TPGS-750-M: A Second-Generation Amphiphile for Metal-Catalyzed Cross-Couplings in Water at Room Temperature

Abstract

An environmentally benign surfactant (“TPGS-750-M”), a diester composed of racemic α-tocopherol, MPEG-750, and succinic acid, has been designed and readily prepared as an effective nanomicelle-forming species for general use in metal-catalyzed cross-coupling reactions in water. Several “name” reactions, including Heck, Suzuki-Miyaura, Sonogashira, and Negishi-like couplings have been studied using this technology, as have aminations, C-H activations, and olefin metathesis reactions. Physical data in the form of DLS and cryo-TEM measurements suggest that particle size and shape are key elements in achieving high levels of conversion and hence, good isolated yields of products. This new amphiphile will soon be commercially available.

PEGylated γ-tocotrienol isomer of vitamin E: Synthesis, characterization, in vitro cytotoxicity, and oral bioavailability

“…The PEGylated a-tocopherol isomer of vitamin E (vitamin E TPGS) has been 36 extensively investigated for its solubilizing capacity as a nonionic surfactant in various drug delivery 37 systems. Limited information, however, is available about the PEG conjugates of the tocotrienol isomers 38 of vitamin E. In this study two PEGylated c-T 3 variants with mPEG molecular weights of 350 (c-T 3 PGS 39 350) and 1000 (c-T 3 PGS 1000) were synthesized by a two-step reaction procedure and characterized by 40 1 H NMR, HPLC, and mass spectroscopy. The physical properties of their self-assemblies in water were 41 characterized by zeta, CMC, and size analysis.…”

“…Synthesis of c-T 3 succinate166 The procedure for the synthesis of c-T 3 succinate was adapted167 from Lipshutz et al[39]. Briefly, triethylamine (0.09 mL) was168 added to a solution of c-T3 (1.125 g) and succinic anhydride169 (0.4 g) in toluene (5.2 mL) and stirred at 85°C.…”

Nanocatalysts for Hiyama, Stille, Kumada, and Negishi C–C Coupling Reactions

“…Figure 5.12 shows images of PTS and TPGS-750-M polymers. 117 High product yields and improved stereoretention in this medium were noted.…”

“…This method was also seen to be of use in zinc-mediated stereoselective sp 3 −sp 2 cross-couplings between an alkyl and alkenyl halide in the presence of a Pd(II) precatalyst and PTS. Only 2 equivalent of the corresponding alkyl halide and 1 mol% of PdCl 2 (Amphos) 2 117 This surfactant was found to possess a high hydrophilic/lipophilic balance (∼13), and formed micelles of optimal shape and size to facilitate Pd-catalyzed C C cross-couplings, which led the authors to suggest that micelles on the order of 50+ nm best accommodate the components associated with Pd-catalyzed couplings described to date. Figure 5.12 shows images of PTS and TPGS-750-M polymers.…”

Trifluoromethylation of heterocycles in water at room temperature

“…As a test case using aqueous micellar conditions based on our designer surfactant TPGS-750-M 25 (Figure 1), 4- t -butylpyridine ( 1 ) was treated sequentially with NaSO 2 CF 3 and then t -butylhydro-peroxide (TBHP), leading to an encouraging 84% conversion to the anticipated trifluoromethylated product ( 2 ) after 24 hours (Scheme 1), a result that is competitive with literature results on this particular educt. 22 …”