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 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

Synthesis of α‑Substituted Vinylsulfonium Salts and Their Application as Annulation Reagents in the Formation of Epoxide- and Cyclopropane-Fused Heterocycles

The discovery of new methods for the synthesis of classes of potentially bioactive molecules remains an important goal for synthetic chemists. Vinylsulfonium salts have been used for the synthesis of a wide variety of small heterocyclic motifs; however, further developments to this important class of reagents has been focused on reaction with new substrates rather than development of new vinylsulfonium salts. We herein report the synthesis of a range of α-substituted vinylsulfonium tetraphenylborates (10 examples) in a 3 step procedure from commercially available styrenes. The important role of the tetraphenylborate counterion on the stability and accessibility of the vinylsulfonium salts is also detailed. The α-substituted vinylsulfonium tetraphenylborates gave good to excellent yields in the epoxyannulation of β-amino ketones (15 examples) and the cyclopropanation of allylic amines (4 examples). Hydrogenation of an epoxyannulation product proceeded with good diastereoselectivity