Synthesis of γ‐Spirolactams by Birch Reduction of Arenes. Issue 10 (23rd February 2021)

• Record Type: Journal Article
• Authors: Krüger, Tobias; Linker, Torsten
• Is Part Of: European journal of organic chemistry. Issue 10(2021)
• Page Start: 1585
• Page End: 1591
• Publication Date: 2021-02-23
• Subjects: Arenes -- Birch reduction -- Hydrogenation -- Lactams -- Synthetic methods; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202100056
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: A convenient method for the synthesis of γ‐spirolactams in only three steps is described. Birch reduction of inexpensive and commercially available aromatic carboxylic acids in the presence of chloroacetonitrile affords nitriles in moderate to good yields. Suitable precursors are methyl‐substituted benzoic acids, naphthoic, and anthroic acid. Subsequent catalytic hydrogenation proceeds smoothly with PtO2 or Raney Ni as catalysts and lactams are isolated in excellent yields and stereoselectivities. Thus, up to 3 new stereogenic centers can be constructed as sole diastereomers from achiral benzoic acids. Furthermore, it is possible to control the degree of saturation at different pressures, affording products with 0, 1, or 2 double bonds. Overall, more than 15 new γ‐spirolactams have been synthesized in analytically pure form. Abstract : Birch reduction of arene carboxylic acids in the presence of chloroacetonitrile affords nitriles and their subsequent catalytic hydrogenation γ‐spirolactams in only 3 steps with excellent stereoselectivities. It is possible to control the degree of saturation by variation of the catalyst at different pressures. Thus, more than 15 new γ‐spirolactams have been synthesized from inexpensive starting materials.