Novel Multicomponent Reaction for the Combinatorial Synthesis of 2-Imidazolines

Bon, Robin S.; Hong, Chongen; Bouma, Marinus J.; Schmitz, Rob F.; Kanter, Frans J. J. de; Lutz, Martin; Spek, Anthony L.; Orru, Romano V. A.

doi:10.1021/ol035521g

Cited by 120 publications

(64 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, when the same reactions were performed in DMF (method C), 5-methoxyoxazole (5 d,k,l,m) formation increased with larger R 1 and R 2 substituents in the oxo component (Table 6, entries 1-4). The same trend was observed when the steric constraints of the amine component 3 were increased (entries [5][6][7][8]. The reaction of 1 d, cyclohexanone (2 e), and the smallest possible amine, ammonia (3 b), could be fully directed to either the formation of 2-imidazoline 4 n or oxazole 5 n (using method B and C, respectively; entry 5).…”

Section: Resultssupporting

confidence: 52%

“…We turned our attention to the use of aaryl-substituted isocyano esters 1 d-j in the 3-CR (Scheme 5). As mentioned in the introduction, so far isocyano esters have been reported to selectively produce 2-imidazolines (4), [5,6] the only notable exception being a-(p-nitrophenyl)-a-isocyanoacetate (1 e), which was found to undergo the MCR leading to the corresponding 5-methoxyoxazoles.…”

Section: Resultsmentioning

confidence: 99%

“…In most cases, however, the isolated yields are typical for 2-imidazolines (67-87 %). [5,6] When the reactions of 1 e-i with 2 a and 3 a were performed in DMF (Table 5, method C) the corresponding oxazoles 5 e-i were formed quantitatively. Typically, the conversion of the isocyanides proceeds twice as fast in this polar aprotic solvent than the reactions performed in MeOH (method A, Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…[6] A wide variety of aldehydes and amines can be used in this MCR. Careful optimization of the reaction conditions showed that the scope of compatible isocyanides could be expanded considerably by selecting MeOH as the solvent.…”

Section: Introductionmentioning

confidence: 99%

“…[9k] Although isocyano esters are substrates that typically yield 2-imidazolines (4), [5,6] a wide variety of aldehydes and amines were used in this MCR to afford the corresponding 5-methoxyoxazoles in moderate to excellent yields.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Selective Formation of 2‐Imidazolines and 2‐Substituted Oxazoles by Using a Three‐Component Reaction

Elders¹,

Ruijter²,

Kanter³

et al. 2008

Chemistry A European J

View full text Add to dashboard Cite

Selective formation of 2H-2-imidazolines and 2-substituted oxazoles by using a multicomponent reaction of amines, either aldehydes or ketones, and alpha-acidic isocyano amides or esters is described. By selecting the appropriate solvent, Ag(I) or Cu(I) catalyst, or by employing a weak Brønsted acid, the product formation can be fully controlled and directed quantitatively to the desired heterocyclic scaffold. The described experimental procedures not only significantly increase the scope of compatible inputs for this complexity-generating three-component reaction, but also allow for considerable chemical diversity: At least four diversity points in two distinct scaffolds can be exploited in this way.

show abstract

Section: Resultssupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Selective Formation of 2‐Imidazolines and 2‐Substituted Oxazoles by Using a Three‐Component Reaction

Elders¹,

Ruijter²,

Kanter³

et al. 2008

Chemistry A European J

View full text Add to dashboard Cite

show abstract

A Half‐Century of the Ugi Reaction: Classic Variant

Ullrich

Kazmaier

2023

Organic Reactions

View full text Add to dashboard Cite

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.

show abstract

A Half‐Century of the Ugi Reaction: Modified Variants

Ullrich

Kazmaier

2023

Organic Reactions

View full text Add to dashboard Cite

The classic Ugi reaction is a four‐component coupling process involving a carboxylic acid, a carbonyl compound, an amine, and an isocyanide, resulting in an N ‐acylamino acid amide product. Modified Ugi reactions employ special, often multifunctional, reaction components, and can involve fewer than or more than four components. This reaction exhibits broad scope and can be used to prepare complex heterocycles. As a result, this method has been employed to prepare diverse libraries of structurally related products, and in addition, is often applied to the synthesis of drugs, drug‐like molecules, and natural products. Applications in target‐directed synthesis are presented, as are comparisons to other related multicomponent reactions and heterocycle syntheses; modifications leading to achiral heteroaromatic ring systems are not included. This chapter covers the literature from the early days of the Ugi reaction in 1961 through the end of 2012.

show abstract

Novel Multicomponent Reaction for the Combinatorial Synthesis of 2-Imidazolines

Abstract: [reaction: see text] The three-component condensation between an amine, an aldehyde, and an alpha-acidic isocyanide efficiently provides substituted 2-imidazolines in a one-pot reaction under mild conditions.

Cited by 120 publications

References 34 publications

Selective Formation of 2‐Imidazolines and 2‐Substituted Oxazoles by Using a Three‐Component Reaction

Selective Formation of 2‐Imidazolines and 2‐Substituted Oxazoles by Using a Three‐Component Reaction

A Half‐Century of the Ugi Reaction: Classic Variant

A Half‐Century of the Ugi Reaction: Modified Variants

Contact Info

Product

Resources

About