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Synthesis of substituted alkanes
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A slow and regular addition of primary alkyl and aryl Grignard reagent
enables a high-yielding copper-catalyzed alkylation with alkyl bromides in the
absence of ligands. With secondary and
tertiary alkyl Grignard reagents, the presence of benzonitrile as a very simple
ligand is sufficent. A copper-catalyzed alkylation of organolithium compounds
was also studied.
G. Cahiez, O. Gager, J. Buendia, Synlett, 2010,
299-303.
A Pd-NHC catalytic system has been developed, that is capable of
cross-coupling various unactivated, primary bromides and alkyl organozinc
reagents in high yield at room temperature.
N. Hadei, E. A. B. Kantchev, C. J. O'Brien, M. G. Organ, Org. Lett.,
2005,
7, 3805-3807.
The use of 2% Pd2(dba)3/8% PCyp3/NMI in
THF/NMP at 80°C achieves the cross-coupling of a range of
β-hydrogen-containing primary alkyl iodides, bromides, chlorides, and
tosylates with an array of alkyl-, alkenyl-, and arylzinc halides. This
method tolerates various functional groups.
J. Zhou, G. C. Fu, J. Am. Chem. Soc.,
2003,
125, 12527-12530.
A cobalt-catalyzed cross-coupling of alkyl (pseudo)halides with alkyl Grignard
reagents proceeds via an ionic mechanism in the presence of 1,3-butadiene as a
ligand precursor and LiI in high yields and high selectivities. Sterically
congested quaternary carbon centers could be constructed by using tertiary alkyl
Grignard reagents. This reaction is compatible with various functional groups.
T. Iwasaki, H. Takagawa, S. P. Singh, H. Kuniyasu, N. Kambe, J. Am. Chem. Soc., 2013,
135, 9604-9607.
A combination of 20% CoCl2 and chelating nitrogen ligands
catalyzes a mild Negishi-type cross-coupling of various
functionalized dialkylzinc reagents with primary and secondary alkyl iodides in
acetonitrile. The method allows the construction of molecules with sensitive
functional groups at room temperature.
F. H. Lutter, L. Grokenberger, M. Benz, P. Knochel,
Org. Lett., 2020, 22, 2941-2945.
Suzuki cross-couplings of alkyl bromides that contain β hydrogens run under
surprisingly mild conditions (room temperature). This work represents a
significant expansion in the scope of the Suzuki reaction.
M. R. Netherton, C. Dai, K. Neuschütz, G. C. Fu, J. Am. Chem. Soc., 2001, 123,
10099-10100.
Pd(acac)2 catalyzes a cross-coupling reaction of alkyl tosylates and bromides with
Grignard reagents in the presence of 1,3-butadiene in good yields. This reaction proceeds efficiently at room temperature using
primary and secondary alkyl and aryl Grignard reagents.
J. Terao, Y. Naitoh, H. Kuniyasu, N. Kambe, Chem. Lett., 2003,
890-891.
A dual photo/nickel catalytic manifold performs cross-coupling via a
complementary sequence involving free radical generation, radical sorting via
selective binding to a Ni(II) center, and bimolecular homolytic substitution (SH2)
at a high-valent nickel-alkyl complex. This catalytic manifold enables the
cross-coupling of diverse aliphatic carboxylic acids to generate valuable C(sp3)-C(sp3)-products.
A. V. Tsymbal, L. D. Bizzini, D. W. C. MacMillan, J. Am. Chem. Soc.,
2022, 144, 21278-21286.
Primary amines can be converted to 1,2-dialkyldiazenes by treatment with O-nosylhydroxylamines
in the presence of atmospheric oxygen. Denitrogenation of the diazenes with an
iridium photocatalyst then produces a new C-C bond. The reaction tolerates a
broad range of functionalities, including heteroaromatics and unprotected
alcohols and acids.
K. A. Steiniger, M. C. Lamb, T. H. Lambert, J. Am. Chem. Soc.,
2023, 145, 11524-11529.
An alkyl-alkyl cross-coupling of organoboranes, formed in situ via
hydroboration of alkenes, and Katritzky alkylpyridinium salts has been developed.
Under the mild reaction conditions, a broad range of functional groups,
including protic groups, is tolerated. The strategy is also effective with
alkynes, enabling a C(sp3)-C(sp2) cross-coupling.
K. M. Baker, D. L. Baca, S. Plunkett, M. E. Daneker, M. P. Watson,
Org. Lett., 2019, 21, 9738-9741.
