Catalytic Asymmetric Aziridination with Borate Catalysts Derived from VANOL and VAPOL Ligands: Scope and Mechanistic Studies

Abstract

An extended study of the scope and mechanism of the catalytic asymmetric aziridination of imines with ethyl diazoacetate mediated by catalysts prepared from the VANOL and VAPOL ligands and triphenylborate is described. Nonlinear studies with scalemic VANOL and VAPOL reveal an essentially linear relationship between the optical purity of the ligand and the product suggesting that the catalyst incorporates a single molecule of the ligand. Two species are present in the catalyst prepared from B(OPh)(3) and either VANOL or VAPOL as revealed by (1)H NMR studies. Mass spectral analysis of the catalyst mixture suggests that one of the species involves one ligand molecule and one boron atom (B1) and the other involves one ligand and two boron atoms (B2). The latter can be formulated as either a linear or cyclic pyroborate and the (11)B NMR spectrum is most consistent with the linear pyroborate structure. Several new protocols for catalyst preparation are developed which allow for the generation of mixtures of the B1 and B2 catalysts in ratios that range from 10:1 to 1:20. Studies with catalysts enriched in the B1 and B2 species reveal that the B2 catalyst is the active catalyst in the VAPOL catalyzed asymmetric aziridination reaction giving significantly higher asymmetric inductions and rates than the B1 catalyst. The difference is not as pronounced in the VANOL series. A series of 12 different imines were surveyed with the optimal catalyst preparation procedure with the finding that the asymmetric inductions are in the low to mid 90s for aromatic imines and in the mid 80s to low 90s for aliphatic imines for both VANOL and VAPOL catalysts. Nonetheless, the crystallinity of the N-benzhydryl aziridines is such that nearly all of the 12 aziridine products screened can be brought to >99 % ee with a single recrystallization.

Catalytic Asymmetric Aziridination with Catalysts Derived from VAPOL and VANOL

“…24 For example, the induction for the reaction of the phenyl-substituted imine 1a was originally reported as 95% ee with 10 mol% catalyst in dichloromethane 19 but now we consistently observe 89% ee with this substrate ( Table 7, entry 1). Since the 95% ee for imine 1a was reproducible at the time, considerable effort was put forth to find the source of the difference when it was first noticed in 2002.…”

“…24 Although the observed linearity does not disprove the association of the boron with two or more ligands, nonetheless, the results of these experiments suggest that it is likely that only one molecule of the VANOL or VAPOL ligand is involved in the active catalyst.…”

“…24 Catalysts enriched in the B1 species could be obtained by slow addition of triphenyl borate to VAPOL (Table 8, entry 2) or, better, by reaction of VAPOL with 1 equivalent of BH 3 ·SMe 2 and 1 equivalent of phenol to give a 10:1 mixture in favor of B1 (Table 8, entry 1). The latter procedure could be used to give an 8:1 mixture of B1/B2 catalyst for VANOL (Table 8, entry 5).…”

“…24 All reactions were performed with 5 mol% VAPOL or VANOL catalyst. The aziridination of the same set of imines was also examined in dichloromethane.…”

Three‐Membered Heterocycles. Structure and Reactivity

“…Some noteworthy asymmetric protocols have been developed using diazoesters, particularly those employing vaulted biaryl ligands [103]. For example, a catalyst derived from (S)-VAPOL (51) and BH 3 ÁTHF complex promotes an enantioselective aziridination reaction between ethyl diazoacetate and N-diphenylmethyl p-bromobenzaldimine (52) with very good yields, almost exclusive cis selectivity and excellent enantiomeric excess (Scheme 2.15).…”