesis Based on Reaction Integration) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. R.H. is a Research Fellow of the Japan Society for the Promotion of Science (JSPS).
3. 4.
5. 6. 7. 8.
9.
10. 11. 12. 13.
Shuker, A. J.; Sutton, J. C.; Taylor, R. E.; Tomooka, K. J. Am. Chem. Soc. 1997, 119, 2755; (e) Mukaiyama, T.; Shiina, I.; Iwadare, H.; Sakoh, H.; Tani, Y.; Hasegawa, M.; Saitoh, K. Proc. Jpn. Acad., Ser. B 1997, 73, 95; (f) Morihira, K.; Hara, R.; Kawahara, S.; Nishimori, T.; Nakamura, N.; Kusama, H.; Kuwajima, I. J. Am. Chem. Soc. 1998, 120, 12980. For a formal synthesis of taxol, see: Doi, T.; Fuse, S.; Miyamoto, S.; Nakai, K.; Sasuga, D.; Takahashi, T. Chem. Asian J. 2006, 1, 370. (a) Holton, R. A.; Juo, R. R.; Kim, H. B.; Williams, A. D.; Harusawa, S.; Lowenthal, R. E.; Yogai, S. J. Am. Chem. Soc. 1988, 110, 6558; (b) Hara, R.; Furukawa, T.; Horiguchi, Y.; Kuwajima, I. J. Am. Chem. Soc. 1996, 118, 9186; (c) Paquette, L. A.; Zhao, M. J. Am. Chem. Soc. 1998, 120, 5203. (a) Rubenstein, S. M.; Williams, R. M. J. Org. Chem. 1995, 60, 7215; (b) Mendoza, A.; Ishihara, Y.; Baran, P. S. Nat. Chem. 2012, 4, 21. Mitachi, K.; Shimizu, T.; Miyashita, M.; Tanino, K. Tetrahedron Lett. 2010, 51, 3983. For a review: Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassilikogiannakis, G. Angew. Chem., Int. Ed. 2002, 41, 1668. (a) Stork, G.; Cama, L. D.; Coulson, D. R. J. Am. Chem. Soc. 1974, 96, 5268; (b) Tanino, K.; Takahashi, M.; Tomata, Y.; Tokura, H.; Uehara, T.; Narabu, T.; Miyashita, M. Nat. Chem. 2011, 3, 484. The pinacol rearrangement reaction of 11 with TfOH in CH2Cl2 resulted in formation of ketone 12 in low yield, because of the low solubility of TfOH. The use of Tf2NH, which is readily soluble in CH2Cl2, afforded 12 in 65%. Finally, the use of (CF3)2CHOH as a solvent was found to enhance the reaction, while the reaction in CF3CH2OH gave 12 in only 12% yield. Nicholas, K. M.; Pettit, R. Tetrahedron Lett. 1971, 12, 3475. Hosokawa, S.; Isobe, M. Tetrahedron Lett. 1998, 39, 2609. Gasper, B.; Carreira, E. M. Angew. Chem., Int. Ed. 2007, 46, 4519. The stereochemistry of the major isomer of cyclization product 18 was established from the analysis of the NOESY spectrum as shown below.
