Dual Functionalization of Alkynes Utilizing the Redox Characteristics of Transition Metal Catalysts

Abstract

Tri-and tetrasubstituted alkene scaffolds are prominent building blocks in many bioactive natural products, drug molecules, and key intermediates in various synthetic transformations. The dual functionalization of alkynes promises an easy introduction of functional groups across the triple bond with a high step and atom economy, exemplifying a class of reactions to construct tri-and tetrasubstituted alkene scaffolds. This review discusses the versatility and advances in the transition metal-catalyzed redox dual functionalization of alkynes, their unique mechanistic features, and the synthetic applications of the methodology. This collection focuses on the formation of simultaneous CÀ C/ CÀ X bonds involving various oxidation states of the metals in the catalytic cycle. Apart from the classical redox reactivity, radical-mediated functionalizations are also discussed in detail.

Recent Progress in Arylmetalative Cyclization/Annulation of Functionalized Alkynes with Organoboranes

“…Carbo/hetero-metalation of alkynes is an outstanding approach to access a wide range of highly substituted olefins with regioand stereo selections. [1][2][3][4][5][6][7][8][9][10][11][12] After the pioneering discovery of carbo-cupration in the early 1970s enormous attention has been paid to carbo and hetero metalation of alkynes (orthogonal activation of alkynes) which has resolved several longlasting problems associated with the selective synthesis of olefins through conventional methods. [1] This strategy is highly reliable because the starting materials required are readily available alkynes and the necessary criteria are usually a simple electron or steric difference.…”

“…The kind of functional groups which can be introduced on olefin, range from halo, silyl, boryl, stanyl, thio, cyano, sulfonyl, amino, carboxyl, alkyl, alkenyl, alkynyl to aryl on both the internal and terminal alkynes. [2][3][4][5][6][7][8][9][10][11][12] Using the high intrinsic electron bias, heteroatomattached alkynes and ynones were also extensively studied for this carbo/hetero metalation. [4] The common challenges in this carbo-metalation of alkynes are a) Regio-and stereoselective addition of carbo-metal species on alkyne, b) Multiple additions of incoming nucleo-metal species, c) Metalation vs addition on terminal alkynes, and d) Instability of newly formed alkenyl metal complex leading to polymerization or may undergo decomposition (Scheme 1).…”

Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes

“…Despite the wealth of reactivity that has been established in the catalytic functionalization of alkynes toward the construction of stereochemically defined olefins, − unsymmetrical dialkyl-substituted alkynes are noticeably absent from most contributions and, when present, typically provide unsatisfactory levels of reactivity and/or regioselectivity . In an effort to enhance the involvement of this class of alkynes, our group has reported an indirect solution that relies on the use of a propargylic SO 2 Py directing group for achieving site-selectivity control .…”

Intermolecular 1,2-Difunctionalization of Terminal Alkynes to Access Trisubstituted Alkenes via Copper/Photoredox Dual Catalysis

“…Cyano-substituted alkenes are particularly appealing, as these robust and highly polarized alkenes may enhance pharmacological potency and selectivity . Over past decades, the 1,2-difunctionalization of alkynes to simultaneously introduce two vicinal functional moieties across a triple bond has emerged as a practical protocol in the construction of multisubstituted alkenes, enabling better stereoselectivity and more precise control over the introduction of two different substituents . In this context, various activation modes involving metal catalysis, photocatalysis, and electrocatalysis have been intensively investigated (Scheme A).…”