A Novel Organocatalytic Tool for the Iminium Activation of α,β-Unsaturated Ketones

Abstract

Asymmetric aminocatalysis has become a well-established and powerful synthetic tool for the chemo- and enantioselective functionalization of carbonyl compounds. Recent studies have established the unique ability of primary amine catalysis to participate in processes between sterically demanding partners, thus overcoming the inherent difficulties of chiral secondary amines in generating congested covalent intermediates. With this in mind, we introduced the primary amine catalyst salt 1, made by combining the easily available 9-amino-9-deoxy-epi-hydroquinine with N-Boc-d-phenylglycine as the chiral counteranion. Salt 1 exhibits high reactivity and selectivity in the enantioselective conjugate additions of a series of different nucleophiles to unsaturated ketones. The rationale behind the development of this general and efficient iminium activator of enones is discussed.

1 Introduction

2 Iminium Catalysis

3 Iminium Activation of Unsaturated Ketones

3.1 Chiral Primary Amines in Iminium Catalysis

3.2 Asymmetric Counteranion-Directed Catalysis

4 A New Catalyst Salt for Iminium Activation of Enones: 9-Amino-9-deoxy-epi-hydroquinine and N-Boc-d-phenylglycine

4.1 Friedel-Crafts Alkylation of Indoles

4.2 Oxa-Michael Addition

4.3 Sulfa-Michael Addition

5 Summary and Outlook

Key words

amines - asymmetric catalysis - ketones - organocatalysis - Michael additions

References

• For general reviews on asymmetric organocatalysis, see:
• 1a Enantioselective Organocatalysis   Dalko PI. Wiley-VCH; Weinheim: 2007. 
• 1b Gaunt MJ. Johansson CCC. McNally A. Vo NT. Drug Discovery Today  2007,  12:  8 
• 1c List B. Yang JW. Science (Washington, D.C.)  2006,  313:  1584 
• 1d The special issue devoted to ‘Asymmetric Organocatalysis’ (List, B., Ed.): Chem. Rev.  2007,  107:  5413-5883  
• 2a Barbas CF. Angew. Chem. Int. Ed.  2008,  47:  42 
• 2b List B. Chem. Commun.  2006,  819 
• 2c Marigo M. Jørgensen KA. Chem. Commun.  2006,  2001 
• 3 For a review, see: Mukherjee S. Yang JW. Hoffmann S. List B. Chem. Rev.  2007,  107:  5471 
• 4a Beeson TD. Mastracchio A. Hong J.-B. Ashton K. MacMillan DWC. Science (Washington, D.C.)  2007,  316:  582 
• 4b Jang H.-Y. Hong J.-B. MacMillan DWC. J. Am. Chem. Soc.  2007,  129:  7004 
• 4c Kim H. MacMillan DWC. J. Am. Chem. Soc.  2008,  130:  398 
• 4d Sibi MP. Hasegawa M. J. Am. Chem. Soc.  2007,  129:  4124 
• For recent highlights, see:
• 4e Mukherjee S. List B. Nature (London)  2007,  447:  152 
• 4f Bertelsen S. Nielsen M. Jørgensen KA. Angew. Chem. Int. Ed.  2007,  46:  7356 
• For reviews on asymmetric iminium ion catalysis, see:
• 5a Lelais G. MacMillan DWC. Aldrichimica Acta  2006,  39:  79 
• 5b Erkkilä A. Majander I. Pihko PM. Chem. Rev.  2007,  107:  5416 
• For recent, general reviews on organocatalytic asymmetric conjugate additions, see:
• 5c Tsogoeva SB. Eur. J. Org. Chem.  2007,  1701 
• 5d Vicario JL. Badia D. Carrillo L. Synthesis  2007,  2065 
• 6a Bertelsen S. Marigo M. Brandes S. Dinér P. Jørgensen KA. J. Am. Chem. Soc.  2006,  128:  12973 
• 6b Hong B.-C. Wu M.-F. Tseng H.-C. Huang G.-F. Su C.-F. Liao J.-H. J. Org. Chem.  2007,  72:  8459 
• 6c de Figueiredo RM. Fröhlich R. Christmann M. Angew. Chem. Int. Ed.  2008,  47:  1450 
• For selected examples of metal-catalyzed asymmetric functionalization of ketones, see:
