Aryl trifluoromethyl ketones

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

A new, efficient and general synthesis of 4-amino-3-arylcinnolines has been described recently, starting from arylhydrazines and aryl trifluoromethyl ketones, and the following is a typical example. Addition of a THF solution of the hydrazone formed from phenylhydrazine and 2-trifluoroacetylthiophene to 5 equivalents of KHMDS in THF at -78°C, then slow warming of the mixture to room temperature and stirring at room temperature for several hours, gave 4-amino-3-(2-thienyl)cinnoline in 68% yield after work-up (quench with ether, then a wash with brine). 

The impact of a carbonyl group on the chemical shift of a CF3 group somewhat emulates the effect of other electronegative substituents. As indicated by the examples of aldehyde and ketones in Scheme 5.28, when the carbonyl carbon is directly attached to the CF3 group, it causes shielding of the CF3 fluorines. Note that aryl trifluoromethyl ketones are considerably less shielded than are alkyl trifluoromethyl ketones. The fluorine signal of trifluoromethyl ketones of course always appears as a sharp singlet. The spectrum of l,l,l-trifluoromethyl-2-butanone, as... 

Various alkyl halides may be used to obtain phosphorus ylides. The dibromodifluoromethane/ triphenylphosphane and sodium ehlorodifluoroacetate/triphenylphosphaiie systems have been employed to synthesize 2-arylpentafluoropropenes 12 from aryl trifluoromethyl ketones. 

In the same way as a,a,(Z-trihalogenated carbonyl compounds are cleaved hydrolytically to produce haloforms, the fluorinated analogs also react by release of trifluoromethane. The fluoroform reaction has been described with aldehydes such as trifluoroacetaldehyde, alkyl trifluoromethyl ketones, and aryl trifluoromethyl ketones, e.g. l-(2,4-dihydroxyphcnyl)-... 

Trifluoroacetylation. Aryl trifluoromethyl ketones are obtained from the Friedel-Crafts acylation with this stable reagent in the presence of aluminum chloride. 

It was already known that amino alcohols of the kind we have just used 78 were good at this kind of asymmetric addition but this particular combination of an acetylenic nucleophile and an aryl trifluoromethyl ketone was uncharted territory. After some exploration, stoichiometric pyrrolidine alcohol 88 prepared by alkylation of norephedrine 87 from the chiral pool (chapter 23) proved the best and the ketone 85 had to be used as its V-4-methoxybenzyl derivative18 89. 

Baeyer-VilUger oxidation. The BuO-Cu(III)-NO species formed on heating Cut with BU4NNO2 in o-xylene at 150° converts aryl isopropyl ketones and aryl trifluoromethyl ketones to hutyl esters. However, the scope of this reaction is limited, ethyl and methyl ketones give low yields of the corresponding esters and phenyl and r-butyl ketones are not oxidized at all under such conditions. ... 

This result is not surprising since it was shown earlier that trichloromethyl ketones react more rapidly with methanol (alcohols) than with water under alkaline conditions.29 The ethanolic cleavage of a trichloromethyl ketone has been used to prepare ethyl 3,3-diethoxypropanoate,30 and aryl trifluoromethyl ketones can be cleaved to give carboxylic acids or esters.31 A similar reaction of 3-trifluoroacetylindole (19) with lithium dialkylamides affords good yields of the corresponding indole-3-carboxamides (20).3... 

Catalytic synthesis of aryl trifluoromethyl ketone via RC(0)-0Ar bond cleavage is also known. Combination of Pd(OAc)2 with 3 equiv of P Bu3 catalyzes the formation of aryl trifluoromethyl ketone from phenyl trilluoroacetate and arylbo-rane (Eq. 3.12) [69]. This reaction is interpreted by RC(0)-0Ph bond oxidative addition to give (acyl)(phenoxo)palladium(II) complex, followed by metathesis (transmetallation) of phenoxopalladium species with arylborane and reductive elimination of acyl and aryl carbons to form the product. 

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

Table 18. Asymmetric reduction of aryl trifluoromethyl ketones with PNAH and sodium borohydride.

Baba N, Matsumura Y, Sugimoto T (1978) Asymmetric reduction of aryl trifluoromethyl ketones with an achiral NADH model compound in a chiral hydrophobic binding site of sodium cholate micelle,... 

ACCESS TO TRIFLUOROMETHYL INDANS 3Y CYCLOALKYLATION OF -ARYL TRIFLUOROMETHYL-KETONES. 

Schlosser et al. prepared substituted 4-trifluoromethyl-2-quLnolinones by the Wittig reaction of 2-(iV-BOC-atnino)aryl-trifluoromethyl-ketones and substituted alkoxycarbonylmethylene-triphenylphosphorane followed by an acid- or base-catalyzed cyclization (Scheme 86). An a,p,y,5-unsaturated trifluoroethyl ester was synthesized in complete tram selectivity by the Wittig reaction of cinnamaldehyde and trifluoromethoxycarbonylmethylene-triphenylphosphorane (Scheme 87). 

Copper-catalysed trifluoromethylation-initiated radical 1,2-aryl migration (neophyl rearrangement) in a,a-diaryl allylic alcohols to give a-aryl / -trifluoromethyl ketones occurs with preferential migration of electron-deficient aryl groups over electron-rich ones, supporting a radical mechanism which has been confirmed by density functional calculations (Scheme 120). ... 

Vovk MV, Bol but AV, Volochnyuk DM, Pinchuk AM (2004) Synthesis of N(5-pyrazolyl) schiff bases derived from aryl trifluoromethyl ketones. Russ J Org Chem 40 63-66... 

Trifluoromethyl lactones 62 were generated in equally impressive yields and stereoselectivities (typically >80% yield and up to >95 5 dr and 99% ee) using precatalyst 63 (with an 7/-2-/-Pr-phenyl substituent) for a range of alkylarylketenes (Scheme 3.14). This protocol delivers the anti (3-lactones in preference however, the scope with respect to the ketone component is limited to the use of a small number of aryl-trifluoromethyl ketones 61. The lactone products also proved incompatible to further derivatization in a limited number of attempted ring opening strategies. 

In contrast to aryl trifluoromethyl ketones, 2,2,2-trichloroacetophenone underwent an extremely slow reaction providing several products. 2-Chloro-2,2-difluoroacetophenone reacted readily with the activated olefins (Scheme 11). 

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