Sodium borohydride, Sodium tetrahydroborate
Name Reactions
Recent Literature
Manganese dioxide is employed as an in situ oxidant for the one-pot conversion
of alcohols into imines. In combination with polymer-supported cyanoborohydride
(PSCBH), a one-pot oxidation-imine formation-reduction sequence enables alcohols
to be converted directly into both secondary and tertiary amines.
L. Blackburn, R. J. K. Taylor, Org. Lett.,
2001, 3, 1637-1639.
In the reductive amination of some aldehydes with primary amines where
dialkylation is a problem, a stepwise procedure involving imine
formation in MeOH followed by reduction with NaBH4 was
developed.
A. F. Abdel-Magid, K. G. Carson, B. D. Harris, C. A. Maryanoff, R. D.
Shah, J. Org. Chem., 1996, 61, 3849-3862.
A simple and convenient procedure enables the reductive alkylation of primary
and secondary amines and N,N-dimethylation of amino acids using sodium
borohydride as reducing agent in 2,2,2- trifluoroethanol without use of a
catalyst or any other additive. The solvent can be revovered and reused.
M. Taibakhsh, R. Hosseinzadeh, H. Alinezhad, S. Ghahari, A. Heydari, S. Khaksar, Synthesis, 2011,
490-496.
A simple and convenient procedure allows the reductive amination of aldehydes
and ketones using sodium borohydride as reducing agent and boric acid, p-toluenesulfonic
acid monohydrate or benzoic acid as activator under solvent-free conditions.
B. T. Cho, S. K. Kang, Tetrahedron, 2005,
61, 5725-5734.
B. T. Cho, S. K. Kang, Tetrahedron, 2005,
61, 5725-5734.
An expeditious and practical method for the reduction of various amides and
lactams to amines in good to excellent yields is consisted of activation with Tf2O
followed by reduction with sodium borohydride in THF at room temperature. This
method offers TBDPS-group tolerance, short reaction time, and a simple workup.
S.-H. Xiang, J. Xu, H.-Q. Yuan, P.-Q. Huang, Synlett, 2010,
1829-1832.
Tf2O/TTBP can serve as an alternative amide activation system for
direct conversions of secondary and tertiary amides. Reductive (di)alkylations,
condensations, and Bischler-Napieralski reactions with TTBP deliver higher or
similar yields compared with pyridine derivatives 2,6-di-tert-butyl-4-methylpyridine
(DTBMP) and 2-fluoropyridine (2-F-Pyr.). TTBP can easily be recovered and reused.
Q. He, J.-L. Ye, F.-F. Xu, H. Geng, T.-T. Chen, H. Chen, P.-Q. Huang, J. Org. Chem., 2021, 86,
16300-16314.
The combination of PhI(OAc)2 and Cs2CO3
mediates an efficient oxidative 1,2-C to N migration of primary amines. The
reaction can be applied to the preparation of both acyclic and cyclic
amines. A mechanistic study shows that the rearrangement proceeds via a
concerted mechanism.
W. Yamakoshi, M. Arisawa, K. Murai,
Org. Lett., 2019, 21, 3023-3027.
A nickel boride catalyst prepared in situ from NiCl2 and sodium
borohydride allowed facile reductions of a wide range of nitroarenes, aliphatic
nitro compounds, and organic azides. Addition of modified nanocellulose enabled
lower catalyst loading in nitro reductions. The protocols are compatible with a
one-pot Boc-protection to provide the corresponding carbamates.
G. Proietti, K. J. Prathap, X. Yu, R. T. Olsson, P. Dinér, Synthesis, 2022, 54,
133-146.
Tin(IV) 1,2-benzenedithiolate catalyzes the conversion of azides to amines in
the presence of NaBH4. Primary, secondary, tertiary, aromatic, and
heteroaromatic azides are reduced in excellent yields under very mild conditions.
I. Bosch, A. M. Costa, M. Martín, F. Urpí, J. Vilarrasa,
Org. Lett., 2000, 2, 397-399.
A photocatalytic direct decarboxylative hydroxylation of carboxylic acids
enables the conversion of various readily available carboxylic acids to alcohols
in good yields under extremely mild reaction conditions using molecular oxygen
as a green oxidant and visible light as a driving force.
H.-T. Song, W. Ding, Q.-Q. Zhou, J. Liu, L.-Q. Lu, W.-J. Xiao, J. Org. Chem.,
2016, 81, 7250-7255.