• 7a Enders D. Eichenauer H. Chem. Ber.  1979,  112:  2933 
• 7b Imai M. Hagihara A. Kawasaki H. Manabe K. Koga K. J. Am. Chem. Soc.  1994,  116:  8829 
• 7c Behenna DC. Stoltz BM. J. Am. Chem. Soc.  2004,  126:  15044 
• 7d Trost BM. Xu J. J. Am. Chem. Soc.  2005,  127:  2846 
• 7e Braun M. Meier T. Synlett  2005,  2968 
• For selected examples of phase-transfer catalysis, see:
• 7f Dolling UH. Davis P. Grabowski EJJ. J. Am. Chem. Soc.  1984,  106:  446 
• 7g O’Donnel MJ. Bennett WD. Wu S. J. Am. Chem. Soc.  1989,  111:  2353 
• 8 For a recent review on chiral primary amine catalysis, see: Peng F. Shao Z. J. Mol. Catal. A: Chem.  2008,  285:  1 
• For indole alkylation, see:
• 9a Bartoli G. Bosco M. Carlone A. Pesciaioli F. Sambri L. Melchiorre P. Org. Lett.  2007,  9:  1403 
• For the oxa-Michael reaction, see:
• 9b Carlone A. Bartoli G. Bosco M. Pesciaioli F. Ricci P. Sambri L. Melchiorre P. Eur. J. Org. Chem.  2007,  5492 
• For the sulfa-Michael reaction, see:
• 9c Ricci P. Carlone A. Bartoli G. Bosco M. Sambri L. Melchiorre P. Adv. Synth. Catal.  2008,  350:  49 
• 10 Amine 2 is easily prepared by the Mitsunobu reaction of the commercially available hydroquinine. For the first reported preparation of 9-amino-9-deoxy-epi-quinine, see: Brunner H. Bügler J. Nuber B. Tetrahedron: Asymmetry  1995,  6:  1699 
• 11a Mayer S. List B. Angew. Chem. Int. Ed.  2006,  45:  4193 
• 11b Martin NJA. List B. J. Am. Chem. Soc.  2006,  128:  13368 
• 11c Zhou J. List B. J. Am. Chem. Soc.  2007,  129:  7498 
• 11d Wang X. List B. Angew. Chem. Int. Ed.  2008,  47:  1119 
• Asymmetric addition of C-based nucleophiles to enones: For direct vinylogous addition of α,α-dicyanoalkenes, see:
• 12a Xie J.-W. Chen W. Li R. Zeng M. Du W. Yue L. Chen Y.-C. Wu Y. Zhu J. Deng J.-G. Angew. Chem. Int. Ed.  2007,  46:  389 
• For addition of cyclic 1,3-dicarbonyl compounds, see:
• 12b Xie J.-W. Yue L. Chen W. Du W. Zhu J. Deng J.-G. Chen Y.-C. Org. Lett.  2007,  9:  413 
• For indole alkylation, see:
• 12c Chen W. Du W. Yue L. Li R. Wu Y. Ding L.-S. Chen Y.-C. Org. Biomol. Chem.  2007,  5:  816 
• For malononitrile addition, see:
• 12d Li X. Cun L. Lian C. Zhong L. Chen Y. Liao J. Zhu J. Deng J. Org. Biomol. Chem.  2008,  6:  349 
• For Diels-Alder reaction, see:
• 12e Singh RP. Bartelson K. Wang Y. Su H. Lu X. Deng L. J. Am. Chem. Soc.  2008,  130:  2422 
• For a recent ACDC approach with a multifunctional primary amine catalyst, see:
• 12f Chen W. Du W. Duan Y.-Z. Wu Y. Yang S.-Y. Chen Y.-C. Angew. Chem. Int. Ed.  2007,  46:  7667 
• Recently, in addition to their generality as iminium activators, 9-amino-9-deoxy-epi-cinchona alkaloids have also been successfully employed for the asymmetric α-functionalization of ketones via enamine catalysis. See:
• 13a McCooey SH. Connon SJ. Org. Lett.  2007,  9:  599 
• 13b Liu T.-Y. Cui H.-L. Zhang Y. Jiang K. Du W. He Z.-Q. Chen Y.-C. Org. Lett.  2007,  9:  3671 
• 13c Zheng B.-L. Liu Q.-Z. Guo C.-S. Wang X.-L. He L. Org. Biomol. Chem.  2007,  5:  2913 
• 14 Ahrendt KA. Borths CJ. MacMillan DWC. J. Am. Chem. Soc.  2000,  122:  4243.  For a personal account by D. W. C. MacMillan on the rationale behind this new organocatalytic concept, see ref. 1a, Chap. 3, pp 95-120
• 15a Jen WS. Wiener JJM. MacMillan DWC. J. Am. Chem. Soc.  2000,  122:  9874 
• 15b Paras NA. MacMillan DWC. J. Am. Chem. Soc.  2001,  123:  4370 
