Several reactions of simple, unactivated alkenes with electrophiles under nickel(0) catalysis are discussed. The coupling of olefins with aldehydes and silyl triflates provides allylic or homoallylic alcohol derivatives, depending on the supporting ligands and, to a lesser extent, the substrates employed. Reaction of alkenes with isocyanates yields N-alkyl acrylamides. In these methods, alkenes act as the functional equivalents of alkenyl- and allylmetal reagents.
Pumiliotoxins 209F and 251D were synthesized using highly selective nickel-catalyzed epoxide−alkyne reductive cyclizations as the final step. The exocyclic (Z)-alkene found in the majority of the pumiliotoxins was formed stereospecifically and regioselectively, without the use of a directing group on the alkyne, and the epoxide underwent ring opening exclusively at the less hindered carbon to provide the requisite tertiary alcohol. The epoxides were prepared using diastereoselective addition of a sulfoxonium anion to a proline-derived methyl ketone.
Nickel-catalysed reductive coupling reactions of alkynes have emerged as powerful synthetic tools for the selective preparation of functionalized alkenes. One of the greatest challenges associated with these transformations is control of regioselectivity. Recent work from our laboratory has provided an improved understanding of several of the factors governing regioselectivity in these reactions, and related studies have revealed that the reaction mechanism can differ substantially depending on the ligand employed. A discussion of stereoselective transformations and novel applications of nickel catalysis in coupling reactions of alkynes is also included.
The nickel(0)-catalyzed coupling of α-olefins and isocyanates proceeds in the presence of the N-heterocyclic carbene ligand IPr to provide α,β-unsaturated amides. Carbon−carbon bond formation occurs preferentially at the 2-position of the olefin. The N-tert-butyl amide products can be converted to the corresponding primary amides under acidic conditions.
The development of a nickel-catalyzed coupling of terminal allenes, aldehydes, and silanes is described. This transformation selectively provides 1,1-disubstituted allylic alcohols, protected as a silyl ether. The choice of the reducing agent is essential for achieving selectivity in this coupling process. A trialkylphosphine (Cyp3P) and an N-heterocyclic carbene (IPr) are complementary in this reaction.
A full account of two recently developed nickel-catalyzed coupling reactions of alkenes, aldehydes, and silyl triflates is presented. These reactions provide either allylic alcohol or homoallylic alcohol derivatives selectively, depending on the ligand employed. These processes are believed to be mechanistically distinct from Lewis acid-catalyzed carbonyl-ene reactions, and several lines of evidence supporting this hypothesis are discussed.
Nickel-catalyzed reductive coupling reactions of aldehydes and 1,6-enynes proceed in excellent regioselectivity in the absence of a phosphine, and the use of a monodentate phosphine additive leads to the formation of the opposite regioisomer with equally high selectivity. Both products are the result of the same fundamental mechanism, with the inversion of regioselectivity being the result of stereospecific ligand substitution at the metal center.
Described are several classes of unusual or unprecedented carbonyl-ene-type reactions, including those between alpha olefins and aromatic aldehydes. Catalyzed by nickel, these processes complement existing Lewis acid-catalyzed methods in several respects. Not only are monosubstituted alkenes, aromatic aldehydes, and tert-alkyl aldehydes effective substrates, but monosubstituted olefins also react faster than those that are more substituted, and large or electron-rich aldehydes are more effective than small or electron-poor ones. Conceptually, in the presence of a nickel−phosphine catalyst, the combination of off-the-shelf alkenes, silyl triflates, and triethylamine functions as a replacement for an allylmetal reagent.
A study of nickel-catalyzed reductive coupling reactions of aldehydes and chiral 1,6-enynes has provided evidence for three distinct mechanistic pathways that govern regioselectivity in this transformation. In the absence of a phosphine additive, high regioselectivity and high diastereoselectivity are obtained as a direct result of coordination of both the alkyne and the olefin to the metal center during the C−C bond-forming step.