Synthesis of Substituted Quinolines Using the Dianion Addition of N-Boc-anilines and α-Tolylsulfonyl-α,β-unsaturated Ketones

• Published in: Journal of organic chemistry Vol. 67; no. 26; pp. 9182 - 9185
• Main Authors: Swenson, Rolf E, Sowin, Thomas J, Zhang, Henry Q
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 27.12.2002; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; ACID-DERIVATIVES; METHODOLOGY; METALATION; REAGENTS; RECEPTOR ANTAGONISTS; COMBINATORIAL SYNTHESIS; INHIBITORS; ANTI-HIV-1 AGENTS; Michael addition; Regioselectivity; Sulfone; Knoevenagel condensation; Nitrogen heterocycle; Quinoline derivatives; Lithium Chlorides; Aniline derivatives; Aldehyde; Ketone; Alkylation; Organic anion; Copper Cyanides; Bicyclic compound; Aromatic compound; Chemical synthesis; Enone; Ethylenic compound; Halogen Organic compounds
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0203387

A short and versatile synthesis of substituted quinolines is provided. Alkylation of sodium tolylsulfinate with bromomethyl- or chloromethyl ketones generates β-keto sulfones. Knoevenagel condensation of the β-keto sulfones with an aldehyde provides α-tolylsulfonyl-α,β-unsaturated ketones. Michael addition of the dianion of N-Boc-anilines in the presence of CuCN and LiCl with the unsaturated ketone generates a 1,4-adduct, which after deprotection of the Boc group and thermal elimination of the tolyl sulfone provides the quinoline.