Secondary deuterium kinetic isotope effects in irreversible additions of hydride and carbon nucleophiles to aldehydes: A spectrum of transition states from complete bond formation to single electron transfer

The competitive kinetics of hydride and organometallic additions to benzaldehyde-H and -D were determined at -78 degrees C using LiAlH4, LiBEt3H, NaBH4, LiBH4, LiAl(O-tert-butoxy)(3)H, NaB(OMe)(3)H, NaB(OAc)(3)H (at 20 degrees C). methyl, phenyl, and allyl Grignard, and methyl-, phenyl-, n-butyl-, tert-butyl-, and allyllithium. The additions of hydride were found to have an inverse secondary deuterium kinetic isotope effects in all cases, but the magnitude of the effect varied inversely with the apparent reactivity of the hydride. In the additions of methyl Grignard reagent and of methyllithium and phenyllithium, inverse secondary deuterium isotope effects were observed; little if any isotope effect was observed with phenyl Grignard or n-butyl- and tert-butyllithium. With allyl Grignard and allyllithium, a normal secondary deuterium kinetic isotope effect was observed. The results indicate that rate-determining single-electron transfer occurs with allyl reagents, but direct nucleophilic reaction occurs with all of the other reagents, with the extent of bond formation dependent on the re activity of the reagent. In the addition of methyllithium to cyclohexanecarboxaldehyde, a less inverse secondary deuterium kinetic isotope effect was observed than that observed in the addition of methyllithium to benzaldehyde, and allyllithium addition to cyclohexanecarboxaldehyde had a kinetic isotope effect near unity. The data with organometallic additions, which are not incompatible with observations of carbonyl carbon isotope effects, suggest that electrochemically determined redox potentials which indicate endoergonic electron transfer with energies less than ca. 13 kcal/mol allow electron-transfer mechanisms to compete well with direct polar additions to aldehydes, provided that the reagent is highly stabilized, like allyl species. Methyl-and phenyllithium and methyl and phenyl Grignard reagents are estimated to undergo electron transfer with endoergonicities greater than 30 kcal/mol with benzaldehyde, so these react by direct polar additions. A working hypothesis is that butyllithium reagents undergo polar additions, despite redox potentials which indicate less than 13 kcal/mol endoergonic electron transfer, because of the great exoergonicity associated with the (t)wo-electron addition, which is responsible for a low barrier for polar reactions.