Isomerisation during carbopalladation reactions:
In the course of developing the palladium-mediated cascade cyclisation route to fused bicyclic ring systems, we detected several unusual palladium-mediated isomerisations; the first effecting a formal anti-carbopalladation / cross-coupling, and the second a triene isomerisation preceding electrocyclisation. The combination of these processes enhanced the overall yield for the reaction sequence, but their mechanism remains unknown. An understanding of these mechanisms could lead to an ability to control reaction outcome, and thus applications in other settings. In the longer term, we also aim to develop an understanding of the precise geometric requirements of triene electrocyclisation reactions in terms of control of stereochemistry in the forming cyclohexadiene ring.
Isomerisation during allene-forming reactions:
Although the palladium-mediated synthesis of chiral allenes from chiral propargylic electrophiles has been fairly widely studied, varying levels of loss of stereochemistry are observed in the transfer of stereochemistry from the propargylic stereogenic centre to the allene axis of asymmetry – up to almost complete racemisation! This poses a serious problem for the use of palladium catalysis in allene synthesis, and is at present the main reason why this reaction has not been more widely used.
The mechanism for this isomerisation is not understood, as although various explanations have been proposed,1 there are inconsistencies. We are examining a completely new explanation for the mechanism of isomerisation in this central-to-axial chirality transfer process, which we hope will lead to the development of reaction conditions which avoid it.
- For example, see: S. Ogoshi, T. Nishida, T. Shinagawa and H. Kurosawa, J. Am. Chem. Soc. 2001, 123, 7164.