The indolizine scaffold has attracted considerable interest owing to its broad potential in medicinal chemistry. We describe a photochemical trifluoromethylation that enables direct C‐3 functionalization of indolizines and imidazo[1,2‐ a ]pyridines without the use of a photocatalyst, allowing the reaction to proceed under milder and more environmentally friendly conditions. Mechanistic investigations support the in situ formation of an electron donor–acceptor (EDA) complex. The protocol exhibits broad functional group tolerance, delivering 27 C‐3 trifluoromethylated indolizine and imidazo[1,2‐ a ]pyridine derivatives with yields up to 82%, underscoring its synthetic robustness and versatility. Overall, this methodology simplifies the access to C‐3 functionalized indolizines and facilitates the exploration of new structures with potential biological relevance.
Organic azides are commonly exploited as precursors to a variety of key functional groups that are increasingly relevant in the manufacturing of active pharmaceutical ingredients . Azides allow access to complex nitrogen‐rich heterocyclic structures that are responsible for the bioactive properties of numerous substances. However, organic azide intermediates and the reagents used to synthesize them are associated with relevant safety risks, due to their potential explosivity and toxicity. These problematic features can be tamed with thorough evaluation prior to scale‐up and by establishing the appropriate safety measures. This review provides an overview of the synthetic relevance of azides as reagents and intermediates, with a summary of reagents used in azide formation. The second part of the review provides some general rules for their handling at various stages, from process development to subsequent industrialization. These include dos and don’ts in terms of chemical compatibility, equipment selection and refinement both at lab and plant scale, strategies for azide quenching, and waste handling. The last section is devoted to recent developments in azide chemistry handling in continuous mode.
Nucleophilic vinylic substitution (SNV) reactions of 2,2-diaryl-substituted 1-chlorovinyl p-tolyl sulfoxides with alkynyllithiums yield 2-chloro-substituted conjugated enynes via Csp & horbar; bond formation. Sulfoxide bearing two 4-chlorophenyl groups at the 2-position is highly reactive toward various alkynyllithiums. The reaction proceeds with configuration retention, which suggests that it follows an SNV pi mechanism. DFT calculations support a concerted SNV pi pathway involving simultaneous C & horbar;C bond formation and C & horbar;S bond cleavage, with an activation barrier of 18.7 kcal mol-1.
