Unprecedented “On-Water” Nucleophilic Addition of Organolithiums and Grignard Reagents to Imines and Nitriles

Despite their enormous synthetic relevance, the use of polar organolithium and Grignard reagents is greatly limited by their requirements of low temperatures in order to control their reactivity as well as the need of dry organic solvents and inert atmosphere protocols to avoid their fast decomposition. One of most momentous challenges in organic synthesis is to perfect the use of polar organometallics under air at room temperature, also replacing harsh and volatile organic compounds by more environmentally benign solvents (1). Building on our recent findings (2,3,4), in this Communication we describe an unprecedented nucleophilic addition of Grignard and organolithium reagents to both aliphatic and aromatic imines and nitriles under “on water” conditions (5). It will be shown that, under optimized protocols, the above additions can be conveniently and safely run at room temperature and under air en route to secondary amines and tertiary carbinamines, which were isolated in up to >98% yield (Scheme 1). This methodology opens up new opportunities to push even more polar organometallic chemistry towards “green” horizons.1. García-Álvarez, J.; Hevia, E.; Capriati, V. Eur. J. Org. Chem. 2015, 6779–6799. 4. 2. Mallardo, V.; Rizzi, R.; Sassone, F. C.; Mansueto, R.; Perna, F. M.; Salomone, A.; Capriati, V. Chem. Commun. 2014, 50, 8655–8658. 3. Sassone, F. C.; Perna, F. M.; Salomone, A.; Florio, S.; Capriati, V. Chem. Commun. 2015, 51, 9459–9462. 4. Cicco, L.; Sblendorio, S.; Mansueto, R.; Perna, F. M.; Salomone, A.; Florio, S.; Capriati. V. Chem. Sci. 2015, 7, 1192–1199. 5. Butler, R. N.; Coyne, A. G. Org. Biom. Chem. 2016, 14, 9945–9960