References and notes 1. For a recent review: Wang, Y.-F.; Shi, Q.-W.; Dong, M.; Kiyota, H.; Gu, Y.-C.; Cong, B. Chem. Rev. 2011, 111, 7652. 2. (a) Holton, R. A.; Somoza, C.; Kim, H.-B.; Liang, F.; Biediger, R. J.; Boatman, P. D.; Shindo, M.; Smith, C. C.; Kim, S.; Nadizadeh, H.; Suzuki, Y.; Tao, C.; Vu, P.; Tang, S.; Zhang, P.; Murthi, K. K.; Gentile, L. N.; Liu, J. H. J. Am. Chem. Soc. 1994, 116, 1597; (b) Nicolaou, K. C.; Yang, Z.; Liu, J. J.; Ueno, H.; Nantermet, P. G.; Guy, R. K.; Claiborne, C. F.; Renaud, J.; Couladouros, E. A.; Paulvannan, K.; Sorensen, E. J. Nature 1994, 367, 630; (c) Masters, J. J.; Link, J. T.; Snyder, L. B.; Young, W. B.; Danishefsky, S. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 1723; (d) Wender, P. A.; Badham, N. F.; Conway, S. P.; Floreancig, P. E.; Glass, T. E.; Gränicher, C.; Houze, J. B.; Jänichen, J.; Lee, D.; Marquess, D. G.; McGrane, P. L.; Meng, W.; Mucciaro, T. P.; Mühlebach, M.; Natchus, M. G.; Paulsen, H.; Rawlins, D. B.; Satkofsky, J.;
14. Chugaev, L. Ber. Dtsch. Chem. Ges. 1899, 32, 3332; For a review: Nace, H. R. Org. React. 1962, 12, 57–100. 15. Marshall, J. A.; Hagan, C. P.; Flynn, G. A. J. Org. Chem. 1975, 40, 1162. 16. Spectral data for 21: IR (neat) m 3398, 2944, 2866, 1463, 1445, 1249, 1170, 1145, 1119, 1069, 1042, 960, 912, 882, 859, 838, 749, 735, 720, 670 cm1. 1H NMR (500 MHz, CDCl3): d 5.14 (br s, 1H), 2.70 (ddd, J = 12.0, 8.0, 3.5 Hz, 1H), 2.45 (dd, J = 18.5, 10.0 Hz, 1H), 2.00 (d, J = 14.5 Hz, 1H), 2.01–1.79 (m, 5H), 1.75–1.54 (m, 4H), 1.58 (s, 3H), 1.57 (s, 3H), 1.46 (d, J = 14.5 Hz, 1H), 1.45–1.20 (m, 5H), 1.09–1.05 (m, 24H), 0.12 (s, 9H); 13C NMR (125 MHz, CDCl3): d 142.6, 127.5, 81.84, 78.90, 72.28, 56.25, 43.34, 40.51, 39.17, 37.85, 35.47, 32.89, 31.73, 31.04, 26.53, 24.87, 21.93, 19.97, 18.90, 18.83, 14.29, 2.72; HRMS (EI+) calcd for C30H58O3Si2 [M]+: 522.3924, found: 522.3911.
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Synthetic studies on taxanes: construction of the tricyclic skeleton on the basis of a [6+2] cycloaddition reaction Ryosuke Hanada a, Katsuhiko Mitachi b, Keiji Tanino b,⇑ a b
Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
a r t i c l e
i n f o
Article history: Received 11 November 2013 Revised 19 December 2013 Accepted 25 December 2013 Available online 4 January 2014 Keywords: Taxanes Total synthesis Cycloaddition reaction Acetylene dicobalt complex Epoxy nitrile
a b s t r a c t The stereoselective synthesis of a tricyclic model compound of taxane diterpenes was achieved. The eight-membered B ring was constructed on the basis of a [6+2] cycloaddition reaction of a dicobalt acetylene complex with an enol silyl ether of cyclohexanone. After conversion of the cobalt complex moiety to an epoxide and introduction of a 3-cyanopropyl group, the A ring was formed via an intramolecular cyclization reaction under basic conditions. Ó 2014 Elsevier Ltd. All rights reserved.
