Asymmetric Synthesis of α‑Allyl-α-Aryl α‑Amino Acids by Tandem Alkylation/π-Allylation of α‑Iminoesters

• Published in: Organic letters Vol. 16; no. 7; pp. 1948 - 1951
• Main Authors: Curto, John M, Dickstein, Joshua S, Berritt, Simon, Kozlowski, Marisa C
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 04.04.2014; Amer Chemical Soc
• Subjects: Alkylation; Amino Acids - chemical synthesis; Amino Acids - chemistry; Carboxylic Acids; Catalysis; Chemistry; Chemistry, Organic; Combinatorial Chemistry Techniques; Esters; Imines - chemistry; Letter; Molecular Structure; Physical Sciences; Proline - analogs & derivatives; Proline - chemical synthesis; Proline - chemistry; Science & Technology; Stereoisomerism; KETONES; ENANTIOSELECTIVE SYNTHESIS; MANNICH REACTIONS; CRYSTAL-STRUCTURE; PHASE-TRANSFER; ISOMERIZATION; N-ALKYLATION; DIALKYLZINC REAGENTS; RECENT PROGRESS; STEREOSELECTIVE-SYNTHESIS
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol500506t

The first asymmetric synthesis of α-allyl-α-aryl α-amino acids by means of a three-component coupling of α-iminoesters, Grignard reagents, and cinnamyl acetate is reported. Notably, the enolate from the tandem process provides a much higher level of reactivity and selectivity than the same enolate generated via direct deprotonation, presumably due to differences in the solvation/aggregation state. A novel method for removal of a homoallylic amine protecting group delivers the free amine congeners. The α-allyl group offers a means to generate further valuable α-amino acid structures as exemplified by ring closing metathesis to generate a higher ring homologue of α-aryl-proline.