Title: Expanding Insight into Asymmetric Palladium‐Catalyzed Allylic Alkylation of N‐Heterocyclic Molecules and Cyclic Ketones
Abstract: Chemistry – A European JournalVolume 19, Issue 14 p. 4414-4418 Communication Expanding Insight into Asymmetric Palladium-Catalyzed Allylic Alkylation of N-Heterocyclic Molecules and Cyclic Ketones Nathan B. Bennett, Nathan B. Bennett Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436 N.B.B. and D.C.D. contributed equally to this article.Search for more papers by this authorDouglas C. Duquette, Douglas C. Duquette Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436 N.B.B. and D.C.D. contributed equally to this article.Search for more papers by this authorDr. Jimin Kim, Dr. Jimin Kim Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this authorDr. Wen-Bo Liu, Dr. Wen-Bo Liu Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this authorDr. Alexander N. Marziale, Dr. Alexander N. Marziale Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this authorDr. Douglas C. Behenna, Dr. Douglas C. Behenna Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this authorDr. Scott C. Virgil, Dr. Scott C. Virgil Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this authorProf. Brian M. Stoltz, Corresponding Author Prof. Brian M. Stoltz [email protected] Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this author Nathan B. Bennett, Nathan B. Bennett Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436 N.B.B. and D.C.D. contributed equally to this article.Search for more papers by this authorDouglas C. Duquette, Douglas C. Duquette Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436 N.B.B. and D.C.D. contributed equally to this article.Search for more papers by this authorDr. Jimin Kim, Dr. Jimin Kim Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this authorDr. Wen-Bo Liu, Dr. Wen-Bo Liu Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this authorDr. Alexander N. Marziale, Dr. Alexander N. Marziale Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this authorDr. Douglas C. Behenna, Dr. Douglas C. Behenna Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this authorDr. Scott C. Virgil, Dr. Scott C. Virgil Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this authorProf. Brian M. Stoltz, Corresponding Author Prof. Brian M. Stoltz [email protected] Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Division of Chemistry and Chemical Engineering, California Institute of Technology, Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA), Fax: (+1) 626-395-8436Search for more papers by this author First published: 27 February 2013 https://doi.org/10.1002/chem.201300030Citations: 41 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 Eeny, meeny, miny …︁ enaminones! Lactams and imides have been shown to consistently provide enantioselectivities substantially higher than other substrate classes previously investigated in the palladium-catalyzed asymmetric decarboxylative allylic alkylation. Several new substrates have been designed to probe the contributions of electronic, steric, and stereoelectronic factors that distinguish the lactam/imide series as superior alkylation substrates (see scheme). These studies culminated in marked improvements on carbocyclic allylic alkylation substrates. Supporting Information As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Filename Description chem_201300030_sm_miscellaneous_information.pdf20.1 MB miscellaneous_information 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 review of approaches for the asymmetric construction of all-carbon quaternary stereocenters, see: 1aJ. Christoffers, A. Baro, Adv. Synth. Catal. 2005, 347, 1473–1482; 1bB. M. Trost, C. Jiang, Synthesis 2006, 369–396. 2For examples of other efforts in the enantioselective allylic alkylation of enolates catalyzed by palladium, see: 2aB. M. Trost, J. Xu, T. Schmidt, J. Am. Chem. Soc. 2009, 131, 18343–18357; 2bB. M. Trost, B. Schäffner, M. Osipov, D. A. A. Wilton, Angew. Chem. 2011, 123, 3610–3613; Angew. Chem. Int. Ed. 2011, 50, 3548–3551; 2cM. Nakamura, A. Hajra, K. Endo, E. Nakamura, Angew. Chem. 2005, 117, 7414–7417; Angew. Chem. Int. 