Direct Asymmetric Aldol Reactions Inspired by Two Types of Natural Aldolases: Water-Compatible Organocatalysts and Zn^IIComplexes

Abstract

In this article the utility of water-compatible amino-acid-based catalysts was explored in the development of diastereo- and enantioselective direct aldol reactions of a broad range of substrates. Chiral C(2)-symmetrical proline- and valine-based amides and their Zn(II) complexes were designed for use as efficient and flexible chiral catalysts for enantioselective aldol reactions in water, on water, and in the presence of water. The presence of 5 mol % of the prolinamide-based catalyst affords asymmetric intermolecular aldol reactions between unmodified ketones and various aldehydes to give anti products with excellent enantioselectivities. We also demonstrate aldol reactions of more demanding substrates with high affinity to water (i.e., acetone and formaldehyde). Newly designed serine-based organocatalyst promoted aldol reaction of hydroxyacetone leading to syn-diols. For presented catalytic systems organic solvent-free conditions are also acceptable, making the elaborated methodology interesting from a green chemistry perspectives.

Bis[( l )prolinate-N,O]Zn: A water-soluble and recycle catalyst for various organic transformations

“…In most cases, the zinc ion is an essential cofactor for the observed biological function of these metalloenzymes. By the virtue of biological activity, thousands of synthetic zinc complexes have been formed either to mimic natural structure or to completely diverge from the natural platform [13], [14], [15], [16], [17], [18]. Moreover zinc is present in active site of class II aldolases (an enzyme) witnessing the bis[( l )prolinate-N,O]Zn as a valid candidate for aldolase mimics.…”

Novel L-threonine-based ionic liquid supported organocatalyst for asymmetric syn-aldol reaction: activity and recyclability design

“…10 Over the past decade, a number of similar syn-aldol reactions have been realized in laboratory (though, with a somewhat lower stereoselectivity) in the presence of properly designed primary aminocatalysts. Among them, O-protected serine or threonine amino acids, [11][12][13][14][15][16] their amides, 17 valine, 18 leucine, 19 iso-leucine 20 or tert-leucine derivatives 21 and some primary-tertiary 1,2-diamine organocatalysts [22][23][24][25][26][27] exhibited promising catalytic performance. However, unlike enzymes, these valuable catalysts could be used just once and until recently no information on their recovery and reuse in the catalytic process has been available.…”

Pepsin-catalyzed direct asymmetric aldol reactions for the synthesis of vicinal diol compounds

“…2a On the other hand, the aldol reactions of 1-hydroxypropan-2-one or 1,3-dihydroxypropan-2-one to aldehydes are crucial for the biosynthesis of sugars and their derivatives. 4 Initially, the aldol condensations for the formation of carbohydrates were catalyzed by type I aldolase or type II aldolase through different mechanism, respectively in nature (Scheme 1). 4 However, many of such reactions were only capable of 1,3-dihydroxypropan-2-one phosphate (DHAP) as a specific donor.…”

“…4 Initially, the aldol condensations for the formation of carbohydrates were catalyzed by type I aldolase or type II aldolase through different mechanism, respectively in nature (Scheme 1). 4 However, many of such reactions were only capable of 1,3-dihydroxypropan-2-one phosphate (DHAP) as a specific donor. 5 This paper first report using hydrolase (pepsin from porcine gastric mucous) to catalyze the aldol reactions with unprotected 1-hydroxypropan-2-one and 1,3-dihydroxypropan-2-one as electron donors.…”