Scope and Mechanistic Analysis of the Enantioselective Synthesis of Allenes by Rhodium-Catalyzed Tandem Ylide Formation/[2,3]-Sigmatropic Rearrangement between Donor/Acceptor Carbenoids and Propargylic Alcohols

Rhodium-catalyzed reactions of tertiary propargylic alcohols with methyl aryl- and styryldiazoacetates result in tandem reactions, consisting of oxonium ylide formation followed by [2,3]-sigmatropic rearrangement. This process competes favorably with the standard O–H insertion reaction of carbenoids. The resulting allenes are produced with high enantioselectivity (88–98% ee) when the reaction is catalyzed by the dirhodium tetraprolinate complex, Rh₂(<i>S</i>-DOSP)₄. Kinetic resolution is possible when racemic tertiary propargylic alcohols are used as substrates. Under the kinetic resolution conditions, the allenes are formed with good diastereoselectivity and enantioselectivity (up to 6.1:1 dr, 88–93% ee), and the unreacted alcohols are enantioenriched to 65–95% ee. Computational studies reveal that the high asymmetric induction is obtained via an organized transition state involving a two-point attachment: ylide formation between the alcohol oxygen and the carbenoid and hydrogen bonding of the alcohol to a carboxylate ligand. The 2,3-sigmatropic rearrangement proceeds through initial cleavage of the O–H bond to generate an intermediate with close-lying open-shell singlet, triplet, and closed-shell singlet electronic states. This intermediate would have significant diradical character, which is consistent with the observation that the 2,3-sigmatropic rearrangement is favored with donor/acceptor carbenoids and more highly functionalized propargylic alcohols

Scope and Mechanistic Analysis of the Enantioselective Synthesis of Allenes by Rhodium-Catalyzed Tandem Ylide Formation/[2,3]-Sigmatropic Rearrangement between Donor/Acceptor Carbenoids and Propargylic Alcohols

Rhodium-catalyzed reactions of tertiary propargylic alcohols with methyl aryl- and styryldiazoacetates result in tandem reactions, consisting of oxonium ylide formation followed by [2,3]-sigmatropic rearrangement. This process competes favorably with the standard O–H insertion reaction of carbenoids. The resulting allenes are produced with high enantioselectivity (88–98% ee) when the reaction is catalyzed by the dirhodium tetraprolinate complex, Rh₂(<i>S</i>-DOSP)₄. Kinetic resolution is possible when racemic tertiary propargylic alcohols are used as substrates. Under the kinetic resolution conditions, the allenes are formed with good diastereoselectivity and enantioselectivity (up to 6.1:1 dr, 88–93% ee), and the unreacted alcohols are enantioenriched to 65–95% ee. Computational studies reveal that the high asymmetric induction is obtained via an organized transition state involving a two-point attachment: ylide formation between the alcohol oxygen and the carbenoid and hydrogen bonding of the alcohol to a carboxylate ligand. The 2,3-sigmatropic rearrangement proceeds through initial cleavage of the O–H bond to generate an intermediate with close-lying open-shell singlet, triplet, and closed-shell singlet electronic states. This intermediate would have significant diradical character, which is consistent with the observation that the 2,3-sigmatropic rearrangement is favored with donor/acceptor carbenoids and more highly functionalized propargylic alcohols

<i>D</i>₂-Symmetric Dirhodium Catalyst Derived from a 1,2,2-Triarylcyclopropanecarboxylate Ligand: Design, Synthesis and Application

Dirhodium tetrakis-(<i>R</i>)-(1-(4-bromophenyl)-2,2-diphenylcyclopropanecarboxylate) (Rh₂(<i>R</i>-BTPCP)₄) was found to be an effective chiral catalyst for enantioselective reactions of aryl- and styryldiazoacetates. Highly enantioselective cyclopropanations, tandem cyclopropanation/Cope rearrangements and a combined C–H functionalization/Cope rearrangement were achieved using Rh₂(<i>R</i>-BTPCP)₄ as catalyst. The advantages of Rh₂(<i>R</i>-BTPCP)₄ include its ease of synthesis, its tolerance to the size of the ester group in the styryldiazoacetates, and its compatibility with dichloromethane as solvent. Computational studies suggest that the catalyst adopts a <i>D</i>₂-symmetric arrangement, but when the carbenoid binds to the catalyst, two of the <i>p</i>-bromophenyl groups on the ligands rotate outward to make room for the carbenoid and the approach of the substrate to the carbenoid

<i>D</i>₂-Symmetric Dirhodium Catalyst Derived from a 1,2,2-Triarylcyclopropanecarboxylate Ligand: Design, Synthesis and Application

Dirhodium tetrakis-(<i>R</i>)-(1-(4-bromophenyl)-2,2-diphenylcyclopropanecarboxylate) (Rh₂(<i>R</i>-BTPCP)₄) was found to be an effective chiral catalyst for enantioselective reactions of aryl- and styryldiazoacetates. Highly enantioselective cyclopropanations, tandem cyclopropanation/Cope rearrangements and a combined C–H functionalization/Cope rearrangement were achieved using Rh₂(<i>R</i>-BTPCP)₄ as catalyst. The advantages of Rh₂(<i>R</i>-BTPCP)₄ include its ease of synthesis, its tolerance to the size of the ester group in the styryldiazoacetates, and its compatibility with dichloromethane as solvent. Computational studies suggest that the catalyst adopts a <i>D</i>₂-symmetric arrangement, but when the carbenoid binds to the catalyst, two of the <i>p</i>-bromophenyl groups on the ligands rotate outward to make room for the carbenoid and the approach of the substrate to the carbenoid