Nickel-Catalyzed Cross-Dehydrogenative Allylation of Aldehydes

Nucleophilic additions to aldehydes play a central role
in synthetic
chemistry. While additions of organometallic nucleophiles are commonly
employed, alternative catalytic processes such as cross-electrophile
couplings and reductive couplings involving various π-systems
have also been developed and extensively used. In this study, we describe
a complementary approach to aldehyde–alkene couplings via direct
nickel-catalyzed cross-dehydrogenative coupling of aldehydes and alkenes.
The process utilizes a combination of zinc powder and di-tert-butyl peroxide, enabling cross-dehydrogenative coupling to allow
the synthesis of β,γ-unsaturated ketones through the catalytic
union of acyl radicals and allylic radicals generated from the aldehyde
and alkene substrates. An array of substrate combinations is demonstrated,
and both experimental and computational studies support the involvement
of a double hydrogen-atom-transfer (HAT) mechanism. Comparative analysis
of di-tert-butyl peroxide with an alternate oxidant,
2-bromo-1,3-bis(trifluoromethyl)benzene, illustrates the substrate-dependent
complementarity of the oxidants and shows an important interdependence
of relative substrate concentrations. Quantum chemical estimates of
the thermodynamics of the two simultaneous HAT events, generating
acyl radicals and allylic radicals, show a correlation between calculated
free energies of reaction and the optimal experimental protocol.