Benzylation Reactions in DMF Lead to an Impurity Which Acts as an Organocatalyst Poison in Thiourea-Catalyzed Glycosylations

The benzylation of alcohols with the commonly used combination of benzyl bromide and sodium hydride in DMF can lead to the formation of an amine side product, <i>N</i>,<i>N</i>′-dimethyl-1-phenyl-1-(<i>o</i>-tolyl)­methanamine. This amine coeluted with benzylated galactal during column chromatography and was found to be a catalyst poison in thiourea-catalyzed glycosylations of galactals. It may also be problematic for other base-sensitive reactions involving benzylated substrates. Solutions to this problem are described

Diastereoselective Synthesis of CF₃‑Substituted, Epoxide-Fused Heterocycles with β‑(Trifluoromethyl)vinylsulfonium Salts

CF₃-substituted vinyl diphenylsulfonium triflate is an effective annulation reagent for the formation of α-CF₃ substituted, epoxide-fused heterocycles (pyrrolidines, piperidines, and tetrahydrofurans). This simple method affords a variety of valuable heterocyclic building blocks in a highly diastereoselective manner (dr >20:1)

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

Stereoselective Glycosylation of 2‑Nitrogalactals Catalyzed by a Bifunctional Organocatalyst

The use of a bifunctional cinchona/thiourea organocatalyst for the direct and α-stereoselective glycosylation of 2-nitrogalactals is demonstrated for the first time. The conditions are mild, practical, and applicable to a wide range of glycoside acceptors with products being isolated in good to excellent yields. The method is exemplified in the synthesis of mucin type Core 6 and 7 glycopeptides

Practical and Highly Selective Sulfur Ylide-Mediated Asymmetric Epoxidations and Aziridinations Using a Cheap and Readily Available Chiral Sulfide: Extensive Studies To Map Out Scope, Limitations, and Rationalization of Diastereo- and Enantioselectivities

The chiral sulfide, isothiocineole, has been synthesized in one step from elemental sulfur, γ-terpinene, and limonene in 61% yield. A mechanism involving radical intermediates for this reaction is proposed based on experimental evidence. The application of isothiocineole to the asymmetric epoxidation of aldehydes and the aziridination of imines is described. Excellent enantioselectivities and diastereoselectivities have been obtained over a wide range of aromatic, aliphatic, and α,β-unsaturated aldehydes using simple protocols. In aziridinations, excellent enantioselectivities and good diastereoselectivities were obtained for a wide range of imines. Mechanistic models have been put forward to rationalize the high selectivities observed, which should enable the sulfide to be used with confidence in synthesis. In epoxidations, the degree of reversibility in betaine formation dominates both the diastereoselectivity and the enantioselectivity. Appropriate tuning of reaction conditions based on understanding the reaction mechanism enables high selectivities to be obtained in most cases. In aziridinations, betaine formation is nonreversible with semistabilized ylides and diastereoselectivities are determined in the betaine forming step and are more variable as a result