Enantioselective preparation of gamma-amino acids and gamma-lactams from nitro olefins and carboxylic acids, with the valine-derived 4-isopropyl-5,5-diphenyl-1,3-oxazolidin-2-one as an auxiliary

Titanium enolates of acyl-oxazolidinones 1, derived from acetic, propanoic, 3-methylbutanoic, and 4-methylpentanoic acids and 4-isopropyl-5,5-diphenyl -1,3-oxazolidin-2-one, are added to aliphatic and aromatic nitro olefins in the presence of TiCl4 (Schemes 2-4). The products, 4-nitro carboxylic-acid derivatives 2, are formed in high diastereoselectivities (ds 80 to > 99%) and in good yields (50-75% of purified samples of ds > 98%). Hydrogenation over Raney-Ni of the NO2 group in the adducts leads directly to the corresp onding gamma-lactams (3 and 8; 80-92%), with recovery of the insoluble auxi liary (ca. 95%). Ring opening is achieved through the N-Boc-lactams (4),whi ch are converted to N-Boc-protected gamma-amino acids 5 or to their benzyl and methyl esters (6 and 7; Scheme 5). The configuration of the products (c ontaining up to three new stereogenic centers; Scheme 1) is assigned by com parison with literature data, by X-ray crystal-structure analysis (for 2c, g, f, 8, Fig.),and by analogy. Thus, the (S)-auxiliary gives rise to combin ation of the trigonal centers of enolate and nitro olefin with Si/Si topici ty (relative topicity all-lk; cf. A).