Enantioselective Henry and Aza‐Henry Reaction in the Synthesis of (R)‐Tembamide Using Efficient, Recyclable Polymeric CuII Complexes as Catalyst. Issue 8 (21st May 2014)

• Record Type: Journal Article
• Authors: Das, Anjan; Choudhary, Manoj K.; Kureshy, Rukhsana I.; Roy, Tamal; Khan, Noor‐ul H.; Abdi, Sayed H. R.; Bajaj, Hari C.
• Is Part Of: ChemPlusChem. Volume 79:Issue 8(2014:Aug.)
• Page Start: 1138
• Page End: 1146
• Publication Date: 2014-05-21
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1002/cplu.201402078
• Languages: English
• ISSNs: 2192-6506

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Chiral copper(II) polymeric [H<sub>4</sub>]salen (salen=bis[(salicylidene)ethylenediaminato]) complexes <bold>Cu<sup>II</sup>‐1</bold>–<bold>3</bold> were generated in situ and used as efficient catalysts in the asymmetric Henry and aza‐Henry reaction of various aromatic and aliphatic aldehydes and <italic>N</italic>‐tosylimines in the presence of various nitroalkanes at room temperature (27±2 °C) for 20 hours. This group of polymeric [H<sub>4</sub>]salen complexes demonstrated excellent performance (product yield and enantiomeric excess <italic>ee</italic> up to 98 %) in the formation of β‐nitroalcohol by using nitromethane with low catalyst loading of 1 mol % (with respect to the monomeric salen unit) and high enantioinduction (<italic>ee</italic> 94 %) in the aza‐Henry product; β‐nitroamines were obtained with moderate yield (78 %). This catalytic system also worked well with nitroethane and 1‐nitropropane in the case of Henry reaction, to furnish the corresponding products in high yields and enantioselectivities for <italic>syn</italic> diastereomers. The <bold>Cu<sup>II</sup>‐2</bold> complex retained its performance at the gram level and was expediently recycled eight times with no significant loss in its performance. The kinetic study with <bold>Cu<sup>II</sup>‐2</bold> complex for the enantioselective aza‐Henry reaction of <italic>N</italic>‐Ts‐benzylimine (Ts=tosyl) revealed a first‐order dependence on catalyst and nitromethane concentration and was zero order with respect to the substrate. The product obtained was transformed straightforwardly to the pharmaceutically important enantiomerically pure (<italic>R</italic>)<bold>‐</bold>tembamide (β‐adrenergic agonist) drug in good yield by the asymmetric nitroaldol reaction of 4‐methoxybenzaldehyde in three successive steps.</p> </abstract>