Copper‐Catalyzed Asymmetric Allylic Alkylation of β‐Keto Esters with Allylic Alcohols

Abstract

The asymmetric allylic alkylation reaction of b-keto esters catalyzed by copper complex tBuBOX-Cu(OTf) 2 employing allylic alcohols as environmentally friendly electrophilic partner, is herein described. This new protocol renders in general the corresponding allylic products with two consecutive all-carbon stereocenters in good both yields and enantioselectivities and with low to modest diastereoselection. The regioselectivity of the process seems to be governed by the formation of the most stable olefin according to the results obtained when non-symmetrically substituted alcohols were employed. The scope, limitations and mechanistic aspects of the process are also discussed.

Hexafluoroisopropanol‐Promoted Metal‐Free Allylation of Silyl Enol Ethers with Allylic Alcohols

“…In all the cases a regioisomeric mixture of products were obtained. [9,10] Firstly, alcohol 1b, which would form a quite reactive carbocationic specie (in comparison with that obtained with alcohol 1a), was submitted to the optimal reaction condition using such enol ethers. Thus, when acetophenonederived enol ether was tested, low conversion towards product 3ba was achieved.…”

“…In both cases, the product with the isomerized double bond was obtained as sole regioisomer with modest to good yields (Table 3, entry 13 and 14). [9,10] …”

Enantioselective Formation of Quaternary Centers by Allylic Alkylation with First-Row Transition-Metal Catalysts

“…A further approach with β-ketoesters and allylic alcohols was recently reported by Trillo and Baeza . This time, the bisoxazoline ligand 60 was identified as a suitable ligand, promoting the Cu-catalyzed allylic alkylation of acyclic α-methyl-substituted ketoester 61a with allylic alcohol 62 in moderate diastereo- and enantioselectivity (Scheme ).…”

“…A further approach with β-ketoesters and allylic alcohols was recently reported by Trillo and Baeza. 77 This time, the bisoxazoline ligand 60 was identified as a suitable ligand, promoting the Cu-catalyzed allylic alkylation of acyclic αmethyl-substituted ketoester 61a with allylic alcohol 62 in moderate diastereo-and enantioselectivity (Scheme 23). Although an improved yield and stereoselectivity were observed with the cyclic ketoester 61b, the substrate scope of this protocol was generally limited for the construction of quaternary stereogenic centers.…”

CuI-Mediated Synthesis of Sulfonyl Benzofuran-3-ones and Chroman-4-ones

“…Copper-mediated cyclization reactions that use prefunctionalized substrates for the rapid and efficient construction of structurally diverse benzo-fused heterocyclic frameworks have been recognized as cost-effective alternatives to classic protocols that involve palladium-mediated C–H activation systems . In most copper-mediated chemical bond forming reactions, however, the focus has been on the formation of only one carbon–carbon (C–C) or carbon–heteroatom (C–N, C–O, or C–S for Ullmann-type reactions) bond. In contrast, cascade reactions are highly efficient for forming multiple bonds in a one-pot procedure.…”