Isotope Effects and Heavy-Atom Tunneling in the Roush Allylboration of Aldehydes

Abstract

Intermolecular 13 C kinetic isotope effects (KIEs) for the Roush allylboration of p-anisaldehyde were determined using a novel approach. The experimental 13 C KIEs fit qualitatively with the expected rate-limiting cyclic transition state, but they are far higher than theoretical predictions based on conventional transition state theory. This discrepancy is attributed to a substantial contribution of heavy-atom tunneling to the reaction, and this is supported by multidimensional tunneling calculations that reproduce the observed KIEs.Tunneling allows reactive trajectories that do not adhere to the classical limitation of the transition state energy, so that conventional transition state theory (TST) underestimates the reaction rate. Large kinetic isotope effects (KIEs) in hydrogen transfer reactions have often been interpreted as a diagnostic for tunneling through the reaction barrier. 1,2 The extent of tunneling is mass dependent and decreases with increasing mass of the atom. The much larger mass of carbon decreases its tunneling probability and consequently the effect of carbon tunneling on reaction rates is often ignored. As a result, carbon tunneling is much less understood and has been addressed for only a handful of chemical reactions. 2 It has been observed that allowance for tunneling improves the prediction of heavy-atom isotope effects, but tunneling corrections in most reactions not involving hydrogen transfer are very small. As a result, heavy-atom KIE predictions based solely on TST, not allowing for tunneling, are still usually reasonably accurate 3 and sufficient for mechanistic interpretation.We describe here a 13 C isotope effect study of the Roush allylboration reaction. The experimental KIEs in this reaction are much larger than expected from TST, and theoretical analysis suggests that the large KIEs result from a surprisingly large contribution of tunneling to the reaction. The results provide several insights into the role of heavy-atom tunneling in ordinary organic reactions.The allylboration of aldehydes (eq 1) affords homoallylic alcohols and formally accomplishes an aldol reaction when coupled with oxidative cleavage of the alkene. Mechanistically, these are well-behaved reactions with straightforward bimolecular kinetics. 5 Gajewski observed a significantly inverse secondary deuterium kinetic isotope effect (KIE) in the addition of the Roush allylboronate 4a to benzaldehyde, consistent with rate-limiting addition to the carbonyl and inconsistent with rate-limiting single-electron transfer. 6 Theoretical studies have supported the basic mechanistic picture derived initially from experimental observations 7 and have identified stereochemical control elements in the enantioselective reactions. 8 From our perspective, the reaction provided a special opportunity to measure a series of differing 13 C KIEs at low temperature.The reaction of the Roush (+)-diisopropyl L-tartrate-modified allylboronate 4 with 5 proceeds smoothly at −78 °C and affords the homoallylic alcohol 6 in quantita...

Atom Tunneling in Chemistry

“…[257] In the Roush allylboration of p-anisaldehyde,m ultidimensional tunneling involving heavy atoms is necessary to explain the experimental 12 C/ 13 CK IEs at À78 8 8C, [258] at emperature commonly used in organic synthesis.A tt his temperature, the reaction is accelerated by afactor of 1.36 by the tunneling of heavy atoms,w hich can not be observed directly by experiments. [258] Thus,the 12 C/ 13 CKIEs are asuitable probe to investigate the agreement of experimental and theoretical methods.The tunneling of oxygen is found in the ring-opening reaction of cyclic O 3 to its usual (open) form. [259] This rearrangement is even observed below 150 K. In this temperature regime,the reaction rate constants are calculated to be almost constant, with a 16 O/ 18 OK IE of up to 10 for the reaction of 18 O 3 .…”

Reactions that involve tunneling by carbon and the role that calculations have played in their study

“…Vetticatt and Singleton have used natural abundance 13 C NMR spectroscopy to measure the 12 C/ 13 C KIEs on the reaction of 29 with Roush's reagent ( 30 ) at −78°C (Figure ) . The largest 12 C/ 13 C KIE found was 1.052 ± 0.005, at the carbonyl carbon.…”

Chemical Exchange Saturation Transfer (CEST) Agents: Quantum Chemistry and MRI

“…Die Bergman‐Reaktion eines zehngliedrigen Endiins unterliegt überraschenderweise dem Schweratomtunneln,108) das die Cyclisierung gegenüber der klassischen Über‐die‐Barriere‐Reaktion bei Raumtemperatur etwa 40 % schneller macht; ähnliches findet sich auch bei Allylborierungen von Aldehyden 109. Es ist davon auszugehen, dass sich (Schweratom)tunneln bald als physikalische Realität in chemischen Reaktionen etablieren wird.…”