Direct Asymmetric Aminoxylation Reaction Catalyzed by Axially Chiral Amino Acids

Abstract

Binaphthyl-based amino acids were prepared and applied for the direct asymmetric aminoxylation of aldehydes with nitrosobenzene. The reaction catalyzed by (S)-1e proceeded smoothly to give the aminoxylated product in good yield and enantioselectivity. This method represents a rare example of the direct asymmetric aminoxylation by a non-proline-type catalyst.

Design of chiral bifunctional secondary amine catalysts for asymmetric enamine catalysis

“…We then investigated the aminoxylation of aldehydes by using our binaphthyl-based amino acid (S)-1 to understand the selectivity difference between proline and (S)-1. 18 As expected, the reaction of propanal with nitrosobenzene in the presence of 5 mol% of (S)-1 gave the aminoxylation product with moderate enantioselectivity (49% ee) (Scheme 15).…”

Organocatalyzed Asymmetric α-Oxidation, α-Aminoxylation and α-Amination of Carbonyl Compounds

“…A few non-proline derivatives have been reported as effective organocatalysts for aminoxylation reactions. These include Maruoka's axially chiral secondary amino acid 31 [ 83 ] and triflamide 32 [ 84 ] ( Table 7 ). The triflamide displayed a remarkable catalytic activity.…”

“…It should be noted that more strongly acidic substituents in place of the alcohol in the structurally related catalysts 31 and 32 provide preferentially O -attack products due to protonation of the nitrogen atom ( Section 3.1.2 ) [ 83 , 84 ]. Other catalysts act on special substrates.…”

Development of Highly Selective Organic Reactions Catalyzed by Designed Amine Organocatalysts

“…We then investigated the aminoxylation of aldehydes by using our binaphthyl-based amino acid (S)-13 to understand the selectivity difference between proline and (S)-13. 49,50 As expected, the reaction of propanal with nitrosobenzene in the presence of 5 mol % of (S)-13 gave the aminoxylation product with moderate enantioselectivity (49% ee) (Scheme 32).…”

“…For instance, the reaction using (S)-29 provided the (R)-isomer with good enantioselectivity (91% ee) (Figure 22 and Scheme 34), and consequently, the preferential formation of the s-trans-enamine intermediate was suggested. 49,50 The reason the reaction catalyzed by (S)-29 proceeds through the s-trans-enamine intermediate is not clear at this stage. Since the direct asymmetric aldol reaction and Mannich reaction using the binaphthyl-based amino sulfonamide (S)-16 gave a single stereoisomer predominantly through the s-cisenamine intermediate, the direct asymmetric aminoxylation reaction with (S)-16 was then examined.…”