The metal-catalyzed coupling of alkynes is a powerful method for the preparation of 1,3-enynes, compounds that are of broad interest in organic synthesis. Numerous strategies have been developed for the homo- and cross coupling of alkynes to enynes via transition metal catalysis. In such reactions, a major issue is the control of regio-, stereo-, and, where applicable, chemoselectivity. Herein, we highlight prominent methods for the selective synthesis of these valuable compounds. Further, we illustrate the utility of these processes through specific examples of their application in carbocycle, heterocycle, and natural product syntheses.

We report the discovery, synthesis, and application of a new class of non-C2-symmetric phosphoramidite ligands derived from pyroglutamic acid for use in both oxidative and redox-neutral palladium-catalyzed asymmetric allylic alkylations of 1,3-diketones. The resulting chiral products are typically obtained in high yield with good to excellent levels of enantioselectivity.

The copper-catalyzed asymmetric propargylation of cyclic aldimines is reported. The influence of the imine trimer to inhibit the reaction was identified, and equilibrium constants between the monomer and trimer were determined for general classes of imines. Asymmetric propargylation of a diverse series of N-alkyl and N-aryl aldimines was achieved with good to high asymmetric induction. The utility was demonstrated by a titanium catalyzed hydroamination and reduction to generate the chiral indolizidines (-)-crispine A and (-)-harmicine.

A new strategy for the synthesis of chiral β-alkynyl esters which relies on sequential Pd and Cu catalysis is reported. Terminal alkynes bearing aryl-, alkyl-, and silyl-groups can be employed without prior activation yielding a wide range of important chiral building blocks. The reaction sequence utilizes a robust Pd(II)-catalyzed hydroalkynylation of ynoates with terminal alkynes providing geometrically-pure ynenoates which are readily reduced by CuH. In contrast to previous reports, where additions to ynenoates proceed with marginal preference for the 1,6-pathway, this conjugate reduction occurs with high 1,4-selectivity yielding β-alkynyl esters with excellent levels of enantioselectivity. Importantly, the method tolerates a wide range of functionality, including allylic carbonates and carbamates, and thus allows for rapid elaboration of the β-alkynyl esters into a variety of chiral, substituted heterocycles.

Triple A: The catalytic asymmetric allylic alkylation (AAA) of 3‐aryloxindoles with allylidene dipivalate is described. This reaction affords stable, synthetically useful enol pivalates in high yield and with excellent regio‐ and enantioselectivity. A broad range of substrates is tolerated, including unprotected and 3‐heteroaryl nucleophiles.