title: 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.
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.affiliation: Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Cheol-Kyu
authors.initials: CK
authors.lastname: Jung
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Krische
mesh_terms: D000438:Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D006859:Hydrogen / Q000737:chemistry*; D006860:Hydrogen Bonding; D006865:Hydrogenation; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D012238:Rhodium / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D014961:X-Ray Diffraction
chemical_list: D000438:Alcohols; D000447:Aldehydes; D007659:Ketones; D009942:Organometallic Compounds; D006859:Hydrogen; D012238:Rhodium