Approach to Chiral 1‑Substituted Isoquinolone and 3‑Substituted Isoindolin-1-one by Addition–Cyclization Process

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.