• 15c Ouellet SG. Tuttle JB. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  32 
• 15d Kunz RK. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  3240 
• Selected examples: For conjugate addition of electron-rich benzenes, see:
• 16a Paras NA. MacMillan DWC. J. Am. Chem. Soc.  2002,  124:  7894 
• For Mukaiyama-Michael reaction, see:
• 16b Brown SP. Goodwin NC. MacMillan DWC. J. Am. Chem. Soc.  2003,  125:  1192 
• For addition of amines, see:
• 16c Chen YK. Yoshida M. MacMillan DWC. J. Am. Chem. Soc.  2006,  128:  9328 
• For [4+3] cycloaddition reactions, see:
• 16d Harmata M. Ghosh SK. Hong X. Wacharasindhu S. Kirchhoefer P. J. Am. Chem. Soc.  2003,  125:  2058 
• For intramolecular Diels-Alder reactions, see:
• 16e Wilson RM. Jen WS. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  11616 
• 16f Selkälä SA. Koskinen AMP. Eur. J. Org. Chem.  2005,  1620 
• For hydride addition, see:
• 16g Yang JW. Hechavarria Fonseca MT. Vignola N. List B. Angew. Chem. Int. Ed.  2005,  44:  108 
• Selected examples of enal conjugate additions: For C-nucleophiles, see:
• 17a Brandau S. Landa A. Franzén J. Marigo M. Jørgensen KA. Angew. Chem. Int. Ed.  2006,  45:  4305 
• 17b Gotoh H. Masui R. Ogino H. Shoji M. Hayashi Y. Angew. Chem. Int. Ed.  2006,  45:  6853 
• 17c Enders D. Bonten MH. Raabe G. Synlett  2007,  885 
• For cycloaddition reactions, see:
• 17d Gotoh H. Hayashi Y. Org. Lett.  2007,  9:  2859 
• For N-Nucleophiles, see:
• 17e Dinér P. Nielsen M. Marigo M. Jørgensen KA. Angew. Chem. Int. Ed.  2007,  46:  1983 
• 17f Ibrahem I. Rios R. Vesely J. Zhao G.-L. Córdova A. Chem. Commun.  2007,  849 
• For O-Nucleophiles, see:
• 17g Bertelsen S. Dinér P. Johansen RL. Jørgensen KA. J. Am. Chem. Soc.  2007,  129:  1536 
• For S-Nucleophiles, see:
• 17h Marigo M. Schulte T. Franzen J. Jorgensen KA. J. Am. Chem. Soc.  2005,  127:  15710 
• For P-Nucleophiles, see:
• 17i Carlone A. Bartoli G. Bosco M. Sambri L. Melchiorre P. Angew. Chem. Int. Ed.  2007,  46:  4504 
• 17j Ibrahem I. Rios R. Vesely J. Hammar P. Eriksson L. Himo F. Córdova A. Angew. Chem. Int. Ed.  2007,  46:  4507 . For a recent review on the use of a,a-diarylprolinol ethers in aminocatalysis, see: (k) Mielgo, A.; Palomo, C. Chem. Asian J. 2008, 3, 922
• 18a Northrup AB. MacMillan DWC. J. Am. Chem. Soc.  2002,  124:  2458 
• For the use of 7 in asymmetric transfer hydrogenation of cyclic enones, see:
• 18b Tuttle JB. Ouellet SG. MacMillan DWC. J. Am. Chem. Soc.  2006,  128:  12662 
• For theoretical studies on iminium-catalyzed Diels-Alder reactions with unsaturated aldehydes and ketones, see:
• 18c Gordillo R. Houk NK. J. Am. Chem. Soc.  2006,  128:  3543 
• For previous studies on proline- and proline-derivative-catalyzed addition of carbogenic nucleophiles to cyclic enones, see:
• 19a Yamaguchi M. Shiraishi T. Hirama M. J. Org. Chem.  1996,  61:  3520 ; and references cited therein
• 19b Hanessian S. Pharm V. Org. Lett.  2000,  2:  2975 
• 20a Halland N. Hazell RG. Jørgensen KA. J. Org. Chem.  2002,  67:  8331 
• 20b Halland N. Aburel PS. Jørgensen KA. Angew. Chem. Int. Ed.  2003,  42:  661 
• 20c Halland N. Aburel PS. Jørgensen KA. Angew. Chem. Int. Ed.  2004,  43:  1272 
• 20d Pulkkinen J. Aburel PS. Halland N. Jørgensen KA. Adv. Synth. Catal.  2004,  346:  1077 
• 21 Heine A. DeSantis G. Luz JG. Mitchell M. Wong C.-H. Science (Washington, D.C.)  2001,  294:  369 ; and references cited therein
