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Origin of Selectivity of Tsuji–Trost Allylic Alkylation of Lactones: Highly Ordered Transition States with Lithium‐Containing Enolates
Author(s) -
Patil Mahendra,
Thiel Walter
Publication year - 2012
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.201201267
Subject(s) - chemistry , selectivity , transition state , tsuji–trost reaction , nucleophile , allylic rearrangement , steric effects , lithium amide , catalysis , lithium (medication) , density functional theory , adduct , electronic effect , computational chemistry , combinatorial chemistry , enantioselective synthesis , stereochemistry , organic chemistry , medicine , endocrinology
We report computational investigations on the mechanism and the selectivity of Pd‐catalyzed allylic alkylation of γ‐valerolactone. Density functional calculations using the B3LYP functional are performed on the selectivity‐determining nucleophilic addition step of this reaction. The B3LYP results of commonly assumed pathways fail to reproduce the observed selectivity of the reaction. Therefore, alternative pathways are considered for the nucleophilic addition step, to explain the experimentally established role of the additives LiCl and lithium diisopropyl amide (LDA) in the Pd‐catalyzed reaction. These pathways involve different approaches of the enolate toward the η 3 ‐allylpalladium complex that are mainly guided by stabilizing Cl δ− ⋅⋅⋅Li δ+ ⋅⋅⋅O(enolate) interactions in the transition state. In the calculations, the experimentally observed trans ‐product selectivity for the prototypical reaction with ( S )‐BINAP ligands is found only when assuming the addition of a “mixed” Li‐enolate/LiCl adduct to the η 3 ‐allylpalladium complex. This mechanism provides a reasonable explanation for the experimental results and sheds light on the role of LiCl in the reaction. The analysis of the different transition‐state models allows us to identify steric and electronic factors that stabilize or destabilize the relevant diastereomeric transition states. Calculations for different combinations of substrates (γ‐valerolactone and δ‐caprolactone) and catalysts (with ( R )‐ and ( S )‐BINAP ligands) reproduce the experimentally observed selectivities well and thus provide further support for the proposed mechanism.