The Rauhut–Currier Reaction: Why Phosphines Are Efficient Catalysts

The crossed Rauhut–Currier
reaction couples matched
pairs
of Michael acceptors under nucleophilic catalysis. The mechanism is
often assumed to be analogous to the Morita–Baylis–Hillman
reaction. However, this does not explain why most Rauhut–Currier
reactions employ tertiary phosphines as catalysts, despite both tertiary
phosphines and amines being effective catalysts in Morita–Baylis–Hillman
reactions. The archetypal crossed Rauhut–Currier reaction between
acrylate and fumarate esters, catalyzed by Cy3P, has been
investigated by in situ 1H, 19F, and 31P NMR spectroscopy, 2H/13C labeling and KIEs,
and computation. The mechanism that is elucidated explains why phosphines
are efficient Rauhut–Currier catalysts and amines are not,
and how the crossed selectivity is achieved through differential β-substitution
in the two Michael acceptors. Reversible addition of the bulky but
nucleophilic phosphine to the less-hindered acrylate generates an
enolate that is selectively trapped by the more electrophilic Michael
acceptor, the fumarate. The catalytic cycle is completed by intramolecular
β → γ′ proton transfer to generate a phosphonium
ylide, tautomerization, and elimination of the phosphine. The intermediacy
of the ylide bypasses a high-barrier α → γ′
pathway and results in the product-determining step for the crossed
Rauhut–Currier product being the enolate addition to the Michael
acceptor, not the proton transfer.