- Email: [email protected]
Construction of 9,10-syn–trans-decalin skeleton via semipinacol rearrangement: asymmetric synthesis of (+)-syn-copalol and a candelalide analog
Accepted Manuscript Construction of 9,10-syn-trans-decalin skeleton via semipinacol rearrangement: asymmetric synthesis of (+)-syn-copalol and a candelalide analog Zhongliang Li, Dan Yang PII: DOI: Reference:
S0040-4039(15)00356-1 http://dx.doi.org/10.1016/j.tetlet.2015.02.075 TETL 45945
To appear in:
Tetrahedron Letters
Received Date: Revised Date: Accepted Date:
14 January 2015 14 February 2015 16 February 2015
Please cite this article as: Li, Z., Yang, D., Construction of 9,10-syn-trans-decalin skeleton via semipinacol rearrangement: asymmetric synthesis of (+)-syn-copalol and a candelalide analog, Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.02.075
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Graphical Abstract To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered.
Construction of 9,10-syn-trans-decalin skeleton via semipinacol rearrangement: asymmetric synthesis of (+ +)-syn-copalol and a candelalide analog Zhongliang Li, Dan Yang
Leave this area blank for abstract info.
1
Tetrahedron Letters j o ur n al h om e p a g e : w w w . e l s e v i er . c o m
Construction of 9,10-syn-trans-decalin skeleton via semipinacol rearrangement: asymmetric synthesis of (+)-syn-copalol and a candelalide analog† Zhongliang Li, Dan Yang∗ Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China
A R T IC LE IN F O
A B S TR A C T
Article history: Received Received in revised form Accepted Available online
The 9,10-syn-trans-decalin skeleton has been constructed from (+)-sclareolide via semipinacol rearrangement as a key step. Subsequent divergent transformation of a pivotal intermediate culminated in asymmetric synthesis of (+)-syn-copalol and one analog of immunosuppressive agent candelalide. This synthetic strategy constitutes a good starting point for generating a panel of biologically active natural products. 2009 Elsevier Ltd. All rights reserved.
Keywords: Syn-trans-decalin Asymmetric synthesis Semipinacol rearrangement (+)-Syn-copalol Candelalide analog
9,10-syn-trans-Decalin is a unique skeleton possessed by many biologically active natural products (Figure 1).1 Peyssonol A, with a hydroquinone moiety on the trans-decalin core, potently inhibits HIV viruses.1g The families of candelalide and subglutinol as well as other analogous natural products, bearing the trans-decalin core with either a pyrone or indole substituent, exhibit promising immunosuppressive or anti-tumor activities.1d,1f,2 Structurally more complex aphidicolin has also been extensively studied as an inhibitor of DNA polymerase in viruses and cancer cells.3 The significant and broad biological activities have prompted many synthetic efforts towards these natural products as well as their analogs for biological and pharmaceutical evaluations. 1g,4 Herein, we report a novel strategy for constructing the syn-trans-decalin skeleton and divergently achieving asymmetric synthesis of (+)-syn-copalol, a possible biosynthetic precursor of aphidicolin, as well as a candelalide analog. A unifying synthetic scheme for 9,10-syn-trans-decalin compounds was proposed in Scheme 1. We envisioned that aldehyde 2 might be attacked by a variety of nucleophiles, affording an array of potentially bioactive molecules 1. Aldehyde 2 might be generated readily from alcohol 3, and its desired C9 stereochemistry might be established by a stereospecific semipinacol rearrangement of epoxy alcohol 4a. Stereoselective ketone reduction and subsequent allyl alcohol epoxidation might provide 4a from 5, the preparation of which from commercially available (+)-sclareolide has been reported in literature.5
Figure 1 Representative natural products possessing 9,10-syntrans-decalin skeleton
———
∗ Corresponding author. Tel.: +852 28592159; fax: +852 28571586; e-mail: [email protected] (D. Yang). †
This paper is dedicated in loving memory of Professor Harry H. Wasserman.
2
Tetrahedron Letters With 3 in hand, we first protected the alcohol with a TBS group, followed by ketone olefination to furnish 8 (Scheme 4). Subsequent n-tetrabutylammonium fluoride (TBAF) deprotection and Dess-Martin periodinane (DMP) oxidation of the newly unmasked alcohol 9 proceeded straightforwardly, and the pivotal intermediate 2 was obtained in 13 steps from (+)-sclareolide with an 11% overall yield. As originally proposed, we next paid our attention to the divergent synthesis of molecules with potential bioactivities.
