Sodium borohydride, Sodium tetrahydroborate
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.
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.
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 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.
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.
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.
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.