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Asymmetric induction in hydrogen-mediated reductive aldol additions to alpha-amino aldehydes catalyzed by rhodium: selective formation of syn-stereotriads directed by intramolecular hydrogen-bonding.
J Am Chem Soc. 2006 Dec 27; 128(51):17051-6.JA

Abstract

Rhodium-catalyzed hydrogenation of methyl vinyl ketone and ethyl vinyl ketone in the presence of N-Boc-alpha-aminoaldehydes 3a-8a at ambient temperature and pressure results in reductive C-C coupling to furnish aldol adducts 3b-8b and 3c-8c, respectively, which incorporate stereotriads that embody high levels of syn-aldol selectivity accompanied by high levels of anti-Felkin-Anh control. The collective data are consistent with a catalytic mechanism involving addition of the Z(O)-rhodium enolate to the sterically less-encumbered aldehyde pi-face of an intramolecularly hydrogen-bonded chelate through a Zimmerman-Traxler type transition structure. Stereochemical assignments are supported by single-crystal X-ray diffraction analysis of 5b-O-3,5-dinitrobenzoate, iso-5b, N-Me-iso-5b-O-3,5-dinitrobenzoate, and 7b. As revealed by HPLC analysis, optical purity of the stereochemically labile alpha-aminoaldehydes is completely preserved under the conditions of hydrogen-mediated aldol coupling. Deletion of the intramolecular hydrogen bond, as in the case of N-methyl-N-Boc-l-leucinal N-Me-5a, inverts stereoselectivity to furnish the Felkin-Anh product N-Me-iso-5b in 17% yield. Additionally, reactions performed in the presence of tert-amyl alcohol (10 equiv) exhibit markedly lower levels of anti-Felkin-Anh control (7:1 versus > or = 20:1). The collective studies suggest that intramolecular hydrogen bonding plays a key role in both activating the alpha-aminoaldehyde toward addition and directing facial selectivity.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17177457

Citation

Jung, Cheol-Kyu, and Michael J. Krische. "Asymmetric Induction in Hydrogen-mediated Reductive Aldol Additions to Alpha-amino Aldehydes Catalyzed By Rhodium: Selective Formation of Syn-stereotriads Directed By Intramolecular Hydrogen-bonding." Journal of the American Chemical Society, vol. 128, no. 51, 2006, pp. 17051-6.
Jung CK, Krische MJ. Asymmetric induction in hydrogen-mediated reductive aldol additions to alpha-amino aldehydes catalyzed by rhodium: selective formation of syn-stereotriads directed by intramolecular hydrogen-bonding. J Am Chem Soc. 2006;128(51):17051-6.
Jung, C. K., & Krische, M. J. (2006). Asymmetric induction in hydrogen-mediated reductive aldol additions to alpha-amino aldehydes catalyzed by rhodium: selective formation of syn-stereotriads directed by intramolecular hydrogen-bonding. Journal of the American Chemical Society, 128(51), 17051-6.
Jung CK, Krische MJ. Asymmetric Induction in Hydrogen-mediated Reductive Aldol Additions to Alpha-amino Aldehydes Catalyzed By Rhodium: Selective Formation of Syn-stereotriads Directed By Intramolecular Hydrogen-bonding. J Am Chem Soc. 2006 Dec 27;128(51):17051-6. PubMed PMID: 17177457.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Asymmetric induction in hydrogen-mediated reductive aldol additions to alpha-amino aldehydes catalyzed by rhodium: selective formation of syn-stereotriads directed by intramolecular hydrogen-bonding. AU - Jung,Cheol-Kyu, AU - Krische,Michael J, PY - 2006/12/21/pubmed PY - 2007/2/21/medline PY - 2006/12/21/entrez SP - 17051 EP - 6 JF - Journal of the American Chemical Society JO - J Am Chem Soc VL - 128 IS - 51 N2 - Rhodium-catalyzed hydrogenation of methyl vinyl ketone and ethyl vinyl ketone in the presence of N-Boc-alpha-aminoaldehydes 3a-8a at ambient temperature and pressure results in reductive C-C coupling to furnish aldol adducts 3b-8b and 3c-8c, respectively, which incorporate stereotriads that embody high levels of syn-aldol selectivity accompanied by high levels of anti-Felkin-Anh control. The collective data are consistent with a catalytic mechanism involving addition of the Z(O)-rhodium enolate to the sterically less-encumbered aldehyde pi-face of an intramolecularly hydrogen-bonded chelate through a Zimmerman-Traxler type transition structure. Stereochemical assignments are supported by single-crystal X-ray diffraction analysis of 5b-O-3,5-dinitrobenzoate, iso-5b, N-Me-iso-5b-O-3,5-dinitrobenzoate, and 7b. As revealed by HPLC analysis, optical purity of the stereochemically labile alpha-aminoaldehydes is completely preserved under the conditions of hydrogen-mediated aldol coupling. Deletion of the intramolecular hydrogen bond, as in the case of N-methyl-N-Boc-l-leucinal N-Me-5a, inverts stereoselectivity to furnish the Felkin-Anh product N-Me-iso-5b in 17% yield. Additionally, reactions performed in the presence of tert-amyl alcohol (10 equiv) exhibit markedly lower levels of anti-Felkin-Anh control (7:1 versus > or = 20:1). The collective studies suggest that intramolecular hydrogen bonding plays a key role in both activating the alpha-aminoaldehyde toward addition and directing facial selectivity. SN - 0002-7863 UR - https://www.unboundmedicine.com/medline/citation/17177457/Asymmetric_induction_in_hydrogen_mediated_reductive_aldol_additions_to_alpha_amino_aldehydes_catalyzed_by_rhodium:_selective_formation_of_syn_stereotriads_directed_by_intramolecular_hydrogen_bonding_ L2 - https://doi.org/10.1021/ja066198q DB - PRIME DP - Unbound Medicine ER -