Design of a Mesoscale Continuous-Flow Route toward Lithiated Methoxyallene.

The unique nucleophilic properties of lithiated methoxyallene allow for C-C bond formation with a wide variety of electrophiles, thus introducing an allenic group for further functionalization. This approach has yielded a tremendously broad range of (hetero)cyclic scaffolds, including precursors to active pharmaceutical ingredients. To date, however, its valorization at scale is hampered by the batch synthesis procedure, which suffers from serious safety issues.

Selective synthesis of cis- and trans-2-(methyl/phenyl)-3-(trifluoromethyl)aziridines and their regio- and stereospecific ring opening.

A convenient and stereoselective approach toward cis- and trans-1-alkyl-2-(methyl/phenyl)-3-(trifluoromethyl)aziridines was developed starting from the corresponding α,α,α-trifluoroketones via imination, α-chlorination, and hydride-induced ring closure. The reactivity of these newly synthesized nonactivated α-CF3-aziridines was evaluated by applying N-protonation or N-alkylation to effect regio- and stereospecific aziridine ring opening by oxygen, halogen, sulfur, and nitrogen nucleophiles. Furthermore, nonactivated α-CF3-aziridines were easily transformed into their activated analogues by replacing the N-benzyl protecting group with a N-tosyl group, rendering these α-CF3-aziridines much more susceptible to nucleophilic ring opening.