Copper Hydride‐Catalyzed Conjugate Reduction‐Aldol Addition Domino Reaction of α,β‐Unsaturated Carboxylates with Ketones

Abstract

Copper hydride-catalyzed conjugate reduction-intermolecular aldol addition domino reactions were realized using α,β-unsaturated carboxylates as hydride acceptors and a silane as the reducing reagent. High diastereoselectivities were achieved with 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene as the ligand and tert-butyl acrylate as the hydride acceptor.

Copper Hydride Catalyzed Reductive Aldol Addition/Lactonization Domino Reactions of α,β-Unsaturated Diesters

“…23 Accordingly, we used substituted acetophenones to explore the generality of the current reaction and its selectivity. As shown in Table 2, good to excellent yields were obtained in all the cases.…”

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

“…Our previous results suggested that higher diastereoselectivity could be achieved with hindered acrylate in the copper hydride-catalyzed reductive aldolization of acetophenone [ 19 ]. Therefore, tert- butyl acrylate ( 1d ) was used to replace methyl acrylate, and several biphosphorous ligands were screened for improving the diastereoselectivity ( Table 3 ).…”

“…Copper-catalyzed reductive intermolecular aldolization reactions have been discussed previously [ 17 – 19 ]. Constantino has demonstrated that aldol reactions of enolates with ketones or aldehydes are much faster than the Claisen condensation [ 20 ].…”

Copper-Catalyzed Dimerization/Cyclization of Itaconates

“…CuF(PPh 3 ) 3 ·2MeOH, with good solubility and high activity in catalyzing conjugate addition and the subsequent reaction [25,26,27], was employed to catalyze the reaction of 1 a , and a 72% yield of 2a was obtained. Interestingly, the cis - 2a isomer was the dominant one with a 61:39 cis -/ trans -ratio (entry 8).…”

“…Previous results indicated that using bulky alkyl α,β-unsaturated esters gave higher diastereoselectivity in reductive aldol domino reactions [26]. Accordingly, we resorted to bulky alkyl groups in the itaconate.…”