The taxane diterpenoids, hundreds of which were isolated and characterized from yew trees (the genus Taxus), have been of great interest to organic and medicinal chemists because of the important activities of taxol and its derivatives in cancer chemotherapy.1 These compounds possess the characteristic 6-8-6 tricyclic skeleton involving a highly strained ‘anti-Bredt rule’ olefin at the bridge-head position of the AB-ring system, which makes taxoids as one of the most challenging synthetic targets. There have been reported a number of synthetic studies of taxoids involving the total synthesis of taxol,2,3 taxusin,4 and taxadiene5 (Fig. 1). It should be noted that how to construct the eight-membered Bring with many substituents is another serious problem in total synthesis of taxoids. We herein report a new method for constructing the tricyclic taxane skeleton through a higher-order cycloaddition reaction affording an eight-membered ring. Recently, we reported a novel method for the stereoselective synthesis of cyclooctanones via the formal intermolecular [6+2] cycloaddition reaction using dicobalt acetylene complex 2 as a six-carbon unit (Scheme 1).6 The reaction proceeds through intermolecular addition of enol triisopropylsilyl (TIPS) ether 1 with dicobalt propargyl cation A generated from 2, giving rise to silyloxonium ion B that in turn undergoes an intramolecular addition reaction. While concerted cycloaddition like the Diels–Alder reaction usually affords a
cis-fused bicyclic compound from a cycloalkene derivative,7 the stepwise mechanism of the [6+2] cycloaddition reaction allowed the formation of a trans-fused bicyclic compound 3 from enol silyl ether 1. These results led us to design a new route for constructing the taxane skeleton as shown in Scheme 2. From the retrosynthetic perspective, we envisioned a tricyclic compound 4 to be obtained from cyano alcohol 5 which would arise from epoxy nitrile 6 exploiting the intramolecular cyclization reaction under basic conditions.8 The cyclization precursor 6 would be obtained from bicyclic ketone 8 via conversion of the cobalt complex moiety to an olefin followed by introduction of the side chain through a stereoselective addition reaction.
⇑ Corresponding author. E-mail address: [email protected] (K. Tanino). 0040-4039/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2013.12.096
Figure 1. Structure of taxane diterpenoids.
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R. Hanada et al. / Tetrahedron Letters 55 (2014) 1097–1099
Scheme 1. Synthesis of cyclooctanone derivative 2 via a [6+2] cycloaddition reaction.
Scheme 4. Construction of the BC-ring system via the [6+2] cycloaddition reaction. Scheme 2. Retrosynthetic analysis of the taxane skeleton.
Scheme 3. Preparation of six-carbon unit 9.
In order to prepare the key intermediate 8 through a [6+2] cycloaddition reaction, new six-carbon unit 9 having a quaternary carbon atom was synthesized as shown in Scheme 3. Diol 11, which was prepared from ketol 10 and methyl propargyl ether, was subjected to the pinacol rearrangement reaction promoted by trifluoromethanesulfonimide (Tf2NH) in 1,1,1,3,3,3hexafluoroisopropanol to afford ketone 12.9 Treatment of 12 with TIPSOTf and triethylamine yielded the corresponding enol silyl ether 13 that in turn was reacted with Co2(CO)8 to afford dicobalt acetylene complex 9.10 With the new six-carbon unit in hand, construction of the BC ring system through the [6+2] cycloaddition reaction was explored (Scheme 4). Under the influence of EtAlCl2, cobalt complex 9 underwent the cycloaddition reaction with enol silyl ether 1 to give the desired bicyclic ketone 8 as a single diastereomer in 72%
yield based on 9. Transformation of the cobalt complex 8 into olefin 7 was then examined by using the protocol of Isobe.11 However, heating of 8 simply with tributyltin hydride resulted in the formation of a 2.5:1 inseparable mixture of enone 7 and its isomer 70 through partial isomerization of the olefin moiety. Although the mechanism of the side reaction was not clear, we found that the reaction in the presence of an excess amount of 1,4-cyclohexadiene brought about an increase in the ratio of 7/70 to 5:1. The resulting mixture was reacted with 4-pentenyllithium, which was prepared from 5-bromo-1-pentene and tert-butyllithium, and introduction of the side chain was achieved in a stereoselective manner to afford the desired alcohol 14 as a single diastereomer. The reaction of diene 14 with m-chloroperbenzoic acid (mCPBA) occurred in regio- and stereoselective manner to afford epoxide 15 as a single isomer, and the impurities arising from 70 were removed at this stage. The stereoselection in the epoxidation of alcohol 14 may be attributable to the directing effect of the hydroxyl group, because oxidation of the corresponding TMS ether resulted in the formation of a 1:2 mixture of epoxide 16 and its diastereomer. Finally, olefin 16 was subjected to the hydrocyanation reaction catalyzed by a cobalt complex according to the Carreira’s protocol,12 giving rise to nitrile 17 as a mixture of diastereomers. The cyclization precursor in hand, the stage was set for construction of the A-ring (Scheme 5). Under the influence of lithium diethylamide, epoxy nitrile 17 underwent the cyclization reaction to afford the desired product 18 in high yield. The cyclization product was obtained as a 10:1 diastereomeric mixture at the a-carbon of the nitrile moiety, and the configuration of the major isomer was determined by the NOE experiment.13 The remaining problem in constructing the taxane skeleton was installation of the highly strained bridgehead olefin in the A-ring. With a view to utilize the cyano group as the precursor of a carbanion species, alcohol 18 was transformed into epoxide 20 through the Chugaev elimination of xanthate 1914 followed by mCPBA
R. Hanada et al. / Tetrahedron Letters 55 (2014) 1097–1099
1099
Scheme 5. Construction of the tricyclic skeleton from epoxy nitrile 17.
