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Hydrogen-mediated reductive coupling of conjugated alkynes with ethyl (N-Sulfinyl)iminoacetates: synthesis of unnatural alpha-amino acids via rhodium-catalyzed C-C bond forming hydrogenation.
J Am Chem Soc. 2005 Aug 17; 127(32):11269-76.JA

Abstract

Rhodium-catalyzed hydrogenation of 1,3-enynes 1a-8a and 1,3-diynes 9a-13a at ambient temperature and pressure in the presence of ethyl (N-tert-butanesulfinyl)iminoacetate and ethyl (N-2,4,6-triisopropylbenzenesulfinyl)iminoacetates, respectively, results in reductive coupling to afford unsaturated alpha-amino acid esters 1b-13b in good to excellent yields with exceptional levels of regio- and stereocontrol. Further hydrogenation of the diene containing alpha-amino acid esters 1b-8b using Wilkinson's catalyst at ambient temperature and pressure results in regioselective reduction to afford the beta,gamma-unsaturated alpha-amino acid esters 1c-8c in good to excellent yields. Exhaustive hydrogenation of the unsaturated side chains of the Boc- and Fmoc-protected derivatives of enyne and diyne coupling products 14b-16b occurs in excellent yield using Crabtree's catalyst at ambient temperature and pressure providing the alpha-amino acid esters 14d-16d, which possess saturated side chains. Finally, cross-metathesis of the Boc-protected reductive coupling product 14b with cis-1,4-diacetoxy-2-butene proceeds readily to afford the allylic acetate 14e. Isotopic labeling studies that involve reductive coupling of enyne 1a and diyne 9a under an atmosphere of elemental deuterium corroborate a catalytic mechanism in which oxidative coupling of the alkyne and imine residues is followed by hydrogenolytic cleavage of the resulting metallacycle. A stereochemical model accounting for the observed sense of asymmetric induction is provided. These studies represent the first use of imines as electrophilic partners in hydrogen-mediated reductive carbon-carbon bond formation.

Authors+Show Affiliations

Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16089454

Citation

Kong, Jong-Rock, et al. "Hydrogen-mediated Reductive Coupling of Conjugated Alkynes With Ethyl (N-Sulfinyl)iminoacetates: Synthesis of Unnatural Alpha-amino Acids Via Rhodium-catalyzed C-C Bond Forming Hydrogenation." Journal of the American Chemical Society, vol. 127, no. 32, 2005, pp. 11269-76.
Kong JR, Cho CW, Krische MJ. Hydrogen-mediated reductive coupling of conjugated alkynes with ethyl (N-Sulfinyl)iminoacetates: synthesis of unnatural alpha-amino acids via rhodium-catalyzed C-C bond forming hydrogenation. J Am Chem Soc. 2005;127(32):11269-76.
Kong, J. R., Cho, C. W., & Krische, M. J. (2005). Hydrogen-mediated reductive coupling of conjugated alkynes with ethyl (N-Sulfinyl)iminoacetates: synthesis of unnatural alpha-amino acids via rhodium-catalyzed C-C bond forming hydrogenation. Journal of the American Chemical Society, 127(32), 11269-76.
Kong JR, Cho CW, Krische MJ. Hydrogen-mediated Reductive Coupling of Conjugated Alkynes With Ethyl (N-Sulfinyl)iminoacetates: Synthesis of Unnatural Alpha-amino Acids Via Rhodium-catalyzed C-C Bond Forming Hydrogenation. J Am Chem Soc. 2005 Aug 17;127(32):11269-76. PubMed PMID: 16089454.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrogen-mediated reductive coupling of conjugated alkynes with ethyl (N-Sulfinyl)iminoacetates: synthesis of unnatural alpha-amino acids via rhodium-catalyzed C-C bond forming hydrogenation. AU - Kong,Jong-Rock, AU - Cho,Chang-Woo, AU - Krische,Michael J, PY - 2005/8/11/pubmed PY - 2005/12/13/medline PY - 2005/8/11/entrez SP - 11269 EP - 76 JF - Journal of the American Chemical Society JO - J Am Chem Soc VL - 127 IS - 32 N2 - Rhodium-catalyzed hydrogenation of 1,3-enynes 1a-8a and 1,3-diynes 9a-13a at ambient temperature and pressure in the presence of ethyl (N-tert-butanesulfinyl)iminoacetate and ethyl (N-2,4,6-triisopropylbenzenesulfinyl)iminoacetates, respectively, results in reductive coupling to afford unsaturated alpha-amino acid esters 1b-13b in good to excellent yields with exceptional levels of regio- and stereocontrol. Further hydrogenation of the diene containing alpha-amino acid esters 1b-8b using Wilkinson's catalyst at ambient temperature and pressure results in regioselective reduction to afford the beta,gamma-unsaturated alpha-amino acid esters 1c-8c in good to excellent yields. Exhaustive hydrogenation of the unsaturated side chains of the Boc- and Fmoc-protected derivatives of enyne and diyne coupling products 14b-16b occurs in excellent yield using Crabtree's catalyst at ambient temperature and pressure providing the alpha-amino acid esters 14d-16d, which possess saturated side chains. Finally, cross-metathesis of the Boc-protected reductive coupling product 14b with cis-1,4-diacetoxy-2-butene proceeds readily to afford the allylic acetate 14e. Isotopic labeling studies that involve reductive coupling of enyne 1a and diyne 9a under an atmosphere of elemental deuterium corroborate a catalytic mechanism in which oxidative coupling of the alkyne and imine residues is followed by hydrogenolytic cleavage of the resulting metallacycle. A stereochemical model accounting for the observed sense of asymmetric induction is provided. These studies represent the first use of imines as electrophilic partners in hydrogen-mediated reductive carbon-carbon bond formation. SN - 0002-7863 UR - https://www.unboundmedicine.com/medline/citation/16089454/Hydrogen_mediated_reductive_coupling_of_conjugated_alkynes_with_ethyl__N_Sulfinyl_iminoacetates:_synthesis_of_unnatural_alpha_amino_acids_via_rhodium_catalyzed_C_C_bond_forming_hydrogenation_ L2 - https://doi.org/10.1021/ja051104i DB - PRIME DP - Unbound Medicine ER -