Organic Chemistry Portal >
Reactions > Organic Synthesis Search

Categories: C-C Bond Formation > Heteroatom-containing Molecules > Trihalomethyl Carbinols, Trifluoromethylation

Synthesis of trifluoromethyl carbinols


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.


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.