A CoCl2/LiI/1,3-pentadiene catalytic system smoothly cleaved aliphatic
C-F bonds under mild conditions and achieved alkyl-alkyl cross-coupling even
when sterically hindered tertiary alkyl Grignard reagents were employed. Since
alkyl fluorides are inert toward many conditions, the
use of the present reaction enables a new multistep synthetic route to construct
carbon frameworks.
T. Iwasaki, K. Yamashita, H. Kuniyasu, N. Kambe, Org. Lett.,
2017, 19, 3691-3694.
In a practical catalytic cross-coupling of secondary alkyl electrophiles with
secondary and primary alkyl nucleophiles under Cu catalysis, the use of TMEDA
and LiOMe is critical for the success of the reaction. This cross-coupling
reaction occurs via an SN2 mechanism with inversion of configuration.
C.-T. Yang, Z.-Q. Zhang, J. Liang, J.-H. Liu, X.-Y. Lu, H.-H. Chen, L. Liu, J. Am. Chem. Soc., 2012,
134, 11124-11127.
A cobalt-catalyzed decarboxylative methylation of primary and secondary
aliphatic redox-active esters with trimethylaluminum provides methylated
products without redox fluctuation under mild conditions. The use of
triethylaluminum enables a decarboxylative ethylation.
Z.-Z. Wang, G.-Z. Wang, B. Zhao, R. Shang, Y. Fu, Synlett, 2020,
31,
1221-1225.
A reductive coupling of a vinyl-substituted aromatic or heteroaromatic and an
alkyl bromide or iodide occurs in an aqueous micellar medium in the presence of
Zn and a catalytic amount of an Fe(II) salt at rt. The new C-C bond is
regiospecifically formed at rt at the β-site of the alkene via a radical process.
H. Pang, Y. Wang, F. Gallou, B. H. Lipshutz, J. Am. Chem. Soc.,
2019, 141, 17117-17124.
The combination of a Ni catalyst with TDAE as sacrificial reductant enables a
dicarbofunctionalization of a broad range of olefins with two electrophilic carbon sources under reductive
conditions via simultaneous formation of one C(sp3)-C(sp3) and one C(sp3)-C(sp2) bond with exquisite selectivity.
W. Shu, A. García-Domínguez, M. T. Quirós, R. Mondal, D. J. Cárdenas, C.
Nevado, J. Am. Chem. Soc.,
2019, 141, 13812-13821.
A Ni-catalyzed regioselective alkylarylation of vinylarenes with alkyl halides
and arylzinc reagents provides 1,1-diarylalkanes. The reaction proceeds
well with primary, secondary and tertiary alkyl halides, and electronically
diverse arylzinc reagents.
S. KC, R. K. Dhungana, B. Shrestha, S. Thapa, N. Khanal, P. Basnet, R. W. Lebrun,
R. Giri, J. Am. Chem. Soc.,
2018,
140, 9801-9805.
A nickel-catalyzed Negishi cross-coupling of alkyl halides, including
unactivated tertiary halides, with the boron-stabilized organozinc reagent
BpinCH2ZnI provides versatile organoboron products with high
functional-group tolerance.
P. Guo, H. Jin, J. Han, L. Xu, P. Li, M. Zhan, Org. Lett., 2023, 25,
1246-1251.
In stereoconvergent, arylamine-directed alkyl-alkyl Suzuki cross-coupling
reactions, structure-enantioselectivity studies are consistent with the nitrogen,
not the aromatic ring, serving as the primary site of coordination of the
arylamine to the catalyst.
Z. Lu, A. Wilsily, G. C. Fu, J. Am. Chem. Soc., 2011,
133, 8154-8157.
Carbamates and sulfonamides serve as directing groups in Ni-catalyzed asymmetric
Suzuki reactions for cross-coupling of unactivated alkyl electrophiles. Racemic
secondary bromides and chlorides undergo C-C bond formation in a
stereoconvergent process in good ee at room temperature in the presence of a
commercially available Ni complex and chiral ligand.
A. Wilsily, F. Tramutola, N. A. Owston, G. C. Fu, J. Am. Chem. Soc., 2012,
134, 5794-5797.
A general alkylamination of vinylarenes and an unprecedented
diastereoselective anti-carboamination of unsaturated esters provide amines
and unnatural β-amino acids. This alkylamination is enabled by an iron catalyst
and alkyl diacyl peroxides, that serve as both alkylating reagents and internal
oxidizing agents.
B. Qian, S. Chen, T. Wang, X. Zhang, H. Bao, J. Am. Chem. Soc., 2017,
139, 13076-13082.
Screening of a 15-member library of phosphaadamantane ligands has allowed
for the rapid determination of the most suitable ligand for facilitating
Suzuki-type couplings of alkyl halides or tosylates containing β-hydrogens
with either boronic acids or alkylboranes.
