Categories: C-F Bond Formation >
Synthesis of vinyl fluorides
The nucleophilic fluorination reagent DMPU/HF offers high acidity and is compatible with cationic metal catalysts. Gold-catalyzed mono- and dihydrofluorination of alkynes using this stable complex yields synthetically important fluoroalkenes and gem-difluoromethlylene compounds regioselectively.
O. E. Okoromoba, J. Han, G. B. Hammond, B. Xu, J. Am. Chem. Soc., 2014, 136, 14381-14384.
A Shapiro fluorination reaction enables a direct access to fluoroalkenes in good stereoselectivity in one- or two-step sequences from widely available ketones. This strategy should be useful for the preparation of fluorinated analogs of peptide-based therapeutics, many of which would be challenging to prepare by alternate strategies.
M.-H. Yang, S. S. Matikonda, R. A. Altman, Org. Lett., 2013, 15, 3894-3897.
A direct fluorination of 1-(2,2-dibromovinyl)benzene derivatives using wet tetra-n-butylammonium fluoride (TBAF·3H2O) as either a base or a fluorine source provided (Z)-1-(2-bromo-1-fluorovinyl)benzene compounds in good yields with high regioselectivities.
M. Zhao, L. Ming, J. Tang, X. Zhao, Org. Lett., 2016, 18, 416-419.
The use of 1,3-diiodo-5,5,-dimethylhydantoin and HF-based reagents enables a regio- and stereoselective iodofluorination of internal and terminal alkynes. A facile method for a controlled regioselective double iodofluorination of terminal alkynes is also presented.
L. Pfeifer, V. Gouverneur, Org. Lett., 2018, 20, 1576-1579.
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.
A stereoselectiv hydrodefluorination reaction of trifluoromethylated alkenes with LiAlH4 provides terminal monofluoroalkenes in very good yields and diastereoselectivities. Mechanistic studies suggested a hydroalumination reaction followed by a stereoselective fluoride elimination.
P. Poutrel, X. Pannecoucke, P. Jubault, T. Poisson, Org. Lett., 2020, 22, 4858-4863.
The visible light mediated coupling of α-fluoroacrylic acids with N-hydroxyphthalimide (NHPI) redox-active esters provides monofluoroalkenes under mild conditions. This decarboxylative reaction exhibited excellent functional group compatibility and delivered monofluoroalkene products with excellent Z-stereoselectivity.
X. Bai, L. Huang, P. Zhou, H. Xi, J. Hu, Z. Zuo, H. Feng, J. Org. Chem., 2022, 87, 4998-5004.
Monofluorovinyl tosylate is a practical vinyl fluoride building block to couple with various arylboronic acids in the presence of a palladium catalyst. A high stereoselectivity in the synthesis of 2-aryl-1-fluoroethene derivatives was achieved. This approach is also applicable to the synthesis of 2,2-diaryl-1-fluoroethenes in good yields.
H. Zhang, C.-B. Zhou, Q.-Y. Chen, J.-C. Xiao, R. Hong, Org. Lett., 2011, 13, 560-563.
Previously unknown halo-substituted molybdenum alkylidene species are exceptionally reactive and are able to participate in high-yielding olefin metathesis reactions that afford acyclic 1,2-disubstituted Z-alkenyl halides. Transformations are promoted by small amounts of a catalyst that is generated in situ and used with unpurified, commercially available and easy-to-handle liquid 1,2-dihaloethene reagents.
M. J. Koh, T. T. Ngyuen, H. Zhang, R. R. Schrock, A. H. Hoveyda, Nature, 2016, 531, 459-465.
Difluoromethyl 2-pyridyl sulfone acts as a novel and efficient gem-difluoroolefination reagent for both aldehydes and ketones. A fluorinated sulfinate intermediate in the reaction is relatively stable and can be observed by 19F NMR and trapped with CH3I.
Y. Zhao, W. Huang, L. Zhu, J. Hu, Org. Lett., 2010, 12, 1444-1447.
A robust copper-catalyzed or transition-metal-free alkylation of gem-difluoroalkenes with alkyl Grignard reagents proceeded very smoothly in the presence of 25 mol % of CuCN or under transition-metal-free conditions. Especially tertiary and secondary alkyl-substituted fluoroalkenes can be isolated in good to excellent yields with excellent Z stereoselectivity.