Scheme 1 Retrosynthetic analysis At the outset, compound 5 was prepared following Li’s procedures in 42% overall yield (Scheme 2).5 The following Luche reduction of 5 selectively gave the desired α-alcohol 6 in 97% yield. Upon exposure to meta-chloroperoxybenzoic acid (mCPBA), allyl alcohol 6 was converted to epoxy alcohols 4a and 4b,6 however, with a low diastereoselectivity (dr = 1.2:1). Scheme 4 Synthesis of the pivotal intermediate 2
Scheme 2 Synthesis of 4a and 4b Nonetheless, we proceeded to study the subsequent semipinacol rearrangement with 4a and 4b, respectively. To our surprise, when treated with ZnBr2, both 4a and 4b afforded the desired product 3 as a single diastereomer, although in low yield (Scheme 3). The formation of 3 from 4a was expected by a normal concerted and thus stereospecific semipinacol rearrangement,7 while that from its diastereomer 4b required either a nonconcerted or a tandem Payne-semipinacol rearrangement pathway. After optimization of the reaction conditions,8 compound 3 could be obtained in 42% yield based on recovered starting material (brsm) from a mixture of 4a and 4b (Scheme 4). To further increase the overall efficiency of this step, bromide 7, a major side product, was successfully converted back to the starting material 4a and 4b under basic conditions in 80% yield (Scheme 3). O
OH
OH OH H
H
H
3, 18%
4a O
OH H
ZnBr2
3, 19%
7, 13%
+
7, 19%
CH2Cl2, rt
H 4b 7
K2CO3 MeOH, rt 80%
OH
+
CH2Cl2, rt
H
Br
O
ZnBr2
We first targeted (+)-syn-copalol, the pyrophosphate ester of which has been proposed as a biosynthesis intermediate towards aphidicolin.9 Thus, aldehyde 2 was homologated with amide 10 to afford a diastereomeric mixture of alcohol 11 (Scheme 5). Straightforward xanthate synthesis and subsequent BartonMcCombie reaction removed the unwanted hydroxyl group in 11, and the resulting Weinreb amide 12 was converted to ketone 13 upon treatment with methyl Grignard reagent. The characterization data of obtained 13 is in accord with that reported by Oikawa et al. during their total synthesis of (±)-syncopalol. 1c,10 Furthermore, the absolute configurations of C5 and C10 in (+)-sclareolide match that in (+)-syn-copalol11 and they are unlikely affected by the foregoing transformation from (+)sclareolide to 13. Therefore, we have accomplished the asymmetric formal synthesis of (+)-syn-copalol by achieving 13 in 63% yield within 4 steps from aldehyde 2.
4a + 4b
Scheme 3 Preliminary results on the semipinacol rearrangement of 4a and 4b
Scheme 5 Synthesis of (+)-syn-copalol (1a) Candelalide B was found to be a potent potassium channel blocker after its initial isolation.1d We next set compound 1b as an interesting target, which lacks the bottom tetrahydropyran moiety compared with candelalide B and thus constitutes a good substrate for structure-activity relationship study (Scheme 6). The pyrone fragment 14 was prepared following reported procedures.4b Straightforward lithium-bromide exchange followed by quenching with aldehyde 2 delivered alcohol adduct 15. Subsequent deoxygenation by employing similar conditions
3 with that for alcohol 11 proceeded readily to furnish 1b in 56% yield over three steps from aldehyde 2.
References and notes 1.
Scheme 6 Synthesis of a candelalide analog In conclusion, we have successfully developed a general synthetic approach towards biologically interesting small molecules featuring a 9,10-syn-trans-decalin core skeleton. Its potential utility was showcased by asymmetric synthesis of ketone 13 and a candelalide analog. Our future work will focus on preparing a number of such molecules for biological studies and the corresponding results will be disclosed in due course.
Acknowledgements We thank The University of Hong Kong and Hong Kong Research Grants Council (HKU705213) for financial support. We thank Dr. Qiangshuai Gu for suggestions in experiment and help in preparation of this manuscript.
