Author: Chunhui JiangPublisher:
ISBN:
Category :
Languages : en
Pages : 854
Book Description
Palladium Catalyzed Asymmetric Allylic Alkylation and TMM Cycloaddition in Natural Product Syntheses
Author: Chunhui JiangPalladium-catalyzed Asymmetric Trimethylenemethane Cycloaddition
Author: Dustin Anthony BringleyPublisher:
ISBN:
Category :
Languages : en
Pages :
Book Description
Cycloadditions are among the most powerful reactions in organic chemistry due to their ability to rapidly build molecular complexity from simple, readily available precursors. In 1979, the Trost group described a novel method for the synthesis of cyclopentane rings by the in situ generation and subsequent [3+2] dipolar cycloaddition of palladium-bound trimethylenemethane (TMM). The method has proven to be a powerful approach for the synthesis of five-membered rings, including tetrahydrofurans and pyrrolidines, as well as larger rings sizes via [4+3] and [6+3] cycloaddition. In 2006, the Trost group demonstrated for the first time a general asymmetric protocol by employing phosphoramidites bearing cyclic amines as the chiral ligands. Using these ligands, highly enantioselective cycloadditions with electron-deficient olefins and imines were described. Herein, we describe the successful extension of the asymmetric methodology to include reactions with carbonyl groups and nitroalkenes, allowing for the synthesis of tetrahydrofurans and nitrocyclopentanes, respectively, with good to excellent enantioselectivity. For reactions with carbonyl groups, the development of novel C1-symmetric phosphoramidites was critical, and the optimized ligand was derived from a BINOL bearing a fused furan. The evolution of the ligand design will be discussed, beginning with the initial discovery that phosphoramidites with mono-substituted BINOL derivatives gave improved selectivity. In addition, since these phosphoramidites are chiral at phosphorus, the impact of this chirality on the TMM reaction is explored. The use of the optimized ligand allowed for reactions with both aromatic aldehydes and ketones. In addition, the asymmetric conditions did not require a Lewis acid co-catalyst, in contrast to the achiral ligands that had been previously investigated. For reactions with nitroalkenes, both [beta]-substituted and [beta], [beta]-disubstituted nitroalkenes could be employed as acceptors, where the use of the latter allowed for the synthesis of nitrocyclopentanes bearing a quaternary stereocenter. The nitrocyclopentane products were demonstrated to be versatile synthetic precursors, capable of undergoing further alkylation with excellent diastereoselectivity or converted to cyclopentylamines and cyclopentenones with little to no racemization. In one example, the asymmetric cycloaddition constitutes a formal synthesis of (+)-cephalotaxine. Finally, substituted TMM donors were explored and the use of a cyano donor was found to proceed with nearly perfect levels of selectivity and yield. Finally, the asymmetric TMM cycloaddition using a cyano-substituted donor was applied to the synthesis of ( - )-marcfortine C. Notably, the reaction proceeds in nearly quantitative yield with high diastereo- and enantioselectivity, and the resulting chiral center was used to establish all remaining stereocenters in the natural product. Additional highlights include a direct allylic oxidation of the exocyclic olefin, a diastereoselective intramolecular Michael addition, and an oxidative radical cyclization. Using this route, ( - )-marcfortine C was prepared in 16 steps and 2.4% overall yield.
Palladium-catalyzed Asymmetric Allylic Alkylation
Author: Nathan Bruce BennettPublisher:
ISBN:
Category : Alkylation
Languages : en
Pages : 1828
Book Description
The asymmetric construction of quaternary stereocenters is a topic of great interest in the organic chemistry community given their prevalence in natural products and biologically active molecules. Over the last decade, the Stoltz group has pursued the synthesis of this challenging motif via a palladium-catalyzed allylic alkylation using chiral phosphinooxazoline (PHOX) ligands. Recent results indicate that the alkylation of lactams and imides consistently proceeds with enantioselectivities substantially higher than any other substrate class previously examined in this system. This observation prompted exploration of the characteristics that distinguish these molecules as superior alkylation substrates, resulting in newfound insights and marked improvements in the allylic alkylation of carbocyclic compounds.
