Categories: C-C Bond Formation > Heteroatom-containing Molecules >
Synthesis of fluoroalkanes, perfluoralkanes and related compounds
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Recent Literature
A cooperative interplay of halogen- and hydrogen-atom transfer enables the
synthesis of gem-difluoroalkanes from unactivated sp3
precursors. The method is characterized by its simplicity, generality, and site
selectivity, including the functionalization of advanced intermediates and
olefin feedstocks.
W.-J. Yue, C. S. Day, A. J. B. Rucisnski, R. Martin, Org. Lett.,
2022, 24, 5109-5114.
Intermolecular addition of perfluoroalkyl radicals on electron rich alkenes and
alkenes with electron withdrawing groups in water, mediated by silyl radicals
gives perfluoroalkyl-substituted compounds in good yields. The radical
triggering events employed consist of thermal decomposition of 1,1′-azobis(cyclohexanecarbonitrile)
(ACCN) or dioxygen initiation.
S. Barata-Vallejo, A. Postigo, J. Org. Chem., 2010,
75, 6141-6148.
Pentafluoroethyl copper (CuC2F5), which can be synthesized
from a cuprate reagent and ethyl pentafluoropropionate in quantitative yield, is
an economical and useful pentafluoroethyl source. The reagent was successfully
applied to two types of pentafluoroethylations with arylboronic acids and aryl
bromides.
H. Serizawa, K. Aikawa, K. Mikami, Org. Lett., 2014,
16, 3456-3459.
H. Serizawa, K. Aikawa, K. Mikami, Org. Lett., 2014,
16, 3456-3459.
A palladium-catalyzed direct monofluoromethylation of arylboronic esters
produces monofluoromethyl arenes at room temperature within 4 h with a good
functional group tolerance. The monofluoromethylating agent, CH2FI,
can readily be prepared via a halogen-exchange process.
J. Hu, B. Gao, L. Li, C. Ni, J. Hu, Org. Lett.,
2015,
17, 3086-3089.
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 simple and efficient 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-promoted
Heck-type alkene perfluoroalkylation of alkenes with perfluoroalkyl iodides in
good yields proceeds smoothly via a radical process under visible light
irradiation in the absence of an additional photocatalyst in ethyl acetate as a
green solvent. DBU acts as both a halogen bond acceptor and a base.
L. Tang, G. Lv, Y. Fu, X.-P. Chang, R. Cheng, L. Wang, Q. Zhou, J. Org. Chem., 2022, 87,
14763-14777.
The use of mesoporous graphitic carbon nitride (mpg-CN) as a recyclable,
nontoxic, and heavy-metal-free photocatalyst enables an efficient, eco-friendly,
and divergent perfluoroalkylation of terminal alkynes. Switching the reaction
solvents provides libraries of perfluoroalkylated alkynes, alkenes, and alkenyl
iodides to be synthesized in good yields.
X. Shi, T. Song, Q. Li, X. Guo, Y. Yang, Org. Lett., 2022, 24,
8724-8728.
An operationally simple Pd-catalyzed three component reaction involving terminal
alkynes, boronic acids, and perfluoroalkyl iodides gives trisubstituted
perfluoroalkenes in a highly regio- and stereocontrolled manner by simultaneous
additions across the triple bond in a radical-mediated process. The reaction is
broad in scope and tolerates many functional groups.
Z. Li, A. García-Domínguez, C. Nevado, J. Am. Chem. Soc., 2015,
137, 11610-11613.
A visible-light-induced perfluoroalkylation reaction of aryl acrylic acids
uses perfluoroalkyl iodides as radical precursors and inexpensive eosin Y as a
photocatalyst. The easy accessibility of perfluoroalkyl iodides and the broad
substrate scope, mild conditions, and metal-free catalyst make this
decarboxylative protocol applicable for the transformation of inexpensive raw
materials to high-value chemicals.
M. Yu, K. Niu, Z. Wang, Y. Liu, Q. Wang, Org. Lett.,
2022, 24, 7622-7626.
The use of catalytic amounts of phosphines and blue light irradiation
enables an efficient metal-free, iodo perfluoroalkylation of olefins under mild
conditions within short reaction times. The reaction presumably proceeds upon
generation of perfluoroalkyl radicals, which are formed by catalyst-induced
absorption enhancement.
L. Helmecke, M. Spittler, K. Baumgarten, C. Czekelius,
Org. Lett., 2019, 21, 7804-7808.
A method for hydrofluoroalkylation of alkenes with trifluoroacetic esters
under visible light irradiation affords difluorinated products using readily
available trimethyltriazinane as a stoichiometric reducing agent. The cleavage
of the C-F bond by a triazinane-derived radical involves a single electron
reduction coupled with fluoride transfer.
V. S. Kostromitin, A. O. Sorokin, V. V. Levin, A. D. Dilman, Org. Lett., 2023, 25,
6598-6602.
