Regioselective Cu-Catalyzed Hydroboration of 1,3-Disubstituted-1,3-Dienes: Functionalization of Conjugated Dienes Readily Accessible through Ene–Yne Metathesis

Abstract

A regioselective Cu-catalyzed formal hydroboration of 1,3-disubstituted-1,3-dienes is reported. Highly substituted 1,3-dienes produced through catalytic ene–yne metathesis provided substrates for the regioselective hydroboration with variable substituents conveniently introduced from a 1-alkene and a terminal alkyne. For the achiral reaction, the diphosphine 1,2-bis­(diphenylphosphino)­benzene (dppbz) was used as the ligand. For the enantioselective reaction, EtDuPhos was used as the diphosphine ligand, and good enantioselectivites were obtained in most cases. Control studies showed that the stereoisomeric purity of the 1,3-diene and the Cu­(I) source were key variables that led to the highest regioselectivity. In situ NMR experiments and deuterium quenching confirmed the presence of an allyl copper intermediate, which did not exchange with other 1,3-dienes. A proposed model for the regioselectivity is based on the addition of Cu-B to the 1,3-diene where steric effects in the 3,4-addition are more severe than those in the favored 1,2-addition mode. The products were further functionalized and were employed in a dual-catalytic cross-coupling reaction.

Ligand Control in Co-Catalyzed Regio- and Enantioselective Hydroboration: Homoallyl Secondary Boronates via Uncommon 4,3-Hydroboration of 1,3-Dienes

“…Products from 2-silyloxy ( 5) and 2-acetoxy ( 6) dienes show that these sensitive functional groups can survive under our reaction conditions, which are relatively more tolerant as compared to the corresponding copper-catalyzed protoboration, 9,13 which is carried out with up to 40 mol % of t-BuOK. Both the silyl enol ether ( 5) and the enol acetate (6) are formed in excellent regio-and enantioselectivity.…”

“…An unprotected hydroxyl group on the side chain is acceptable even though the yield of the reaction is somewhat reduced under the standard conditions. The corresponding −OTBS ether or the mesylate restores the reactivity, and very good yields of the corresponding [4,3]adducts are obtained (12,13). Only a single enantiomer is seen in most of these reactions.…”

“…However, this method required aryl substituents at the 4-position for high regioselectivity, and simple alkyl-substituted linear 1,3-dienes lead to poor regioselectivity with [1,4]-adducts formed as the major product. Recently, while our manuscript was in preparation, Diver et al reported [4,3]-hydroborations of 2,4-disubstituted 1,3-dienes using chiral ligands in a Cu-catalyzed protoborylation . This reaction gave good regioselectivities (ranging from 3:1 to 20:1) but modest enantioselectivities (er of 83:17 to 93:7) (Figure C).…”

Cu-Catalyzed Asymmetric Dicarboxylation of 1,3-Dienes with CO2

“…Specifically, we envisioned that Cu-catalyzed boracarboxylation of 1,3-dienes with CO 2 would give carboxylated allyl boronic ester intermediates, which might undergo a subsequent Cu-catalyzed second carboxylation of C–B bonds with CO 2 to give dicarboxylates . However, such a design of Cu self-relay catalysis in a single synthetic operation faces several challenges: (i) it is difficult to achieve high enantioselectivity in asymmetric C–C bond formation with CO 2 due to its low reactivity and weak coordination ability to transition metals; , (ii) it is a significant challenge to control the regioselectivity toward 1,2-, 1,4-, or 3,4-addition in the difunctionalizing metalation of 1,3-dienes because of the various coordination and insertion modes conceivable for copper catalysis; (iii) high compatibility and efficiency of copper catalysis in these two carboxylations, which are the key to the success of this challenging dicarboxylation, should be achieved; (iv) it is also important to suppress other side reactions, including reduction of CO 2 , hydrocarboxylation, hydroborylation, and C–H bond carboxylation . Herein, we report the first Cu-catalyzed asymmetric dicarboxylation of 1,3-dienes with CO 2 (Figure C).…”

Cu-Catalyzed Enantioselective Protoboration of 2,3-Disubstituted 1,3-Dienes

“…Among notable achievements, typical electrophiles include acyl silanes, aldehydes, ketones, imines, aryl halides, and cyanamides . In contrast, examples of enantioselective protoborations remain scarce ( E + = H + , Figure A) . Even though little is known regarding their exact mechanism, it can be surmised that protonation of the putative Cu–allyl intermediate is likely to be enantio-determining in certain cases and, thereby, adds a layer of complexity to the development of these processes, in particular for acyclic substrates .…”