Enantioselective and Diastereodivergent Allylation of Propargylic C–H Bonds

Abstract

An iridium-catalyzed stereoselective coupling of allylic ethers and alkynes to generate 3,4-substituted 1,5-enynes is reported. Under optimized conditions, the coupling products are formed with excellent regio-, diastereo-, and enantioselectivities, and the protocol is functional group tolerant. Moreover, we report conditions that allow the reaction to proceed with complete reversal of diastereoselectivity. Mechanistic studies are consistent with an unprecedented dual role for the iridium catalyst, enabling the propargylic deprotonation of the alkyne through π-coordination, as well as the generation of a π-allyl species from the allylic ether starting material.

Enantioselective and Regiodivergent Synthesis of Propargyl‐ and Allenylsilanes through Catalytic Propargylic C−H Deprotonation

“…We posited that a π ‐complexation‐assisted deprotonation strategy for the generation of a chiral allenylmetal reagent from an alkyne (Scheme 1B, top left) could enable the desired reactivity [9] . Liming Zhang and co‐workers previously demonstrated the utility of this approach using bifunctional Au/Brønsted base catalysts for intramolecular coupling of alkyne and aldehydes, [10] while more recently, our group reported an intermolecular propargylic allylation in the presence of an Ir catalyst (Scheme 1B, bottom left) [11] . The successful development of this highly stereo‐ and regioselective system for propargylic C−H allylation using allylic ethers as allylic cation equivalents led us to explore the feasibility using other easily accessible electrophilic reagents for introducing heteroatom‐based functional groups (Scheme 1B, right).…”

Enantioselective and Regiodivergent Synthesis of Propargyl‐ and Allenylsilanes through Catalytic Propargylic C−H Deprotonation

“…[9] Liming Zhang and coworkers previously demonstrated the utility of this approach using bifunctional Au/Brønsted base catalysts for intramolecular coupling of alkyne and aldehydes, [10] while more recently, our group reported an intermolecular propargylic allylation in the presence of an Ir catalyst (Scheme 1B, bottom left). [11] The successful development of this highly stereo-and regioselective system for propargylic CÀ H allylation using allylic ethers as allylic cation equivalents led us to explore the feasibility using other easily accessible electrophilic reagents for introducing heteroatom-based functional groups (Scheme 1B, right).…”

A C–H functionalization approach to diverse nitrogenous scaffolds through conjugate addition of catalytic allyliron nucleophiles

“…Our group and others have shown that coordination of a cationic late transition metal complex to a C-C p-bond can greatly enhance the C-H acidity of the neighboring allylic, propargylic, or allenic protons. 26,27 In particular, through the use of cyclopentadienyliron(II) dicarbonyl derivatives as catalysts, 28 this acidity enhancement enables the use of weak, functional group-tolerant amine bases to effect the allylic deprotonation of olens to generate nucleophilic allyliron intermediates that react with electrophiles with S E 2 0 selectivity. [29][30][31][32][33][34][35] We further discovered that these nucleophilic organoiron species will undergo electrophilic functionalization with chalcone derivatives through a 1,4-addition process.…”