scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Proline-catalyzed one-step asymmetric synthesis of 5-hydroxy-(2E)-hexenal from acetaldehyde.

11 Jan 2002-Journal of Organic Chemistry (American Chemical Society)-Vol. 67, Iss: 1, pp 301-303
TL;DR: For the first time, the L-proline-catalyzed direct asymmetric self-aldolization of acetaldehyde is described affording (+)-(5S)-hydroxy-(2E)-hexenal 2 with ee's ranging from 57 to 90%.
Abstract: For the first time, the L-proline-catalyzed direct asymmetric self-aldolization of acetaldehyde is described affording (+)-(5S)-hydroxy-(2E)-hexenal 2 with ee's ranging from 57 to 90%. Further transformations of 2 into synthetically valuable building blocks are presented. A mechanism for the formation of 2 is proposed.
Citations
More filters
Journal ArticleDOI
TL;DR: This Minireview discusses the current development of domino reactions mediated by organocatalysts, as this principle is used very efficiently in the biosynthesis of complex natural products starting from simple precursors.
Abstract: The current status of organic synthesis is hampered by costly protecting-group strategies and lengthy purification procedures after each synthetic step. To circumvent these problems, the synthetic potential of multicomponent domino reactions has been utilized for the efficient and stereoselective construction of complex molecules from simple precursors in a single process. In particular, domino reactions mediated by organocatalysts are in a way biomimetic, as this principle is used very efficiently in the biosynthesis of complex natural products starting from simple precursors. In this Minireview, we discuss the current development of this fast-growing field.

1,432 citations

Journal ArticleDOI
TL;DR: The contributions of this laboratory to converting enzymatic enamines, and in some cases imines, into a versatile catalytic asymmetric strategy powered by small organic molecules are summarized.
Abstract: Enamines and imines have long been recognized as key intermediates in enzyme catalysis, particularly within a class of enzymes organic chemists would very much like to emulate, the aldolases. Here we summarize the contributions of this laboratory to converting enzymatic enamines, and in some cases imines, into a versatile catalytic asymmetric strategy powered by small organic molecules.

1,192 citations

Journal ArticleDOI
TL;DR: This Review describes this "Asymmetric Aminocatalysis Gold Rush" and charts the milestones in its development.
Abstract: Catalysis with chiral secondary amines (asymmetric aminocatalysis) has become a well-established and powerful synthetic tool for the chemo- and enantioselective functionalization of carbonyl compounds. In the last eight years alone, this field has grown at such an extraordinary pace that it is now recognized as an independent area of synthetic chemistry, where the goal is the preparation of any chiral molecule in an efficient, rapid, and stereoselective manner. This has been made possible by the impressive level of scientific competition and high quality research generated in this area. This Review describes this "Asymmetric Aminocatalysis Gold Rush" and charts the milestones in its development. As in all areas of science, progress depends on human effort.

1,083 citations

References
More filters
Journal ArticleDOI
TL;DR: The finding that the amino acid proline is an effective asymmetric catalyst for the direct aldol reaction between unmodified acetone and a variety of aldehydes is reported.
Abstract: Most enzymatic transformations have a synthetic counterpart. Often though, the mechanisms by which natural and synthetic catalysts operate differ markedly. The catalytic asymmetric aldol reaction as a fundamental C-C bond forming reaction in chemistry and biology is an interesting case in this respect. Chemically, this reaction is dominated by approaches that utilize preformed enolate equivalents in combination with a chiral catalyst.1 Typically, a metal is involved in the reaction mechanism.1d Most enzymes, however, use a fundamentally different strategy and catalyze the direct aldolization of two unmodified carbonyl compounds. Class I aldolases utilize an enamine based mechanism,2 while Class II aldolases mediate this process by using a zinc cofactor.3 The development of aldolase antibodies that use an enamine mechanism and accept hydrophobic organic substrates has demonstrated the potential inherent in amine-catalyzed asymmetric aldol reactions.4 Recently, the first small-molecule asymmetric class II aldolase mimics have been described in the form of zinc, lanthanum, and barium complexes.5,6 However, amine-based asymmetric class I aldolase mimics have not been described in the literature.7 Here we report our finding that the amino acid proline is an effective asymmetric catalyst for the direct aldol reaction between unmodified acetone and a variety of aldehydes. Recently we developed broad scope aldolase antibodies that show very high enantioselectivities, have enzymatic rate accelerations, and use the enamine mechanism of class I aldolases.4 During the course of these studies, we found that one of our aldolase catalytic antibodies (Aldolase Antibody 38C2, Aldrich) is an efficient catalyst for enantiogroup-differentiating aldol cyclodehydrations of 2,6-heptanediones to give cyclohexenones, including the Wieland-Miescher ketone.8,9 These intramolecular reactions are also catalyzed by proline (Hajos-Eder-Sauer-Wiechert reaction)10 and it has been postulated that they proceed via an enamine mechanism.11 However, the proline-catalyzed direct intermolecular asymmetric aldol reaction has not been described. Further, there are no asymmetric small-molecule aldol catalysts that use an enamine mechanism.7 Based on our own results and Shibasaki’s work on lanthanum-based small-molecule aldol catalysts,4,6 we realized the great potential of catalysts for the direct asymmetric aldol reaction. We initially studied the reaction of acetone with 4-nitrobenzaldehyde. Reacting proline (30 mol %) in DMSO/acetone (4:1) with 4-nitrobenzaldehyde at room temperature for 4 h furnished aldol product (R)-1 in 68% yield and 76% ee (eq 1). This result

2,283 citations

Journal ArticleDOI
TL;DR: Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with commercially available chiral cyclic secondary amines as catalysts and the observed stereochemistry of the products is in accordance with the proposed transition state.
Abstract: Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with commercially available chiral cyclic secondary amines as catalysts Structure-based catalyst screening identified l-proline and 5,5-dimethyl thiazolidinium-4-carboxylate (DMTC) as the most powerful amino acid catalysts for the reaction of both acyclic and cyclic ketones as aldol donors with aromatic and aliphatic aldehydes to afford the corresponding aldol products with high regio-, diastereo-, and enantioselectivities Reactions employing hydroxyacetone as an aldol donor provide anti-1,2-diols as the major product with ee values up to >99% The reactions are assumed to proceed via a metal-free Zimmerman−Traxler-type transition state and involve an enamine intermediate The observed stereochemistry of the products is in accordance with the proposed transition state Further supporting evidence is provided by the lack of nonlinear effects The reactions tolerate a small amount o

1,018 citations