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Approach to Chiral 1-Substituted Isoquinolone and 3-Substituted Isoindolin-1-one by Addition-Cyclization Process
Wen Zhou1, Yan-Xue Zhang1, Xiao-Di Nie1
1Department of Natural Products Chemistry, School of Pharmacy , Fudan University , 826 Zhangheng Road , Shanghai , 201203 , The People's Republic of China.
Abstract:
An approach to access 1-substituted isoquinolones has been developed through the addition-cyclization of imines with Grignard reagents in the presence of 2,2'-dipyridyl. A number of substituted aromatic magnesium reagents were amenable to this process, and the desired products were obtained with excellent yields and outstanding diastereoselectivities ( dr > 99:1). The utility of this convenient approach is demonstrated by the formal synthesis of ( S)-cryptostyline II. Moreover, N-methylmorpholine (NMM) was found to be an effective additive for the formation of 3-substituted isoindolin-1-ones using one-pot addition-cyclization-deprotection of imine with Grignard reagents.
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