Catalytic Enantioselective Synthesis of Allylic Boronates Bearing a Trisubstituted Alkenyl Fluoride and Related Derivatives

Abstract

The first catalytic method for diastereo‐ and enantioselective synthesis of allylic boronates bearing a Z‐trisubstituted alkenyl fluoride is disclosed. Boryl substitution is performed with either a Z‐ or E‐allyldifluoride and is catalyzed by bisphosphine/Cu complexes, affording products in up to 99 % yield with >98:2 Z/E selectivity and 99:1 enantiomeric ratio. A variety of subsequent modifications are feasible, and notable examples are diastereoselective additions to aldehydes/aldimines to access homoallylic alcohols/amines containing a fluorosubstituted stereogenic quaternary center.

Catalytic Enantioselective Allylic C–F Bond Functionalization

“…In 2019, the enantioselective Cu-catalyzed defluoroborylation was also extended to difluoromethyl-substituted alkenes by Ito and Hoveyda (Scheme 9). 16 In this system, both isomers such as Z-or E-allyldifluoride substrates could convert into the corresponding (Z )-γ-monofluoroallylic boronates with high stereoselectivity. Using chiral bisphosphine 20 as ligand, the selective (S)-borylated products were obtained with high enantioselectivity.…”

Transition‐Metal‐Catalyzed Synthesis of Chiral Allylboronates†

“…Defluoroborylation of trifluoromethyl‐substituted alkenes has paved the way for the synthesis of gem‐difluoroallylboronates. [ 61‐67 ] In 2018, the Ito group and the Shi group achieved the synthesis of enantiopure γ , γ ‐gem‐difluoroallylboronates via a copper‐catalyzed asymmetric γ ‐boryl substitution of CF 3 ‐substituted alkenes, respectively (Scheme 11). [ 68‐69 ] Furthermore, difluoromethylene‐containing homoallylic alcohols can be readily obtained via a borylation/allylboration process [ 68 ] .…”

Beyond Carbon: Enantioselective and Enantiospecific Reactions with Catalytically Generated Boryl- and Silylcopper Intermediates

“…Just recently, Ito and Hoveyda extended this strategy to allylic difluorides by modification of the reaction setup ( Scheme 4 b). 85 Either ( E )- 6 or ( Z )- 7 participated in the borylative substitution under slightly different conditions. In addition to high enantioselectivity, good Z / E selectivity was also observed in both reactions.…”