Supplementary data Supplementary data included the experimental procedures and characterization data (1H NMR, 13C NMR, IR, HRMS, etc) for all compounds.
(a) Lee, J. C.; Lobkovsky, E.; Pliam, N. B.; Strobel, G.; Clardy, J. J. Org. Chem 1995, 60, 7076–7077. (b) Engel, B.; Erkel, G.; Anke, T.; Sterner, O. J. Antibiot. 1998, 51, 518–521. (c) Oikawa, H.; Toyomasu, T.; Toshima, H.; Ohashi, S.; Kawaide, H.; Kamiya, Y.; Ohtsuka, M.; Shinoda, S.; Mitsuhashi, W.; Sassa, T. J. Am. Chem. Soc. 2001, 123, 5154–5155. (d) Singh, S. B.; Zink, D. L.; Dombrowski, A. W.; Dezeny, G.; Bills, G. F.; Felix, J. P.; Slaughter, R. S.; Goetz, M. A. Org. Lett. 2001, 3, 247–250. (e) Fueki, S.; Tokiwano, T.; Toshima, H.; Oikawa, H. Org. Lett. 2004, 6, 2697–2700. (f) Kikuchi, H.; Hoshi, T.; Kitayama, M.; Sekiya, M.; Katou, Y.; Ueda, K.; Kubohara, Y.; Sato, H.; Shimazu, M.; Kurata, S.; Oshima, Y. Tetrahedron 2009, 65, 469–477. (g) Treitler, D. S.; Li, Z.; Krystal, M.; Meanwell, N. A.; Snyder, S. A. Bioorg. Med. Chem. Lett. 2013, 23, 2192–2196. 2. (a) Lee, W.-G.; Kim, W.-S.; Park, S.-G.; Kim, H.; Hong, J.; Ko, H.; Kim, Y.-C. ChemMedchem 2012, 7, 218–222. (b) Katou, Y.; Endo, N.; Suzuki, T.; Yu, J.; Kikuchi, H.; Oshima, Y.; Homma, Y. Life Sci. 2014, 103, 1–7. 3. (a) Krokan, H.; Wist, E.; Krokan, R. H. Nucleic Acids Res. 1981, 9, 4709–4719. (b) Baranovskiy, A. G.; Babayeva, N. D.; Suwa, Y.; Gu, J.; Pavlov, Y. I.; Tahirov, T. H. Nucleic Acids Res. 2014, in press. 4. (a) Toyota, M.; Sasaki, M.; Ihara, M. Org. Lett. 2003, 5, 1193– 1195. (b) Watanabe, K.; Iwasaki, K.; Abe, T.; Inoue, M.; Ohkubo, K.; Suzuki, T.; Katoh, T. Org. Lett. 2005, 7, 3745–3748. (c) Kim, H.; Baker, J. B.; Lee, S.-U.; Park, Y.; Bolduc, K. L.; Park, H.-B.; Dickens, M. G.; Lee, D.-S.; Kim, Y.; Kim, S. H.; Hong, J. J. Am. Chem. Soc. 2009, 131, 3192–3194. (d) Oguchi, T.; Watanabe, K.; Ohkubo, K.; Abe, H.; Katoh, T. Chem. Eur. J. 2009, 15, 2826– 2845. (e) Kikuchi, T.; Mineta, M.; Ohtaka, J.; Matsumoto, N.; Katoh, T. Eur. J. Org. Chem. 2011, 5020–5030. 5. Sun, Y.; Li, R.; Zhang, W.; Li, A. Angew. Chem., Int. Ed. 2013, 52, 9201–9204. 6. The stereochemistry of 4a and 4b was determined by 2D NOE analysis. See Supplementary data for details. 7. Song, Z.-L.; Fan, C.-A.; Tu, Y.-Q. Chem. Rev. 2011, 111, 7523– 7556. 8. We screened many Lewis and Brønsted acids and found ZnBr2 afforded the best results. 9. Mohan, R. S.; Yee, N. K. N.; Coates, R. M.; Ren, Y.-Y.; Stamenkovic, P.; Mendez, I.; West, C. A., Arch. Biochem. Biophys. 1996, 330, 33–47. 10. Toshima, H.; Oikawa, H.; Yada, H.; Ono, H.; Toyomasu, T.; Sassa, T. Biosci. Biotechnol. Biochem. 2002, 66, 2504–2510. 11. Yee, N. K. N.; Coates, R. M., J. Org. Chem. 1992, 57, 4598–4608.
