Categories: N-H Bond Formation >
Reduction of nitriles
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 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, 12269-122274.
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.
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.
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.