Organocatalytic <i>syn</i>-Aldol Reactions of Dioxanones with (<i>S</i>)-Isoserinal Hydrate: Synthesis of <scp>l</scp>-Deoxymannojirimycin and <scp>l</scp>-Deoxyidonojirimycin

Palyam, Nagarjuna; Majewski, Marek

doi:10.1021/jo900263s

Cited by 30 publications

(21 citation statements)

References 47 publications

(15 reference statements)

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“…Next, we performed the reaction with cyclohexanediamine‐based catalysts. Surprisingly, the primary amine/sulfonamide catalyst 9 5e, 14 showed excellent enantioselectivity (97 % ee ), though its reactivity was low. The best result was obtained with the primary amine/thiourea 10 15.…”

Section: Methodsmentioning

confidence: 99%

anti‐Selective Asymmetric Michael Reactions of Aldehydes and Nitroolefins Catalyzed by a Primary Amine/Thiourea

Uehara¹,

Barbas²

2009

Angewandte Chemie

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In the last decade, remarkable progress has been made toward direct catalytic asymmetric assembly of simple and readily available precursor molecules into stereochemically complex products under operationally simple and environmentally friendly conditions. [1] In enamine catalysis, significant effort has focused on understanding the origin of diastereo-and enantioselectivity in organocatalysis. These studies have facilitated the design of syn-selective aldol and anti-selective Mannich reactions not originally addressed by organocatalytic methods. [2][3][4][5] The organocatalytic Michael reaction is often regarded as one of the most efficient and broadly applicable carbon-carbon bond-forming reactions known because a wide variety of acceptors can be employed and high stereoselectivity has been realized. [6] Although a large number of reports on the organocatalytic Michael reaction of aldehydes have been published, to the best of our knowledge, all of these reactions are syn selective. [7] Several studies, however, have reported success in the anti-selective organocatalytic Michael reaction of ketones. [8] Herein, we report the first highly anti-selective asymmetric Michael reactions of aldehydes and nitroolefins using a strategy designed to control the configuration of the reacting enamine.The predominant stereochemical outcome of the enamine-based Michael reaction was first explained in the classic studies of Seebach and co-workers. [9] Seebach deduced that high syn selectivity can be explained by an acyclic synclinal transition-state model (Scheme 1 a). [9a] In this transition state, the thermodynamically stable E enamine reacts with E nitroolefins in a synclinal arrangement, in which the actual donor and acceptor atoms are situated close to each other (see NO 2 and NR'R'' in Scheme 1 a).We have explored two routes for control of the overall diastereoselectivity of organocatalytic enamine reactions: 1) controlling the face selectivity of the reactive enamine to affect anti-Mannich reactions [2] and 2) controlling the E/Z configuration of the reactive enamine to affect anti-Mannich and syn-aldol reactions (Scheme 1 b). [3] For the anti-Michael reactions described herein, we have taken the latter approach.The classic organocatalytic Michael reaction of aldehydes and ketones utilizes pyrrolidine-based catalysts which react via E-enamine intermediates with nitroolefins and other Michael acceptors in synclinal transition states to provide predominately syn-configured Michael products. The Z-enamine intermediate formed using secondary amine catalysts are significantly less favored. Movement from a secondary amine catalyst to a primary amine catalyst provides steric latitude which enables Z-enamine formation with ketones. A caveat, however, is that Z-enamine formation from aldehydes is likely to be more difficult than that from ketones since the E-configured enamine derived from an aldehyde minimizes steric conflicts between the catalyst and Scheme 1. a) Synclinal transition-state model, b) anti-Mannich and synaldo...

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Section: Methodsmentioning

confidence: 99%

anti‐Selective Asymmetric Michael Reactions of Aldehydes and Nitroolefins Catalyzed by a Primary Amine/Thiourea

