Silicon compounds as stoichiometric coupling reagents for direct amidation

Davies, Joshua J.; Braddock, D. Christopher; Lickiss, Paul D.

doi:10.1039/d1ob01003d

Cited by 16 publications

(8 citation statements)

References 54 publications

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“…The use of stoichiometric silanes in direct amidation is not new, as SiCl 4 was reported to facilitate this transformation over 50 years ago. Despite many advances in this area in recent years, 166 no examples in process chemistry other than the one described in section 4.36 of this review have been reported. In general, silicon compounds display lower toxicity than many other activators and are costeffective, and the byproducts (e.g., polysiloxane) display low solubility and can be easily removed by filtration.…”

Section: Discussionmentioning

confidence: 99%

Large-Scale Amidations in Process Chemistry: Practical Considerations for Reagent Selection and Reaction Execution

Magano

2022

Org. Process Res. Dev.

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This review describes the practical aspects involved in the implementation of large-scale amidations in process chemistry. Coupling reagent, base, additive, and solvent selections are critically analyzed to highlight their pros and cons. Other important factors to be considered on large scale, such as atom economy, cost, safety, and toxicity, are also examined. These concepts are then showcased through selected examples from the literature for the synthesis of active pharmaceutical ingredients.

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Section: Discussionmentioning

confidence: 99%

Large-Scale Amidations in Process Chemistry: Practical Considerations for Reagent Selection and Reaction Execution

Magano

2022

Org. Process Res. Dev.

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“…Silanes have been reported as good amide bond coupling agents, although carboxylic acid activation by silanes typically requires high reactant concentrations (>1 M) and a long reaction time. − As a control, we conducted the model reaction with phenylsilane in the absence of any diselenides and phosphines (Figure b). Unsurprisingly, at the low 50 mM substrate concentration, only 23% conversion was observed after 6 h. Further studies (Table entries 1–7 and Supporting Information Figure S1) established that both diselenide catalyst 1 and phosphine oxide catalyst 2a-[O] accelerate the amide bond formation in cooperation with phenylsilane.…”

Section: Resultsmentioning

confidence: 99%

Two-Component Redox Organocatalyst for Peptide Bond Formation

2022

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Peptides are fundamental therapeutic modalities whose sequence-specific synthesis can be automated. Yet, modern peptide synthesis remains atom uneconomical and requires an excess of coupling agents and protected amino acids for efficient amide bond formation. We recently described the rational design of an organocatalyst that can operate on Fmoc amino acidsthe standard monomers in automated peptide synthesis (J. Am. Chem. Soc. 2019, 141, 15977). The catalytic cycle centered on the conversion of the carboxylic acid to selenoester, which was activated by a hydrogen bonding scaffold for amine coupling. The selenoester was generated in situ from a diselenide catalyst and stoichiometric amounts of phosphine. Although the prior system catalyzed oligopeptide synthesis on solid phase, it had two significant requirements that limited its utility as an alternative to coupling agentsit depended on stoichiometric amounts of phosphine and required molecular sieves as dehydrating agent. Here, we address these limitations with an optimized method that requires only catalytic amounts of phosphine and no dehydrating agent. The new method utilizes a two-component organoreductant/organooxidantrecycling strategy to catalyze amide bond formation.

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“…42 Interest and exploration in the field of silane-mediated coupling for the synthesis of amides have increased over the past decade. 43 Highly efficient, operationally simple, and greener methods for direct amidation using silicon-based coupling reagents have been developed and have also been used to make amide intermediates.…”

Section: Making Amides From Silyl Estersmentioning

confidence: 99%

Silyl Esters as Reactive Intermediates in Organic Synthesis

et al. 2023

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Silyl esters have been exploited as meta-stable reaction intermediates – both purposefully and unintentionally – since at least the 1960s. Their reactivity is broadly related to the substituents on the silicon, and in this way their properties can be readily modulated. Silyl esters have unique reactivity profiles that have been used to generate downstream products of a range of functionalities, and because of this many excellent methods for the synthesis of a variety of value-added chemicals have been developed. Furthermore, because of the frequent use of hydrosilanes as terminal reductants in catalytic processes, silyl ester intermediates are likely more commonly utilized by synthetic chemists than currently realized. This review comprehensively summarizes the reactions known to take advantage of reactive silyl ester intermediates and discusses examples of catalytic reactions that proceed in an unanticipated manner through silyl ester intermediates.

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Silicon compounds as stoichiometric coupling reagents for direct amidation

Abstract: This review covers all the reported use of stoichiometric silicon reagents for direct amidation of carboxylic acids with amines, commencing with the first example in 1969 up until April 2021.

Cited by 16 publications

References 54 publications

Large-Scale Amidations in Process Chemistry: Practical Considerations for Reagent Selection and Reaction Execution

Large-Scale Amidations in Process Chemistry: Practical Considerations for Reagent Selection and Reaction Execution

Two-Component Redox Organocatalyst for Peptide Bond Formation

Silyl Esters as Reactive Intermediates in Organic Synthesis

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