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Computational Study of the Mechanism and Selectivity of Palladium‐Catalyzed Propargylic Substitution with Phosphorus Nucleophiles
Author(s) -
JiménezHalla J. Oscar C.,
Kalek Marcin,
Stawinski Jacek,
Himo Fahmi
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.201201026
Subject(s) - nucleophile , chemistry , propargyl , phosphonate , catalysis , selectivity , palladium , transition state , ligand (biochemistry) , heteroatom , medicinal chemistry , combinatorial chemistry , computational chemistry , stereochemistry , organic chemistry , alkyl , biochemistry , receptor
Abstract The mechanism and sources of selectivity in the palladium‐catalyzed propargylic substitution reaction that involves phosphorus nucleophiles, and which yields predominantly allenylphosphonates and related compounds, have been studied computationally by means of density functional theory. Full free‐energy profiles are computed for both H‐phosphonate and H‐phosphonothioate substrates. The calculations show that the special behavior of H‐phosphonates among other heteroatom nucleophiles is indeed reflected in higher energy barriers for the attack on the central carbon atom of the allenyl/propargyl ligand relative to the ligand‐exchange pathway, which leads to the experimentally observed products. It is argued that, to explain the preference of allenyl‐ versus propargyl‐phosphonate/phosphonothioate formation in reactions that involve H‐phosphonates and H‐phosphonothioates, analysis of the complete free‐energy surfaces is necessary, because the product ratio is determined by different transition states in the respective branches of the catalytic cycle. In addition, these transition states change in going from a H‐phosphonate to a H‐phosphonothioate nucleophile.