Regio- and Stereoselective Synthesis of Multi-Alkylated Allylic Boronates through Three-Component Coupling Reactions between Allenes, Alkyl Halides, and a Diboron Reagent

Abstract

Multisubstituted allylic boronates are attractive and valuable precursors for the rapid and stereoselective construction of densely substituted carbon skeletons. Herein, we report the first synthetic approach for differentially 2,3,3-trialkyl-substituted allylic boronates that contain a stereodefined tetrasubstituted alkene structure. Copper­(I)-catalyzed regio- and stereoselective three-component coupling reactions between gem-dialkylallenes, alkyl halides, and a diboron reagent afforded sterically congested allylic boronates. The allylboration of aldehydes diastereoselectively furnished the corresponding homoallylic alcohols that bear a quaternary carbon. A computational study revealed that the selectivity-determining mechanism was correlated to the coordination of a boryl copper­(I) species to the allene substrate as well as the borylcupration step.

Practical Synthesis of Chiral Allylboronates by Asymmetric 1,1‐Difunctionalization of Terminal Alkenes

“…Chiral homoallyl alcohol ( 5 ) was prepared through the addition of allylboronate 4 a to an aldehyde [11] . A homoallylic alcohol with an allylic stereocenter ( 6 ) was obtained by a Matteson homologation [25] . An all carbon quaternary stereogenic center ( 7 ) was constructed using a palladium‐catalyzed cross‐coupling protocol reported by the Morken group [12] and a homoallyl alcohol with two adjacent carbon stereocenters ( 8 ) was afforded by unsymmetrical allyl addition of the 1,1‐disubstituted allylboronate product to benzaldehyde [26]…”

Recent Advances in Non-Precious Metal Catalysis

“…In terms of recent advances in C−B bond formation catalyzed by Cu catalysis, Ito and co-workers reported an approach of three-component coupling reactions between allenes, alkyl halides, and B 2 (pin) 2 to synthesize multisubstituted allylic boronates regio-and stereoselectively. 42 Previously, the 1,2-addition of Cu−B(pin) to an allene usually generated allyl copper species with B(pin) at the C(2) position. In this study, the proper choice of ligand revealed the possibility of forming an alkenyl copper species that can further react with an alkyl halide to generate tetrasubstituted allylic boronates.…”

“…In terms of recent advances in C–B bond formation catalyzed by Cu catalysis, Ito and co-workers reported an approach of three-component coupling reactions between allenes, alkyl halides, and B 2 (pin) 2 to synthesize multisubstituted allylic boronates regio- and stereoselectively . Previously, the 1,2-addition of Cu–B­(pin) to an allene usually generated allyl copper species with B­(pin) at the C(2) position.…”

Regioselectivity Switch Towards the Development of Innovative Diels‐Alder Cycloaddition and Productive Applications in Organic Synthesis

“…The enantiomerically enriched allylboronates were easily accessed via variety of pathways (general pathway shown in Scheme 7a) [86–90] . Allylic boronates are versatile intermediates in a range of valuable synthetic transformations due to their promising stability and reactivity [91–95] . However, the particular challenge in accomplishing a stereospecific and regioselective cross‐coupling reaction is not only maintaining enantiomeric purity, but also controlling the regiochemical outcomes in the same sequence [96] .…”

“…[86][87][88][89][90] Allylic boronates are versatile intermediates in a range of valuable synthetic transformations due to their promising stability and reactivity. [91][92][93][94][95] However, the particular challenge in accomplishing a stereospecific and regioselective cross-coupling reaction is not only maintaining enantiomeric purity, but also controlling the regiochemical outcomes in the same sequence. [96] Towards this end, authors were successful in keeping both aspects and reported a novel regio-and stereocontrolled coupling ap-proach.…”