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(S-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.铑催化的三级炔丙醇与芳基重氮乙酸甲酯、苯乙烯基重氮乙酸甲酯的反应可经由串联路径进行，该串联过程依次包含氧鎓叶立德生成与[2,3]-σ迁移重排两步。该路径相较于经典的类卡宾O-H插入反应更具竞争优势。当以四脯氨酸二铑配合物Rh₂(S-DOSP)₄为催化剂时，所得联烯产物具有优异的对映选择性（88%~98% 对映体过量值 ee (enantiomeric excess)）。若采用消旋三级炔丙醇作为反应底物，该体系可实现动力学拆分。在此动力学拆分条件下，联烯产物可获得良好的非对映选择性与对映选择性（最高可达6.1:1的非对映体比率 dr (diastereomeric ratio)，88%~93% ee），未反应的原料醇可被富集至65%~95% ee。计算研究表明，该反应的高不对称诱导效应源于一种有序过渡态，该过渡态存在两点相互作用：一是醇氧与类卡宾形成叶立德，二是醇与羧酸酯配体形成氢键。[2,3]-σ迁移重排过程始于O-H键的初始断裂，生成具有能量相近的开壳层单重态、三重态与闭壳层单重态电子态的中间体。该中间体具有显著的双自由基特征，这与实验观测到的给体/受体类卡宾以及高官能化三级炔丙醇更利于该[2,3]-σ迁移重排反应的结果相一致。