W. Dai, H. Shi, X. Zhao, S. Cao, Org. Lett., 2016, 18, 4284-4287.
A catalyst-induced defluorinative, alkylation or metal-free hydroalkylation of gem-difluoroalkenes provides a mild and practical approach to important and monofluoroalkenes and difluoromethylene-containing compounds under visible light irradiation with good yields.
F. Liu, Z. Zhuang, Q. Qian, X. Zhang, C. Yang, J. Org. Chem., 2022, 87, 2730-2739.
A mild and efficient zinc-mediated decarboxylative alkylation of gem-difluoroalkenes with N-hydroxyphthalimide (NHP) esters provides Z-monofluoroalkenes in good yields. The reaction tolerates a broad range of functional groups and can be easily scaled up.
L. Yu, M.-L. Tang, C.-M. Si, Z. Meng, Y. Liang, J. Han, X. Sun, Org. Lett., 2018, 20, 4579-4583.
A transition-metal-free cross-coupling of two carbene fragments proceeds through the direct nucleophilic addition of diazo compounds to difluorocarbene derived from Ruppert-Prakash reagent (TMSCF3) or TMSCF2Br followed by elimination of N2. This transition-metal-free protocol efficiently affords various disubstituted 1,1-difluoroalkenes, including difluoroacrylates, diaryldifluoroolefins, as well as arylalkyldifluoroolefins.
M. Hu, C. Ni, L. Li, Y. Han, J. Hu, J. Am. Chem. Soc., 2015, 137, 14496-14501.
A Cu-catalyzed gem-difluoroolefination of diazo compounds with TMSCF3 affords the desired 1,1-difluoroalkene products via trifluoromethylation followed by C-F bond cleavage.
M. Hu, Z. He, B. Gao, L. Li, C. Ni, J. Hu, J. Am. Chem. Soc., 2013, 135, 17302-17305.
A fast and practical cross-coupling between difluorocarbene and carbene-derived intermediates generated from diazocompounds provides hindered gem-difluoroolefins. Whereas the cross-coupling between difluorocarbene and aryl diazoacetates proceeded smoothly in the presence of a copper source, the coupling with diaryl diazomethanes occurred well under metal-free conditions.
J. Zheng, J.-H. Lin, L.-Y. Yu, Y. Wei, X. Zheng, J.-C. Xiao, Org. Lett., 2015, 17, 6126-6129.
A domino reaction of enolizable carbonyl compounds with Me3SiCF2Br provides α-fluoroenones and α-fluoroenals via formation of difluorocarbene and silyl enol ether, difluorocyclopropanation, desilylation, ring-opening, and defluorination. Me3SiCF2Br acts as not only the difluorocarbene source but also the TMS transfer agent as well as internal bromide and fluoride anion catalyst. Only a catalytic amount of n-Bu4NBr as initiator is needed.
X. Song, J. Chang, D. Zhu, J. Li, C. Xu, Q. Liu, M. Wang, Org. Lett., 2015, 17, 1712-1715.
A highly stereoselective olefination reaction of α-fluoro-β-keto esters enables the synthesis of α-fluoro-α,β-unsaturated esters via nucleophilic addition, intramolecular nucleophilic addition, and elimination. α-Fluoro-α,β-unsaturated esters are important units in many biologically active compounds and useful precursors in a variety of functional-group transformations.
J. Qian, W. Yi, M. Lv, C. Cai, Synlett, 2015, 26, 127-132.
Phosphazene P4-tBu effectively catalyzes a nucleophilic substitution reaction of gem-difluoroalkenes with ketene silyl acetals under mild conditions to provide monofluoroalkenes possessing an alkoxycarbonylmethyl group in high yields with high Z selectivities.
A. Kondoh, K. Koda, M. Terada, Org. Lett., 2019, 21, 2277-2280.
With a suitable combination of N-heterocyclic carbene precatalyst, base, and fluorine reagent, a fluorination of alkynals proceeded smoothly to yield a wide range of α-fluoroallenoates with excellent chemoselectivity. α-Fluorinated allenoates are versatile synthetic intermediates toward other useful fluorine-containing building blocks.
X. Wang, Z. Wu, J. Wang, Org. Lett., 2016, 18, 576-579.