Ammonium compounds trifluoromethyl

The enantioselective addition of a nucleophile to a carbonyl group is one of the most versatile methods for C C bond formation, and this reaction is discussed in Chapter 2. Trifluoromethylation of aldehyde or achiral ketone via addition of fluorinated reagents is another means of access to fluorinated compounds. Trifluoromethyl trimethylsilane [(CF SiCFs] has been used by Pra-kash et al.87 as an efficient reagent for the trifluoromethylation of carbonyl compounds. Reaction of aldehydes or ketones with trifluoromethyltrime-thylsilane can be facilitated by tetrabutyl ammonium fluoride (TBAF). In 1994, Iseki et al.88 found that chiral quaternary ammonium fluoride 117a or 117b facilitated the above reaction in an asymmetric manner (Scheme 8-42). 

Scheme 8-42. Asymmetric trifluoromethylation of carbonyl compounds by chiral quaternary ammonium fluorides.

Miscellaneous PTC Reactions The field of PTC is constantly expanding toward the discovery of new enantioselective transformations. Indeed, more recent applications have demonstrated the capacity of chiral quaternary ammonium salts to catalyze a number of transformations, including the Neber rearrangement (Scheme 11.19a), ° the trifluoromethylation of carbonyl compounds (Scheme 11.19b), ° the Mannich reaction (Scheme 11.19c), and the nucleophilic aromatic substitution (SnAt)... 

Trifluoro-2-oxopropanal l-(dimethylhydrazone) 1447 is a synthetic equivalent of trifluoropyruvaldehyde. Like its 1,2-dicarbonyl counterpart, compound 1447 participates in the condensation reaction with aldehydes and ammonium acetate to afford 4-trifluoromethylimidazoles 1448 in 42-72% yield <2003H(60)1185>. 1,1,1-Trifluoro-2,3-alkanediones 1449, also 1,2-dicarbonyl equivalents, condense with aldehydes and aqueous ammonia to yield 4-(trifluoromethyl)imidazoles 1450 <2001JHC773>. 3-(Dimethylhydrazono)-l,l,l,4,4,4-hexafluoro-2-butanone... 

In 1994, the first enantioselective trifluoromethylation reaction was achieved with the Ruppert-Prakash reagent, TMSCF3, in the presence of the cinchona-based quaternary ammonium fluoride 140 [65]. The chiral induction can arise from the dual activation mode of the catalyst, that is, the fluoride anion acts as the nucleophilic activator of (TMS)CF3 and the chiral ammonium cation activates the carbonyl group of 141. However, the observed ee values of the obtained carbinols 142 do not exceed 51 % and decrease considerably when nonaromatic carbonyl compounds (15% ee for R1 = n-C7H15 R2 = H) are used, which implies that 7t-7t stacking interactions between the carbonyl compound and cinchoninium occur (Scheme 8.54). 

The replacement of a hydrocarbon-based hydrophobic group by a fluorocarbon-based one with the same number of carbon atoms appears to cause a decrease in the CMC (Shinoda, 1977). By contrast, the replacement of the terminal methyl group of a hydrocarbon-based hydrophobic group by a trifluoromethyl group has been shown to cause the CMC to increase. For 12, 12, 12-trifluorododecyltrimethyl-ammonium bromide and 10, 10, 10-trifluorodecyltrimethylammonium bromide, the CMCs are twice those of the corresponding nonfluorinated compounds (Muller, 1972). 

METHYLETHENE (115-07-1) Flammable gas (flash point - 162°F/- lOS C). Able to form unstable peroxides that may cause polymerization. Violent reaction with strong oxidizers, trifluoromethyl hypofluorite, fluoride, chlorine, and many other compounds. Incompatible with ammonium hydroxide. Forms explosive materials with nitrogen oxide compounds. May accumulate static electrical charges, and may cause ignition of its vapors. 

Trifluoromethylation. Carbonyl compounds are converted into the trifluoro-methyl carbinols in excellent yields by this reagent in the presence of a quaternary ammonium fluoride. Moderate asymmetric induction is observed when a chiral catalyst is used. 

Recently, two methods were published that have attracted some interest, because no metal salts are necessary as oxidation reagents. Shi and Xu (1990) found that substituted (trifluoromethyl)-diazoalkanes (CF3CRN2, R = alkyl or aryl) are obtained by refluxing trifluoromethyl ketones and 2,4,6-tri(isopropyl)benzenesulfonyl hydrazone in a methanolic solution of KOH. Kumar (1991) synthesized a-diazocar-bonyl compounds under tri-phase phase-transfer catalysis using a polystyrene-supported (tributyl)(methyl)-ammonium chloride catalyst, methanesulfonyl chloride, NaN3, and methylsulfonyl azide in 1,2-dichloroethane and a carbonyl-activated substrate (69-94% yield). 

Amides can be easily prepared under mild conditions from acid chlorides with ammonium acetate and from oximes by a mild modification of the Beckmann rearrangement Lactams can be prepared by this method from cyclic oximes. and 7-Lactams have been synthesized in a simple manner from aminomalonates a-Aminoacids can be converted into a-ketoacids and related compounds through 2-trifluoromethyl-5-oxazolones... 

Non-fluoride initiators have been employed satisfactorily as well, including Lewis bases (amines, amine A-oxides, carbonates and phosphates," LiOAc," " f-BusF ), Lewis acids," A-heterocyclic carbenes, or even without initiator in DMSO as solvent. The addition of TMSCF3 to carbonyl compounds in the presence of a chiral initiator allows the enantioselective preparation of trifluoromethyl alcohols. For this purpose, quaternary ammonium fluorides derived from cinchona alkaloids (1) have been employed, affording moderate (up to 51% ee) " to high enantioselectivities (up to 92% ee). Also, the corresponding bromides were used in combination with an external fluoride source (KF or TMAF, up to 94% ee) or with disodium (R)-binaphtholate (up to 71% ee), or simply a cinchonidine-derived ammoniumphenoxide (up to 87% ee). Moreover, the use of a chiral TASF derivative (2) has also been reported (up to 52% ee). ... 

Fig. 11 Separation of compounds belonging to different classes on aromatic-derivatized CF6 CSPs (Columns 25 cm, 4.6 mm i.d.). Aromatic derivatization groups (a) 3,5-dichlorophenyl carbamate (b) 3,5-bis(trifluoromethyl)phenyl carbamate (c), and (d) / -naphthylethyl carbamate. Mobile phases (A) heptane/ethanol 80/20 (b) acetonitrile/methanol/acetic acid/triethylamine 75/25/0.3/0.2 (c) heptane/isopropanol/trifluoroacetic acid 98/2/0.1 (d) acetonitrile/methanol 40/60 with 25 mM ammonium nitrate. All mobile phases in % v/v and used at 1 mL/min flow rate. UV detection 254 nm...

Although the reaction is usually conducted under homogeneous conditions, a chiral ammonium fluoride-catalyzed trifluoromethylation of carbonyl compounds should be described in this section. The catalytic asymmetric trifluoromethylation of an acetophenone derivative with Ruppert s reagent was investigated by a research group of Pfizer for process research and development of a substance-P (neuro-kini-1) receptor antagonist CJ-17,493 149 (Scheme 4.35). ° The commercially available alcohol 150 was acylated to... 

---