oxidation from the convex face. It is noteworthy that formation of the strained C10–C11 olefin was favored over the regio isomer with the C9–C10 double bond (D10,11:D9,10 = 5:1). Finally, epoxy nitrile 20 was reduced with Li metal in the presence of di(tertbutyl)bipheny to generate an anionic species which underwent b-elimination of the epoxide,15 and the desired allyl alcohol 2116 was obtained in excellent yield. In conclusion, we have achieved the stereoselective synthesis of a model compound of taxane diterpenoids. The BC-ring system was constructed on the basis of a [6+2] cycloaddition reaction of a dicobalt acetylene complex with a six-membered enol silyl ether. After conversion of the cobalt complex moiety to an epoxide and introduction of a 3-cyanobutyl group, the A-ring was formed via an intramolecular substitution reaction under basic conditions. Introduction of the highly strained ‘anti-Bredt rule’ olefin at the bridgehead position of the AB-ring system was achieved by reductive cleavage of an epoxy nitrile. The studies toward the total synthesis of taxane diterpenoids are now under progress. Acknowledgments This work was partially supported by the Grant-in-Aid for Scientific Research on Innovative Areas (Project No. 2105: Organic Synthesis Based on Reaction Integration) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. R.H. is a Research Fellow of the Japan Society for the Promotion of Science (JSPS).
3. 4.
5. 6. 7. 8.
9.
10. 11. 12. 13.
Shuker, A. J.; Sutton, J. C.; Taylor, R. E.; Tomooka, K. J. Am. Chem. Soc. 1997, 119, 2755; (e) Mukaiyama, T.; Shiina, I.; Iwadare, H.; Sakoh, H.; Tani, Y.; Hasegawa, M.; Saitoh, K. Proc. Jpn. Acad., Ser. B 1997, 73, 95; (f) Morihira, K.; Hara, R.; Kawahara, S.; Nishimori, T.; Nakamura, N.; Kusama, H.; Kuwajima, I. J. Am. Chem. Soc. 1998, 120, 12980. For a formal synthesis of taxol, see: Doi, T.; Fuse, S.; Miyamoto, S.; Nakai, K.; Sasuga, D.; Takahashi, T. Chem. Asian J. 2006, 1, 370. (a) Holton, R. A.; Juo, R. R.; Kim, H. B.; Williams, A. D.; Harusawa, S.; Lowenthal, R. E.; Yogai, S. J. Am. Chem. Soc. 1988, 110, 6558; (b) Hara, R.; Furukawa, T.; Horiguchi, Y.; Kuwajima, I. J. Am. Chem. Soc. 1996, 118, 9186; (c) Paquette, L. A.; Zhao, M. J. Am. Chem. Soc. 1998, 120, 5203. (a) Rubenstein, S. M.; Williams, R. M. J. Org. Chem. 1995, 60, 7215; (b) Mendoza, A.; Ishihara, Y.; Baran, P. S. Nat. Chem. 2012, 4, 21. Mitachi, K.; Shimizu, T.; Miyashita, M.; Tanino, K. Tetrahedron Lett. 2010, 51, 3983. For a review: Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassilikogiannakis, G. Angew. Chem., Int. Ed. 2002, 41, 1668. (a) Stork, G.; Cama, L. D.; Coulson, D. R. J. Am. Chem. Soc. 1974, 96, 5268; (b) Tanino, K.; Takahashi, M.; Tomata, Y.; Tokura, H.; Uehara, T.; Narabu, T.; Miyashita, M. Nat. Chem. 2011, 3, 484. The pinacol rearrangement reaction of 11 with TfOH in CH2Cl2 resulted in formation of ketone 12 in low yield, because of the low solubility of TfOH. The use of Tf2NH, which is readily soluble in CH2Cl2, afforded 12 in 65%. Finally, the use of (CF3)2CHOH as a solvent was found to enhance the reaction, while the reaction in CF3CH2OH gave 12 in only 12% yield. Nicholas, K. M.; Pettit, R. Tetrahedron Lett. 1971, 12, 3475. Hosokawa, S.; Isobe, M. Tetrahedron Lett. 1998, 39, 2609. Gasper, B.; Carreira, E. M. Angew. Chem., Int. Ed. 2007, 46, 4519. The stereochemistry of the major isomer of cyclization product 18 was established from the analysis of the NOESY spectrum as shown below.
