Urea-Catalyzed Vinyl Carbocation Formation Enables Mild Functionalization of Unactivated C–H Bonds

Abstract

Herein we report the 3,5bistrifluoromethylphenyl urea-catalyzed functionalization of unactivated C-H bonds. In this system, the urea catalyst mediates the formation of high-energy vinyl carbocations that undergo facile C-H insertion and Friedel-Crafts reactions. We introduce a new paradigm for these privileged scaffolds where the combination of hydrogen bonding motifs and strong bases affords highly active Lewis acid catalysts capable of ionizing strong C-O bonds. Despite the highly Lewis acidic nature of these catalysts that enables triflate abstraction from sp 2 carbons, these newly found reaction conditions allow for the formation of heterocycles and tolerate highly Lewis basic heteroaromatic substrates. This strategy showcases the potential utility of dicoordinated vinyl carbocations in organic synthesis.

A Pyridine‐StabilizedN‐PhosphinoamidinatoN‐Heterocyclic Carbene‐Diboravinyl Cation: Boron Analogue of Vinyl Cation

“…However, high intrinsic kinetic barrier arising from sp 2 ‐C↔ sp ‐C rehybridization makes the formation of vinyl cations sluggish [3] . Recently, a major breakthrough in overcoming the high intrinsic kinetic barrier was achieved by using catalysts containing weakly coordinating anions (WCAs) such as [Et 3 Si][HCB 11 Cl 11 ] (Figure 1a), [4] Li[Al(OC(CF 3 ) 3 ) 4 ], [5] [Ph 3 C][B(C 6 F 5 ) 4 ] [6] and Li[Urea] [7] . The role of WCAs is to enhance the Lewis acidity of the cations to abstract the leaving group X − , as well as to stabilize the generated vinyl cation intermediates.…”

Decarboxylative Claisen Condensations with Substituted Malonic Acid Half Oxyesters

“…R f = 0.33 (cyclohexane/EtOAc, 90:10). 33 Following GP1 performed with SMAHO 1c (131 mg, 0.75 mmol, 1.5 equiv) and p-toluoyl chloride (2c; 66 L, 0.5 mmol, 1.0 equiv), the desired product was obtained after purification by flash chromatography [silica gel, 50 mL, cyclohexane/EtOAc, 95:5 (250 mL), 90:10 (250 mL)] as a colorless oil; yield: 112 mg (90%). R f = 0.37 (cyclohexane/EtOAc, 90:10).…”

Unactivated C(sp3)-H functionalization via vinyl cations

“…It was found that various functional groups could be compatible with the system, such as pinacol boronic ester, chloro, bromo, and iodo, which were unreactive under previously reported silylium conditions. A shortcome of the In an effort to extend the range of catalysts for these fascinating transformations, the same group recently discovered 3,5-bistrifluoromethylphenyl ureas, common hydrogenbonding motifs, could catalyze C-H insertion reactions of vinyl triflates 16 under basic conditions (Scheme 6) [17]. Highly active lithiated urea catalyst, which could ionize strong C-O bonds and abstract triflate from sp 2 carbons, were generated from the combination of ureas and strong bases.…”