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Domino Reaction of 1,3‐Bis(trimethylsilyloxy)‐1,3‐dienes with Oxalyl Chloride: General and Stereoselective Synthesis of γ‐Alkylidenebutenolides
Author(s) -
Langer Peter,
Schneider Toni,
Stoll Martin
Publication year - 2000
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20000901)6:17<3204::aid-chem3204>3.0.co;2-g
Subject(s) - chemistry , lewis acids and bases , synthon , steric effects , stereoselectivity , trimethylsilyl trifluoromethanesulfonate , oxalyl chloride , medicinal chemistry , amide , stereochemistry , catalysis , organic chemistry
The Lewis acid catalyzed cyclization of oxalyl chloride with 1,3‐bis(trimethylsilyloxy)‐1,3‐dienes 3 , derived from 1,3‐dicarbonyl compounds 1 , provides a new and general approach for the synthesis of γ‐alkylidenebutenolides 4 , a pharmacologically and synthetically important class of substances. A variety of butenolides were efficiently prepared in good yields and with very good regio‐ and stereoselectivities. An up‐scaling of the reaction was possible. The use of the Lewis acid trimethylsilyl‐trifluoromethanesulfonate (TMSOTf) proved to be superior to other activation conditions. Sterically undemanding γ‐alkylidenebutenolides could be prepared alternatively by reaction of the corresponding 1,3‐dicarbonyl dianions with N , N ′‐dimethoxy‐ N , N ′‐dimethylethanediamide ( 2 d ). In contrast to the dianion method, the Lewis acid catalyzed reaction also facilitated the cyclization of sterically hindered, base‐labile, cyclic and functionalized substrates. From a methodology viewpoint, the dianion reaction represents the first cyclization of a bis‐Weinreb amide and the first cyclization of an oxalic acid‐synthon with an ambident dianion. The TMSOTf‐catalyzed reactions are both the first cyclizations of 1,3‐bis(trimethylsilyloxy)‐1,3‐dienes with a C 2 dielectrophile and the first cyclizations of 1,3‐bis(trimethylsilyloxy)‐1,3‐dienes with a carboxylic acid dichloride or a related dielectrophile.