Reaction Route of Nucleophilic Addition to Carbonyl Compounds : Intermediate, Transition State and Selectivity

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A carbonyl addition reaction, in general, proceeds by way of either a polar direct nucleophilic attack in one step or a two-step process going through a radical ion intermediate. In this project, the mechanism of the addition reaction of a series of nucleophlies including Wittig reagents and organolithium reagents (MeLi.PhLi, CH_2=CHCH_2Li, PhSCH_2Li, LiCH_2CN,and (CH_3) _3CCH_2C (OLi) =CH_2) with benzophenone and benzaldehyde. As for the organilithium reagents, it was found that the reaction of lithium pinacolone enolate with benzaldehyde goes through the polar mechansim whereas the reactions of other Li reagets with benzaldehyde and benzophenone proceed via the rate-determining electron transfer mechanism. The mechanistic difference correlates with the stability of the reagents measured by the intrinsic acidity of the conjugative acids of R anions in the gas phase. The intrinsic acidity of R-H can be estimated from the gas phase heat of formation from the data compiled in the literature : 416.8kcal/mol (R=Me), 400.8 (Ph), 390.8 (CH_2=CHCH_2), 381.6 (PhSCH_2), 372.8 (NCCH_2), and 368.0 ((CH_3) _3CC (=O) CH_2). The enolate reagent whose conjugate acids the most acidic reacts with benzaldehyde via the polar mechanism whereas the reagents whose conjugate acids are less acidic go through the ET process. It is thus implied that the rate of the ET step depends more on the reactivity of a nucleophile than the rate of the PL step and that the crossing points is in between cyanomethyllithium and lithium pinacolone enolate for the reaction of the present series of the reagents with benzaldehyde.