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 benzald ehyde-H and -D were determined at -78 degrees C using LiAlH4, LiBEt3H, NaBH 4, LiBH4, LiAl(O-tert-butoxy)(3)H, NaB(OMe)(3)H, NaB(OAc)(3)H (at 20 degree s C). methyl, phenyl, and allyl Grignard, and methyl-, phenyl-, n-butyl-, t ert-butyl-, and allyllithium. The additions of hydride were found to have a n inverse secondary deuterium kinetic isotope effects in all cases, but the magnitude of the effect varied inversely with the apparent reactivity of t he hydride. In the additions of methyl Grignard reagent and of methyllithiu m and phenyllithium, inverse secondary deuterium isotope effects were obser ved; little if any isotope effect was observed with phenyl Grignard or n-bu tyl- and tert-butyllithium. With allyl Grignard and allyllithium, a normal secondary deuterium kinetic isotope effect was observed. The results indica te that rate-determining single-electron transfer occurs with allyl reagent s, but direct nucleophilic reaction occurs with all of the other reagents, with the extent of bond formation dependent on the re activity of the reage nt. In the addition of methyllithium to cyclohexanecarboxaldehyde, a less i nverse secondary deuterium kinetic isotope effect was observed than that ob served in the addition of methyllithium to benzaldehyde, and allyllithium a ddition to cyclohexanecarboxaldehyde had a kinetic isotope effect near unit y. The data with organometallic additions, which are not incompatible with observations of carbonyl carbon isotope effects, suggest that electrochemic ally determined redox potentials which indicate endoergonic electron transf er with energies less than ca. 13 kcal/mol allow electron-transfer mechanis ms to compete well with direct polar additions to aldehydes, provided that the reagent is highly stabilized, like allyl species. Methyl-and phenyllith ium and methyl and phenyl Grignard reagents are estimated to undergo electr on transfer with endoergonicities greater than 30 kcal/mol with benzaldehyd e, so these react by direct polar additions. A working hypothesis is that b utyllithium reagents undergo polar additions, despite redox potentials whic h 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.