Base-Catalyzed Transesterification of Thionoesters

Abstract

Here we report a convenient synthesis of thionoesters by base-catalyzed transesterification. Benzyl and alkyl thionobenzoates and thionoheterobenzoates were efficiently prepared using various alcohols catalyzed by the corresponding sodium alkoxide. This methodology features a broad substrate scope, good to excellent yields, short reaction times, while simultaneously driving the reaction toward completion through the removal of the methanol byproduct. We also report the conversion of a small collection of thionobenzoates into the corresponding α,α-difluorobenzyl ethers to demonstrate the conversion of alcohols into difluorobenzyl or difluoroheterobenzyl ethers, a process that could prove useful for lead optimization in medicinal chemistry.

A Convenient Synthesis of Difluoroalkyl Ethers from Thionoesters Using Silver(I) Fluoride

“…Considering the widespread applications of difluoroalkyl ethers, many strategies have been developed for their synthesis, some of which are summarized in Figure . Prominent among these approaches is fluorodesulfurization using highly reactive fluorinating agents including SF 4 gas or BrF 3 (Type I), or combinations of oxidizing agents with hydrofluoric acid (Type II) . Alternatively, both DAST and DeoxoFluor (Type III) have demonstrated utility in the deoxyfluorination or fluorodesulfurization of esters or thionoesters, respectively.…”

“…Considering that AgF is similar in cost to aminosulfuranes and relatively nontoxic, this convenient process represents an excellent alternative to all existing strategies used for the fluorination of thionoesters. To assess the scope of AgF fluorination, several thionoesters were readily prepared through reaction of the corresponding ester with Lawesson's reagent, and/or transesterification . As summarized in Figure , a wide range of thionoesters could be rapidly converted into difluoroalkyl ethers at room temperature using this straightforward protocol.…”

“…To assess the scope of AgF fluorination, severalt hionoesters were readily prepared through reactiono ft he corresponding ester with Lawesson's reagent, [19] and/or transesterification. [10] As summarized in Figure2,awide range of thionoestersc ould be rapidlyc onverted into difluoroalkyl ethers at room temperature using this straightforward protocol. Notably,a cid-sensitivef unctionalities including oxetanesa nd acetalsw ere fully compatible as were Scheme1.Discovery of AgF-promoted difluoroalkyl ether synthesis.…”

β‐Ketoesters: An Overview and It's Applications via Transesterification

“…Iron(III) dimer complex, [31] Modified Vilsmeier-Haack reagents TCCA/DMF, TCTA/DMF (SOCl 2 /DMF, POCl 3 /DMF), [32] FeÀ Mn cyanide, [33] Stefan et. al., reported the boronic acid synthesis via monophasic transesterification by evaporation of reagents/ byproducts, [34] Zn-PAM, [35] MCS, [36] ultrasonic technique, [37] DBU-CO 2 , [38] enzymatic transesterification, [39] M 2 CO 3 or MI (M = Li, Na, K, Cs), [40] pPh-SO 3 H & pBPA-SO 3 H, [41] Ti(Oi-pr) 4 , [42] NaOR, [43] Metal/ ETS-10, [44] BBAIL, [45] EmimOAc, [46] BF 3 .OEt 2 , [47] Zn(Me) 2 , [48] N-Heterocyclic olefins, [49] microwave irradiation, [50] dilithium tetra-tertbutylzincate, [51] K 2 CO 3 /DMSO, [52] Ionic liquid (references therein), [53] methylboronic acid, [54] AuÀ Cu nanoparticles, [55] CO 2 / Novozym-435, [56] CuFe 2 O 4 , [57] Cesium carbonate, [58] Ion-exchange resins (Lewatit K1221), [59] imidazolium ionic liquids, [60] 4-(3methyl-1-imidazolio)-1-butanesulfonic acid triflate, [61] Mn(II) Carbonate & Mn(II)Sulfate, [62] DBU at high pressure, [63] ball-mill technique, [64] AgOTf, [65] Sol-Gel MoO 3 /TiO 2 , [66] lipase from Aspergillus niger, [67] TEA, [68] Sn-catalyst, [69] lanthanum(III) Isopropoxide, [70] Candida rugo...…”

Dithioesters: simple, tunable, cysteine-selective H2S donors

“…We recently demonstrated that related thionoesters, which are structural isomers of thioesters bearing a thiocarbonyl motif, undergo a chemoselective reaction with cysteine to generate a dihydrothiazole and hydrogen sulfide (H 2 S) 4. Despite recent advancements in the synthesis of thionoesters,5 the ability to prepare a diverse library of thionoester-based H 2 S donors is limited by the availability of stable, readily-accessible starting materials. However, based on structural similarities between thionoesters and dithioesters, we hypothesized that dithioesters could provide similar reactivity in the presence of cysteine and allow for the development of tunable H 2 S donors with precise control over H 2 S release rates and efficiencies.…”