Asymmetric Synthesis of Tertiary Alcohols and Thiols via Nonstabilized Tertiary α-Oxy- and α-Thio-Substituted Organolithium Species.

Alexander P Pulis,Varinder K Aggarwal,Daniele Leonori,Ana Varela,Cinzia Citti,Pradip Songara

doi:10.1002/anie.201706722

Alexander P Pulis, Varinder K Aggarwal + Show 4 more

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https://doi.org/10.1002/anie.201706722

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Abstract

Nonstabilized α‐O‐substituted tertiary organolithium species are difficult to generate, and the α‐S‐substituted analogues are configurationally unstable. We now report that they can both be generated easily and trapped with a range of electrophiles with high enantioselectivity, providing ready access to a range of enantioenriched tertiary alcohols and thiols. The configurational stability of the α‐S‐organolithium species was enhanced by using a less coordinating solvent and short reaction times.

Highlights

Nonstabilized a-O-substituted tertiary organolithium species are difficult to generate, and the a-S-substituted analogues are configurationally unstable
Chiral a-heteroatom (O, N, and S)-substituted organolithium compounds are a versatile class of nucleophiles that are useful in the asymmetric synthesis of chiral alcohols, amines, and thiols.[1]
The use of secondary and mesomerically stabilized tertiary a-O- and a-S-substituted organolithium reagents in synthesis is well established,[1c–e] the use of non-mesomerically stabilized tertiary reagents is not. This discontinuity is due to contrasting problematic features governing a-O- and a-S-substituted organolithium species

Summary

Introduction

Nonstabilized a-O-substituted tertiary organolithium species are difficult to generate, and the a-S-substituted analogues are configurationally unstable. We have discovered reaction conditions for the generation of enantioenriched, tertiary, nonstabilized a-Sorganolithium compounds and report their subsequent trapping with electrophiles in high enantioselectivity (Scheme 1 C).

Results

Conclusion