Chiral Ammonium Aryloxides as Brønsted Base Catalysts for the Henry Reaction of Nitroalkanes to Aromatic and Aliphatic Aldehydes

Abstract

An enantioselective organocatalyzed Henry reaction was reported using chiral ammonium aryloxides as Brønsted base organocatalysts. A wide range of aliphatic and aromatic aldehydes along with several nitroalkanes are tolerated providing the corresponding enantioenriched β‐nitroalcohols with moderate to high diastereomeric ratios and up to 83 % ee. An inversion of the diastereoselectivity was observed when changing from aromatic to aliphatic aldehydes. Transition state models were proposed in order to account for this phenomenon.

New Developments in Chiral Cooperative Ion Pairing Organocatalysis by Means of Ammonium Oxyanions and Fluorides: From Protonation to Deprotonation Reactions.

“…Having in hand several ammonium aryloxides, we sought to determine whether these catalytic tools could be exploited as chiral Brønsted base organocatalysts. As a model reaction, we selected the nitroaldol reaction (also known as Henry reaction), nitroalkanes 11 generally exhibiting p K a values compatible with those of phenoxides . One should note that among all reported organocatalytic enantioselective Henry reactions, only a few are general in terms of substrate scope (aromatic and aliphatic aldehydes 7 , nitroalkanes 11 other than nitromethane 11 a ) underlining the need for the development of general methods .…”

“…As a model reaction, we selected the nitroaldol reaction (also known as Henry reaction), nitroalkanes 11 generally exhibiting pK a values compatible with those of phenoxides. [29] One should note that among all reported organocatalytic enantioselective Henry reactions, only a few are general in terms of substrate scope (aromatic and aliphatic aldehydes 7, nitroalkanes 11 other than nitromethane 11 a) underlining the need for the development of general methods. [30] Whereas a simple ammonium aryloxide was able to catalyze efficiently the addition of nitropropane 11 b to benzaldehyde 7 b, we 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 managed to improve the isolated yield when using an in situ generated ammonium phenoxide obtained through ion metathesis between the corresponding ammonium halide and sodium aryloxide.…”