Polymeric Ethyl Glyoxylate in an Asymmetric Aldol Reaction Catalyzed by Diarylprolinol

Abstract

Diarylprolinol was found to be an effective organocatalyst of the direct, enantioselective aldol reaction of commercially available polymeric ethyl glyoxylate, affording gamma-ethoxycarbonyl-beta-hydroxy aldehydes, versatile synthetic intermediates, in good yield with excellent enantioselectivity.

Novel Diarylprolinol-derived Amino Perfluoroalkanesulfonamide Catalysts: Highly Enantio- and Diastereoselective Aldol Reaction

“…In 2010, Hayashi et al disclosed the diarylprolinol-catalyzed reaction of polymeric ethyl glyoxylate with aldehydes, giving preferentially anti-aldol products in high yields with excellent levels of enantiomeric excess. 10 In line with those findings, we have recently reported the synthesis of bis-THF alcohol 5 via the asymmetric aldol reaction of ethyl glyoxylate 2 with aldehyde 3 catalyzed by diphenylprolinol 1 (Scheme 1). 11 The diastereomeric ratio and the optical purity remained unchanged during the transformation of 4 to 5.…”

Organocatalyzed Aldol Reactions

“…The one-pot synthesis of α-substituted β,γ-epoxy aldehydes (291 and 292) through a sequential aldol reaction of chloroacetaldehyde (290, 40 mol% in water) with aldehydes 55, followed by either an acetalization and epoxide formation or a Wittig reaction and epoxide formation, was possible [344]. Also, compound 289 (10 mol%) catalyzed the aldol reaction of the hemiacetal of trifluromethylacetaldehyde (262) [345] and polymeric ethyl glyoxylate (217) [346] with enolizable aldehydes (55) in toluene at 25 • C and aqueous acetonitrile, respectively. In both cases, the achieved aldol products were sequentially treated with a Wittig-type reagent to yield the corresponding α, β-unsaturated esters with up to 96 and 99% ee, respectively.…”

Asymmetric Aldol Reaction of α,α‐Disubstituted Acetaldehydes Catalyzed by Diphenylprolinol Silyl Ether for the Construction of Quaternary Stereogenic Centers

“…Our group has continuing interest to develop a general organocatalyst for the asymmetric cross-aldol reaction of aldehydes. Through our efforts, we have found trifluoromethyl-substituted diarylprolinol as an effective organocatalyst in the aldol reaction of not only acetaldehyde as the pro-nucleophile, [4] but also ethyl glyoxylate, [5] chloroacetaldehye, [6] trifluoroacetaldehyde ethyl acetal, [7] pyruvaldehyde, [8] succinaldehyde, [9] glyoxal, [10] alkynyl aldehyde, [11] and formaldehyde [12] as the electrophilic aldehyde.An equally continuing challenge for contemporary synthetic organic chemistry is the asymmetric synthesis of allcarbon quaternary stereogenic centers. [13] In this context, there have been only two reports, as far as we are aware, that describe the intermolecular asymmetric aldol reaction to form all-carbon quaternary stereogenic centers.…”

“…[16] Due to practical reasons, we have already adopted the direct use of commercially available polymer solutions of ethyl glyoxylate in the asymmetric aldol reaction of mono-substituted acetaldehydes catalyzed by diarylprolinol. [5] We thus began to investigate the aldol reaction of commercial ethyl glyoxylate with α,α-disubstituted acetaldehydes. For this purpose, 2-phenylpropanal was selected as a model nucleophilic aldehyde.…”

“…First, the optimal catalyst was surveyed ( Figure 1). Although diarylprolinol 1 is an effective catalyst in other aldol reactions of α-mono-substituted acetaldehydes, [5][6][7][8][9][10][11][12] it afforded products with low enantioselectivity (Table 1, entry 1). Use of the silyl ether 2 gave better results.…”