Applications of Palladum [sic] Catalyzed Asymmetric Allylic Alkylation
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Author: Jennifer Ann VanceNew Strategies for the Synthesis of Bioactive Natural and Unnatural Products Via Palladium Catalyzed Asymmetric Allylic Alkylation
Author: Weiping TangThe Palladium Catalyzed Asymmetric Allylic Alkylation (AAA)
Author: Daniel Edward PattersonPublisher:
ISBN:
Category :
Languages : en
Pages : 734
Book Description
Transition Metal Catalyzed Enantioselective Allylic Substitution in Organic Synthesis
Author: Uli KazmaierPublisher: Springer
ISBN: 364222749X
Category : Science
Languages : en
Pages : 354
Book Description
Giovanni Poli, Guillaume Prestat, Frédéric Liron, Claire Kammerer-Pentier: Selectivity in Palladium Catalyzed Allylic Substitution.- Jonatan Kleimark and Per-Ola Norrby: Computational Insights into Palladium-mediated Allylic Substitution Reactions.- Ludovic Milhau, Patrick J. Guiry: Palladium-catalyzed enantioselective allylic substitution.- Wen-Bo Liu, Ji-Bao Xia, Shu-Li You: Iridium-Catalyzed Asymmetric Allylic Substitutions.- Christina Moberg: Molybdenum- and Tungsten-Catalyzed Enantioselective Allylic Substitutions.- Jean-Baptiste Langlois, Alexandre Alexakis: Copper-catalyzed enantioselective allylic substitution.- Jeanne-Marie Begouin, Johannes E. M. N. Klein, Daniel Weickmann, B. Plietker: Allylic Substitutions Catalyzed by Miscellaneous Metals.- Barry M. Trost, Matthew L. Crawley: Enantioselective Allylic Substitutions in Natural Product Synthesis.
Expanding the Scope of the Palladium-catalyzed Asymmetric Allylic Alkylation Reaction and Applications Towards Alkaloid Syntheses
Author: Megan BrennanPalladium-catalyzed Asymmetric Trimethylenemethane Cycloaddition
Author: Steven Mark SilvermanPublisher:
ISBN:
Category :
Languages : en
Pages :
Book Description
The development of new methods for chemical synthesis is motivated by the desire to add efficient chemo-, regio-, diastereo-, and enantioselective reactions to the repository of transformations available to researchers. In addition to reaction development, a primary goal of methodology research is to fundamentally understand chemical reactivity. This understanding provides the impetus for further discovery, inevitably allowing for the rapid synthesis of complex molecules as well as the development of industrially feasible processes. The research described herein discusses method development and seeks to place it within this context. Cycloaddition reactions have been widely used in organic synthesis since initial accounts of the Diels-Alder reaction were reported over 80 years ago. These reactions can proceed by either stepwise or concerted processes, can be thermally or photochemically initiated, metal catalyzed or non-metal catalyzed, but one unifying feature of this reaction class is the ability to quickly assemble a complex molecular architecture. A method for the synthesis of cyclopentane rings was disclosed by the Trost group in 1979 through the controlled generation of trimethylenemethane (TMM), a three-carbon dipole capable of participating in a palladium-catalyzed stepwise cycloaddition. Over the ensuing 20 years, this procedure was expanded to other five-membered rings, including pyrrolidines and tetrahydrofurans. It was generalized to include [4+3] and [6+3] cycloadditions in addition to the initial [3+2] reaction. However, only minimal advances were made in the establishment of a catalytic, asymmetric variant of the reaction, which would have enormous value in that chiral variants of the above molecules could be prepared. A protocol for the enantioselective TMM reaction was developed and is described herein. The synthesis of novel phosphoramidite ligands was critical in this effort, and the preparation and reactivity of these ligands is detailed. The evolution of the ligand design, commencing with acyclic amine-derived phosphoramidites and leading to cyclic azetidine and pyrrolidine structures is discussed. The initial conditions used to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of alkene acceptors, providing the desired cyclopentanes with high levels of enantioselectivity. The donor scope was also explored and various substituted systems were tolerated, including one bearing a nitrile moiety and a one bearing a propiolate function. These were reactive with unsaturated acylpyrroles, giving the product cyclopentane rings bearing three stereocenters in high enantioselectivity and complete diastereoselectivity. The nitrile donor was reactive with methyleneoxindoles, providing products containing up to three adjacent stereocenters, two being all-carbon quaternary. Furthermore, ligand controlled diastereoselection was seen. The methodology was further applied to the synthesis of heterocycles. The parent donor successfully reacted with N-aryl and N-Boc imines. A nitrile donor was found to react with a series of N-Tosyl imines, giving the pyrrolidines in high yield. Multiple regioisomers were formed and reaction conditions were developed to favor each product. In the case of N-Tosyl ketimines, the desired cycloadducts containing tetrasubstituted centers were prepared with nearly complete enantio- and diastereoselectivity. The protecting group could be removed to afford a synthetically versatile compound with several handles for further elaboration. Conditions were also developed to perform an enantioselective TMM reaction with aldehydes, giving the desired tetrahydrofurans in moderate to good enantioselectivity. Finally, an asymmetric [4+3] cycloaddition utilizing ortho-quinone methides was successfully performed in an effort to prepare oxepanes. Taken collectively, these results demonstrate that the palladium-phosphoramidite catalyst system represents a versatile method for the rapid assembly of complex molecular architectures from simple starting materials via cycloaddition.
Author: Karna Lyn Sacchi