α-Alkylidene-γ-butyrolactone Formation via Bi(OTf)₃-Catalyzed, Dehydrative, Ring-Opening Cyclizations of Cyclopropyl Carbinols: Understanding Substituent Effects and Predicting E/Z Selectivity

Abstract

A Bi(OTf)-catalyzed ring-opening cyclization of (hetero)aryl cyclopropyl carbinols to form α-alkylidene-γ-butyrolactones (ABLs) is reported. This transformation represents different chemoselectivity from previous reports that demonstrated formation of (hetero)aryl-fused cyclohexa-1,3-dienes upon acid-promoted cyclopropyl carbinol ring opening. ABLs are obtained in up to 89% yield with a general preference for the E-isomers. Mechanistically, Bi(OTf) serves as a stable and easy to handle precursor to TfOH. TfOH then catalyzes the formation of cyclopropyl carbinyl cations, which undergo ring opening, intramolecular trapping by the neighboring ester group, subsequent hydrolysis, and loss of methanol resulting in the formation of the ABLs. The nature and relative positioning of the substituents on both the carbinol and the cyclopropane determine both chemo- and stereoselective outcomes. Carbinol substituents determine the extent of cyclopropyl carbinyl cation formation. The cyclopropane donor substituents determine the overall reaction chemoselectivity. Weakly stabilizing or electron-poor donor groups provide better yields of the ABL products. In contrast, copious amounts of competing products are observed with highly stabilizing cyclopropane donor substituents. Finally, a predictive model for E/Z selectivity was developed using DFT calculations.

Urea-Catalyzed Functionalization of Unactivated C–H Bonds

“…6,7 Specifically we were inspired by Reisman and Jacobsen's use of thioureas to generate resonance-stabilized tricoordinate carbocations that engage in highly-selective bond-forming processes (Figure 1b). 8 The same group later showed that squaramides, combined with trimethylsilyl triflate (TMSOTf), enhance the electrophilicity of the silicon center via triflate binding. 9 Inspired by these studies, we sought to apply an analogous mode of ionization to vinyl triflates, which would provide vinyl cations capable of C-C bond-forming reactions.…”

“…Having found that urea catalyst 4 afforded the desired product in the highest yield, we next explored the effect of catalyst substitution on the product outcome. Probing monosubstituted trifluoromethyl urea catalysts (6)(7)(8) revealed the importance of a meta-trifluoromethyl group (79% yield for entry 10 vs. 3-9% yield for entries 9 and 11). Lastly, the N-methylated catalyst 9 delivered the desired product in a meager 19% yield, highlighting the importance of having both N-H hydrogenbond donors (entry 12).…”

Urea-Catalyzed Functionalization of Unactivated C–H Bonds

“…6,7 Specifically we were inspired by Reisman and Jacobsen's use of thioureas to generate resonance-stabilized tricoordinate carbocations that engage in highly-selective bond-forming processes (Figure 1b). 8 The same group later showed that squaramides, combined with trimethylsilyl triflate (TMSOTf), enhance the electrophilicity of the silicon center via triflate binding. 9 Inspired by these studies, we sought to apply an analogous mode of ionization to vinyl triflates, which would provide vinyl cations capable of C-C bond-forming reactions.…”

“…Having found that urea catalyst 4 afforded the desired product in the highest yield, we next explored the effect of catalyst substitution on the product outcome. Probing monosubstituted trifluoromethyl urea catalysts (6)(7)(8) revealed the importance of a meta-trifluoromethyl group (79% yield for entry 10 vs. 3-9% yield for entries 9 and 11). Lastly, the N-methylated catalyst 9 delivered the desired product in a meager 19% yield, highlighting the importance of having both N-H hydrogenbond donors (entry 12).…”