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Chem. 2005, 117, 7084–7087; Angew. Chem. Int. Ed. 2005, 44, 6924–6927. 7D. C. Behenna, J. T. Mohr, N. H. Sherden, S. C. Marinescu, A. M. Harned, K. Tani, M. Seto, S. Ma, Z. Novák, M. R. Krout, R. M. McFadden, J. L. Roizen, J. A. Enquist Jr., D. E. White, S. R. Levine, K. V. Petrova, A. Iwashita, S. C. Virgil, B. M. Stoltz, Chem. Eur. J. 2011, 17, 14199–14223. 8For examples of total syntheses, see: 8aR. M. McFadden, B. M. Stoltz, J. Am. Chem. Soc. 2006, 128, 7738–7739; 8bJ. A. Enquist Jr., B. M. Stoltz, Nature 2008, 453, 1228–1231; 8cJ. J. Day, R. M. McFadden, S. C. Virgil, H. Kolding, J. L. Alleva, B. M. Stoltz, Angew. Chem. 2011, 123, 6946–6950; Angew. Chem. Int. Ed. 2011, 50, 6814–6818; 8dA. Y. Hong, B. M. Stoltz, Angew. Chem. 2012, 124, 9812—9816; Angew. Chem. Int. Ed. 2012, 51, 9674–9678. 9 9aJ. A. Keith, D. C. Behenna, J. T. Mohr, S. Ma, S. C. Marinescu, J. Oxgaard, B. M. Stoltz, W. A. Goddard III, J. Am. Chem. Soc. 2007, 129, 11876–11877; 9bN. H. Sherden, D. C. Behenna, S. C. Virgil, B. M. Stoltz, Angew. Chem. 2009, 121, 6972–6975; Angew. Chem. Int. Ed. 2009, 48, 6840–6843; 9cJ. A. Keith, D. C. Behenna, N. Sherden, J. T. Mohr, S. Ma, S. C. Marinescu, R. J. Nielsen, J. Oxgaard, B. M. Stoltz, W. A. Goddard III, J. Am. Chem. Soc. 2012, 134, 19050–19060. 10D. C. Behenna, Y. Liu, T. Yurino, J. Kim, D. E. White, S. C. Virgil, B. M. Stoltz, Nat. Chem. 2011, 4, 130–133. 11For examples of research on vinylogous esters, see: 11aD. E. White, I. C. Stewart, R. H. Grubbs, B. M. Stoltz, J. Am. Chem. Soc. 2008, 130, 810–811; 11bM. R. Krout. Progress Toward the Asymmetric Total Synthesis of Variecolin and Gas-Phase Studies of the Twisted Amide 2-Quinuclidone, Ph.D. Dissertation, California Institute of Technology, CA, September 2009; 11cA. Y. Hong, M. R. Krout, T. Jensen, N. B. Bennett, A. M. Harned, B. M. Stoltz, Angew. Chem. 2011, 123, 2808–2812; Angew. Chem. Int. Ed. 2011, 50, 2756–2760; 11dN. B. Bennett, A. Y. Hong, A. M. Harned, B. M. Stoltz, Org. Biomol. Chem. 2012, 10, 56–59; 11eA. Y. Hong, N. B. Bennett, M. R. Krout, T. Jensen, A. M. Harned, B. M. Stoltz, Tetrahedron 2011, 67, 10234–10248. 12For examples of research on vinylogous thioesters, see: 12aS. R. Levine, M. R. Krout, B. M. Stoltz, Org. Lett. 2009, 11, 289–292; 12bK. V. Petrova, J. T. Mohr, B. M. Stoltz, Org. Lett. 2009, 11, 293–295. 13Concurrent with our efforts, Trost has also performed palladium-catalyzed asymmetric allylic alkylations to form enantioenriched α-quaternary vinylogous esters and thioesters. See: 13aB. M. Trost, C. Pissot-Soldermann, I. Chen, G. M. Schroeder, J. Am. Chem. Soc. 2004, 126, 4480–4481; 13bB. M. Trost, G. M. Schroeder, Chem. Eur. J. 2005, 11, 174–184; 13cB. M. Trost, C. Pissot-Soldermann, I. Chen, Chem. Eur. J. 2005, 11, 951–959; 13dB. M. Trost, R. N. Bream, J. Xu, Angew. Chem. 2006, 118, 3181–3184; Angew. Chem. Int. Ed. 2006, 45, 3109–3112. 14For another example of a screen performed in our laboratory with a Symyx core module, see: N. T. McDougal, S. C. Virgil, B. M. Stoltz, Synlett 2010, 1712–1716. 15See Supporting Information. 16Corresponding electron-rich lactams (N-substituent=Me or Bn) exhibit little to no conversion to the desired products and, as such, are poor alkylation substrates. 17For example, selectivities for lactam 5 a vary from 99 % ee with (S)-8 to 86 % ee with (S)-3 in toluene and to 96 % ee with (S)-8 in THF. 18For example, with (S)-8 in toluene, observed selectivities for lactams vary from 99 % ee (5 a, R=Bz) to 37 % ee (5 b, R=Ts). 19Employing optimized conditions with (S)-3 in Et2O, enone 13 a has been isolated in 90 % ee. See ref. [6b]. 20The increase in steric bulk for substrates 4 i–j also slows the reaction dramatically. See Supporting Information. Citing Literature Volume19, Issue14April 2, 2013Pages 4414-4418 ReferencesRelatedInformation