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Reduction of nitriles


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Diisopropylaminoborane [BH2N(iPr)2] in the presence of a catalytic amount of lithium borohydride (LiBH4) reduces a large variety of aliphatic and aromatic nitriles in excellent yields.BH2N(iPr)2 can also reduce nitriles in the presence of unconjugated alkenes and alkynes. Unfortunately, selective reduction of a nitrile in the presence of an aldehyde is not possible.
D. Haddenham, L. Pasumansky, J. DeSoto, S. Eagon, B. Singaram, J. Org. Chem., 2009, 74, 1964-1970.

A wide range of nitriles were reduced to primary amines by 1.2 equiv of ammonia borane under thermal decomposition conditions without any catalyst to primary amines in very good yields. The reactions are environmentally benign with H2 and NH3 generated as byproducts. The reactions are also tolerant of many functional groups.
M. Ding, J. Chang, J.-X. Mao, J. Zhang, X. Chen, J. Org. Chem., 2022, 87, 16230-16235.

The use of 9-BBN dimer as a catalyst and pinacolborane as a turnover reagent enables an efficient hydroboration of nitriles to provide N,N-diborylamines, which act as efficient synthons for the synthesis of primary amines and secondary amides.
S. Pradhan, R. V. Sankar, C. Gunanathan, J. Org. Chem., 2022, 87, 12386-12396.

A practical and cost-efficient reductive deuteration of nitriles under single-electron transfer conditions enables the synthesis of α,α-dideuterio amines in excellent yields using bench stable and commercially available sodium dispersions and EtOD-d1.
Y. Ding, S. Luo, A. Adijiang, H. Zhao, J. An, J. Org. Chem., 2018, 83, 12269-12274.

Silylative reduction of nitriles under transition metal-free conditions converts alkyl and (hetero)aryl nitriles efficiently to primary amines under mild conditions. The use of sterically bulky silanes enabled a partial reduction leading to N-silylimines.
N. Gandhamsetty, J. Jeong, Y. Park, S. Park, S. Chang, J. Org. Chem., 2015, 80, 7281-7287.

The conversion of nitriles to silylated primary amines was achieved in the presence of TMDS as the reducing agent, a catalytic amount of Co(OPiv)2, and an isocyanide ligand. Acid hydrolysis or treatment with acid chlorides provided the corresponding primary amines or imides in good yields.
A. Sanagawa, H. Nagashima, Org. Lett., 2019, 21, 287-291.

Low loadings of AgSbF6 catalyze the hydroboration of nitriles, alkens, and aldehydes under base- and solvent-free conditions. This atom-economic chemoselective protocol shows excellent functional group tolerance and compatibility with structurally and electronically diverse substrates.
V. K. Pandey, C. S. Tiwari, A. Rit, Org. Lett., 2021, 23, 1681-1686.

A conjugated bis-guanidinate (CBG)-supported aluminum dihydride complex catalyzes a chemoselective hydroboration of various nitriles and alkynes. The reaction leaves other reducible groups intact. Moreover, aluminum-catalyzed hydroboration is expanded to more challenging substrates such as alkene, pyridine, imine, carbodiimide, and isocyanides.
N. Sarkar, S. Bera, S. Nembenna, J. Org. Chem., 2020, 85, 4999-5009.

A simple [Ru(p-cymene)Cl2]2 complex is used as a catalyst precursor in a catalyzed hydroboration of nitriles and imines using pinacolborane with unprecedented catalytic efficiency.
A. Kaithal, B. Chatterjee, C. Gunanathan, J. Org. Chem., 2016, 81, 11153-11161.

The ruthenium complex [(η6-p-cymene){(IMes)P}RuCl] was used for efficient hydroborations of a wide range of nitriles, carboxylic esters, and carboxamides in neat pinacolborane (HBpin) under comparatively mild reaction conditions (60-80 °C, 3-5 mol % catalyst loading).
J. Bhattacharjee, D. Blockfeld, M. Tamm, J. Org. Chem., 2022, 87, 1098-1109.

A continuous flow method for the selective reduction of aromatic nitriles to the corresponding primary amines is based on a ruthenium-catalysed transfer-hydrogenation process with isopropanol as both solvent and reducing agent.
R. Labes, D. González-Calderón, C. Battilocchio, C. Mateos, G. R. Cumming, O. de Frutos, J. A. Rincón, S. V. Ley, Synlett, 2017, 28, 2855-2858.

Activation of SmI2 (Kagan’s reagent) with Lewis bases enables a mild general reduction of nitriles to primary amines under single electron transfer conditions. Activated samarium diiodide features excellent functional group tolerance and is therefore an attractive alternative to pyrophoric alkali metal hydrides. Notably, an electron transfer from Sm(II) to bench stable nitrile precursors generates imidoyl-type radicals.
M. Szostak, B. Sautier, M. Spain, D. J. Procter, Org. Lett., 2014, 16, 1092-1095.

Odorless Dod-S-Me and MMS are developed as efficient borane carriers. The yields of hydroborations and reductions with the borane complex of Dod-S-Me are very high. The recovery of Dod-S-Me after the reaction is quantitative.
P. K. Patra, K. Nishide, K. Fuji, M. Node, Synthesis, 2004, 1003-1006.

The scope of nickel boride mediated reduction of nitriles has been extended further to allow the preparation of Boc protected amines via a mild catalytic process.
S. Caddick, D. B. Judd, A. K. de K. Lewis, M. T. Reich, M. R. V. Williams, Tetrahedron, 2003, 59, 5417-5423.