References and notes 1. For a recent review: Wang, Y.-F.; Shi, Q.-W.; Dong, M.; Kiyota, H.; Gu, Y.-C.; Cong, B. Chem. Rev. 2011, 111, 7652. 2. (a) Holton, R. A.; Somoza, C.; Kim, H.-B.; Liang, F.; Biediger, R. J.; Boatman, P. D.; Shindo, M.; Smith, C. C.; Kim, S.; Nadizadeh, H.; Suzuki, Y.; Tao, C.; Vu, P.; Tang, S.; Zhang, P.; Murthi, K. K.; Gentile, L. N.; Liu, J. H. J. Am. Chem. Soc. 1994, 116, 1597; (b) Nicolaou, K. C.; Yang, Z.; Liu, J. J.; Ueno, H.; Nantermet, P. G.; Guy, R. K.; Claiborne, C. F.; Renaud, J.; Couladouros, E. A.; Paulvannan, K.; Sorensen, E. J. Nature 1994, 367, 630; (c) Masters, J. J.; Link, J. T.; Snyder, L. B.; Young, W. B.; Danishefsky, S. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 1723; (d) Wender, P. A.; Badham, N. F.; Conway, S. P.; Floreancig, P. E.; Glass, T. E.; Gränicher, C.; Houze, J. B.; Jänichen, J.; Lee, D.; Marquess, D. G.; McGrane, P. L.; Meng, W.; Mucciaro, T. P.; Mühlebach, M.; Natchus, M. G.; Paulsen, H.; Rawlins, D. B.; Satkofsky, J.;
14. Chugaev, L. Ber. Dtsch. Chem. Ges. 1899, 32, 3332; For a review: Nace, H. R. Org. React. 1962, 12, 57–100. 15. Marshall, J. A.; Hagan, C. P.; Flynn, G. A. J. Org. Chem. 1975, 40, 1162. 16. Spectral data for 21: IR (neat) m 3398, 2944, 2866, 1463, 1445, 1249, 1170, 1145, 1119, 1069, 1042, 960, 912, 882, 859, 838, 749, 735, 720, 670 cm1. 1H NMR (500 MHz, CDCl3): d 5.14 (br s, 1H), 2.70 (ddd, J = 12.0, 8.0, 3.5 Hz, 1H), 2.45 (dd, J = 18.5, 10.0 Hz, 1H), 2.00 (d, J = 14.5 Hz, 1H), 2.01–1.79 (m, 5H), 1.75–1.54 (m, 4H), 1.58 (s, 3H), 1.57 (s, 3H), 1.46 (d, J = 14.5 Hz, 1H), 1.45–1.20 (m, 5H), 1.09–1.05 (m, 24H), 0.12 (s, 9H); 13C NMR (125 MHz, CDCl3): d 142.6, 127.5, 81.84, 78.90, 72.28, 56.25, 43.34, 40.51, 39.17, 37.85, 35.47, 32.89, 31.73, 31.04, 26.53, 24.87, 21.93, 19.97, 18.90, 18.83, 14.29, 2.72; HRMS (EI+) calcd for C30H58O3Si2 [M]+: 522.3924, found: 522.3911.