Organocatalyzed Solvent-Free Aza-Henry Reaction:  A Breakthrough in the One-Pot Synthesis of 1,2-Diamines

Abstract

A nitrogen-containing superbase such as TMG was found to be an effective catalyst for the reaction between N-diphenylphosphinoyl imines and nitroalkanes. Exploiting a protocol that avoids the use of any solvent also during workup procedure, we synthesized a series of beta-nitroamines in excellent yields and high diastereomeric ratios. These results, combined with the capability of the indium in conjunction with Zn as the stoichiometric reducing agent to perform in aqueous medium reduction of the nitro group under mild reaction conditions, led us to devise a three-step, one-pot synthesis of a range of 1,2-diamines, making use of environmentally friendly procedures in the various steps.

Conjugate addition nitro-Mannich reaction of carbon and heteroatom nucleophiles to nitroalkenes

“…1 The product β-nitroamines have emerged as flexible synthetic building blocks due to the complimentary oxidation states of the two nitrogen atoms. They have been used in the synthesis of many nitrogen containing functional groups including α-amino carbonyls, 2, 3 1,2-diamines, [4][5][6][7] peptidomimetics, 8 natural products [9][10][11][12][13][14][15] and many heterocyclic small molecules. [16][17][18][19][20][21][22][23][24][25][26][27][28][29] To address the paucity of structurally diverse nitroalkanes we have developed conjugate addition nitro-Mannich protocols (Scheme 1).…”

Cu-catalyzed cross-dehydrogenative coupling: A versatile strategy for C–C bond formations via the oxidative activation of sp 3 C–H bonds

“…An efficient synthetic approach toward such compounds is through the nitro-Mannich (aza-Henry) reaction. The nucleophilic addition of nitroalkanes to imines generates ␤-nitroamine derivatives (31), which are readily converted into 1,2-diamines or ␣-amino carbonyl compounds by the reduction of the nitro group (32,33) or through the Nef reaction (34).…”

Stereoselective Synthesis of Orthogonally Protected 1,2-Diaminoinositols from d-Mannose

“…Thus, reaction of the resulting protected nitroinositol 8 with zinc powder in the presence of dilute hydrochloric acid as protic medium afforded 1,2-diaminoinositol 9 in good yield, preserving the stereochemistry of all stereogenic centres. 16 Finally, the free amino group of the 1,2-diaminoinositol 9 was protected with a Cbz group under SchottenBaumann 17 conditions to afford the desired 1,2-diaminoinositol 10 (Scheme 3).…”