T. Brenstrum, D. A. Gerristma, G. M. Adjabeng, C. S. Frampton, J. Britten,
A. J. Robertson, J. McNulty, A. Capretta, J. Org. Chem., 2004,
69, 7635-7639.
A rhodium-catalyzed methylenation-hydrogenation cascade process allows the
homologation of carbonyl compounds to alkanes in high yields.
H. Lebel, C. Ladjel, J. Org. Chem., 2005,
70, 10159-10161.
An electrochemical reductive functionalization of alkenes with strategic
choice of reagents and reaction conditions enables an addition of two distinct
electrophiles in a highly chemo- and regioselective fashion. Intermolecular
carboformylation, anti-Markovnikov hydroalkylation, and carbocarboxylation of
alkenes can be achieved via electroreductive generation of alkyl radical and
carbanion intermediates.
W. Zhang, S. Lin, J. Am. Chem. Soc.,
2020, 142, 19844-19849.
A nickel-catalyzed reductive cross-coupling reaction of aryl cyclopropyl
ketones with easily accessible unactivated alkyl bromides provides
γ-alkyl-substituted ketones. Initial mechanistic studies revealed that the
reaction proceeds via radical cleavage of the alkyl bromide.
N. Cui, T. Lin, Y.-E. Wang, J. Wu, Y. Han, X. Xu, F. Xue, D. Xiong, P. J.
Walsh, J. Mao, Org. Lett.,
2022, 24, 3987-3992.
By using synergetic photoredox/copper catalysis, a visible-light-induced,
enantioselective carbocyanation of 1,3-dienes with carboxylic acid derivatives and trimethylsilyl
cyanide is achieved under mild and
neutral conditions.
A diverse range of chiral allyl cyanides is produced in generally good
efficiency and with high enantioselectivity from bench-stable and user-safe
chemicals.
F.-D. Lu, L. Q. Lu, G.-F. He, J.-C. Bai, W.-J. Xiao, J. Am. Chem. Soc.,
2021, 143, 4168-4173.
A sequential installation of a carbenoid and a hydride into a carbonyl provides halomethyl alkyl derivatives
with uniformly high yields and chemocontrol. The tactic is flexible and is
not limited to carbenoids. Also, diverse carbanion-like species can act as
nucleophiles.
M. Miele, A. Citarella, T. Langer, E. Urban, M. Zehl, W. Holzer, L. Ielo, V.
Pace,
Org. Lett., 2020, 22, 7629-7634.
An asymmetric nickel-catalyzed borylative coupling of terminal alkenes with
nonactivated alkyl halides provides a broad range of chiral boronic esters with
high regio- and enantioselectivity under mild reaction conditions. The success
of this three-component strategy is ascribed to the application of a chiral
anionic bisoxazoline ligand.
Z. Li, H. Shi, X. Chen, L. Peng, Y. Li, G. Yin, J. Am. Chem. Soc.,
2023, 145, 13603-13614.
A transition-metal-free reaction of alkyl sulfonylhydrazones with alkyl
boronic acids provides C(sp3)-rich and sterically hindered alkyl
boron reagents in a practical and modular manner. The reaction offers broad
generality and functional group tolerance.
Y. Yang, J. Tsien, A. B. David, J. M. E. Hughes, R. R. Merchant, T. Qin, J. Am. Chem. Soc.,
2021, 143, 471-480.
The reaction of 1,1-bis(pinacolboronate) esters with alkyl halides promoted by
metal alkoxides provides organoboronate compounds via alkoxide-induced
deborylation and generation of a boron-stabilized carbanion.
K. Hong, X. Liu, J. P. Morken, J. Am. Chem. Soc., 2014,
136, 10581-10584.
A titanocene complex catalyzes a regioselective carbosilylation of terminal
alkenes and 2,3-disubstituted 1,3-butadienes with alkyl halides and
chlorotrialkylsilanes efficiently at 0°C in THF in the presence of Grignard
reagents. Terminal alkenes afford addition products in good yields, whereas in
reaction with dienes, alkyl and silyl units are introduced at the 1- and
4-positions to provide allylsilanes.
S. Nii, J. Terao, N. Kambe, J. Org. Chem., 2000,
65, 5291-5297.
A light-induced, Ru-catalyzed three-component alkyl-fluorination of olefins
under mild reaction conditions provides a wide range of fluorinated products
with good functional group tolerance. A key advantage of this photoredox
reaction is the use of generic alkyl groups and nucleophilic fluoride.
W. Deng, W. Feng, Y. Li, H. Bao, Org. Lett.,
2018, 20, 4245-4249.