Lewis Acid‐Assisted Ene Cyclization of 2‐Azetidinone‐Tethered Enals: Synthesis of Enantiopure Carbacepham Derivatives |
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Authors: | Benito Alcaide Prof?Dr Pedro Almendros Dr Carmen Pardo Prof Carolina Rodríguez‐Ranera Dr Alberto Rodríguez‐Vicente Dr |
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Institution: | 1. Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense de Madrid, E‐28040 Madrid (Spain), Fax: (+34)?91‐3944103;2. Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas, CSIC, Juan de la Cierva 3, 28006 Madrid (Spain), Fax: (+34)?91‐5644853 |
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Abstract: | Diastereocontrolled Lewis acid‐catalyzed preparation of enantiopure carbacepham derivatives have been developed starting from 2‐azetidinone‐tethered enals. The BF3?Et2O‐promoted reaction of alkenylaldehydes 1 and 16 is effective as carbocyclization protocol to afford 4‐substituted 5‐hydroxycarbacephams or 3‐substituted 4,5‐dihydroxycarbacephams, respectively, by a type I carbonyl‐ene reaction, while the BF3?Et2O or SnCl4‐mediated type II carbonyl‐ene cyclization of alkenylaldehydes 2 furnishes 3‐methylene 5‐hydroxycarbacephams along with the corresponding 3‐halo 5‐hydroxycarbacepham. The stereochemical outcome of these carbonyl‐ene cyclizations leading to carbacepham derivatives can be explained in terms of six‐membered, cyclic chair‐like transition‐state models. The formation of halocarbacepham derivatives is proposed to proceed by a stepwise mechanism. |
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Keywords: | aldehydes alkenes cyclization ene reaction lactams |
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