A nickel-catalyzed asymmetric reductive cross-coupling trifluoroalkylation of
acyl chlorides enables an enantioselective synthesis α-trifluoromethylated
ketones. A one-pot reduction furnished alcohols bearing β-CF3-substituted
stereogenic carbons with excellent diastereoselectivity. The reactions offer
high yields/enantioselectivity, mild conditions, and good functional group
compatibility.
B.-B. Wu, J. Xu, K.-J. Bian, Q. Gao, X.-S. Wang, J. Am. Chem. Soc.,
2022, 144, 6543-6550.
Aldehyde α-hydroperoxides can be accessed from α-substituted acroleins with
triethylsilane and water under Pd/C catalysis and aerobic conditions via a Pd/C-catalyzed
conjugate reduction step and a subsequent hydroperoxidation step. Upon
reduction, 2,2-disubstituted 1,2-diols are obtained.
S. Tuokko, P. M. Pihko,
Synlett, 2016, 27, 1649-1652.
A highly regio- and enantioselective hydroxyamination of aldehydes with in situ
generated nitrosocarbonyl compounds from hydroxamic acid derivatives was
realized by combining TEMPO and BPO as oxidants in the presence of a
binaphthyl-modified amine catalyst.
T. Kano, F. Shirozu, K. Maruoka, J. Am. Chem. Soc., 2013,
135, 17735-17738.
The use of the commercially available trichloromethanesulfonyl chloride enables
an efficient α-chlorination of aldehydes, including a catalytic asymmetric
version, under very mild reaction conditions. This chlorinating reagent
facilitates workup and purification of the product, and minimizes the formation
of toxic, chlorinated organic waste.
C. Jimeno, L. Cao, P. Renaud, J. Org. Chem.,
2016,
81, 1251-1255.
An organocatalytic system of L-proline and salicylic acid enables a highly
stereoselective synthesis of α,α-difluoro-γ,γ-disubstituted butenals. The
reaction offers a wide substrate scope and excellent E stereoselectivity
in most cases.
S. Arimitsu, M. Nakasone, J. Org. Chem.,
2016, 81, 6707-6713.
A reductive alkenylation of secondary amides with enamines provides allylamines
using trifluoromethanesulfonic anhydride as an amide activation reagent and
enamines as unconventional alkenylation reagents.
A.-E. Wang, C.-C. Yu, T.-T. Chen, Y.-P. Liu, P.-Q. Huang, Org. Lett.,
2018, 20, 999-1002.
In situ aerobic dual oxidation with asymmetric organocatalysis enables an
enantioselective synthesis of α-hydrazino aldehydes from alcohols and N-Boc
hydrazine instead of the conventional combination of aldehydes with
azodicarboxylates. This reaction tolerates various substituents on the alcohol
component and features excellent enantiocontrol, cheap starting materials,
operational simplicity, and scalability.
Z. Cui, D.-M. Du, Org. Lett.,
2016, 18, 5616-5619.
A catalytic system of cobalt(II) chloride and diisopropylamine in combination
with NaBH4 showed excellent activity in the chemoselective reduction
of various carboxylic esters to their corresponding alcohols in very good
yields under mild conditions. Unsaturated carboxylic esters give saturated
alcohols in high yields.
A. R. Jagdale, A. S. Paraskar, A. Sudalai, Synthesis, 2009,
660-664.
A. R. Jagdale, A. S. Paraskar, A. Sudalai, Synthesis, 2009,
660-664.
A simple and practical protocol for the reduction of carboxylic acids via in
situ formation of hydroxybenzotriazole esters followed by reaction with sodium
borohydride gives the corresponding alcohols. The reaction proceeds with
excellent yields in the presence of water.
J. A. Morales-Serna, E. García-Rios, J. Bernal, E. Paleo, R. Gaviño, J. Cárdenas, Synthesis, 2011,
1375-1382.
A powerful one-pot method for the reductive alkylation of stoichiometric amounts
of malononitrile with aromatic aldehydes incorporates water as the catalyst in
ethanol for the condensation step. The subsequent reduction step takes place
quickly and efficiently with sodium borohydride to give monosubstituted
malononitriles.
F. Tayyari, D. E. Wood, P. E. Fanwick, R. E. Sammelson, Synthesis, 2008,
279-285.
Copper(II) trifluoromethanesulfonate catalyzed a mild amidation of cyclic ethers
with iminoiodanes with good yields and selectivity. A subsequent reductive
ring-opening of the tosylamidated products gives α,ϖ-amino alcohols.
