Synthesis of α-(Trifluoromethyl)styrenes and 1,3-Di(trifluoromethyl)indanes via Electrophilic Activation of TMS Ethers of (Trifluoromethyl)benzyl Alcohols in Brønsted Acids

Abstract

TMS ethers of CF3-benzyl alcohols (and their heterocyclic analogues) undergo elimination of TMSOH molecule with the formation of α-(trifluoromethyl)styrenes in yields of up to 90% under the action of strong Brønsted acids TfOH or H2SO4. Under the acidic conditions upon prolongation of the reaction, the α-(trifluoromethyl)styrenes are further dimerized into cis-/trans-1,3-di(trifluoromethyl)indanes in yields of up to 100%. Plausible reaction mechanisms of these electrophilic transformations including the intermediate formation of CF3-benzyl carbocations are discussed.

TfOH-promoted multichannel transformations of trifluoromethyl side chain substituted thiophene and furan families to access antimicrobial agents

“…We further investigated some of the thiophenes and (benzo)furans obtained in this work 2-6, 8, 9, 11, 13, and 14 (Fig. S268, ESI ‡) and structurally close substrata from our previous study 2, 3, 5, 6, and 16-18 24,28 For 66 out of the 95 tested objects, the MIC values are 256 mg mL À1 for S. aureus and 128 mg mL À1 for E. coli and C. albicans. Three compounds exhibit better biological activity: thiophenes 3kb and 2dd suppress S. aureus strains at a concentration of 128 mg mL À1 , whereas the derivative of 2chlorofurfural 2cf demonstrates the best result of a MIC of 64 mg mL À1 against C. albicans (Fig.…”

“…of 1,3-di(trifluoromethyl)indane-like carboheterocyclic structures VI (Scheme 1), which are products of electrophilic ''dimerization'' of starting compounds. 24,28 Furan derivatives 1a and c (with R = H) successfully react with sterically hindered arenes (durene, pseudocumene, and mesitylene), yielding arylation products 2ae-2ag, 2cd and ce in yields of 62-100% (Scheme 3). At the same time, bromosubstituted thiophene 1j upon interaction with such arenes undergoes a side chain arylation and hydrodehalogenation, giving compounds V (Scheme 1) (see our previous data 24 ).…”

“…On the other hand, trifluoropropyl substituted compounds 1b , d , e , and g do not react with benzene as a nucleophile, resulting in the formation of 1,3-di(trifluoromethyl)indane-like carboheterocyclic structures VI (Scheme 1), which are products of electrophilic “dimerization” of starting compounds. 24,28…”

“…The properties of compounds 1b, 1d, and 1e and 1f, 1g, and 1j were given in our preliminary communications. 24,28 (1-(Benzofuran-2-yl)-2,2,2-trifluoroethoxy)trimethylsilane (1a). It was obtained from benzofuran-2-carbaldehyde (734.0 mg, 5.0 mmol) at room temperature for 1.5 h. Yield of 1.303 g (90%).…”

Base-catalyzed addition of silylacetylenes to ketones: a route to protected tertiary propargyl alcohols

“…To the best of our knowledge, this is the first example of direct elimination of –OTMS group from alkynols leading to enynes (please note that recently, Vasilyev reported on similar acid-mediated elimination of TMS ethers of CF 3 -benzyl alcohols). 57 To date, unprotected alkynols were generally converted to enynes by using methanesulfonyl chloride/triethylamine system. Lastly, our initial idea was to deliver a sustainable synthetic protocol.…”