Tailored Biocatalysts For Carbon Carbon Bond Forming And Cleaving Reactions

Author : Souvagya Biswas
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (951 download)

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Download or read book Asymmetric Catalysis of Carbon-carbon Bond Forming Reactions written by Souvagya Biswas and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Nature has established numerous methods for synthesis of complex molecules utilizing simple and abundant resources such as the use of CO2, H2O and N2 using sunlight as a source of energy. Even more impressive are the high chemo-, regio-, and stereoselectivites observed in these transformations with a wide variety of both prochiral and chiral substrates. However, methods for the enantioselective incorporation of feedstock materials such as CO, HCN, CO2 or simple alkenes into prochiral molecules are limited and remain an important challenge in the field. The hydrovinylation reaction (HV), where ethylene is added across a carbon-carbon double bond, has been known for nearly fifty years, starting with the works of Hata, Alderson and Wilke. During the past few years, through an approach that relied mostly on mechanistic insights and systematic examination of ligand effects, our group discovered a number of protocols for Ni(II)- and Co(II)-catalyzed enantioselective hydrovinylation (HV) reactions of vinylarenes, 1,3-dienes and strained olefins. While the Ni(II)-catalyzed hydrovinylation (HV) reaction is one of the most selective asymmetric catalyzed carbon-carbon bond forming reactions, its use has been limited to alkenes conjugated to an aromatic ring and strained alkenes. We recently found Co(II)-bisphosphine complexes show much improved regioselectivity with broader functional group compatibility in 1,3-dienes. By utilizing finely tuned catalysts derived from Co(II)-bisphosphine complexes and Me3Al or methylaluminoxane (MAO) acyclic (E) and (Z)-1,3-dienes were found to undergo efficient hydrovinylation giving mostly 1,4-hydrovinylation products in an atmosphere of ethylene. In order to expand the hydrovinylation chemistry, we turned our attention to one of the mostly widely used intermediates on organic chemistry, viz., silyl enol ethers. Trialkylsilyl enol ethers are exceptionally versatile intermediates often used as enolate surrogates for the synthesis of carbonyl compounds. Yet there are no reports of broadly applicable, catalytic methods for the synthesis of chiral silyl enol ethers carrying latent functionalities useful for synthetic operations beyond the many possible reactions of the enol ether moiety itself. The work presented herein reports a general procedure for highly catalytic (substrate : catalyst ratio up to 1000:1) and enantioselective (96% to 98% major enantiomer) synthesis of silyl enol ethers bearing a vinyl group at a chiral carbon at the beta-position. The reactions, run under ambient conditions, use trialkylsiloxy-1,3-dienes and ethylene (1 atmosphere) as precursors, and readily available (bis-phosphine)-cobalt(II) complexes as catalysts. Once we have established the HV reaction conditions of the siloxydienes, we turn our attention towards diastereoselective functionalization of the hydrovinylated products. Under optimized conditions, we are able to successfully utilize our 1,4-hydrovinylated products as reactive nucleophilic synthons for several electrophilic reactions keeping moderate to good diastereomeric ratios. The silyl enolates can be readily converted into novel enantiopure vinyl triflates, a class of highly versatile cross-coupling reagents, enabling the syntheses of other enantiomerically pure trisubstituted alkene intermediates not easily accessible by current methods.