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Synthesis of alkenyl halides
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β-Oxido phosphonium ylides, generated in situ from aldehydes and Wittig reagents
react readily with electrophilic halogen sources to form predominantly or
exclusively E-bromo- or iodosubstituted alkenes. The stereochemical
outcome on halogenation is remarkably sensitive to alkylidene size [ethylidene(triphenyl)phosphorane
is highly Z-selective].
D. M. Hodgson, T. Arif, J. Am. Chem. Soc., 2008,
130, 16500-16501.
(E)-β-Aryl vinyl halides are synthesized in good yield with excellent
stereoselectivity and functional group tolerance from benzyl bromides. The
convenient conditions involve a nucleophilic substitution with anions of CH2I2,
ICH2Cl, or CH2Br2 and a subsequent
stereoselective base-induced elimination. A facile purification allows rapid
access to a wide range of functionalized vinyl halides.
J. A. Bull, J. J. Mousseau, A. B. Charette, Org. Lett., 2008,
10, 5485-5488.
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.
An efficient protocol for a highly stereoselective one-pot synthesis of (E)-β-aryl
vinyl iodides and (E)-β-aryl vinyl bromides from styrenes is based on a
ruthenium-catalyzed silylative coupling followed by a N-halosuccinimide-mediated
halodesilylation reaction.
P. Pawluć, G. Hreczycho, J. Szudkowska, M. Kubicki, B. Marciniec, Org. Lett., 2009,
11, 3390-3393.
Trapping of a diazo species in an intermolecular fashion by two independent ion
species in tandem at the carbene center installs an electrophile and a
nucleophile on the same carbon. This metal-free concept enables regioselective
syntheses of various vinyl halides, vinyl sulfones, and alkyne derivatives.
D. P. Ojha, K. R. Prabhu, Org. Lett.,
2015,
17, 18-21.
An optimized Julia olefination between readily available α-halomethyl sulfones and a variety of
aldehydes afforded alkenyl halides in good to excellent yields with high E/Z
stereoselectivities.
M.-E. Lebrun, P. Le Marquand, C. Berthelette, J. Org. Chem., 2006,
71, 2009-2013.
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.
An efficient synthesis of α-iodo/bromo-α,β-unsaturated aldehydes/ketones
directly from propargylic alcohols is catalyzed collaboratively by Ph3PAuNTf2
and MoO2(acac)2, and Ph3PO as an additive helps
suppress undesired enone/enal formation. Notable features of this method include
low catalyst loadings, mild reaction conditions, and mostly good
diastereoselectivity.
L. Ye, L. Zhang, Org. Lett., 2009,
11, 3646-3649.
A copper-catalyzed formal SN2' defluorinative borylation of
3-substituted 3,3-difluoropropenes provides 3-fluoroallylboronic esters in high
yields with excellent Z:E ratios. The primary 3-fluoroallylboronic esters
undergo several synthetic sequences involving sigmatropic rearrangements, SE2'
substitutions, and SN2' substitutions to give tertiary allylic
fluorides.
T. W. Butcher, J. L. Yang, J. F. Hartwig,
Org. Lett., 2020, 22, 6805-6809.
A copper-amine catalyst system enables a general and facile synthetic method
for β-fluoroenones from silyl enol ethers or ketones via tandem process of
difluoroalkylation-hydrolysis-dehydrofluorination. This reaction offers high
yields, excellent Z/E ratios, a low-cost catalyst, and a broad
substrate scope.
Y. Li, J. Liu, S. Zhao, Y. Du, M. Guo, W. Zhao, X. Tang, G. Wang, Org. Lett.,
2018, 20, 917-920.
Stoichiometric bromotrichloromethane in acetonitrile can replace solvent
quantities of carbon tetrachloride in the synthesis of gem-dichloroalkenes
from aldehydes in the presence of triphenylphosphine. Similarly,
bromotrichloromethane in dichloromethane can be used for the Appel reaction of
benzyl alcohols to form benzyl chlorides at r.t., which is commonly carried out
in refluxing carbon tetrachloride.
