Kinetic Resolution of 2H-Azirines by Asymmetric Allylation Reactions

Abstract

A practical and efficient method for kinetic resolution of azirines has been achieved via asymmetric allylations of racemic 2H-azirines with boron allylation reagents enabled by Bi­(OAc)3/chiral phosphoric acid catalysis. A broad range of azirine substrates with electron-withdrawing and electron-donating groups at the two aromatic rings, as well as the different allyl boron reagents, were well tolerated in this methodology, providing high kinetic resolution performance (with an s-factor of up to 127) under very mild reaction conditions with only 2 mol % catalyst loading. In addition, the synthetic utility of the protocol was proved by the scaled-up reaction and transformations of the product. Computational studies suggested that the various weak interactions are essential for enantioselectivity. Moreover, the effect of different metal acetates and counteranions on the reaction outcome was also interpreted by the calculations.

Modular approach to non-aromatic and aromatic pyrroles through gold-catalyzed [3 + 2] cycloaddition of 2H-azirines and ynamides

“…2 H -Azirines, as easily accessible building blocks, have been actively employed for an easy increase of the molecular complexity. 37–43 Owing to the intrinsic strain, 2 H -azirines can undergo a facile ring opening, and thus function as C–C–N or C–N–C triatomic synthons. In turn, ynamides are customizable, highly reactive alkynes, i.e.…”

Recent Advances in Asymmetric Catalysis Using p‐Block Elements

“…The developed protocol was applied to the synthesis of (+)‐AG‐041R as a gastrin receptor antagonist, and the total synthesis of (−)‐psychotriasine as naturally occurring bioactive molecules. The same group also reported the highly enantioselective allylation of azirins from a racemic mixture of (2 H )‐azirines 89 using the same catalytic system (Scheme 21b) [72] . As described by the authors, the Bi‐CPA catalyst first bound to the allyl species 86 which then reacted with the racemic azirins at different rates resulting in excellent kinetic resolution ( s ‐factor of up to 127).…”

“…The same group also reported the highly enantioselective allylation of azirins from a racemic mixture of (2H)-azirines 89 using the same catalytic system (Scheme 21b). [72] As described by the authors, the Bi-CPA catalyst first bound to the allyl species 86 which then reacted with the racemic azirins at different rates resulting in excellent kinetic resolution (s-factor of up to 127).…”

Asymmetric difluorocarbonylation reactions of non-active imines catalyzed by Bi(OAc)3/chiral phosphoric acid

“…According to our previous work, 19,20 a plausible mechanistic pathway was rationalized as outlined in Scheme 5a. First, an anion exchange between CPA ( S )- 6c and Bi(OAc) 3 occurs beforehand to form the chiral phosphate diacetate Bi( iii ) as the active catalytic species.…”

“…17 Since fluorine has unique and excellent properties, 2 it is very meaningful to introduce fluorine atoms into the dibenzo[ b,f ][1,4]oxazepine framework. Recently, we have developed a Bi(OAc) 3 /chiral phosphoric acid (CPA) 18 catalytic system, which was successfully applied in the asymmetric allylation of the CX (X = N or O) bond 19 and the asymmetric Friedel–Crafts alkylation of phenols. 20 We found that chiral bismuth phosphate catalysts have some unique advantages (Scheme 2c).…”