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

摘要

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 a-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 >= 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.