Dirhodium-Catalyzed Asymmetric Transformations of Alkynes via Carbene Intermediates

Functionalization of alkynes is an established cornerstone of organic synthesis. While numerous transition metals exhibit promising activities in the transformations of alkynes via pi-insertion or oxidative cyclometalation, Lewis pi-acids offer a different approach. By coordinating with alkynes through pi-bonding, Lewis pi-acids facilitate nucleophilic addition, leading to the formation of alkenyl metal species. These species can undergo electron rearrangement to generate metal carbenes, which are crucial intermediates for subsequent carbene transfer reactions. This reaction pathway provides a versatile route for alkyne functionalization, especially in an asymmetric manner. Although the Lewis pi-acid, gold(I), pioneered this reaction mode, the development of asymmetric variants remains challenging due to the linear coordination of gold(I). Therefore, expanding the range of catalysts beyond gold(I) complexes to other metal catalysts would facilitate further advances in chiral molecule construction and the exploration of novel reaction modes.In this Account, we present a concise review of alkyne multifunctionalization via dirhodium-catalyzed asymmetric transformations, providing the development of the modulation strategies and substrates and plausible reaction mechanisms. In the aromatization-driven strategy, the furanyl dirhodium carbene is generated from an enynone, which is terminated by enantioselective intramolecular C-H insertion, cyclopropanation, aromatic substitution, or the Buchner reaction, giving chiral dihydroindoles, dihydrobenzofurans, cyclopropane-fused tetrahydroquinolines, fluorenes, or cyclohepta[b]benzofurans. The cap-tether modulation strategy was developed in a subsequent study to balance the reactivity and selectivity of an azo-enyne. This strategy gave the first catalytic asymmetric cycloisomerization of azo-enyne, affording centrally and axially chiral isoindazole derivatives. The synergistic activation strategy, i.e., EWG activation and C-H<middle dot><middle dot><middle dot>O interaction, was introduced to achieve the first dirhodium-catalyzed asymmetric cycloisomerization of enynes, providing a range of chiral cyclopropane-annulated bicyclic systems from enynals. Benefiting from these successes, difluoromethyl-substituted enynes were designed and proven to be effective substrates. With the corresponding benzo-1,6-enynes as the substrates, the enantioselective biscyclopropanation and the cascaded cyclopropanation/cyclopropenation were achieved using alkynes as dicarbene equivalents. Additionally, benzo-1,5-enynal generated vinyl dirhodium carbene, which reacted with a variety of alkenes via [2 + 1] cycloaddition, [4 + 3] cycloaddition, or formal allylation, giving spiro and fused polycyclic heterocycles. Coupling the synergistic activation strategy with desymmetrization, we further successfully achieved the asymmetric cycloisomerization of diynals, constructing furan-fused dihydropiperidines with an alkyne-substituted aza-quaternary stereocenter. Notably, by analyzing X-ray structures of several dirhodium-alkyne pi-complexes, together with the results of DFT calculations and control experiments, we obtained evidence supporting the synergistic activation mode, making the well-defined paddlewheel-like dirhodium(II) stand out among the other metal complexes. We anticipate that our research will significantly advance the fields of dirhodium, alkyne, and carbene chemistry.