Thermal Effects in the Organocatalytic Asymmetric α‐Amination of Disubstituted Aldehydes with Azodicarboxylates: A High‐Temperature Organocatalysis

Abstract

This article describes the thermally accelerated organocatalytic α‐amination of disubstituted aldehydes with azodicarboxylates under microwave conditions. Compared to the results previously obtained at room temperature, both yield and enantioselectivity could be significantly increased. Employing microwave irradiation resulted in a considerably reduced reaction time. Therefore, this improved protocol allows the fast and efficient synthesis of α,α‐disubstituted amino aldehydes and provided the best results for the α‐amination of disubstituted aldehydes to date. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A Convenient Methodology for Nitro-Michael Addition of Carbonyl Compounds Catalyzed by L-Proline Using Microwave Heating

“…Cyclic, acyclic ketones and acetylacetone afforded high yields, good to high diastereocontrol and modest enantioselectivity (entries [6][7][8][9][10] [17]. For comparison purposes, the conversion and stereocontrol observed under conditions previously reported in the literature (room temperature in methanol using 20 mol% loading of L-proline) [13c] are shown in parentheses for selected substrates.…”

“…As a result, there has been recent interest in the application of microwave heating in organocatalyzed reactions. Examples include the direct aldol reaction catalyzed by L-proline in DMSO [6], Mannich reactions catalyzed by L-proline [7,8], and organocatalytic asymmetric -amination of disubstituted aldehydes with azodicarboxylates [9]. Much of this work was performed using simultaneous cooling in conjunction with microwave heating, however, accurate temperature measurement is very important [10].…”

Asymmetric synthesis of deuterated and fluorinated aromatic α,α-disubstituted amino acid derivatives

“…We have previously reported the microwave-enhanced addition of diethyl azodicarboxylate to aromatic a-methylaldehydes. 21 When screening the most commonly used solvents, the incapability of low-absorbing solvents such as 1,4-dioxane or chloroform became visible. On the other hand, acetonitrile was found to be the solvent with the best conversion and the best enantiomeric ratio.…”

Recent Advances on the Organocatalyzed Enantioselective α-heterofunctionalization of Carbonyl Compounds

“…However, these compounds could be further converted in the more stable corresponding (R)-oxazolidinones by the in situ reduction and cyclization. Due to the high catalyst loading used and the relatively long reaction times needed for completion, microwave conditions were applied to carry out this process [23].…”