Improved Auxiliary for the Synthesis of Medium‐Sized Bis(lactams)

Springer, Jasper; Jansen, Thomas Paul; Ingemann, Steen; Hiemstra, Henk; Maarseveen, Jan H. van

doi:10.1002/ejoc.200700832

Cited by 14 publications

(3 citation statements)

References 41 publications

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“…Isopropoxy-substituted benzylamines were prepared by modification of a reported reductive amination procedure . These reactions were carried out in air with nondried solvents.…”

Section: Methodsmentioning

confidence: 99%

Decomposition of a Phosphine-Free Metathesis Catalyst by Amines and Other Bronsted Bases: Metallacyclobutane Deprotonation as a Major Deactivation Pathway

2015

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Reactions are described of the second-generation Hoveyda catalyst HII with amines, pyridine, and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), in the presence and absence of olefin substrates. These nitrogen bases have a profoundly negative impact on metathesis yields, but in most cases are innocuous toward the pre-catalyst. HII adducts were formed by primary and secondary amines (n-butylamine, sec-butylamine, benzylamine, pyrrolidine, morpholine), pyridine, and DBU at room temperature. No reaction was evident for NEt 3 , even at 60 °C. On longer reaction at RT, unencumbered primary amines abstract the benzylidene ligand from HII. With 10 equiv NH 2 n Bu, this process was complete in 12 h, affording NH n Bu(CH 2 Ar) (Ar = o-C 6 H 4 -O i Pr) and [RuCl(H 2 IMes)(NH 2 n Bu) 4 ]Cl. For benzylamine, benzylidene abstraction occurred over days at RT. No such reaction was observed for sec-butylamine, secondary amines, NEt 3 , pyridine, or DBU. All of these bases, however, strongly inhibited metathesis of styrene by HII, with a general trend toward more deleterious effects with higher Bronsted basicity. Studies at 10 mol% HII and 10 equiv DBU, NEt 3 , and pyrrolidine (60 °C, C 6 D 6 ) indicated that the primary mechanism for decomposition involved base-induced deprotonation of the metallacyclobutane intermediate, rather than the Lewis base-mediated decomposition pathways previously established for the Grubbs catalysts. In the corresponding metathesis of ethylene, this decomposition process is rapid even at RT, highlighting the vulnerability of the monosubstituted metallacyclobutane.

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“…Isopropoxy-substituted benzylamines were prepared by modification of a reported reductive amination procedure . These reactions were carried out in air with nondried solvents.…”

Section: Methodsmentioning

confidence: 99%

Decomposition of a Phosphine-Free Metathesis Catalyst by Amines and Other Bronsted Bases: Metallacyclobutane Deprotonation as a Major Deactivation Pathway

2015

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“…First, an enthalpic activation is brought about due to the high reactivity of aryl esters towards aminolysis. Second, an entropic activation results from the auxiliary correctly positioning the secondary amine and carbonyl functional groups in close proximity for the ring contraction 80 . This strategy has been successfully applied to the synthesis of several homodiketopiperazines that are difficult to synthesize.…”

Section: Ring-contraction Strategies Involving Lactonesmentioning

confidence: 99%

Contemporary strategies for peptide macrocyclization

2011

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Peptide macrocycles have found applications that range from drug discovery to nanomaterials. These ring-shaped molecules have shown remarkable capacity for functional fine-tuning. Such capacity is enabled by the possibility of adjusting the peptide conformation using the techniques of chemical synthesis. Cyclic peptides have been difficult, and often impossible, to prepare using traditional synthetic methods. For macrocyclization to occur, the activated peptide must adopt an entropically disfavoured pre-cyclization conformation before forming the desired product. Here, we review recent solutions to some of the major challenges in this important area of contemporary synthesis.

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“…41 The use of auxiliary molecules for the RCS synthesis of cyclopeptides has been reported. 42,43 In this case the auxiliary molecule helps to form a less constrained ring and after the ring contraction step the auxiliary is removed. Examples of these auxiliary mediated approaches that have been used for the synthesis of cyclotetrapeptides are described below.…”

Section: Ring Contraction Strategiesmentioning

confidence: 99%

An update on new methods to synthesize cyclotetrapeptides

2015

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Cyclotetrapeptides are important bioactive lead drug molecules that display a wide spectrum of pharmacological activities. However, the synthesis of cyclotetrapeptides from their linear precursors is challenging due to the highly constrained conformation required for cyclisation, thus hampering their progress to a clinical setting. This review provides an account of the reported methods used for the synthesis of cyclotetrapeptides.

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Improved Auxiliary for the Synthesis of Medium‐Sized Bis(lactams)

Cited by 14 publications

References 41 publications

Decomposition of a Phosphine-Free Metathesis Catalyst by Amines and Other Bronsted Bases: Metallacyclobutane Deprotonation as a Major Deactivation Pathway

Decomposition of a Phosphine-Free Metathesis Catalyst by Amines and Other Bronsted Bases: Metallacyclobutane Deprotonation as a Major Deactivation Pathway

Contemporary strategies for peptide macrocyclization

An update on new methods to synthesize cyclotetrapeptides

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