A photochemically mediated defluorinative hydroalkylation of ethyl
trifluoroacetate with a diverse suite of alkenes in the presence of sodium
formate enables a concise synthetic approach to novel gem-difluoro
analogs of FDA-approved pharmaceutical compounds. Furthermore,
trifluoroacetamides can also be functionalized via synergistic Lewis acid/photochemical
activation.
M. W. Campbell, V. C. Polites, S. Patel, J. E. Lipson, J. Majhi, G. A.
Molander, J. Am. Chem. Soc.,
2021, 143, 19648-19654.
Under mild irradiation conditions using violet light-emitting diodes, a
catalytic amount of N-(4-mercaptophenyl)pivalamide promotes monoselective
defluoroalkylation of trifluoroacetates with a variety of aliphatic alkenes in
the presence of a formate salt to provide valuable α,α-difluoro substituted
aliphatic carboxylate esters.
C. Liu, N. Shen, R. Shang, Synthesis, 2023,
55,
1401-1409.
The addition of (pentafluoroethyl)- and (heptafluoropropyl)lithium to Weinreb
and morpholine amides led to polyfluoro ketones in high to quantitative yields
in short reaction times. The methodology can provide inhibitors for various
lipolytic enzymes, including phospholipase A2.
C. G. Kokotos, C. Baskakis, G. Kokotos, J. Org. Chem., 2008,
73, 8623-2626.
Alkoxide-induced nucleophilic pentafluoroethylation and trifluoromethylation
of aldehydes, ketones, and imines using pentafluoroethyl phenyl sulfone and
trifluoromethyl phenyl sulfone, respectively, have been successfully achieved.
G. K. S. Prakash, Y. Wang, R. Mogi, J. Hu, T. Mathew, G. A. Olah, Org. Lett., 2010,
12, 2932-2935.
G. K. S. Prakash, Y. Wang, R. Mogi, J. Hu, T. Mathew, G. A. Olah, Org. Lett., 2010,
12, 2932-2935.
A direct and straightforward nucleophilic fluoromethylation of organic
compounds employs a very labile lithium fluorocarbenoid (LiCH2F)
generated from commercially available fluoroiodomethane. The versatility of the
strategy is showcased in reactions involving a plethora of electrophiles
providing highly valuable chemicals such as fluoroalcohols, fluoroamines, and
fluoromethylated oxygenated heterocycles in very good yields.
G. Parisi, M. Colella, S. Monticelli, G. Romanazzi, W. Holzer, T. Langer, L.
Degennaro, V. Pace, R. Luisi, J. Am. Chem. Soc., 2017,
139, 13648-13651.
A kinetic-controlled photocatalyst-free visible-light-induced stereoselective
synthesis of synthetically important α,α-gem-difluoro-Z-allyl esters was
succeeded at room temperature in good yields and excellent Z-selectivity
through a reductive radical ethoxycarbonyldifluoromethylation of terminal aryl
alkynes with blue LED (465 nm)-excited Hantzsch ester.
J. Hao, W. Ding, Z. Zheng, L. Sun, J. Dong, M. Li, W. Wan, J. Org. Chem., 2022, 87,
13750-13756.
A method for the homologation of ketones with the CF2 fragment
involves silylation, room-temperature difluorocyclopropanation of silyl enol
ethers, and selective ring opening of cyclopropanes under acidic conditions. The
whole three-step sequence is conveniently performed in one-pot.
M. D. Kosobokov, V. V. Levin, M. I. Struchkova, A. D. Dilman, Org. Lett.,
2015,
17, 760-763.
An iridium photocatalyst enables the addition of fluorinated groups to nitrones
using ascorbic acid as a stoichiometric reducing agent. Partially fluorinated
alkyl iodides can also be effectively used. The resulting hydroxylamines can be
readily converted to valuable fluorinated amines by reduction with zinc.
V. I. Supranovich, V. V. Levin, M. I. Struchkova, A. D. Dilman, Org. Lett.,
2018, 20, 840-843.
The application of continuous flow technology enabled a controlled generation of
difluorocarbene from TMSCF3 and a catalytic quantity of NaI. The in
situ generated electrophilic carbene reacts smoothly with a broad range of
alkenes and alkynes to provide the corresponding difluorocyclopropanes and
difluorocyclopropenes within 10 min residence time at high reaction
concentrations.
P. Rullière, P. Cyr, A. B. Charette, Org. Lett., 2016, 18,
1988-1991.
A MW-based protocol enables a rapid preparation of 1,1-difluorocyclopropanes,
using fluorinated acetate salts. The new procedure is not only considerably
faster than conventional methods, but it also employs easily removed, low
boiling-point solvents and avoids the use of highly toxic or ozone-depleting
substances.
D. M. Gill, N. McLay, M. J. Waring, C. T. Wilkinson, J. B. Sweeney,
Synlett, 2014, 25, 1756-1758.
Sodium bromodifluoroacetate (BrCF2CO2Na) is an effective
difluorocarbene source for high-yielding synthesis of gem-difluorocyclopropanes
and gem-difluorocyclopropenes under mild conditions.
K. Oshiro, Y. Morimoto, H. Amii, Synthesis, 2010,
2080-2084.