L. He, J. Yu, J. Zhang, X.-Q. Yu, Org. Lett., 2007,
9, 2277-2280.
The reaction of aldehydes with trichloromethide followed by reductive ring
opening under basic conditions
affords homologated carboxylic acids in high yields. This operationally simple
procedure provides a practical, efficient alternative to other homologation
protocols and is compatible with sensitive aldehydes including enals
and enolizable substrates.
L. R. Cafiero, T. S. Snowden, Org. Lett.,
2008,
10, 3853-3856.
Preparation of One-Carbon Homologated Amides from Aldehydes or Primary
Alcohols
M. K. Gupta, Z. Li, T. S. Snowden, Org. Lett., 2014,
16, 1602-1605.
Phthalimides are converted to primary amines in an efficient, two-stage,
one-flask operation using NaBH4/2-propanol, then acetic acid.
Phthalimides of α-amino acids are smoothly deprotected with no measurable loss
of optical activity.
J. O. Osby, M. G. Martin, B. Ganem, Tetrahedron Lett., 1984,
25, 2093-2096.
A high-yielding, asymmetric synthesis of novel 4-formyl-1-(2- and
3-haloalkyl)azetidin-2-ones was developed as valuable starting materials for the
synthesis of different enantiomerically enriched bicyclic azetidin-2-ones, such
as piperazine, morpholine, and 1,4-diazepane annulated β-lactam derivatives.
W. Van Brabandt, M. Vanwalleghem, M. D'hooghe, N. De Kimpe, J. Org. Chem., 2006, 71, 7083-7086.
The selective aldimine cross-coupling represents a simple and flexible
method for the synthesis of highly substituted unsymmetrical 1,2-diamines.
In addition, either the syn- or anti-configurated vicinal
diamine can be obtained, depending on the choice of the workup and reduction
conditions.
C. Kison, N. Meyer, T. Opatz, Angew. Chem. Int. Ed., 2005,
44, 5662-5664.
A simple method for the chemo- and regioselective, direct catalytic allylic
alkylation of aldehydes and cyclic ketones has been developed. The
combination of palladium and enamine catalysis furnished α-allylic alkylated
aldehydes and cyclic ketones in high yields.
I. Ibrahem, A. Córdova, Angew. Chem. Int. Ed., 2006, 45, 1952-1956.
An enantioselective α-arylation of aldehydes has been accomplished using
diaryliodonium salts and a combination of copper and organic catalysts. These
mild catalytic conditions allow the enantioselective construction and retention
of enolizable α-formyl benzylic stereocenters, a valuable synthon for the
production of medicinal agents.
A. E. Allen, D. W. C. MacMillan, J. Am. Chem. Soc., 2011,
133, 4260-4263.
A novel, convenient and stereoselective synthesis of trisubstituted E-alkenones
has been achieved by InCl3-mediated chemoselective reduction of Baylis-Hillman
adducts with NaBH4 as reductant.
B. Das, J. Banerjee, N. Chowdhury, A. Majhi, H. Holla, Synlett, 2006,
1879-1882.
Optically pure C2-symmetrical cyclic amines were
efficiently synthesized from the corresponding diols obtained from an
enantioselective borohydride reduction of diketones in the presence of a chiral
β-ketoiminato cobalt(II) catalyst.
M. Sato, Y. Gunji, T. Ikeno, T. Yamada, Synthesis, 2004,
1434-1438.
A nickel boride catalyzed reduction of nitriles allows the preparation of Boc protected
amines. The catalytic
use of nickel(II) chloride in combination with excess sodium borohydride is
environmental benign and tolerates air and moisture. Although the yield is
sometimes moderate, the cleanliness of the method is exceptional.
S. Caddick, D. B. Judd, A. K. de K. Lewis, M. T. Reich, M. R. V. Williams, Tetrahedron, 2003, 59, 5417-5423.
Benzyl esters of various acids can be chemoselectively cleaved on treatment with
nickel boride in methanol at ambient temperature to give the parent carboxylic
acids in high yields. Esters such as methyl, ethyl, tert-butyl, and
trityl esters as well as benzyl ethers, tert-butyl ethers, and N-benzylamides
remain unaffected under these conditions.
J. M. Khurana, R. Arora, Synthesis, 2009,
1127-1130.
A selective and direct access to secondary amines by reductive
mono-N-alkylation of primary amines with carbonyl compounds in the presence
of Ti(i-PrO)4 and NaBH4 gave exclusively
secondary amines.