Click here to remove instruction text...
S0040-4039(15)00356-1 http://dx.doi.org/10.1016/j.tetlet.2015.02.075 TETL 45945
To appear in:
Tetrahedron Letters
Received Date: Revised Date: Accepted Date:
14 January 2015 14 February 2015 16 February 2015
Please cite this article as: Li, Z., Yang, D., Construction of 9,10-syn-trans-decalin skeleton via semipinacol rearrangement: asymmetric synthesis of (+)-syn-copalol and a candelalide analog, Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.02.075
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Graphical Abstract To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered.
Construction of 9,10-syn-trans-decalin skeleton via semipinacol rearrangement: asymmetric synthesis of (+ +)-syn-copalol and a candelalide analog Zhongliang Li, Dan Yang
Leave this area blank for abstract info.
1
Tetrahedron Letters j o ur n al h om e p a g e : w w w . e l s e v i er . c o m
Construction of 9,10-syn-trans-decalin skeleton via semipinacol rearrangement: asymmetric synthesis of (+)-syn-copalol and a candelalide analog† Zhongliang Li, Dan Yang∗ Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China
A R T IC LE IN F O
A B S TR A C T
Article history: Received Received in revised form Accepted Available online
The 9,10-syn-trans-decalin skeleton has been constructed from (+)-sclareolide via semipinacol rearrangement as a key step. Subsequent divergent transformation of a pivotal intermediate culminated in asymmetric synthesis of (+)-syn-copalol and one analog of immunosuppressive agent candelalide. This synthetic strategy constitutes a good starting point for generating a panel of biologically active natural products. 2009 Elsevier Ltd. All rights reserved.
Keywords: Syn-trans-decalin Asymmetric synthesis Semipinacol rearrangement (+)-Syn-copalol Candelalide analog
9,10-syn-trans-Decalin is a unique skeleton possessed by many biologically active natural products (Figure 1).1 Peyssonol A, with a hydroquinone moiety on the trans-decalin core, potently inhibits HIV viruses.1g The families of candelalide and subglutinol as well as other analogous natural products, bearing the trans-decalin core with either a pyrone or indole substituent, exhibit promising immunosuppressive or anti-tumor activities.1d,1f,2 Structurally more complex aphidicolin has also been extensively studied as an inhibitor of DNA polymerase in viruses and cancer cells.3 The significant and broad biological activities have prompted many synthetic efforts towards these natural products as well as their analogs for biological and pharmaceutical evaluations. 1g,4 Herein, we report a novel strategy for constructing the syn-trans-decalin skeleton and divergently achieving asymmetric synthesis of (+)-syn-copalol, a possible biosynthetic precursor of aphidicolin, as well as a candelalide analog. A unifying synthetic scheme for 9,10-syn-trans-decalin compounds was proposed in Scheme 1. We envisioned that aldehyde 2 might be attacked by a variety of nucleophiles, affording an array of potentially bioactive molecules 1. Aldehyde 2 might be generated readily from alcohol 3, and its desired C9 stereochemistry might be established by a stereospecific semipinacol rearrangement of epoxy alcohol 4a. Stereoselective ketone reduction and subsequent allyl alcohol epoxidation might provide 4a from 5, the preparation of which from commercially available (+)-sclareolide has been reported in literature.5
Figure 1 Representative natural products possessing 9,10-syntrans-decalin skeleton
———
∗ Corresponding author. Tel.: +852 28592159; fax: +852 28571586; e-mail: [email protected] (D. Yang). †
This paper is dedicated in loving memory of Professor Harry H. Wasserman.
2
Tetrahedron Letters With 3 in hand, we first protected the alcohol with a TBS group, followed by ketone olefination to furnish 8 (Scheme 4). Subsequent n-tetrabutylammonium fluoride (TBAF) deprotection and Dess-Martin periodinane (DMP) oxidation of the newly unmasked alcohol 9 proceeded straightforwardly, and the pivotal intermediate 2 was obtained in 13 steps from (+)-sclareolide with an 11% overall yield. As originally proposed, we next paid our attention to the divergent synthesis of molecules with potential bioactivities.
