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ABSTRACT: Siloxy group migration: A rhodium(II) carbenoid approach has been developed for the synthesis of alkynoates. This transformation combines the addition of enol ethers at the vinylogous position of β-siloxy-substituted vinyldiazo derivatives with a siloxy group migration to give the products as single diastereomers.
Angewandte Chemie International Edition 07/2012; 51(34):8636-9. · 13.45 Impact Factor
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ABSTRACT: The development of methods for the stereoselective functionalization of sp(3) C-H bonds is a challenging undertaking. This Account describes the scope of the combined C-H functionalization/Cope rearrangement (CHCR), a reaction that occurs between rhodium-stabilized vinylcarbenoids and substrates containing allylic C-H bonds. Computational studies have shown that the CHCR reaction is initiated by a hydride transfer to the carbenoid from an allyl site on the substrate, which is then rapidly followed by C-C bond formation between the developing rhodium-bound allyl anion and the allyl cation. In principle, the reaction can proceed through four distinct orientations of the vinylcarbenoid and the approaching substrate. The early examples of the CHCR reaction were all highly diastereoselective, consistent with a reaction proceeding via a chair transition state with the vinylcarbenoid adopting an s-cis conformation. Recent computational studies have revealed that other transition state orientations are energetically accessible, and these results have guided the development of highly stereoselective CHCR reactions that proceed through a boat transition state with the vinylcarbenoid in an s-cis configuration. The CHCR reaction has broad applications in organic synthesis. In some new protocols, the CHCR reaction acts as a surrogate to some of the classic synthetic strategies in organic chemistry. The CHCR reaction has served as a synthetic equivalent of the Michael reaction, the vinylogous Mukaiyama aldol reaction, the tandem Claisen rearrangement/Cope rearrangement, and the tandem aldol reaction/siloxy-Cope rearrangement. In all of these cases, the products are generated with very high diastereocontrol. With a chiral dirhodium tetracarboxylate catalyst such as Rh(2)(S-DOSP)(4) or Rh(2)(S-PTAD)(4), researchers can achieve very high levels of asymmetric induction. Applications of the CHCR reaction include the effective enantiodifferentiation of racemic dihydronaphthalenes and the total synthesis of several natural products: (-)-colombiasin A, (-)-elisapterosin B, and (+)-erogorgiaene. By combining the CHCR reaction into a further cascade sequence, we and other researchers have achieved the asymmetric synthesis of 4-substituted indoles, a new class of monoamine reuptake inhibitors.
Accounts of Chemical Research 05/2012; 45(6):923-35. · 21.64 Impact Factor
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ABSTRACT: Asymmetric functionalization of N-heterocycles by vinylcarbenoids in the presence of catalytic amounts of Rh(2)(S-biTISP)(2) has been successfully developed. This bridged dirhodium catalyst not only selectively enforces the reaction to occur at the vinylogous position of the carbenoid but also affords high levels of asymmetric induction.
Organic Letters 03/2012; 14(7):1934-7. · 5.86 Impact Factor
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Angewandte Chemie International Edition 09/2011; 50(40):9370-3. · 13.45 Impact Factor
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ABSTRACT: Vinyl ethers selectively undergo the combined C-H functionalization/Cope rearrangement reaction via an s-cis/boat transition state. With chiral dirhodium catalysts, products are generated in a highly diastereoselective and enantioselective fashion. This reaction can be considered as a surrogate to the traditional vinylogous Mukaiyama aldol reaction. Effective kinetic resolution has been achieved, leading to the recovery of a cyclic vinyl ether with axial chirality of high enantiomeric purity.
Journal of the American Chemical Society 08/2011; 133(31):11940-3. · 9.91 Impact Factor
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Angewandte Chemie International Edition 06/2011; 50(26):5938-42. · 13.45 Impact Factor
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ABSTRACT: The combined C-H activation/Cope rearrangement (CHCR) is an effective C-H functionalization process that has been used for the asymmetric synthesis of natural products and pharmaceutical building blocks. Up until now, a detailed understanding of this process was lacking. Herein, we describe a combination of theoretical and experimental studies that have resulted in a coherent description of the likely mechanism of the reaction. Density functional studies on the reactions of rhodium vinylcarbenoids at allylic C-H sites demonstrate that the CHCR proceeds through a concerted, but highly asynchronous, hydride-transfer/C-C bond-forming event. Even though most of the previously known examples of this process are highly diastereoselective, the calculations demonstrate that other transition-states and stereochemical outcomes might be possible by appropriate modifications of the reagents, and this was confirmed experimentally. The calculations also indicate that there is a potential energy surface bifurcation between CHCR and the competing direct C-H insertion.
Journal of the American Chemical Society 03/2011; 133(13):5076-85. · 9.91 Impact Factor
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ABSTRACT: The tandem cyclopropanation/Cope rearrangement between bicyclic dienes and siloxyvinyldiazoacetate, catalyzed by the dirhodium catalyst Rh(2)(R-PTAD)(4), effectively accomplishes enantiodivergent [4 + 3] cycloadditions. The reaction proceeds by a cyclopropanation followed by a Cope rearrangement of the resulting divinylcyclopropane. This methodology was applied to the synthesis of (+)-barekoxide (1) and (-)-barekol (2).
Journal of the American Chemical Society 09/2010; 132(35):12422-5. · 9.91 Impact Factor
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ABSTRACT: An unusual rhodium carbenoid approach for introduction of 4-substituted (Z)-pent-2-enoates into sterically encumbered pyrroles and indoles is described. These studies show that (Z)-vinylcarbenoids have a greater tendency than (E)-vinylcarbenoids to react at the vinylogous position of the carbenoid rather than at the carbenoid center.
Organic Letters 03/2010; 12(5):924-7. · 5.86 Impact Factor
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ABSTRACT: An effective Rh(2)(S-DOSP)(4)-catalyzed asymmetric cyclopentannulation of indolyl rings has been developed. Depending on the substitution pattern of the indole, two distinct regioisomeric products can be generated. These studies demonstrate that rhodium-catalyzed reactions of donor/acceptor carbenoids proceeding by means of zwitterionic intermediates can be carried out with very high asymmetric induction.
Journal of the American Chemical Society 12/2009; 132(2):440-1. · 9.91 Impact Factor
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ABSTRACT: The total synthesis of (-)-5-epi-vibsanin E (2) has been achieved in 18 steps. The synthesis combines the rhodium-catalyzed [4 + 3] cycloaddition between a vinylcarbenoid and a diene to rapidly generate the tricyclic core with an effective end game strategy to introduce the remaining side-chains. The [4 + 3] cycloaddition occurs by a cyclopropanation to form a divinylcyclopropane followed by a Cope rearrangement to form a cycloheptadiene. The quaternary stereogenic center generated in the process can be obtained with high asymmetric induction when the reaction is catalyzed by the chiral dirhodium complex, Rh(2)(S-PTAD)(4).
Journal of the American Chemical Society 06/2009; 131(23):8329-32. · 9.91 Impact Factor