H. J. Kumpaty, S. Bhattacharyya, E. W. Rehr, A. M. Gonzalez, Synthesis, 2003, 2206-2210.
Treatment of ketones with
ammonia in ethanol and titanium(IV) isopropoxide, followed by in situ reduction
with sodium borohydride allows a highly chemoselective reductive
mono-alkylation of ammonia. A simple workup afforded primary amines in good to
excellent yields. Reductive alkylation of ammonia with aldehydes afforded the corresponding symmetrical secondary amines selectively.
B. Miriyala, S. Bhattacharyya, J. S. Williamson, Tetrahedron, 2004, 60, 1463-1471.
A highly efficient and catalytic organotin reagent on soluble support has
been developed for free radical reactions. A variety of alkyl
halides (1°, 2°, 3°, aryl) underwent radical reductions in good isolated yields using only 0.01-0.2 equiv of the polymer catalyst.
E. J. Enholm, J. P. Schulte,
Org. Lett., 1999, 1, 1275-1277.
Reduction of (RS)-N-tert-butanesulfinyl α-halo
imines with NaBH4 in THF, in the presence of 10 equiv of MeOH, and
subsequent cyclization with KOH afforded the corresponding (RS,S)-N-(tert-butylsulfinyl)aziridines
in quantitative yields. On the contrary, its epimer, (RS,R)-N-(tert-butylsulfinyl)aziridine
was synthesized in good yields and diastereoselectivity by switchover of the
reducing agent from NaBH4 to LiBHEt3.
B. Denolf, E. Leemans, N. De Kimpe, J. Org. Chem., 2007,
72, 3211-3217.
A catalytic, direct asymmetric cross-aldol reaction of two different
aldehydes in the presence of water is catalyzed by a novel combined
proline-surfactant organocatalyst. Neither an organic cosolvent nor additional
acid is necessary.
Y. Hayashi, S. Aratake, T. Okano, J. Takahashi, T. Sumiya, M. Shoji, Angew. Chem. Int. Ed., 2006, 45, 5527-5529.
An efficient one-pot multistep strategy comprising auto-oxidative
difunctionalization of alkenes, oxidation of sulfides, and a further reduction
of peroxides enables the synthesis of complex β-hydroxysulfone derivatives from
thiophenols and alkenes. This method offers readily available substrates,
low-cost and environmental benign reagents, nontoxic and renewable solvents, and
mild reaction conditions.
Y. Wang, W. Jiang, C. Huo, J. Org. Chem.,
2017, 82, 10628-10634.
The use of CuCl and NaBH4 enables an efficient, one-pot method for
the highly chemoselective synthesis of δ-lactols from α,β-unsaturated δ-lactones
in methanol.
Y. Matsumoto, M. Yonaga,
Synlett, 2014, 25, 1764-1768.
An expeditious synthesis of α-substituted tert-butyl acrylates from
commercially available aldehydes and Meldrum's acid includes a telescoped
condensation-reduction sequence to afford 5-monosubstituted Meldrum's acid
derivatives followed by a Mannich-type reaction triggered by a rapid
cycloreversion of the dioxinone ring on heating with tert-butyl alcohol.
C. G. Frost, S. D. Penrose, R. Gleave, Synthesis, 2009,
627-635.
Reliable and Versatile Synthesis of 2-Aryl-Substituted Cinnamic Acid Esters
A. Ianni, S. R. Waldvogel, Synthesis, 2006, 2103-2112.
Salicylic acids and alcohols can be reduced to 2-methylphenols by a simple
two steps procedure. Reaction conditions were optimized carrying out a study
on the solvent effect and the amount of the reducing agent. The improved
procedure resulted particularly useful in the synthesis of deuterated
building blocks of biological interest.
F. Mazzini, P. Salvadori, Synthesis, 2005, 2479-2481.
γ-Hydroxy-α,β-acetylenic esters are used as precursors for the preparation of γ-hydroxy-α,β-alkenoic esters
by means of trans-selective additions of two hydrogen atoms or one hydrogen atom
and one iodine atom across the triple bonds. These methods allow the preparation
of β-substituted and α,β-disubstituted alkenoic esters in highly stereoselective
manners.
C. T. Meta, K. Koide, Org. Lett., 2004,
6, 1785-1787.
