Redox-enabled direct stereoconvergent heteroarylation of simple alcohols

Yongbing Liu,Yu Zhao,Guoqiang Yang,Zhi-Keng Lin,Ran Tao

doi:10.1038/s41467-021-25268-1

Yongbing Liu, Yu Zhao + Show 3 more

Open Access

https://doi.org/10.1038/s41467-021-25268-1

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Abstract

The direct transformation of racemic feedstock materials to valuable enantiopure compounds is of significant importance for sustainable chemical synthesis. Toward this goal, the radical mechanism has proven uniquely effective in stereoconvergent carbon-carbon bond forming reactions. Here we report a mechanistically distinct redox-enabled strategy for an efficient enantioconvergent coupling of pyrroles with simple racemic secondary alcohols. In such processes, chirality is removed from the substrate via dehydrogenation and reinstalled in the catalytic reduction of a key stabilized cationic intermediate. This strategy provides significant advantage of utilizing simple pyrroles to react with feedstock alcohols without the need for leaving group incorporation. This overall redox-neutral transformation is also highly economical with no additional reagent nor waste generation other than water. In our studies, oxime-derived iridacycle complexes are introduced, which cooperate with a chiral phosphoric acid to enable heteroarylation of alcohols, accessing a wide range of valuable substituted pyrroles in high yield and enantioselectivity.

Highlights

The direct transformation of racemic feedstock materials to valuable enantiopure compounds is of significant importance for sustainable chemical synthesis
As a large number of feedstock materials from nature or the petrochemical industry are racemic, how to convert them to value-added enantiopure compounds in high yield has been pursued as a holy grail in catalysis and synthesis[2]
In an effort to achieve truly practical enantioconvergent C−C bond formation employing all feedstock materials, we considered the redox process as a distinct racemization mechanism to allow more step- and atom-economical heteroarene functionalization

Summary

Introduction

The direct transformation of racemic feedstock materials to valuable enantiopure compounds is of significant importance for sustainable chemical synthesis. The Fu group and others developed a series of highly efficient, enantioconvergent base metal-catalyzed cross-coupling reactions to access a wide range of chiral products from racemic alkyl halides or mesylates (Strategy A, Fig. 1b)[12,13]. We report our development of catalytic enantioconvergent heteroarylation of readily available, unactivated secondary alcohols with pyrroles (Fig. 1d).

Results

Conclusion