Title: A Chiral Primary Amine Thiourea Catalyst for the Highly Enantioselective Direct Conjugate Addition of α,α‐Disubstituted Aldehydes to Nitroalkenes
Abstract: Angewandte Chemie International EditionVolume 45, Issue 38 p. 6366-6370 Communication A Chiral Primary Amine Thiourea Catalyst for the Highly Enantioselective Direct Conjugate Addition of α,α-Disubstituted Aldehydes to Nitroalkenes† Mathieu P. Lalonde, Mathieu P. Lalonde Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA, Fax: (+1) 617-496-1880Search for more papers by this authorYonggang Chen Dr., Yonggang Chen Dr. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA, Fax: (+1) 617-496-1880Search for more papers by this authorEric N. Jacobsen Prof. Dr., Eric N. Jacobsen Prof. Dr. [email protected] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA, Fax: (+1) 617-496-1880Search for more papers by this author Mathieu P. Lalonde, Mathieu P. Lalonde Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA, Fax: (+1) 617-496-1880Search for more papers by this authorYonggang Chen Dr., Yonggang Chen Dr. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA, Fax: (+1) 617-496-1880Search for more papers by this authorEric N. Jacobsen Prof. Dr., Eric N. Jacobsen Prof. Dr. [email protected] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA, Fax: (+1) 617-496-1880Search for more papers by this author First published: 19 September 2006 https://doi.org/10.1002/anie.200602221Citations: 360 † This work was supported by the NIH (GM-43214 and P50 GM069721). M.P.L. gratefully acknowledges the NSERC and La Fondation Baxter et Alma Ricard for graduate scholarships. Dr. Richard Staples is acknowledged for the determination of the crystal structure of 22. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Graphical Abstract Dual activation: The bifunctional primary amine thiourea catalyst 1 promotes the highly enantioselective direct conjugate addition of α-branched aldehydes to nitroalkenes (see scheme). Cooperative activation of both the nucleophile and electrophile allows the use of mild reaction conditions and provides access to a wide variety of adducts with vicinal quaternary and tertiary stereogenic centers (>90 % ee). Supporting Information Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z602221_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. References 1For a timely review, see: B. List, Chem. Commun. 2006, 819–824. 2 2aS. Pizzarello, A. L. Weber, Science 2004, 303, 1151; 2bF. Tanaka, R. Thayumanavan, N. Mase, C. F. Barbas III, Tetrahedron Lett. 2004, 45, 325–328; 2cA. Córdova, I. Ibrahem, J. Casas, H. Sundén, M. Engqvist, E. Reyes, Chem. Eur. J. 2005, 11, 4772–4784; 2dM. Amedjkouh, Tetrahedron: Asymmetry 2005, 16, 1411–1414; 2eA. Córdova, W. Zou, I. Ibrahem, E. Reyes, M. Engqvist, W.-W. Liao, Chem. Commun. 2005, 3586–3588; 2fW. Zou, I. Ibrahem, P. Dziedzic, H. Sundén, A. Córdova, Chem. Commun. 2005, 4946–4948; 2gI. 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Relative to nitrostyrene derivatives, inferior product yields have been reported in additions of aldehydes to β-alkyl-substituted nitroalkenes (see Refs. [11 a, c–e]). 15Direct Michael additions to nitroalkenes promoted by secondary amine catalysts typically require large (e.g. tenfold) excess of aldehyde due to competing aldol pathways (see Ref. [11]). 162-Phenylpropionaldehyde was recovered in 2.5 % ee, thus indicating that a simple kinetic resolution mechanism is not operative. 17The addition of 2-methylvaleraldehyde to trans-β-nitrostyrene catalyzed by 20 mol % 3 proceeded with less than 10 % conversion. 18The benefit of added water has been observed in other primary amine catalyzed transformations (see references [2 c–j, 8 a]). 19For the conjugate addition of α-amino acid esters to trans-3,3,3-trifluoro-1-nitropropene, see: M. Molteni, A. Volonterio, M. Zanda, Org. Lett. 2003, 5, 3887–3890. 20The addition of amines to nitroalkenes has been extensively studied with very few stable adducts isolated. Anilines and electron-deficient nitroalkenes lead to relatively stable adducts. For representative studies, see: 20aD. E. Worrall, J. Am. Chem. Soc. 1927, 49, 1598–1605; 20bR. L. Heath, J. D. Rose, J. Chem. Soc. 1947, 1486–1489; 20cF. Brower, H. Burkett, J. Am. Chem. Soc. 1953, 75, 1082–1084; 20dJ. C. Sowden, A. Kirkland, K. O. Lloyd, J. Org. Chem. 1963, 28, 3516–3518; 20eÉ. S. Lipina, Z. F. Pavlova, T. Y. Paperno, V. V. Perekalin, L. V. Prikhod'ko, Zh. Org. Khim. 1970, 6, 1123–1129. 21Diastereomers are assumed to arise from competitive reaction of E and Z enamines rather than poor nitroalkene facial selectivity. Consistent with this notion, catalyst 1 promotes the reaction of nitrostyrene with isobutyraldehyde in 99 % ee (see Supporting Information for details). 22For a relevant analysis, see: D. A. Yalalov, S. B. Tsogoeva, S. Schmatz, Adv. Synth. 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Perkin Trans. 1 1992, 2331–2335. 24See Supporting Information for experimental evidence for the formation of G. 25For a discussion of dual activation within the context of asymmetric catalysis by chiral hydrogen-bond donors, see Ref. [6 b]. 26Yields are of isolated products after column chromatography. Diastereomeric ratios and enantiomeric excesses were determined by SFC or HPLC analysis compared with authentic racemic material. The absolute configuration of 22 was determined by X-ray crystallography, whereas those of 6–21 were inferred. Citing Literature Volume45, Issue38September 25, 2006Pages 6366-6370 ReferencesRelatedInformation
Publication Year: 2006
Publication Date: 2006-08-28
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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