Enantioselective bromination of axially chiral cyanoarenes in the presence of bifunctional organocatalysts

Yuuki Wada,Seijiro Matsubara,Keisuke Asano,Akira Matsumoto

doi:10.1039/c9ra05532k

Abstract

Enantioselective bromination of axially chiral cyanoarenes bearing high intrinsic rotational barriers via dynamic kinetic resolution using bifunctional organocatalysts is reported. Sequential addition of a brominating reagent in several portions at an optimized temperature was effective in accomplishing high enantioselectivities.

Highlights

Enantioselective bromination of axially chiral cyanoarenes bearing high intrinsic rotational barriers via dynamic kinetic resolution using bifunctional organocatalysts is reported
In 2015, the Miller group reported an elegant example of this type of dynamic kinetic resolution via bromination of 3-arylquinazolin-4(3H)-ones, the rotational barrier of which is $19 kcal molÀ1, by slow addition of a brominating agent.5e Here, we present enantioselective bromination of axially chiral cyanoarenes bearing intrinsic rotational barriers exceeding 18 kcal molÀ1 (Scheme 1)
To the best of our knowledge, there has been no report of a catalytic asymmetric reaction affording axially chiral cyanoarenes,[6] despite their prevalence in bioactive agents[7] and the rich chemistry of cyano compounds as synthetic intermediates.[8]

Summary

Introduction

Enantioselective bromination of axially chiral cyanoarenes bearing high intrinsic rotational barriers via dynamic kinetic resolution using bifunctional organocatalysts is reported. Among recent accomplishments on catalytic atroposelective transformations[4] toward the synthesis of densely substituted axially chiral biaryls, powerful strategies include organocatalytic dynamic kinetic resolution involving ortho-functionalization of existing biaryls via the introduction of additional rotational barriers.[5] In this method, substrates should in principle have rotational barriers low enough to enable fast rotation about the biaryl axis, leading to their rapid racemization.

Results

Conclusion