Employing Small Polyfunctionalized Molecules for a Diastereoselective Synthesis of Highly Substituted Indolines. Issue 24 (21st June 2018)

• Record Type: Journal Article
• Authors: de Souza Fernandes, Fábio; Cormanich, Rodrigo A.; Zeoly, Lucas A.; Formiga, André Luiz B.; Coelho, Fernando
• Is Part Of: European journal of organic chemistry. Issue 24(2018)
• Page Start: 3211
• Page End: 3223
• Publication Date: 2018-06-21
• Subjects: Nitrogen heterocycles -- Palladium -- Cross‐coupling -- Diastereoselectivity -- Density functional calculations; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201800528
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : An efficient approach has been developed for the diastereoselective synthesis of 1, 2, 3‐trisubstituted indolines. The reaction sequence includes the highly diastereoselective reductive amination of 2‐oxo‐1, 3‐propanediols, which are prepared by postfunctionalization of Morita–Baylis–Hillman (MBH) adducts, to give substituted 2‐amino‐1, 3‐propanediols with an anti relative configuration. A subsequent intramolecular palladium‐catalyzed Buchwald coupling reaction provided the 1, 2, 3‐trisubstituted indolines in 47–82 % yield. The preference for the anti diastereomer was investigated by Gibbs free energy diagrams and applying theoretical calculations at the M06–2X/6‐31+G** level. Abstract : We herein have described a straightforward approach for the synthesis of 1, 2, 3‐trisubstituted indolines by using small polyfunctionalized molecules as building blocks. The indolines were prepared in few steps with high trans diastereoselectivity and overall yields of up to 35 %. This is the first report of the synthesis of 1, 2, 3‐trisubstituted indolines from Morita–Baylis–Hillman adducts.