• 22a Clark RA. Parker DC. J. Am. Chem. Soc.  1971,  93:  7257 
• 22b Boyd DR. Jennings WB. Waring LC. J. Org. Chem.  1986,  51:  992 
• 22c Capon B. Wu Z.-P. J. Org. Chem.  1990,  55:  2317 ; and references cited therein
• 23a List B. Tetrahedron  2002,  58:  5573 
• 23b Movassaghi M. Jacobsen EN. Science (Washington, D.C.)  2002,  298:  1904 
• For selected examples, see:
• 24a Bassan A. Zou W. Reyes E. Himo F. Córdova A. Angew. Chem. Int. Ed.  2005,  44:  7028 
• 24b Ramasastry SSV. Zhang H. Tanaka F. Barbas CF. J. Am. Chem. Soc.  2007,  129:  288 
• 24c Luo S. Xu H. Li J. Zhang L. Cheng J.-P. J. Am. Chem. Soc.  2007,  129:  3074 ; and references cited therein
• 25a Xu Y. Zou W. Sundén H. Ibrahem I. Córdova A. Adv. Synth. Catal.  2006,  348:  418 
• 25b Xu Y. Córdova A. Chem. Commun.  2006,  460 ; and references cited therein
• For very meaningful examples of the potential of primary amines in enamine activation of ketones, see:
• 26a Tsogoeva SB. Wei S. Chem. Commun.  2006,  1451 
• 26b Huang H. Jacobsen EN. J. Am. Chem. Soc.  2006,  128:  7170 
• See also:
• 26c Lalonde MP. Chen Y. Jacobsen EN. Angew. Chem. Int. Ed.  2006,  45:  6366 
• 27a Ishihara K. Nakano K. J. Am. Chem. Soc.  2005,  127:  10504 
• See also:
• 27b Sakakura A. Suzuki K. Nakano K. Ishihara K. Org. Lett.  2006,  8:  2229 
• 27c Ishihara K. Nakano K. J. Am. Chem. Soc.  2007,  129:  8930 
• 28a Kim H. Yen C. Preston P. Chin J. Org. Lett.  2006,  8:  5239 
• 28b Halland N. Hansen T. Jørgensen KA. Angew. Chem. Int. Ed.  2003,  42:  4955 
• For an early example of iminium activation of cyclic enones by primary amine catalysis, see:
• 28c Tsogoeva SB. Jagtap SB. Synlett  2004,  2624 
• For recent reviews, see:
• 29a Akiyama T. Chem. Rev.  2007,  107:  5744 
• 29b Connon SJ. Angew. Chem. Int. Ed.  2006,  45:  3909 
• 30a Bartoli G. Bosco M. Carlone A. Locatelli M. Mazzanti A. Sambri L. Melchiorre P. Chem. Commun.  2007,  722 
• 30b Bartoli G. Bosco M. Carlone A. Cavalli A. Locatelli M. Mazzanti A. Ricci P. Sambri L. Melchiorre P. Angew. Chem. Int. Ed.  2006,  45:  4966 
• 30c Bartoli G. Bosco M. Carlone A. Locatelli M. Melchiorre P. Sambri L. Angew. Chem. Int. Ed.  2005,  44:  6219 
• 31 For a recent review, see: Tian S.-K. Chen Y. Hang J. Tang L. McDaid P. Deng L. Acc. Chem. Res.  2004,  37:  621 
• For reviews on asymmetric catalysis by chiral hydrogen-bonding donors, see:
• 32a Taylor MS. Jacobsen EN. Angew. Chem. Int. Ed.  2006,  45:  1520 
• 32b Marcelli T. van Maarseveen JH. Hiemstra H. Angew. Chem. Int. Ed.  2006,  45:  7496 
• For a review, see:
• 33a Connon SJ. Chem.-Eur. J.  2006,  12:  5418 
• For leading references, see:
• 33b Vakulya B. Varga S. Csámpai A. Soós T. Org. Lett.  2005,  7:  1967 
• 33c McCooey SH. Connon SJ. Angew. Chem. Int. Ed.  2005,  44:  6367 
• 34a Sundberg RJ. Indoles   Academic Press; San Diego: 1996.  p.175 
• 34b Nicolaou KC. Snyder SA. Classics in Total Synthesis II   Wiley-VCH; Weinheim: 2003. 
• For recent reviews on catalytic asymmetric Friedel-Crafts reactions, see:
• 35a Bandini M. Melloni A. Umani-Ronchi A. Angew. Chem. Int. Ed.  2004,  43:  550 
• 35b Jørgensen KA. Synthesis  2003,  1117 
• For selected, recent examples, see:
• 36a Jensen KB. Thorhauge J. Hazell RG. Jørgensen KA. Angew. Chem. Int. Ed.  2001,  40:  160 
• 36b Palomo C. Oiarbide M. Kardak BG. Garcia JM. Linden A. J. Am. Chem. Soc.  2005,  127:  4154 
