Organocatalytic Synthesis of α-Trifluoromethyl Allylboronic Acids by Enantioselective 1,2-Borotropic Migration.

Sybrand J T Jonker,Marie Deliaval,Lars Eriksson,Kálmán J Szabó,Tautvydas Kireilis,Ramasamy Jayarajan

doi:10.1021/jacs.0c09923

Sybrand J T Jonker, Marie Deliaval + Show 4 more

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https://doi.org/10.1021/jacs.0c09923

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Abstract

Chiral α-substituted allylboronic acids were synthesized by asymmetric homologation of alkenylboronic acids using CF3/TMS-diazomethanes in the presence of BINOL catalyst and ethanol. The chiral α-substituted allylboronic acids were reacted with aldehydes or oxidized to alcohols in situ with a high degree of chirality transfer. The oxygen-sensitive allylboronic acids can be purified via their isolated diaminonaphthalene (DanH)-protected derivatives. The highly reactive purified allylboronic acids reacted in a self-catalyzed reaction at room temperature with ketones, imines, and indoles to give congested trifluoromethylated homoallylic alcohols/amines with up to three contiguous stereocenters.

Highlights

Chiral α-substituted allylboronic acids were synthesized by asymmetric homologation of alkenylboronic acids using CF3/TMS-diazomethanes in the presence of BINOL catalyst and ethanol
Chiral allylboronic acids[1] are ideal reagents for asymmetric synthesis because of their high reactivity in self-catalyzed allylboration reactions that occur with high stereochemical fidelity
We hypothesized that the synthesis of chiral allylboronic acids may be devised by using an organocatalytic homologation strategy

Summary

Introduction

Chiral α-substituted allylboronic acids were synthesized by asymmetric homologation of alkenylboronic acids using CF3/TMS-diazomethanes in the presence of BINOL catalyst and ethanol. We present a new methodology for the synthesis of chiral α-CF3 allylboronic acids (Figure 1e). When a commercially available alkenylboronic acid was used as the substrate (entry 7), the reaction proceeded in poor yield (18%) but with excellent selectivity (97% ee).

Results

Conclusion