Ketones, alkynyl trifluoromethyl

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

Trifluoromethyl ketones have been alkenylated, alkynylated, and phenylated in high ee using silane reagents and a chiral copper(I)-diphosphine complex.178... 

Alkenylboronic acids and esters underwent conjugated addition to ct,/ -unsaturated ketones in the presence of trifluoroborane etherate589 or cyanuric fluoride (Equation (129)).590,591 Alkadienyl trifluoromethyl ketones were stereoselectively prepared from (2-alkoxyvinyl) trifluoromethyl ketones (Equation (130)).592 Alkynyl boronates can transfer the alkynyl groups regioselectively and enantioselectively to enones (Equation (131 )).593... 

Alkynylation. The reaction of 1-alkynes with trifluoromethyl ketones in water is promoted by AgF (with hgand CysP). ... 

Aryl trifluoromethyl ketones have been alkynylated in high ee using readily available chiral cinchona alkaloids that afford either propargylic tertiary alcohol product... 

The catalytic enantio-selective addition of zinc alkynylides to various trifluo-romethyl ketones with selectivities that surpass 94% ee has been reported. By using 0 pseudoenantiomeric cinchona alkaloids as chiral ligands (e.g. 22), both enantiomers of the trifluoromethylated products were synthesized. The first experimental and computational evidence has been provided in support of alkynyl group transfer from an intermediate complex formed by transmetallation reaction between the alkynylide and the titanium catalyst. 

The route via racemic carbinol 7 requires its derivatization into a mixture of dia-stereomers, their separation by crystallization and final removal of the derivatizing agent [16]. Moreover, the wrong enantiomer of ferf-alcohol 7 cannot be racemized via oxidation-reduction, a process that was successfully applied in the S5mthetic approach to sertraline, as presented in Chap. 7. At Merck Research Laboratories, the enantioselective alkynylation of trifluoromethyl ketone 5 by cyclopropylacety-lene 6 was therefore studied as the key step in the asymmetric s5mthesis of enan-tiopure efavirenz (5)-l (Scheme 13.2) [16]. The observation that the Li-acetylide of... 

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