Uehara¹,

Barbas²

2009

Angewandte Chemie

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“…Their sphingoid part is a long-chain aminodiol or triol, which can be synthesized by reaction of cyclic ketone 63 with pentadecanal (107) catalyzed by proline (Scheme 3.23), and subsequent diastereoselective amino reduction and deprotection to yield the expected product [147]. A similar route permitted the synthesis of carbasugar ceramide KRN7000 and 1-epi-(+)-MK7607 [148], interesting azasugars and iminocyclitols [80,149]. The diastereoselective aldol reaction between ketone 63 and several chiral aldehydes allowed the synthesis of carbasugar.…”

mentioning

confidence: 99%

Organocatalyzed Aldol Reactions

Guillena¹

2013

Modern Methods in Stereoselective Aldol Reactions

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The use of catalytic enantioselective methods to perform an aldol reaction provides a direct entry for the synthesis of chiral compounds and is probably the most attractive way to achieve this goal with high control of the chemo-, regio-, diastereo-, and enantioselectivity. The application of biochemical methods based on enzyme aldolases or antibodies, which are discussed in other chapters, avoid the use of preformed enolates or their equivalents for enhancing the global atom efficiency of the process [1] for which the narrow substrate scope is a major drawback. The discovery of methodologies to carry out the enantioselective direct aldol reaction [2] has eluded the production of stoichiometric by-products increasing the substrate scope. This task could be accomplished by using small molecules as catalysts, such as metal complexes (which are covered along this book) and organic molecules, also known as organocatalysts [3]. The growth of this last research area and the direct aldol reaction are closely linked [4], with the report on the use of (S)-proline as catalyst for the intermolecular aldol [5] definitely being the push for the development of the organocatalytic methods as a competitive methodology for the synthesis of chiral compounds.In a strict sense, an organocatalyzed reaction is a process in which all the involved reagents and catalysis are purely organic compounds of low-molecular weight, excluding boron-and silicon-containing derivatives. However, in some cases, the presence of a silyl group only plays a steric role and therefore can also be considered as an organocatalyzed process. Also, if the organocatalyst involved in a reaction is immobilized in a polymer, a dendrimer, or even an inorganic material that serves only as a support to facilitate its recovery [6], it could still be considered as an organocatalyst, although those types of derivatives have been scarcely used in the natural product synthesis and therefore will be excluded from this chapter. Therefore, a comprehensive overview of the direct aldol reaction [7], emphasizing the reactivity, scope, selectivity, and limitations of the methodology and giving several examples of their application to the synthesis of biologically active compounds, is discussed in this chapter.

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“…We evaluated diverse set of chiral α‐branched aldehydes 2a – 2i with hetero (N or O), or carbon atom in the α‐position. It is known that proline‐catalyzed aldol reactions are anti ‐selective, which could be rationalized by the Houk–List model, through the formation of an intermolecular hydrogen bond between the enamine intermediate and the aldehyde . The minor product of these anti ‐selective aldolization reactions should be syn aldol (not the other anti isomer), as predicted by Houk and co‐workers by computational methods ,.…”

Section: Resultsmentioning

confidence: 85%

On the Asymmetric Induction in Proline‐Catalyzed Aldol Reactions: Reagent‐Controlled Addition Reactions of 2,2‐Dimethyl‐1,3‐dioxane‐5‐one to Acyclic Chiral α‐Branched Aldehydes

Trajkovic¹,

Milanović

Ferjancic

et al. 2017

Eur J Org Chem

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Reagent stereocontrol in the proline‐catalyzed aldol reaction of 2,2‐dimethyl‐1,3‐dioxane‐5‐one 1 with chiral aldehydes has been investigated. Synthetically useful levels of diastereoselectivity could be achieved in reactions with acyclic chiral α‐oxy and α‐amino aldehydes in both matched and mismatched cases. By using this reaction as a key step, two medicinally relevant azasugars, 1‐deoxy‐galactonojirimycin (9) and 2,5‐dideoxy‐2,5‐imino‐d‐altritol (10), were efficiently synthesized.

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Organocatalytic syn-Aldol Reactions of Dioxanones with (S)-Isoserinal Hydrate: Synthesis of l-Deoxymannojirimycin and l-Deoxyidonojirimycin

Cited by 30 publications

References 47 publications

anti‐Selective Asymmetric Michael Reactions of Aldehydes and Nitroolefins Catalyzed by a Primary Amine/Thiourea

anti‐Selective Asymmetric Michael Reactions of Aldehydes and Nitroolefins Catalyzed by a Primary Amine/Thiourea

Organocatalyzed Aldol Reactions

On the Asymmetric Induction in Proline‐Catalyzed Aldol Reactions: Reagent‐Controlled Addition Reactions of 2,2‐Dimethyl‐1,3‐dioxane‐5‐one to Acyclic Chiral α‐Branched Aldehydes

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