• 36c Evans DA. Fandrick KR. Song H.-J. Scheidt KA. Xu R. J. Am. Chem. Soc.  2007,  129:  10029 
• 37a Austin JF. MacMillan DWC. J. Am. Chem. Soc.  2002,  124:  1172 
• 37b Austin JF. Kim S.-G. Sinz CJ. Xiao W.-J. MacMillan DWC. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5482 
• 37c Lee S. MacMillan DWC. J. Am. Chem. Soc.  2007,  129:  15438 
• 38 Bandini M. Fagioli M. Melchiorre P. Umani-Ronchi A. Tetrahedron Lett.  2003,  44:  5843 
• For organocatalytic indole alkylation with enones promoted by an achiral amine, see:
• 39a Li D.-P. Guo Y.-C. Ding Y. Xiao W.-J. Chem. Commun.  2006,  799 
• In this report, an initial attempt to perform an asymmetric version of the reaction using the MacMillan second generation imidazolidinone 7 afforded poor selectivity (28% ee). Recently, a low selectivity (up to 29% ee) addition of indole to chalcone promoted by d-camphorsulfonic acid was reported, see:
• 39b Zhou W. Xu L.-W. Li L. Yang L. Xia C.-G. Eur. J. Org. Chem.  2006,  5225 
• See also:
• 39c Tang H.-Y. Lu A.-D. Zhou Z.-H. Zhao G.-F. He L.-N. Tang C.-C. Eur. J. Org. Chem.  2008,  1406 
• For a recent, Brønsted acid catalyzed asymmetric F-C alkylation of indoles with unsaturated α-keto esters, see:
• 39d Rueping M. Nachtsheim BJ. Moreth SA. Bolte M. Angew. Chem. Int. Ed.  2008,  47:  593 
• 40a Török B. Abid M. London G. Esquibel J. Török MS. Mhadgut C. Yan P. Prakash GKS. Angew. Chem. Int. Ed.  2005,  44:  3086 
• 40b Herrera RP. Sgarzani V. Bernardi L. Ricci A. Angew. Chem. Int. Ed.  2005,  44:  6576 . In reference 12e the possibility that 9-amino-9-deoxy-epi-cinchona alkaloids can act as bifunctional activators of both the unsaturated ketones and the nucleophiles was advanced
• 41a Vanderwal CD. Jacobsen EN. J. Am. Chem. Soc.  2004,  126:  14724 
• 41b Miyabe H. Matsumura A. Moriyama K. Takemoto Y. Org. Lett.  2004,  6:  4631 
• 41c Bertelsen S. Dinér P. Johansen RL. Jørgensen KA. J. Am. Chem. Soc.  2007,  129:  1536 
• 41d Dinér P. Nielsen M. Bertelsen S. Niess B. Jørgensen KA. Chem. Commun.  2007,  3646 
• 42a Bode SE. Wolberg M. Müller M. Synthesis  2006,  557 
• 42b Evans DA. Hoveyda AH. J. Org. Chem.  1990,  55:  5190 
• 43 Carreira EM. Lee W. Singer RA. J. Am. Chem. Soc.  1995,  117:  3649 
• 44a Fraústo da Silva JR. Williams RJP. The Biological Chemistry of the Elements   Oxford University Press; New York: 2001. 
• 44b Metzner P. Thuillier A. Sulfur Reagents in Organic Synthesis   Academic Press; New York: 1994. 
• 44c Nudelman A. The Chemistry of Optically Active Sulfur Compounds   Gordon & Breach; New York: 1984. 
• 44d Chatgilialoglu C. Asmus K.-D. Sulfur-Centered Reactive Intermediates in Chemistry and Biology   Springer; New York: 1991. 
• 45 For a comprehensive review on asymmetric sulfa-Michael additions, see: Enders D. Lüttgen K. Narine AA. Synthesis  2007,  959 
• For selected examples, see:
• 46a Kanemasa S. Oderaotoshi Y. Wada E. J. Am. Chem. Soc.  1999,  121:  8675 
• For an organocatalytic asymmetric strategy, see:
• 46b Zu L. Wang J. Li H. Xie H. Jiang W. Wang W. J. Am. Chem. Soc.  2007,  129:  1036 
• For organocatalytic asymmetric strategies, see:
• 47a Hiemstra H. Wynberg H. J. Am. Chem. Soc.  1981,  103:  417 
• 47b McDaid P. Chen Y. Deng L. Angew. Chem. Int. Ed.  2002,  41:  338 
• 48a Brandau S. Maerten E. Jørgensen KA. J. Am. Chem. Soc.  2006,  128:  14986 
• 48b Wang W. Li H. Wang J. Zu L. J. Am. Chem. Soc.  2006,  128:  10354 
• 48c

