Facile access to functionalized chiral secondary benzylic boronic esters via catalytic asymmetric hydroboration

Authors

Suman Chakrabarty, University of Nebraska-LincolnFollow
Hector Palencia, University of Nebraska KearneyFollow
Martha D. Morton, University of Nebraska–LincolnFollow
Ryan O. Carr, University of Nebraska-Lincoln
James M. Takacs, University of Nebraska - LincolnFollow

ORCID IDs

Suman Chakrabarty, http://orcid.org/0000-0002-6611-3839

Hector Palencia, http://orcid.org/0000-0001-8634-8232

Martha D. Morton, http://orcid.org/0000-0002-6411-1733

Ryan O. Carr http://orcid.org/0000-0002-4833-9885

James M. Takacs http://orcid.org/0000-0002-1903-6535

Date of this Version

2019

Citation

Chem. Sci., 2019, 10, 4854–4861

DOI: 10.1039/c8sc05613g

Comments

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.

Abstract

Allylic and homoallylic phosphonates bearing an aryl or heteroaryl substituent at the γ- or δ-position undergo rhodium-catalyzed asymmetric hydroboration by pinacolborane to give functionalized chiral secondary benzylic boronic esters in yields up to 86% and enantiomer ratios up to 99 : 1. Compared to minimally-functionalized terminal and 1,1-disubstituted vinyl arenes, there are relatively few reports of efficient catalytic asymmetric hydroboration (CAHB) of more highly functionalized internal alkenes. Phosphonate substrates bearing a variety of common heterocyclic ring systems, including furan, indole, pyrrole and thiophene derivatives, as well as those bearing basic nitrogen substituents (e.g., morpholine and pyrazine) are tolerated, although donor substituents positioned in close proximity of the alkene can influence the course of the reaction. Stereoisomeric (E)- and (Z)-substrates afford the same major enantiomer of the borated product. Deuterium-labelling studies reveal that rapid (Z)- to (E)-alkene isomerization accounts for the observed (E/Z)-stereoconvergence during CAHB. The synthetic utility of the chiral boronic ester products is illustrated by stereospecific C–B bond transformations including stereoretentive electrophile promoted 1,2-B-to-C migrations, stereoinvertive S_E2 reactions of boron-ate complexes with electrophiles, and stereoretentive palladium- and rhodium-catalyzed cross-coupling protocols.