Report

Rh-catalyzed C–C bond cleavage by transfer hydroformylation

+ See all authors and affiliations

Science  02 Jan 2015:
Vol. 347, Issue 6217, pp. 56-60
DOI: 10.1126/science.1261232

You are currently viewing the abstract.

View Full Text

Shifting hydroformylation into reverse

The hydroformylation reaction is applied on large scale in the chemical industry to make aldehydes by adding hydrogen and carbon monoxide to olefins. The reverse process could also prove useful in modifying complex molecules for pharmaceutical research, but methods directed toward that end often strip off the CO without the hydrogen. Murphy et al. now show that a rhodium catalyst can achieve selective dehydroformylation of a diverse range of compounds under mild conditions (see the Perspective by Landis). The protocol relies on effective transfer of the CO and H2 equivalents to a sacrificial strained olefin added to the mix.

Science, this issue p. 56; see also p. 29

Abstract

The dehydroformylation of aldehydes to generate olefins occurs during the biosynthesis of various sterols, including cholesterol in humans. Here, we implement a synthetic version that features the transfer of a formyl group and hydride from an aldehyde substrate to a strained olefin acceptor. A Rhodium (Xantphos)(benzoate) catalyst activates aldehyde carbon-hydrogen (C–H) bonds with high chemoselectivity to trigger carbon-carbon (C–C) bond cleavage and generate olefins at low loadings (0.3 to 2 mole percent) and temperatures (22° to 80°C). This mild protocol can be applied to various natural products and was used to achieve a three-step synthesis of (+)-yohimbenone. A study of the mechanism reveals that the benzoate counterion acts as a proton shuttle to enable transfer hydroformylation.

View Full Text