S. G. Newman, C. S. Bryan, D. Perez, M. Lautens, Synthesis, 2011,
342-346.
The Ramberg-Bäcklund reaction of alkyl triflones provides structurally
diverse, fully substituted gem-difluoroalkenes that are difficult to
prepare by treatment with specific Grignard reagents. The Grignard reagent
serves both as a base to remove the α-proton and as a Lewis acid to assist C-F
bond activation.
Y. Maekawa, M. Nambo, D. Yokogawa, C. M. Crudden, J. Am. Chem. Soc.,
2020, 142, 15667-15672.
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.
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 gem-difluoroolefination of trifluoroacetaldehyde N-triftosylhydrazone
with organoboronic acids - including alkylboronic acids - is operationally
simple, free of transition metals, and suitable for a broad range of substrates.
Moreover, the utility of the products was demonstrated by further conversion of
the gem-difluorovinyl group.
Y. Ma, B. R. P. Reddy, X. Bi,
Org. Lett., 2019, 21, 9860-9863.
A copper-catalyzed enantioselective defluoroalkylation of linear
1-(trifluoromethyl)alkenes with arylboronate-activated alkyl Grignard reagents
provides various gem-difluoroalkenes. Tetraorganoborate complexes
generated in situ were the key reactive species for this transformation.
M. Wang, X. Pu, Y. Zhao, P. Wang, Z. Li, C. Zhu, Z. Shi, J. Am. Chem. Soc.,
2018,
140, 9061-9065.
Zn mediates a decarboxylative/defluorinative alkylation of α-trifluoromethyl
alkenes with N-hydroxyphthalimide esters as radical precursors. Several
α-trifluoromethyl alkenes were readily coupled to a wide range of primary,
secondary, and tertiary radicals, affording the desired gem-difluoroethylenes
in good yields.
H.-W. Du, Y. Chen, J. Sun, Q.-S. Gao, H. Wang, M.-D. Zhou, Org. Lett., 2020, 22, 9342-9345.
An organic photoredox-catalyzed gem-difluoroallylation of
α-trifluoromethyl alkenes with alkyl iodides provides gem-difluoroalkene
derivatives via C-F bond cleavage. This transition-metal-free transformation
utilizes a readily available organic dye (4CzIPN) as the sole photocatalyst and
N,N,N',N'-tetramethylethylenediamine as the radical activator.
S. Yan, W. Yu, J. Zhang, H. Fan, Z. Lu, Z. Zhang, T. Wang, J. Org. Chem., 2022, 87,
1574-1584.
An efficient photoredox catalytic radical addition/defluoroalkylation
coupling reaction between derivatives of primary amines and
trifluoromethyl-substituted alkenes provides a series of gem-difluoroalkenes
under visible light irradiation. This reaction offers a broad substrate scope
and good functional group tolerance.
B. Wang, C.-T. Wang, X.-S. Li, X.-Y. Liu, Y.-M. Liang, Org. Lett.,
2022, 24, 6566-6570.
An efficient photoredox catalytic radical addition/defluoroalkylation
coupling reaction between derivatives of primary amines and
trifluoromethyl-substituted alkenes provides a series of gem-difluoroalkenes
under visible light irradiation. This reaction offers a broad substrate scope
and good functional group tolerance.
B. Wang, C.-T. Wang, X.-S. Li, X.-Y. Liu, Y.-M. Liang, Org. Lett.,
2022, 24, 6566-6570.
Hydroboration of α,β-unsaturated carbonyl substrates followed by
1,2-elimination provides gem-difluoroalkenes under mild conditions.
gem-Difluoroalkenes can be converted into β-CF2H- and β-CFH2-α,β-unsaturated
carbonyls.
S. An, J. Zhang, G. Jiang, Synlett, 2021,
32,
91-94.
The generation of a
tribromomethyl radical from tetrabromomethane (CBr4) with the assistance of a persulfate salt (K2S2O8)
enables a single step conversion of terminal alkynes to gem-dibromoenones
in the presence of water. The reaction features readily available
chemicals, a broad substrate scope, a green solvent, and mild reaction
conditions.
