“…Not unexpectedly, lower reactivity is observed compared to aldehydes. The carbon−chlorine bond in the resulting carbinols can be reduced with hydride-transfer reagents giving secondary difluoromethylated alcohols which are of interest as potential enzyme inhibitors. , …”
Section: 2 Halodifloromethylation
Difluoromethylation
and Related Rea...mentioning
in the Chemistry Department at USC in the tenure track. He was promoted to full professorship in 1994. Currently, he holds the Olah Nobel Laureate Chair in Hydrocarbon Chemistry with research contributions and interests in new fluorination methods, new synthetic methods, mechanistic studies of organic reactions, electrochemistry, and superacid and hydrocarbon chemistry. He has published more than 300 papers, book chapters, and review articles; coauthored 4 books; and holds 3 patents. He has received many honors and recognition. He is currently an Advisory Editor of the International Journal of Porphyrins and Pthalocyanins.
“…Not unexpectedly, lower reactivity is observed compared to aldehydes. The carbon−chlorine bond in the resulting carbinols can be reduced with hydride-transfer reagents giving secondary difluoromethylated alcohols which are of interest as potential enzyme inhibitors. , …”
Section: 2 Halodifloromethylation
Difluoromethylation
and Related Rea...mentioning
in the Chemistry Department at USC in the tenure track. He was promoted to full professorship in 1994. Currently, he holds the Olah Nobel Laureate Chair in Hydrocarbon Chemistry with research contributions and interests in new fluorination methods, new synthetic methods, mechanistic studies of organic reactions, electrochemistry, and superacid and hydrocarbon chemistry. He has published more than 300 papers, book chapters, and review articles; coauthored 4 books; and holds 3 patents. He has received many honors and recognition. He is currently an Advisory Editor of the International Journal of Porphyrins and Pthalocyanins.
“…At this point, we thought that the low yields could be due to a lack of reactivity of adduct 6. [14] Different hydrazines (i.e., hydrazine hydrate and methyl-, phenyl-, and tert-butylhydrazine) were also used for the cyclocondensation, and the results are summarized in Table 2. We therefore decided to examine various additives with the hope of finding a Lewis acid that would facilitate the 1,4-addition of hydrazine to the adduct (Table 1, Entries 5-10).…”
Herein we describe the first practical method for the regioselective preparation of 3,5‐bis(fluoroalkyl)pyrazoles. Starting from commercially available fluoroacetoacetates and by using (tetrafluoroethyl)dimethylamine as a convenient CF2H transfer reagent, this straightforward one‐pot sequence affords highly substituted pyrazoles in good yields and excellent regioselectivity. Furthermore, these carboxylate intermediates were converted into the corresponding pyrazolic acids, which are valuable building blocks for the design of novel bioactive ingredients.
“…The importance of these compounds for the preparation of difluoromethylated enzyme inhibitors is well established. Recently, the synthesis and microbial resolution of the CF 2 Cl-containing alcohols from ethyl chlorodifluoroacetate were reported by Kitazume et al Reduction of the C−Cl bond of the resulting carbinols proceeds readily, providing the corresponding difluromethylated derivatives. The target compounds could be obtained in 5−6 steps.…”
Section: Resultsmentioning
confidence: 99%
“…All chemical shifts are reported in parts per million (δ) and are relative to residual CHCl 3 for 1 H, CDCl 3 for 13 C, CFCl 3 for 19 F, and (CH 3 ) 4 Si for 29 Si NMR. The fluorinated alcohols 5a − d , 7a − d , 11a − c , ,33 12 , and 13 30 were characterized by comparison of their spectral properties with the literature data.…”
Section: Methodsmentioning
confidence: 99%
“…A similar procedure was used for the preparation of compounds 7b − d . Their spectral properties are reported in the literature …”
CF2BrCl reacts with
aluminum/N-methylpyrrolidinone in the presence of
chlorotrimethylsilane to give
Me3SiCF2Cl in high yield.
Similarly, CF2Br2 gives
Me3SiCF2Br with bromotrimethylsilane.
Chlorodifluoromethylation of aldehydes using Me3SiCF2Cl
and a catalytic amount of TBAF in polar solvents occurs at room
temperature,
providing difluoromethylated alcohols in two steps.
Electroreduction of Me3SiCF2Cl
in the presence of chlorotrimethylsilane gives
Me3SiCF2SiMe3
(anion-derived product) and
Me3SiCF2CF2SiMe3
(radical-derived product). Using
THF/HMPA strongly favors the former, whereas THF/TDA-1
(tris(3,6-dioxaheptyl)amine) the latter.
Me3SiCF2SiMe3 difluoromethylates aldehydes acting as a
difluoromethylene dianion
(“CF2
2-” equivalent), whereas
Me3SiCF2CF2SiMe3 acts at room temperature as an in
situ source for the perfluorovinyl anion (due to β-elimination
of
fluorotrimethylsilane). However, at low temperature the
elimination pathway is suppressed and tetrafluoroethylene
dianion
(“-CF2CF2
-”
equivalent) behavior is observed. The structure of
Me3SiCF2CF2SiMe3
was analyzed by X-ray
diffraction. All of the studied fluoroalkylating reagents are
moisture- and air-stable and can be readily obtained
from a single convenient precursor
(CF2BrCl).
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