  See also reference 17h.

• 49a Skarżewski J. Zielińska-Blajet M. Turowska-Tyrk I. Tetrahedron: Asymmetry  2001,  12:  1923 
• 49b Li H. Zu L. Wang J. Wang W. Tetrahedron Lett.  2006,  47:  3145 
• 51 Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   3rd ed.:  Wiley-VCH; New York: 1999.  Chap. 6. p.454 
• 52 In the absence of an acidic counteranion, the non-protonated 9-amino-9-deoxy-epi-hydroquinine is still able to promote the sulfa-Michael addition, albeit with lower reactivity, presumably by activating the nucleophilic component 36 through Brønsted-base catalysis; however, the observed low optical purity (8% ee) together with reversal in the stereochemistry supports an iminium ion activation mode of catalysis when the chiral salt 1 is employed. The iminium ion activation path is also corroborated by the lower reactivity observed when more encumbered α-substituted enones are employed. For similar mechanistic considerations on this type of catalyst salt, see: Wang X. Reisinger CM. List B. J. Am. Chem. Soc.  2008,  130:  6070 
• For reviews on organocatalytic domino reactions, see:
• 54a Enders D. Grondal C. Hüttl MRM. Angew. Chem. Int. Ed.  2007,  46:  1570 
• 54b Guillena G. Ramón DJ. Yus M. Tetrahedron: Asymmetry  2007,  18:  693 

50

The results obtained when using 9-amino-9-deoxy-epi-hydroquinine (2) in combination with various acidic counterparts (TFA, PTSA, N-Boc-l-phenylalanine) in the organocatalyzed SMA did not show any appreciable improvement in terms of enantioselectivity, confirming the superior efficiency of the catalyst salt 1. Remarkably, consistent with previous observations, use of the opposite enantiomeric counteranion (N-Boc-l-phenylglycine) afforded the same enantiomeric sulfa-Michael adduct with lower reactivity and selectivity, illustrating a marked case of a matched/mismatched catalyst-ion pair combination.

53

Preliminary studies on conjugate additions to (E)-4-phenyl-3-buten-2-one (11) promoted by catalyst salt 1 afforded encouraging results: aza-Michael addition of N-(benzyl-oxycarbonyl)hydroxylamine: 96% ee; phospha-Michael addition of diphenylphosphine: 56% ee.