Enantioselective Preparation of <i>γ</i> ‐Amino Acids and <i>γ</i> ‐Lactams from Nitro Olefins and Carboxylic Acids, with the Valine‐Derived 4‐Isopropyl‐5,5‐diphenyl‐1,3‐oxazolidin‐2‐one as an Auxiliary

Abstract

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 corresponding γ-lactams (3 and 8; 80 – 92%), with recovery of the insoluble auxiliary (ca. 95%). Ring opening is achieved through the N-Boc-lactams (4), which are converted to N-Boc-protected γ-amino acids 5 or to their benzyl and methyl esters (6 and 7; Scheme 5). The configuration of the products (containing up to three new stereogenic centers; Scheme 1) is assigned by comparison 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 combination of the trigonal centers of enolate and nitro olefin with Si/Si topicity (relative topicity all-lk; cf. A).