Intramolecular vinylation of carbanions using N-acyl benzomorpholines as masked vinylureas and vinylcarbamates

Treatment of urea or carbamate derived benzomorpholines with lithium diisopropylamide generates N-vinyl ureas or N-vinyl carbamates by elimination of a phenoxide anion, cleaving the benzomorpholine ring. Simultaneous formation of a carbanion a to a stabilising aryl or nitrile group allows migration of the newly formed N-vinyl substituent to the carbanionic centre, in some cases with high enantiospecificity. Mild hydrolysis of the resulting urea or carbamate returns a C-vinylated amine, alcohol or hydantoin, in some cases with high enantiomeric purity. This 'masked' vinylation strategy avoids the need to use the reactive and volatile vinyl isocyanate as a starting material. (C) 2017 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved

Medium-Ring Nitrogen Heterocycles through Migratory Ring Expansion of Metalated Ureas

Simple benzo-fused nitrogen heterocycles (indolines, tetrahydroquinolines, and their homologues) undergo migratory ring expansion through deprotonation of their benzylic urea derivatives with lithium diisopropylamide (LDA) in the presence of N,N′-dimethylpropylideneurea (DMPU). The products of the reactions are benzodiazepines, benzodiazocines, and their homologues, with ring sizes of 8–12. The reactions tolerate a range of substituent patterns and types, and may exhibit enantiospecificity or diastereoselectivity. Considerable complexity is rapidly generated in an efficient synthesis of these otherwise difficult-to-obtain medium-ring nitrogen heterocycles

Synthesis of Isothiocineole and Application in Multi-gram Scale Sulfur Ylide-mediated Asymmetric Epoxidation and Aziridination

The synthesis of the chiral sulfide isothiocineole from limonene and elemental sulfur on multi-gram scale and its alkylation to make >50 g of the corresponding benzylsulfonium salt are described. The application of this salt to the sulfur ylide-mediated asymmetric epoxidation of aldehydes and the asymmetric aziridination of imines on a >5 g scale is demonstrated.Irish Research CouncilScience Foundation IrelandUniversity of BristolMarie-Curie Action COFUN

Synthesis of Isothiocineole and Application in Multigram-Scale Sulfur Ylide Mediated Asymmetric Epoxidation and Aziridination

The synthesis of the chiral sulfide isothiocineole from limonene and elemental sulfur on multi-gram scale and its alkylation to make >50 g of the corresponding benzylsulfonium salt are described. The application of this salt to the sulfur ylide-mediated asymmetric epoxidation of aldehydes and the asymmetric aziridination of imines on a >5 g scale is demonstrated

Synthesis of 6- and 7‑Membered <i>N</i>‑Heterocycles Using α‑Phenylvinylsulfonium Salts

A concise synthesis of stereodefined <i>C</i>-substituted morpholines, piperazines, azepines, and oxazepines in moderate to excellent yields (27% to 75%) is reported by reaction of 1,2- or 1,3-amino alcohol/1,2- or 1,3-diamine with an α-phenylvinylsulfonium salt. High levels of regio- and diastereoselectivity (from 2:1 to >20:1) are observed through judicious choice of base (Cs₂CO₃) and solvent (CH₂Cl₂). Reactions are performed at ambient temperature and open to air and do not require anhydrous solvent. The deprotection of the <i>N</i>-sulfonamide protecting groups (<i>N</i>-Ts and <i>N</i>-Ns) is also demonstrated. Factors affecting regio- and diastereocontrol are discussed