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Enantioselective and Diastereoselective Tsuji–Trost Allylic Alkylation of Lactones: An Experimental and Computational Study
Author(s) -
Meletis Panos,
Patil Mahendra,
Thiel Walter,
Frank Walter,
Braun Manfred
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201101406
Subject(s) - tsuji–trost reaction , enantioselective synthesis , chemistry , allylic rearrangement , nucleophile , alkylation , selectivity , adduct , density functional theory , stereochemistry , medicinal chemistry , computational chemistry , catalysis , organic chemistry
The Tsuji–Trost protocol has been successfully employed for the allylic alkylation of preformed lactone enolates. It has been demonstrated that this Pd‐catalyzed reaction can be carried out in an enantio‐ and diastereoselective manner. The use of additives, such as LiCl, was found to be crucial for reaching high levels of product selectivity. For one particular pair of reactants, density functional theory was used to investigate the mechanism of the nucleophilic addition. Among the five pathways considered, the reaction between an (allyl)Pd(BINAP) complex and a LiCl–lithium enolate adduct is predicted to be the most likely route for CC bond formation. LiCl plays a key role as the connecting link between the noble metal and the enolate in the kinetically favored transition state. The computed diastereoselectivity ratio is in good agreement with the experimentally observed value.