Helical chiral 2-aminopyridinium ions were designed as a significantly more acidic (active) dual hydrogen-bonding catalyst than commonly used (thio)urea-based systems. The helicene framework was specifically utilized to position an inherently chiral barrier on the hydrogen-bonding side of the catalyst. The catalyst reactivity and enantioselectivity were successfully demonstrated in additions of 4,7-dihydroindoles to nitroalkenes (0.5-2 mol % catalyst loadings, up to 98:2 er).

The design, synthesis, and study of new catalyst structures have had an enormous impact on chemical synthesis, and continue to be a central challenge in asymmetric catalysis.[1]We recently described that a 2-aminopyridinium ion might be a promising catalaphore [2] for the design of new asymmetric hydrogen-bond donor catalysts. [3] In that connection, we became interested in 1-aza [6]helicene [4] 1 as a chiraphore [2] because a first-order analysis of the crystal structure of an analogous 1,16-diaza[6]helicene [5] suggests that its pyridine ring is well-desymmetrized in terms of both top-from-bottom and left-from-right differentiations. To our knowledge, the application of 1 and analogous helical chiral pyridines [5][6][7] in asymmetric catalysis has not been studied, even though 1 has been known in the literature since 1975.[4d] In this context, we were prompted to develop an efficient synthesis of 1-azahelicenes, which allows systematic structural variation-important for the elucidation of the relationship between catalyst structure, reactivity, and selectivity-and to exploit them as chiraphores. In view of the utility of helical chiral pyridines such as 1, it occurred to us that the corresponding pyridine N-oxides might prove to be effective asymmetric catalysts.[8] Herein, we describe the scalable synthesis of 1-azahelicenes and the structural characterization of the corresponding N-oxides, and we apply this new family of compounds to the catalytic enantioselective desymmetrization of meso epoxides (see Table 1). This study provides the first report of the application of azahelicenes in asymmetric catalysis. [9] An examination of the structure of 1 suggests that the chiral environment in the vicinity of the nitrogen atom can be tuned by structural modification at cabon atoms 11-16. Therefore, we devised a convergent synthetic route to 1 in which benzoquinoline unit 2 and C11-C16 unit 3 could be expeditiously united (Scheme 1). This strategy would allow ready access to the necessary 1-azahelicene derivatives by simply replacing 3 with its readily available structural analogues, such as 9 and 12 (Scheme 2). Preparation of key unit 8 starts from commercially available pyridine 4 and phosphonium salt 5, which was readily synthesized in three steps from commercially available 2-bromo-4-methyl benzaldehyde. The highly Z-selective Wittig reaction [6b, 10] of 4 and 5 and subsequent Stille-Kelly reaction [5,11] provided benzoquinoline 6. The catalytic C À H functionalization method developed by Sanford and co-workers [12] readily converted 6 into 7 from which 8 was obtained in an ordinary way. The second sequence of the highly Z-selective Wittig reaction and the Stille-Kelly reaction of 8 with 9, 11, or 12 provided 1-azahelicenes 10, 1, or 13, respectively. The scalability of this Scheme 1. Synthesis design.Scheme 2. Syntheses of 1-azahelicenes: a) NaHMDS, DMF, 78 %; b) [PdCl 2 (Ph 3 P) 2 ], (Me 3 Sn-) 2 , PhMe, 77 %; c) Pd(II) catalyst, [12] NBS, CH 3 CN, 84 %; d) benzoyl peroxide, NBS, PhH, 71 %; e) 2-nitropropane,...

2-Aminopyridinium ions were found to activate nitroalkenes toward conjugate addition of heteroaromatic compounds with low catalyst loadings and the Diels-Alder reaction with the periselectivity opposite to that observed with metal Lewis acids, raising the possibility that a 2-aminopyridinium core might be a promising catalaphore for the asymmetric catalyst design.

The design, synthesis, and study of new catalyst structures have had an enormous impact on chemical synthesis, and continue to be a central challenge in asymmetric catalysis.[1]We recently described that a 2-aminopyridinium ion might be a promising catalaphore [2] for the design of new asymmetric hydrogen-bond donor catalysts. [3] In that connection, we became interested in 1-aza [6]helicene [4] 1 as a chiraphore [2] because a first-order analysis of the crystal structure of an analogous 1,16-diaza[6]helicene [5] suggests that its pyridine ring is well-desymmetrized in terms of both top-from-bottom and left-from-right differentiations. To our knowledge, the application of 1 and analogous helical chiral pyridines [5][6][7] in asymmetric catalysis has not been studied, even though 1 has been known in the literature since 1975.[4d] In this context, we were prompted to develop an efficient synthesis of 1-azahelicenes, which allows systematic structural variation-important for the elucidation of the relationship between catalyst structure, reactivity, and selectivity-and to exploit them as chiraphores. In view of the utility of helical chiral pyridines such as 1, it occurred to us that the corresponding pyridine N-oxides might prove to be effective asymmetric catalysts.[8] Herein, we describe the scalable synthesis of 1-azahelicenes and the structural characterization of the corresponding N-oxides, and we apply this new family of compounds to the catalytic enantioselective desymmetrization of meso epoxides (see Table 1). This study provides the first report of the application of azahelicenes in asymmetric catalysis. [9] An examination of the structure of 1 suggests that the chiral environment in the vicinity of the nitrogen atom can be tuned by structural modification at cabon atoms 11-16. Therefore, we devised a convergent synthetic route to 1 in which benzoquinoline unit 2 and C11-C16 unit 3 could be expeditiously united (Scheme 1). This strategy would allow ready access to the necessary 1-azahelicene derivatives by simply replacing 3 with its readily available structural analogues, such as 9 and 12 (Scheme 2). Preparation of key unit 8 starts from commercially available pyridine 4 and phosphonium salt 5, which was readily synthesized in three steps from commercially available 2-bromo-4-methyl benzaldehyde. The highly Z-selective Wittig reaction [6b, 10] of 4 and 5 and subsequent Stille-Kelly reaction [5,11] provided benzoquinoline 6. The catalytic C À H functionalization method developed by Sanford and co-workers [12] readily converted 6 into 7 from which 8 was obtained in an ordinary way. The second sequence of the highly Z-selective Wittig reaction and the Stille-Kelly reaction of 8 with 9, 11, or 12 provided 1-azahelicenes 10, 1, or 13, respectively. The scalability of this Scheme 1. Synthesis design.Scheme 2. Syntheses of 1-azahelicenes: a) NaHMDS, DMF, 78 %; b) [PdCl 2 (Ph 3 P) 2 ], (Me 3 Sn-) 2 , PhMe, 77 %; c) Pd(II) catalyst, [12] NBS, CH 3 CN, 84 %; d) benzoyl peroxide, NBS, PhH, 71 %; e) 2-nitropropane,...

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