Organogel delivery vehicles for the stabilization of organolithium reagents.

Organolithium reagents are a vital tool in modern organic chemistry, enabling the synthesis of carbon-carbon bonds. However, due to their high reactivity, low temperatures, inert atmospheres and strictly dried solvents are usually necessary for their use. Here we report an encapsulating method for the stabilization of sensitive organolithium reagents-PhLi, n-BuLi and s-BuLi-in a low-cost hexatriacontane (C36H74) organogel. The use of this technology is showcased in nucleophilic addition reactions under ambient conditions, low-temperature bromine-lithium exchange, ortho-lithiation and C-H functionalization. The gel substantially enhances organolithium stability, allows simple storage, handling and delivery, and enables reproducible reagent portioning. The use of gels as easily divided delivery vehicles for hazardous organometallics has the potential to transform this area of synthetic chemistry, making these powerful reactions safer and more accessible to non-specialist researchers, and enabling the more widespread use of these common synthetic methods.

Lithiation Substitution of Unprotected Benzyltetrazoles.

1H-Tetrazoles occupy an important role in modern medicinal chemistry, but few methods for their modification exist. Many extant protocols require the use of a difficult to remove N-alkyl-protecting group, precluding the products from use as carboxylate bioisosteres, the major role of tetrazoles in pharmaceuticals. We herein report a convenient, protecting-group-free lithiation-substitution protocol for benzylic tetrazoles. Metalation with n-BuLi at 0 °C followed by electrophilic trapping gave a range of α-functionalized benzyltetrazoles in up to 91% yield.