title: Highly enantioselective phase-transfer-catalyzed alkylation of protected alpha-amino acid amides toward practical asymmetric synthesis of vicinal diamines, alpha-amino ketones, and alpha-amino alcohols.
abstract: Highly enantioselective alkylation of protected glycine diphenylmethyl (Dpm) amide 1 and Weinreb amide 10 has been realized under phase-transfer conditions by the successful utilization of designer chiral quaternary ammonium salts of type 4 as catalyst. Particularly, remarkable reactivity of the chiral ammonium enolate derived from 1b and 4c allowed the reaction with less reactive simple secondary alkyl halides with high efficiency and enantioselectivity. An additional unique feature of this chiral ammonium enolate is its ability to recognize the chirality of beta-branched primary alkyl halides, which provides impressive levels of kinetic resolution and double stereodifferentiation during the alkylation, allowing for two alpha- and gamma-stereocenters to be controlled. Combined with the subsequent reduction using LiAlH4 in cyclopentyl methyl ether (CPME), this system offers a facile access to structurally diverse optically active vicinal diamines. Furthermore, the optically active alpha-amino acid Weinreb amide 11 can be efficiently converted to the corresponding amino ketone by a simple treatment with Grignard reagents. In addition, reduction and alkylation of the optically active alpha-amino ketone into both syn and anti alpha-amino alcohols with almost complete relative and absolute stereochemical control have been achieved. With (S,S)- and (R,R)-4 in hand, the present approach renders both enantiomers of alpha-amino amides including Weinreb amides readily available with enormous structural variation and also establishes a general and practical route to vicinal diamines, alpha-amino ketones, and alpha-amino alcohols with the desired stereochemistry.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ooi
authors.forename: Mifune
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kato
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Uematsu
authors.forename: Eiji
authors.initials: E
authors.lastname: Tayama
authors.forename: Daiki
authors.initials: D
authors.lastname: Sakai
authors.forename: Keiji
authors.initials: K
authors.lastname: Maruoka
mesh_terms: D000478:Alkylation; D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D000605:Amino Alcohols / Q000138:chemical synthesis*; D001559:Benzhydryl Compounds / Q000737:chemistry; D002384:Catalysis; D003959:Diamines / Q000138:chemical synthesis*; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: D000577:Amides; D000596:Amino Acids; D000605:Amino Alcohols; D001559:Benzhydryl Compounds; D003959:Diamines; D007659:Ketones; C018556:glycine amide; D005998:Glycine