Scheme 1 Retrosynthetic analysis At the outset, compound 5 was prepared following Li’s procedures in 42% overall yield (Scheme 2).5 The following Luche reduction of 5 selectively gave the desired α-alcohol 6 in 97% yield. Upon exposure to meta-chloroperoxybenzoic acid (mCPBA), allyl alcohol 6 was converted to epoxy alcohols 4a and 4b,6 however, with a low diastereoselectivity (dr = 1.2:1). Scheme 4 Synthesis of the pivotal intermediate 2
Scheme 2 Synthesis of 4a and 4b Nonetheless, we proceeded to study the subsequent semipinacol rearrangement with 4a and 4b, respectively. To our surprise, when treated with ZnBr2, both 4a and 4b afforded the desired product 3 as a single diastereomer, although in low yield (Scheme 3). The formation of 3 from 4a was expected by a normal concerted and thus stereospecific semipinacol rearrangement,7 while that from its diastereomer 4b required either a nonconcerted or a tandem Payne-semipinacol rearrangement pathway. After optimization of the reaction conditions,8 compound 3 could be obtained in 42% yield based on recovered starting material (brsm) from a mixture of 4a and 4b (Scheme 4). To further increase the overall efficiency of this step, bromide 7, a major side product, was successfully converted back to the starting material 4a and 4b under basic conditions in 80% yield (Scheme 3). O
OH
OH OH H
H
H
3, 18%
4a O
OH H
ZnBr2
3, 19%
7, 13%
+
7, 19%
CH2Cl2, rt
H 4b 7
K2CO3 MeOH, rt 80%
OH
+
CH2Cl2, rt
H
Br
O
ZnBr2
We first targeted (+)-syn-copalol, the pyrophosphate ester of which has been proposed as a biosynthesis intermediate towards aphidicolin.9 Thus, aldehyde 2 was homologated with amide 10 to afford a diastereomeric mixture of alcohol 11 (Scheme 5). Straightforward xanthate synthesis and subsequent BartonMcCombie reaction removed the unwanted hydroxyl group in 11, and the resulting Weinreb amide 12 was converted to ketone 13 upon treatment with methyl Grignard reagent. The characterization data of obtained 13 is in accord with that reported by Oikawa et al. during their total synthesis of (±)-syncopalol. 1c,10 Furthermore, the absolute configurations of C5 and C10 in (+)-sclareolide match that in (+)-syn-copalol11 and they are unlikely affected by the foregoing transformation from (+)sclareolide to 13. Therefore, we have accomplished the asymmetric formal synthesis of (+)-syn-copalol by achieving 13 in 63% yield within 4 steps from aldehyde 2.
4a + 4b
Scheme 3 Preliminary results on the semipinacol rearrangement of 4a and 4b
Scheme 5 Synthesis of (+)-syn-copalol (1a) Candelalide B was found to be a potent potassium channel blocker after its initial isolation.1d We next set compound 1b as an interesting target, which lacks the bottom tetrahydropyran moiety compared with candelalide B and thus constitutes a good substrate for structure-activity relationship study (Scheme 6). The pyrone fragment 14 was prepared following reported procedures.4b Straightforward lithium-bromide exchange followed by quenching with aldehyde 2 delivered alcohol adduct 15. Subsequent deoxygenation by employing similar conditions
3 with that for alcohol 11 proceeded readily to furnish 1b in 56% yield over three steps from aldehyde 2.
References and notes 1.
Scheme 6 Synthesis of a candelalide analog In conclusion, we have successfully developed a general synthetic approach towards biologically interesting small molecules featuring a 9,10-syn-trans-decalin core skeleton. Its potential utility was showcased by asymmetric synthesis of ketone 13 and a candelalide analog. Our future work will focus on preparing a number of such molecules for biological studies and the corresponding results will be disclosed in due course.
Acknowledgements We thank The University of Hong Kong and Hong Kong Research Grants Council (HKU705213) for financial support. We thank Dr. Qiangshuai Gu for suggestions in experiment and help in preparation of this manuscript.
Supplementary data Supplementary data included the experimental procedures and characterization data (1H NMR, 13C NMR, IR, HRMS, etc) for all compounds.
