Design of a Binaphthyl‐Based Axially Chiral Amino Acid as an Organocatalyst for Direct Asymmetric Aldol Reactions

Abstract

A novel and robust binaphthyl-based amino acid was designed and successfully applied to the direct asymmetric aldol reaction. In some cases, this catalyst leads to higher yields and selectivities than the well-known proline catalyst. For instance, the direct asymmetric aldol reaction of acetone with 4-nitrobenzaldehyde in the presence of the binaphthyl-based amino acid catalyst proceeded smoothly to give the aldol adduct in 82% yield with 95% ee. This catalyst was also found to catalyze effectively the reactions of cyclic or unsymmetrical ketones to give the corresponding aldol adducts with excellent diastereo- and enantioselectivities.

A Designer Axially Chiral Amino Sulfonamide as an Efficient Organocatalyst for Direct Asymmetric anti‐Selective Mannich Reactions and syn‐Selective Cross‐Aldol Reactions

“…[11] In this context we were interested in the possibility of obtaining anti-6 via the s-cis-enamine intermediate B by using an amino acid that has a longer spatial distance between the amino and carboxy groups than the proline catalyst. Our recently designed axially chiral amino acid (S)-1, [13] which catalyzes direct asymmetric aldol reactions between acetone and aldehydes, seemed to be an appropriate candidate for achieving the hitherto difficult s-cis-enamine intermediate B because there is no substituent at the position a to the amine nitrogen unlike proline. Thus, we first examined the direct Mannich reaction between 3-methylbutanal and a-imino ester 5 derived from p-anisidine and ethyl glyoxylate in the presence of 5 mol % of (S)-1.…”

“…[13] Bromination of the neopentyl ester (S)-7 was achieved by ortho magnesiation using magnesium bis(2,2,6,6-tetramethylpiperamide) [MgA C H T U N G T R E N N U N G (tmp) 2 ] followed by trapping with bromine. [14] Reduction of the resulting mixture of di-and monobrominated esters (S)-8 with LiAlH 4 gave the corresponding diol (S)-9 (42 % yield over two steps) after chromatographic separation.…”

“…Treatment of (S)-9 with BBr 3 afforded the tribromo compound (S)-10 in a yield of 86 %, which was converted with allylamine into the cyclic amine (S)-11 in a yield of 89 %. [13] Amination of (S)-11 with benzophenone imine and [Pd 2 A C H T U N G T R E N N U N G (dba) 3 ] shown in the legend to Scheme 3 gave diamine (S)-12 in a yield of 93 %. [15] Treatment of (S)-12 with the corresponding sulfonylating agents gave methanesulfonamide (S)-13, trifluoromethanesulfonamide (S)-14, and pentafluorophenylsulfonamide (S)-15.…”

Synthesis of Phenylcyclopropane-Based Secondary Amine Catalysts and Their Applications in Enamine Catalysis

“…In our previous studies, binaphthyl-based secondary amine catalysts ( S )- 1 and ( S )- 2 bearing an acid functionality at the 3-position have been designed for enamine catalysis (Figure ). − Several asymmetric reactions are successfully catalyzed by these amines, which show unique reactivity and unusual selectivity in comparison with frequently used pyrrolidine-based amines such as proline and its derivatives. C 1 -Symmetric binaphthyl-based amine structures were also found in amine organocatalysts ( S )- 3 and ( S )- 4 .…”

2.07 The Aldol Reaction: Organocatalysis Approach

“…Maruoka and coworkers have found that the binaphthyl-based amino acid 151 is an efficient catalyst for direct asymmetric aldol reaction of acetone 113 with the aldehydes (Scheme 22). 81,82 With 5 mol% of catalyst 151, adduct 123a was obtained in good yield and enantioselectivity (82%, 95% ee). The same reaction with (S)-proline 6 gave the desired aldol product 123a in low yield with moderate enantioselectivity, as well as a side product, 1,3-oxazolidine 150 (48% yield based on proline), which is derived from (S)-proline itself and two equivalents of 4-nitrobenzaldehyde 124.…”