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On the Relative Preference of Enamine/Iminium Pathways in an Organocatalytic Michael Addition Reaction
Author(s) -
Patil Mahendra P.,
Sunoj Raghavan B.
Publication year - 2009
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200800351
Subject(s) - iminium , enamine , chemistry , michael reaction , organocatalysis , nucleophile , ketone , methyl vinyl ketone , electrophile , nucleophilic addition , pyrrolidine , reaction mechanism , catalysis , solvent effects , organic chemistry , solvent , enantioselective synthesis
The right path : The mechanism of organocatalyzed Michael addition between propanal and methyl vinyl ketone is investigated using the density functional and ab intio methods. The kinetic preference for the formation of key intermediates is established in an effort to identify the competing pathways associated with the reaction. The effect of co‐catalyst/protic solvent on the energetics of the reaction is also studiedThe mechanism of the organocatalyzed Michael addition between propanal and methyl vinyl ketone is investigated using the density functional and ab intio methods. Different modes of substrate activation offered by a secondary amine (pyrrolidine) organocatalyst are reported. The electrophilic activation of enone ( P‐I ) through the formation of an iminium ion, and nucleophilic activation of propanal ( P‐II ) in the form of enamine have been examined by identifying the corresponding transition states. The kinetic preference for the formation of key intermediates is established in an effort to identify the competing pathways associated with the title reaction. A comparison of barriers associated with different pathways as well as intermediate formation allows us to provide a suitable mechanistic rationale for Michael addition reactions catalyzed by a secondary amine. The overall barriers for the CC bond formation pathways involving enol or iminium intermediates are identified as higher than the enamine pathway. Additionally, the generation of iminium is found to be less favored as compared to enamine formation. The effect of co‐catalyst/protic solvent on the energetics of the overall reaction is also studied using the cluster continuum approach. Significant reduction in the activation energies for each step of the reaction is predicted for the solvent‐assisted models. The co‐catalyst assisted addition of propanal–enamine to methyl vinyl ketone is identified as the most preferred pathway ( P‐IV ) for the Michael addition reaction. The results are in concurrence with the available experimental reports on the rate acceleration by the use of a co‐catalyst in this reaction.