X. Zeng, Y. Xu, J. Liu, Y. Deng, Org. Lett., 2021, 23,
9058-9062.
An efficient, practical photocatalytic deoxygenation/defluorination protocol
provides γ,γ-difluoroallylic ketones from commercially available aromatic
carboxylic acids and α-trifluoromethyl alkenes in the presence of
triphenylphosphine. The protocol offers good functional group tolerance and a
broad substrate scope.
Y.-Q. Guo, R. Wang, H. Song, Y. Liu, Q. Wang,
Org. Lett., 2020, 22, 709-713.
Bis(2,2,2-trifluoroethyl)bromophosphonoacetate, a Novel HWE Reagent for the
Preparation of (E)-α-Bromoacrylates: A General and Stereoselective Method for
the Synthesis of Trisubstituted Alkenes
K. Tago, H. Kogen,
Org. Lett., 2000, 2, 1975-1978.
Deprotonation of a 64:36 mixture of ethyl bromo(diphenylphosphono)acetate and
ethyl dibromo(diphenylphosphono)acetate using NaH as base at 0 °C and subsequent
reaction with various aldehydes provided unsaturated α-bromoesters in good
yields and high E-selectivities.
T. Olpp, R. Brückner, Synthesis,
2004, 2135-2152.
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.
The reaction of aromatic ketones with bis(trichloromethyl) carbonate afforded
aryl-(Z)-vinyl chlorides in the presence of scandium triflate, DMF, and
benzoyl chloride as catalysts. A plausible addition-elimination mechanism is
proposed. This catalytic method enables a green route to aryl-(Z)-vinyl
chlorides.
W. Su, C. Jin, Org. Lett., 2007,
9, 993-996.
(E)-β-Arylvinyl bromides were efficiently and stereoselectively prepared in high
yields by microwave irradiation of the corresponding anti-3-aryl-2,3-dibromopropanoic
acids in AcOH in the presence of AgOAc.
C. Kuang, H. Senboku, M. Tokuda, Tetrahedron, 2005,
61, 637-642.
(Z)-1-Bromo-1-alkenes were stereoselectively efficiently prepared in high yields by microwave irradiation of the corresponding anti-2,3-dibromoalkanoic
acids in DMF using Et3N as base. Microwave-assisted one-pot syntheses of terminal alkynes
and enynes from 2,3-dibromoalkanoic acids were also developed.
C. Kuang, Q. Yang, H. Senboku, M. Tokuda, Tetrahedron, 2005,
61, 4043-4052.
Application of (PhO)3P-halogen-based reagents allows the preparation
of vinyl halides in good to
excellent yields from enolizable ketones, whereas aldehydes afforded the
corresponding gem-dihalides. The halogenation proceeded smoothly under mild
conditions.
A. Spaggiari, D. Vaccari, P. Davoli, G. Torre, F. Prati, J. Org. Chem., 2007,
72, 2216-2219.
Allylic gem-dichlorides undergo regio- and enanantioselective
copper-catalyzed allylic alkylation with Grignard reagents to afford chiral Z-vinyl
chlorides. Subsequent Suzuki cross coupling reactions afford optically active
Z-alkenes and 1,3-cis,trans dienes.
M. Giannerini, M. Fañanás-Mastral, B. L. Feringa, J. Am. Chem. Soc., 2012,
134, 4108-4111.
An efficient copper-catalyzed reductive defluorination of β-trifluoromethylated
enones proceeds smoothly with a wide range of substrates to provide gem-difluoroolefin
ketones in the presence of Grignard reagents as reducing agents. The
simultaneous homocoupling process of the Grignard reagents is effective for both
Csp2-Csp2 and Csp3-Csp3 bond
formations to afford coupling products with high yields.
X. Wu, F. Xie, I. D. Gridnev, W. Zhang, Org. Lett.,
2018, 20, 1638-1642.