Iridium Complex‐Catalyzed Cross‐Coupling Reaction of Terminal Alkynes with Internal Alkynes via CH Activation of Terminal Alkynes

Abstract

Abstract:The cross-dimerization of an electron-rich terminal alkyne with an electron-deficient internal alkyne was promoted by an iridium complex to produce a 1 : 1 adduct in high regio-and stereoselectivities. This reaction was extended to various combinations of terminal alkynes with internal alkynes such as alkynyl esters and alkynyl aldehydes. The selectivity of the reaction was found to markedly depend on the ligands used. When dppe was used as a ligand, the 1 : 2 cross-cyclotrimerization reaction took place to form substituted benzene derivatives. A plausible reaction path was suggested based on a labeling experiment. This reaction provides a method for the production of complicated enynes which are difficult to be prepared by conventional methods.

How Accurate is DFT for Iridium-Mediated Chemistry?

“…C–H bond formation is an elementary step in various Ir-catalyzed reactions, e.g., in hydrogenation of unsaturated substrates (CC, CO, and CN). , C–C bond formation is relevant for example in Ir-mediated cross-coupling reactions . We have evaluated the ability of DFT to reproduce three experimentally reported C–H and C–C coupling barriers.…”

“…An iridium-catalyzed transformation will typically consist of several steps with very different chemical nature. For example, an Ir-mediated alkene hydrogenation might involve formation of different isomers of an Ir–alkene complex, followed by H 2 association, C–H bond formation steps, and a product–substrate ligand exchange (Scheme a). − Equally, a proposed mechanism for alkyne cross-coupling might consist of substrate association, C–C coupling involving formation of different isomers, and C–H coupling (Scheme b) . In order to be able to make reliable conclusions, a chosen computational protocol should adequately describe the energetics of all steps in a reaction cycle.…”

“… a Proposed mechanisms: (A) Ir-catalyzed alkene hydrogenation . (B) Ir-catalyzed alkyne cross-coupling (alkenes and alkynes drawn simplified, L n = other ligands on iridium). …”

Atom-Economical Cross-Coupling of Internal and Terminal Alkynes to Access 1,3-Enynes

“…Trost reported pioneering work on redox-neutral, palladiumcatalyzed terminal alkyne homocoupling in 1987, 12 with improved scope and selectivity subsequently being realized by Trost, Pfaltz, Gevorgyan, and others over the ensuing decades. 4,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Cross-coupling between a terminal alkyne and an electronically activated (i.e., conjugated) alkyne has also been described. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Relevant to the approach described herein, Trost has also described examples in which silyl-substituted and terminal propargyl alcohols are coupled with terminal alkynes, leading to C(sp)-C(sp 2 ) bond formation proximal to the alcohol.…”

Atom-Economical Cross-Coupling of Internal and Terminal Alkynes to Access 1,3-Enynes

“…4,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Cross-coupling between a terminal alkyne and an electronically activated (i.e., conjugated) alkyne has also been described. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Relevant to the approach described herein, Trost has also described examples in which silyl-substituted and terminal propargyl alcohols are coupled with terminal alkynes, leading to C(sp)-C(sp 2 ) bond formation proximal to the alcohol. 14 While useful in their own right, existing methods are limited in scope, regioselectivity, stereoselectivity/specificity, and efficiency.…”