Treatment of 3-[(alkoxycarbonyl)alkyl]-substituted conjugated cycloalkenones
with diisobutylaluminum hydride at -78 °C followed by acid quenching
furnishes spiro ethers, whereas the corresponding 3-(carboxyalkyl)-substituted
cycloalkenones generate spiro lactones upon reaction with sodium borohydride
at 30 °C followed by acid quenching.
M.-C. P. Yeh, Y.-C. Lee, T.-C. Young,
Synthesis, 2006, 3621-3624.
A series of propargylic amides were transformed to the corresponding
alkylideneoxazolines by a gold(I) catalyst. A subsequent autoxidation to
hydroperoxides bearing the heteroaromatic oxazoles followed by reduction to the
corresponding alcohols with sodium borohydride enables a highly efficient, and
atom-economic access to a series of functionalized 2,5-disubstituted oxazoles.
A. S. K. Hashmi, M. C. B. Jaimes, A. M. Schuster, F. Rominger, J. Org. Chem., 2012,
77, 6394-6408.
Sodium borohydride in the presence of iodine in anhydrous THF converts
various sulfoxides to their thioethers in excellent yields. A chemoselective
deoxygenation of sulfoxides can be achieved in the presence of other
reducible functional groups such as esters, nitriles and double bonds.
B. Karimi, D. Zareyee, Synthesis, 2003, 335-336.
A CuI-catalyzed coupling reaction of aryl iodides and sulfur powder takes place
in the presence of K2CO3 at 90°C in DMF as solvent. The
coupling mixture is directly treated with NaBH4 or triphenylphosphine
to afford aryl thiols in good to excellent yields. A wide range of substituted
aryl thiols that bear methoxy, hydroxyl, carboxylate, amido, keto, bromo, and
fluoro groups can be synthesized.
Y. Jiang, Y. Qin, S. Xie, X. Zhang, J. Dong, D. Ma, Org. Lett., 2009,
11, 5250-5253.
An oxidation-free method provides sulfinic acids and sulfinate salts from easily
prepared sulfone-substituted benzothiazole derivatives under mild reaction
conditions. One-pot syntheses of sulfones and sulfonamides are also described.
J. J. Day, D. L. Neill, S. Xu, M. Xian, Org. Lett.,
2017, 19, 3819-3822.
NaBH4-TMEDA as hydride source and catalytic PdCl2(dppf) in
THF is an efficient system for the hydrodehalogenation of
bromo(chloro)-heteropentalenes with one or two heteroatoms, while Pd(OAc)2/PPh3
is able to reduce reactive haloheteropentalenes, and PdCl2(tbpf)
allows the removal of the 2-chlorine from a thiophene ring. The reaction
conditions tolerate various functional groups and allow highly chemo- and
regioselective reactions.
G. Chelucci, S. Baldino, A. Ruiu, J. Org. Chem., 2012,
77, 9921-9925.
Dichloroindium hydride (Cl2InH) generated in situ from the
combination of a catalytic amount of indium(III) chloride and sodium borohydride
in acetonitrile reduces activated vic-dibromides to the corresponding (E)-alkenes
in excellent yields.
B. C. Ranu, A. Das, A. Hajira, Synthesis, 2003, 1012-1014.
B. C. Ranu, A. Das, A. Hajira, Synthesis, 2003, 1012-1014.
Pd/C along with NaBH4 in aqueous ethanol or methanol and either K2CO3
or KOH as base at room temperature under molecular oxygen or air is capable of
oxidizing alcohols to its desired carbonyl or carboxyl counterpart. Room
temperature reaction in aqueous system and recyclability of the catalyst make
the process safe and cheaper.
G. An, H. Ahn, K. A. De Castro, H. Rhee, Synthesis, 2010,
477-485.
Pd/C in aqueous alcohol with molecular oxygen, sodium borohydride,
and potassium carbonate efficiently oxidized benzylic and allylic alcohols.
Sodium borohydride allows a remarkable reactivation of active sites of the Pd
surface.
G. An, M. Lim, K.-S. Chun, H. Rhee, Synlett, 2007, 95-98.
Upon activation with trifluoromethanesulfonyl anhydride, secondary N-arylamides
undergo smooth intermolecular dehydrative [4 + 2] aza-annulation with alkenes
under mild conditions to give 3,4-dihydroquinolines, amenable to further
functionalization. The use of NaBH4 or DDQ in a subsequent step
enables the synthesis of tetrahydroquinolines or quinolines, respectively.
Y.-H. Huang, S.-R. Wang, D.-P. Wu, P.-Q. Huang,
Org. Lett., 2019, 21, 1681-1685.
