One‐Pot Synthesis of Trisubstituted 1,2‐Amino Alcohols from Deprotonated α‐Amino Nitriles

Abstract

A short synthesis of N,1,2-trisubstituted vicinal amino alcohols by 1,2-addition of deprotonated N-monosubstituted α-amino nitriles to aldehydes and subsequent one-pot reduction of the intermediates with borane-THF is described.

The reductive decyanation reaction: an overview and recent developments

“…NaBH 4 [ 45 – 51 ] or NaBH 3 CN [ 47 , 52 – 59 ] are widely used hydride donors and, less frequently, BH 3 [ 60 – 61 ], AgBF 4 /Zn(BH 4 ) 2 [ 62 – 64 ] or LiAlH 4 [ 65 – 66 ]. These reactions usually require mild conditions but the course of the reaction depends on the ease of formation of the iminium ion [ 48 , 67 – 69 ].…”

The Chemistry of Deprotonated α-Aminonitriles

“…175,177 1,2-Addition of the potassium keteniminates 195 to aldehydes and imines and subsequent reduction in a one-pot reaction sequence furnishes trisubstituted amino alcohols and tetrasubstituted 1,2-diamines, respectively. [178][179][180] Ad- dition to imines followed by aerobic oxidation of the intermediate enediamines yields 1,2-diimines 197, which can be cyclized to tetrasubstituted imidazolium salts 198. The latter are suitable as carbene precursors or can be reduced to 1,2-diamines with high diastereoselectivity.…”

Pyrroles and Indolizidines from Deprotonated α-(Alkylideneamino)nitriles

“…baseinduced dehydrocyanation, if the correct base, such as potassium hexamethyldisilazanide, is employed at low temperatures. [4][5][6] The resulting keteniminates can serve as stabilized a-aminocarbanion equivalents in one-pot syntheses of highly substituted a-branched amines, 7 pyrrolidines, 8 1,2-diamines, 9 b-amino alcohols, 10 or g-amino acids. 11 After reaction with a suitable electrophile, the nitrile substituent can be removed under mild conditions as delocalization of the amine nitrogen lone pair into the s*orbital of the C-CN bond leads to its scission with formation of an iminium ion which can subsequently be trapped by suitable nucleophiles.…”