Transformation of Carbohydrate Derived 4‐Azidopentanals Into Highly Functionalized Pyrrolidines <i>Via</i> a Tandem Staudinger/aza‐Wittig/Ugi Multicomponent Reaction

Bonger, Kimberly M.; Wennekes, Tom; Lavoir, Sebastiaan V. P. de; Esposito, Davide; Berg, Richard J. B. H. N. van den; Litjens, Remy E. J. N.; Marel, Gijs A. van der; Overkleeft, Herman S.

doi:10.1002/qsar.200540198

Cited by 25 publications

(38 citation statements)

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“…For comparison, when these reactions are performed in methanol without Lewis acid the 2,3-cis substituted pyrrolidines are almost exclusively formed, as reported previously. [3] In all cases for the Lewis acid mediated Ugi-3C reaction with 2 formation of the 2,3-trans product equaled or exceeded the formation of the 2,3-cis product. However, the 2,3-cis/trans ratio is highly dependent on the carboxylic acid and isocyanide used.…”

Section: Resultsmentioning

confidence: 90%

“…Among all Lewis acids tested, InCl 3 [8] and HgBr 2 (Entries 11 and 15) gave the highest amount of the 2,3-trans product 4 with good overall yields. For the other Lewis acids that showed high amounts of the 2,3-trans product 4 [that is, AlCl 3 , SnCl 4 and Yb(OTf) 3 ], a significantly lower yield was observed. 5 5 4 5 6 3 10 ZnCl 2 50 50 85 11 InCl 3 42 58 75 12 AlCl 3 40 60 47 13 SnCl 4 34 66 42 14 Yb (OTf) 3 33 67 58 15 HgBr 2 29 71 84 [a] Ratio and yield based on products purified by column chromatography.…”

Section: Resultsmentioning

confidence: 99%

“…The same set of experiments was also performed in acetonitrile with one equiv. of InCl 3 . In this system, immediate formation of the Ugi-products was observed in all cases (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…[3] Variation of the stoichiometry of the carboxylic acid and isocyanide component or of the reaction solvent and temperature also did not alter this preference for 2,3-cis products (unpublished results). In the study reported here we investigated what factors do influence the stereochemical outcome of the Ugi-3C reaction with -lyxo-pyrroline 2.…”

Section: Introductionmentioning

confidence: 88%

“…This cyclic imine is subsequently used as a component together with a carboxylic acid and an isocyanide in the Ugi three-component reaction In our studies on the scope of the SAWU-3CR, we observed that the 4-azidoaldehyde 1 produces pyrrolidines with counter-intuitive 2,3-cis stereochemistry at the new stereogenic centre (Scheme 2). [3] This stereochemistry is established in the final Ugi-3CR step with the cyclic imine [4] (-lyxo-pyrroline 2). The Ugi-3CR mechanism consists of a series of successive equilibria where the C-2 stereogenic center is created upon attack of the isocyanide and fixed in the irreversible Mumm-rearrangement (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Lewis Acids on the Stereochemistry in the Ugi Three‐Component Reaction with D‐lyxo‐Pyrroline

et al. 2008

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Keywords: Multicomponent reactions / Diastereoselectivity / Indium(III) chloride / Imines / Nitrogen heterocycles A library of polyhydroxylated pyrrolidines was obtained by performing a tandem Staudinger/aza-Wittig/Ugi three-component reaction on a L-ribose-derived 4-azido aldehyde. In this paper we describe the effect of Lewis acids on the diastereoselectivity of the final Ugi three-component reaction step that the intermediate (D-lyxo-pyrroline) cyclic imine undergoes. When the Ugi reaction was performed in methanol almost exclusively pyrrolidines with a 2,3-cis relationship

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Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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The Effect of Lewis Acids on the Stereochemistry in the Ugi Three‐Component Reaction with D‐lyxo‐Pyrroline

et al. 2008

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A Half‐Century of the Ugi Reaction: Classic Variant

Ullrich

Kazmaier

2023

Organic Reactions

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The classic Ugi reaction is a four‐component coupling process that involves a carboxylic acid, a carbonyl compound, an amine, and an isocyanide. All reaction components are in a dynamic equilibrium with several intermediates, until an irreversible intramolecular 1,4‐ O → N acyl transfer leads to the formation of an N ‐acylamino acid amide. If chiral components are used in this reaction, a mixture of diastereomers is generally formed with moderate‐to‐low stereoselectivity. The broad scope of substrates that can be used in the Ugi reaction allows for the straightforward synthesis of libraries of structurally related amino acid and peptide derivatives. Therefore, this methodology is often applied to the synthesis of drugs, drug‐like molecules, and natural products. This chapter describes different variations of classic Ugi reactions, including the use of functionalized and cleavable reaction components to illustrate the broad scope of the reaction. In addition, applications in target‐directed synthesis and comparisons to other related multicomponent reactions are presented. Tabular surveys are organized according to the isocyanides used. The literature is discussed from the first disclosure of an Ugi reaction in 1961 through to the end of 2012.

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Ugi Reaction

2010

Comprehensive Organic Name Reactions and Reagents

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This reaction is a one‐pot “domino” reaction of an amine, a carbonyl compound, a carboxylic acid, and an isonitrile to form an α‐acylamino amide with four different substituents. This reaction is known as the Ugi reaction. Currently, other names are also used for this versatile reaction. It has been reported that many components participate in this reaction system and a single reaction step involving more than three components is disfavored due to the low kinetic probability. Thus, the overall reaction actually is the result of a domino reaction of several subreactions. Such reaction series can be divided into several groups. Besides the Ugi reaction, many multicomponent condensations have been identified till today. The study also finds high level of stereoselectivity in this reaction. This reaction has been modified by attaching one of the components to a solid phase or a fluorous phase to simplify the purification process. This reaction has wide application in the organic synthesis.

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Transformation of Carbohydrate Derived 4‐Azidopentanals Into Highly Functionalized Pyrrolidines Via a Tandem Staudinger/aza‐Wittig/Ugi Multicomponent Reaction

Abstract: The preparation of highly functionalized pyrrolidines by a tandem Staudinger/aza-Wittig/ Ugi Three-Component Reaction (SAWU-3CR) is presented. The SAWU-3CR was applied on two different carbohydrate derived 4-azidopentanals and two libraries of chemically diverse products were prepared.

Cited by 25 publications

References 25 publications

The Effect of Lewis Acids on the Stereochemistry in the Ugi Three‐Component Reaction with D‐lyxo‐Pyrroline

The Effect of Lewis Acids on the Stereochemistry in the Ugi Three‐Component Reaction with D‐lyxo‐Pyrroline

A Half‐Century of the Ugi Reaction: Classic Variant

Ugi Reaction

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