Categories: C-C Bond Formation > Heteroatom-containing Molecules > Trihalomethyl Carbinols, Trifluoromethylation
Synthesis of trifluoromethyl carbinols
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Recent Literature
In the presence of molecular sieves in DMSO, trifluoromethylation of various
aldehydes and ketones with trifluoromethyltrimethylsilane proceeded very
smoothly to give the corresponding trifluoromethylated adduct in good to
quantitative yields without a base catalyst.
K. Iwanami, T. Oriyama, Synlett,
2006, 112-114.
Potassium alkoxide is a highly active catalyst for the nucleophilic
trifluoromethylation of both aldehydes and ketones, affording the corresponding
trifluoromethylated products in high yields at low catalyst loadings.
T. Yurino, H. Yamashita, Y. Shan, Z. Wu, T. Ohkuma, Synlett, 2022,
33,
1739-1744.
The use of TMS-CF3 enables a versatile nucleophilic
trifluoromethylation of carbonyl compounds. The reaction is induced by fluoride
ions.
G. K. S. Prakash, R. Krishnamurti, G. A. Olah, J. Am. Chem. Soc., 1989,
111, 393-395.
A photoinduced reduction of trifluoromethyl iodide by
tetrakis(dimethylamino)ethylene (TDAE) enables a nucleophilic
trifluoromethylation of aldehydes and ketones.
S. Aït-Mohand, N. Takechi, M. Médebielle, W. R. Dolbier, Org. Lett., 2001, 3,
4271-4273.
A stable (trifluoromethyl)zinc reagent can be generated from CF3I and
ZnEt2. Trifluoromethylation of carbonyl compounds proceeds smoothly
with diamine as a ligand and ammonium salt as an initiator. Moreover, the (trifluoromethyl)zinc
reagent can also be employed as a difluorocarbene source for gem-difluoroolefination
of carbonyl compounds as well as gem-difluorocyclization of alkenes or
alkynes.
K. Aikawa, W. Toya, Y. Nakamura, K. Mikami, Org. Lett.,
2015,
17, 4966-4999.
A nucleophilic trifluoromethylation reaction of carbonyl
compounds with Ruppert’s reagent, Me3SiCF3, was efficiently
promoted by a P(t-Bu)3-DMF system. Imines were also converted to the desired
α-trifluoromethyl amines under similar reaction conditions.
S. Mizuta, N. Shibata, T. Sato, H. Fujimoto, S. Nakamura, T. Toru, Synlett,
2006, 267-270.
An amidinate salt of hexafluoroacetone hydrate is a powerful and air-stable
reagent for the preparation of fluorinated organic molecules. This reagent is
soluble in many polar organic solvents and produces fluoroform, following the
release of trifluoroacetate. Reactions with this reagent and common
electrophiles provide excellent yields of trifluoromethylated products.
M. V. Riofski, A. D. Hart, D. A. Colby, Org. Lett., 2013,
15, 208-211.
The stable 4-[2,2,2-trifluoro-1-[(trimethylsilyl)oxy]ethyl]morpholine is a
nucleophilic trifluoromethylating agent, that reacts with non nonenolizable
carbonyl compounds to provide α-trifluoromethyl alcohols.
T. Billard, S. Bruns, B. R. Langlois,
Org. Lett., 2000, 2, 2101-2103.
Mercury(II) chloride efficiently activates magnesium metal to induce a
desulfonylative trifluoromethylation process. The new reductive
trifluoromethylation provides an alternative method for efficient
trifluoromethylation of non-enolizable or enolizable aldehydes with readily
available phenyl trifluoromethyl sulfone reagent.
Y. Zhao, J. Zhu, C. Ni, J. Hu, Synthesis, 2010,
1899-1904.
Reactions of enones with TMSCF3 in the presence of catalytic amounts
of CsF in ethylene glycol dimethyl ether provide α-trifluoromethyl silyl ethers
in essentially quantitative yield. On hydrolysis with aqueous HCl, the
corresponding trans-α-trifluoromethyl allylic alcohols were formed in >90%
isolated yield.
R. P. Singh, R. L. Kirchmeier, J. M. Shreeve,
Org. Lett., 1999, 1, 1047-1049.
Related
A photochemically induced nickel-catalyzed radical cross-coupling of
phthalimido trifluoroethanol with aryl bromides provides
α-aryl-α-trifluoromethyl alcohols. This reaction proceeds via a photoinduced
charge transfer of an electron donor-acceptor complex between Hantzsch ester and
phthalimido trifluoroethanol, followed by 1,2-hydrogen atom transfer, to
generate the α-hydroxytrifluoroethyl radical.
F. Chen, X.-H. Xu, L. Chu, F.-L. Qing, Org. Lett., 2022, 24,
9332-9336.
A visible-light induced direct C(sp3)-H functionalization of
alkylarenes with trifluoromethyl ketones provides valuable benzyl-substituted
trifluoromethyl alcohols in a stoichiometric manner. With a bromine radical as
the hydrogen atom transfer reagent, primary, secondary, and tertiary benzyl C-H
bonds are suitable coupling partners.
Q.-L. Wang, H. Huang, M. Zhu, T. Xu, G. Mao, G.-J. Deng, Org. Lett., 2023, 25,
3800-3805.
N-Heterocyclic Carbene Catalyzed Highly Chemoselective Intermolecular
Crossed Acyloin Condensation of Aromatic Aldehydes with Trifluoroacetaldehyde
Ethyl Hemiacetal
B. T. Ramanjaneyulu, S. Mahesh, R. V. Anand, Org. Lett.,
2015,
17, 6-9.
Visible-light-induced singlet nucleophilic carbene intermediates can be
trapped by fluorinated ketones via 1,2-carbonyl addition to afford benzoin-type
products. This efficient, user-friendly, and scalable process provides
fluorinated tertiary alcohol derivatives without exogenous catalysts or
additives.
D. L. Priebbenow, R. L. Pilkington, K. N. Hearn, A. Polyzos, Org. Lett., 2021, 23,
2783-2789.
An Ir-catalyzed reductive coupling of diverse 1,1-disubstituted
allenes with fluoral hydrate in the presence of 2-propanol provides CF3-substituted
secondary alcohols with acyclic quaternary carbon-containing stereodiads.
A stereochemical model shows that the ortho-CH2 group of the
cyclometalated iridium-PhanePhos complex plays a key role in directing
diastereo- and enantioselectivity.
L. A. Schwartz, M. Holmes, G. A. Brito, T. P. Gonçalves, J. Richardson, J. C.
Ruble, K.-W. Huang, M. J. Krische, J. Am. Chem. Soc.,
2019,
141, 2087-2096.
An efficient copper-catalyzed aldol reaction of readily available vinyl azides with
trifluoromethyl ketones provides trifluoromethylated compounds under mild conditions in
very good
yield.
Z. Liu, Z. Zhang, G. Zhu, Y. Zhou, L. Yang, W. Gao, L. Tong, B. Tang,
Org. Lett., 2019, 21, 7324-7328.