(a) Lee, J. C.; Lobkovsky, E.; Pliam, N. B.; Strobel, G.; Clardy, J. J. Org. Chem 1995, 60, 7076–7077. (b) Engel, B.; Erkel, G.; Anke, T.; Sterner, O. J. Antibiot. 1998, 51, 518–521. (c) Oikawa, H.; Toyomasu, T.; Toshima, H.; Ohashi, S.; Kawaide, H.; Kamiya, Y.; Ohtsuka, M.; Shinoda, S.; Mitsuhashi, W.; Sassa, T. J. Am. Chem. Soc. 2001, 123, 5154–5155. (d) Singh, S. B.; Zink, D. L.; Dombrowski, A. W.; Dezeny, G.; Bills, G. F.; Felix, J. P.; Slaughter, R. S.; Goetz, M. A. Org. Lett. 2001, 3, 247–250. (e) Fueki, S.; Tokiwano, T.; Toshima, H.; Oikawa, H. Org. Lett. 2004, 6, 2697–2700. (f) Kikuchi, H.; Hoshi, T.; Kitayama, M.; Sekiya, M.; Katou, Y.; Ueda, K.; Kubohara, Y.; Sato, H.; Shimazu, M.; Kurata, S.; Oshima, Y. Tetrahedron 2009, 65, 469–477. (g) Treitler, D. S.; Li, Z.; Krystal, M.; Meanwell, N. A.; Snyder, S. A. Bioorg. Med. Chem. Lett. 2013, 23, 2192–2196. 2. (a) Lee, W.-G.; Kim, W.-S.; Park, S.-G.; Kim, H.; Hong, J.; Ko, H.; Kim, Y.-C. ChemMedchem 2012, 7, 218–222. (b) Katou, Y.; Endo, N.; Suzuki, T.; Yu, J.; Kikuchi, H.; Oshima, Y.; Homma, Y. Life Sci. 2014, 103, 1–7. 3. (a) Krokan, H.; Wist, E.; Krokan, R. H. Nucleic Acids Res. 1981, 9, 4709–4719. (b) Baranovskiy, A. G.; Babayeva, N. D.; Suwa, Y.; Gu, J.; Pavlov, Y. I.; Tahirov, T. H. Nucleic Acids Res. 2014, in press. 4. (a) Toyota, M.; Sasaki, M.; Ihara, M. Org. Lett. 2003, 5, 1193– 1195. (b) Watanabe, K.; Iwasaki, K.; Abe, T.; Inoue, M.; Ohkubo, K.; Suzuki, T.; Katoh, T. Org. Lett. 2005, 7, 3745–3748. (c) Kim, H.; Baker, J. B.; Lee, S.-U.; Park, Y.; Bolduc, K. L.; Park, H.-B.; Dickens, M. G.; Lee, D.-S.; Kim, Y.; Kim, S. H.; Hong, J. J. Am. Chem. Soc. 2009, 131, 3192–3194. (d) Oguchi, T.; Watanabe, K.; Ohkubo, K.; Abe, H.; Katoh, T. Chem. Eur. J. 2009, 15, 2826– 2845. (e) Kikuchi, T.; Mineta, M.; Ohtaka, J.; Matsumoto, N.; Katoh, T. Eur. J. Org. Chem. 2011, 5020–5030. 5. Sun, Y.; Li, R.; Zhang, W.; Li, A. Angew. Chem., Int. Ed. 2013, 52, 9201–9204. 6. The stereochemistry of 4a and 4b was determined by 2D NOE analysis. See Supplementary data for details. 7. Song, Z.-L.; Fan, C.-A.; Tu, Y.-Q. Chem. Rev. 2011, 111, 7523– 7556. 8. We screened many Lewis and Brønsted acids and found ZnBr2 afforded the best results. 9. Mohan, R. S.; Yee, N. K. N.; Coates, R. M.; Ren, Y.-Y.; Stamenkovic, P.; Mendez, I.; West, C. A., Arch. Biochem. Biophys. 1996, 330, 33–47. 10. Toshima, H.; Oikawa, H.; Yada, H.; Ono, H.; Toyomasu, T.; Sassa, T. Biosci. Biotechnol. Biochem. 2002, 66, 2504–2510. 11. Yee, N. K. N.; Coates, R. M., J. Org. Chem. 1992, 57, 4598–4608.
Click here to remove instruction text...