Synthesis of trifluoromethyl alkenes
Tri(9-anthryl)borane catalyzes a visible-light-induced trifluoromethylation of unactivated alkenes with CF3I. The mild reaction conditions tolerate various functional groups, and the reaction could be extended to perfluoroalkylations with C3F7I and C4F9I.
J. Moon, Y. K. Moon, D. D. Park, S. Choi, Y. You, E. J. Cho, J. Org. Chem., 2019, 84, 12925-12932.
A method for trifluoromethylation of alkenes uses visible light photoredox catalysis with CF3I, Ru(Phen)3Cl2, and DBU. This process works especially well for terminal alkenes to give alkenyl-CF3 products with only E-stereochemistry and tolerates various functional groups.
N. Iqbal, S. Choi, E. Kim, E. J. Cho, J. Org. Chem., 2012, 77, 11383-11387.
A formal hydrotrifluoromethylation of alkynes is achieved via hydroboration/trifluoromethylation using the inexpensive fluoroform-derived [CuCF3] reagent. Synthetically useful (E)-alkenyl-CF3 building blocks and 1,1-bis(trifluoromethyl)-substituted alkenes can be prepared under ambient conditions in one pot/one step from alkynes.
L. He, X. Yang, G. C. Tsui, J. Org. Chem., 2017, 82, 6192-6201.
The use of a Cu(III)-CF3 reagent and a silane enables an efficient and selective hydro-trifluoromethylation of terminal alkynes in DMF to provide 1,2-disubstituted trifluoromethylated Z-alkenes. The unusual Z-selectivity and the compatibility of various functional groups make this reaction complementary to previously reported methods producing predominantly E-products.
S.-L. Zhang, C. Xiao, J. Org. Chem., 2018, 83, 10908-10915.
An electro-oxidative strategy enables an efficient decarboxylative trifluoromethylation of α,β-unsaturated carboxylic acids using the Langlois reagent as a trifluoromethyl precursor. Under catalyst-free and external oxidant-free conditions, a series of trifluoromethylated styrenes are obtained with a high regioselectivity in good yields.
H. Hong, Y. Li, L. Chen, B. Li, Z. Zhu, X. Chen. L. Chen, Y. Huang, J. Org. Chem., 2019, 84, 5980-5986.
A copper-catalyzed decarboxylative trifluoromethylation of various α,β-unsaturated carboxylic acids was achieved by using a stable and inexpensive solid, sodium trifluoromethanesulfinate (CF3SO2Na, Langlois reagent). In addition, an iron-catalysis enables a difluoromethylation of aryl-substituted acrylic acids by using zinc difluoromethanesulfinate (DFMS, (CF2HSO2)2Zn, Baran reagent) via a similar radical process.
Z. Li, Z. Cui, Z.-Q. Liu, Org. Lett., 2013, 15, 406-409.
A copper(I)-catalyzed, regioselective C-H α-trifluoromethylation of α,β-unsaturated carbonyl compounds as well as α,β-unsaturated esters, thioesters, and amides using Togni’s reagent afforded the corresponding (E)-α-trifluoromethylated products in good yields.
Z. Fang, Y. Ning, P. Mi, P. Liao, X. Bi, Org. Lett., 2014, 16, 1522-1525.
A novel domino copper-catalyzed trifluoromethylated Meyer-Schuster rearrangement reaction with Togni’s reagent provides α-trifluormethyl enones with moderate to good yields. Furthermore, these α-CF3 enones can be transformed toward interesting trifluoromethyl-substituted heterocycles in a one-pot reaction.
Y.-P. Xiong, M.-Y. Wu, X.-Y. Zhang, C.-L. Ma, L. Huang, L.-J. Zhao, B. Tan, X.-Y. Liu, Org. Lett., 2014, 16, 1000-1003.
Phenyl bromodifluoroacetate as bench-stable trifluoromethylation reagent converts readily available alcohols to trifluoromethanes in a Cu-catalyzed deoxytrifluoromethylation reaction. This reaction should be useful for a variety of medicinal, agricultural, and materials chemists.
F. de Azambuja, S. M. Lovrien, P. Ross, B. R. Amber, R. A. Altman, J. Org. Chem., 2019, 84, 2061-2071.
The ability of bipyridyl-derived ligands to control the regioselectivity of Cu-catalyzed nucleophilic trifluoromethylation reactions of propargyl electrophiles provides various di-, tri-, and tetrasubstituted (trifluoromethyl)allenes, which can be further modified to generate complex fluorinated substructures.
B. R. Ambler, S. Peddi, R. A. Altman, Org. Lett., 2015, 17, 2506-2509.
An ammonium hydrogen-bonding-assisted α-F elimination from Cu-CF3 compounds generates R3N·HF reagents in situ. This strategy enables a dual fluorination and trifluoromethylation of terminal alkynes in the presence of a single Cu(III)-CF3 compound and a tertiary amine with excellent regio- and stereoselectivity.
S.-L. Zhang, J.-J. Dong, Org. Lett., 2019, 21, 6893-6896.
The collaboration of (phen)CuIII(CF3)3 and CsF enables a one-step concurrent fluoro-trifluoromethylation across the triple bond of arylacetylenes in a syn mode to provide chemo-, regio-, and stereoselectively (Z)-α-fluoro-β-CF3 styrenes. This method can be extended to achieve syn-oxy-trifluoromethylation and syn-aryl-trifluoromethylation.
S.-L. Zhang, H.-X. Wan, W.-F. Bie, Org. Lett., 2017, 19, 6372-6375.
An efficient Pd-catalyzed stereoselective vinyltrifluoromethylation of aryl halides, through decarboxylative cross-coupling with 2-(trifluoromethyl)acrylic acid offers ready availability of the starting materials, high level of functional group tolerance, and excellent E/Z selectivity. This protocol is a safe and operationally convenient strategy for an efficient synthesis of vinyltrifluoromethyl derivatives.
S. Kathiravan, I. A. Nicholls, Org. Lett., 2015, 17, 1874-1877.
A Pd-catalyzed hydrogenation of potassium (3,3,3-trifluoroprop-1-yn-1-yl)trifluoroborate provides either the (Z)- or (E)-isomer of the vinylborate in >98% purity. Coupling with bromo- and iodoarenes provides a variety of (Z)- or (E)-β-trifluoromethylstyrenes. Also, a safe synthesis of the alkynyltrifluoroborate has been described.
P. V. Ramachandran, W. Mitsuhashi, Org. Lett., 2015, 17, 1252-1255.
An operationally simple, inexpensive, and rapid route for the olefination of a wide array of trifluoromethyl ketones using a Peterson olefination approach gives very good yields of 3,3,3-trifluoromethylpropene products and can be performed without purification of the β-hydroxysilyl intermediate. The reaction can be extended to other perfluoroalkyl substituents and is easily scaled up.
T. A. Hamlin, C. B. Kelly, R. M. Cywar, N. E. Leadbeater, J. Org. Chem., 2014, 79, 1145-1155.