Solvent-free amide bond formation using a variety of methoxysilanes as coupling agent

Lainer, Thomas; Czerny, Frank; Haas, Michael

doi:10.1039/d2ob00589a

Cited by 15 publications

(13 citation statements)

References 32 publications

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“…Blanchet and co-workers concluded that the phenylsilane-mediated reaction does not proceed through the chemical ligation amide synthesis (i.e. intermediate 43), 79,80 but rather through a diester (67) or triester (68) formed by dehydrogenative addition of phenylsilane to the carboxylic acids (Figure 57). They were unable to isolate any reactive intermediates, and so to test this mechanistic hypothesis they explored the acetylation of morpholine with various silyl acetates (Figure 58).…”

Section: Synthesismentioning

confidence: 99%

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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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Section: Synthesismentioning

confidence: 99%

“…Each silicon in 28 and 29 acts as a reactive site for the formation of the silyl ester by reaction with the carboxylic acid. 68…”

Section: Making Amides From Silyl Estersmentioning

confidence: 99%

Silyl Esters as Reactive Intermediates in Organic Synthesis

et al. 2023

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“…Significant progress has been made with the development of boron-based catalysts, − oxophilic metal catalysts, and other catalytic systems . However, while there are several reports of successful silicon-based reagents and silica gels for direct amidation, there are no examples of silicon-centered molecular catalysts for direct amidations . Furthermore, while various proposals for the mechanistic operation of catalytic amidations have been moot, − only limited direct experimental evidence for presumed activated intermediates has been garnered .…”

Section: Introductionmentioning

confidence: 99%

On the Use of Triarylsilanols as Catalysts for Direct Amidation of Carboxylic Acids

et al. 2023

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Triarylsilanols have been reported as the first silicon-centered molecular catalysts for direct amidation of carboxylic acids with amines as identified after a screen of silanols, silanediols, disiloxanediols, and incompletely condensed silsesquioxanes as potential homogeneous catalysts. Subsequent synthesis and testing of various electronically differentiated triarylsilanols have identified tris(p-haloaryl)silanols as more active than the parent triarylsilanol, where the bromide congener is found to be the most active. Catalyst decomposition can be observed by NMR methods, but RPKA methods reveal that product inhibition is operative, where tertiary amides are more inhibitory than secondary amides. Studies using an authentically synthesized triaryl silylester as a putative intermediate in the catalytic system enable a plausible mechanism to be proposed as supported by computationals.

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“…The development of environmentally‐friendly methods for amide bond formation is crucial, as demonstrated by the emergence of innovative techniques [15] that use non‐activated starting materials, [16] solvent‐free processes, [17–19] electrochemical reactions, [20,21] or catalysis [22–27] …”

Section: Introductionmentioning

confidence: 99%

“…This leads to the production of large quantities of waste, which is even more problematic for industrial scaleup. [13,14] The development of environmentally-friendly methods for amide bond formation is crucial, as demonstrated by the emergence of innovative techniques [15] that use non-activated starting materials, [16] solvent-free processes, [17][18][19] electrochemical reactions, [20,21] or catalysis. [22][23][24][25][26][27] Two types of catalysts have been developed for amide synthesis: enzymes [28] and Lewis acids (boron-based [23,[29][30][31] and metal-based catalysts [32,33] ).…”

Section: Introductionmentioning

confidence: 99%

Catalytic and Sustainable Amide Bond Formation using a DABCO/Dichlorotriazine System

2023

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Amides are one of the most important functional groups in organic chemistry and play essential roles in both the pharmaceutical industry and life sciences. However, due to the natural reactivity of carboxylic acids and amines, their direct coupling is challenging and often leads to reactions that are not atom-economic and produce large amounts of nonrecoverable by-products. Despite the impressive number of coupling reagents available, sustainable methods for amide bond formation are still needed. To address this challenge, a new catalytic approach for the direct preparation of amides from carboxylic acids and amines is reported here. This method combines organocatalysis with a substoichiometric amount of activating agent under mild conditions (open air, room temperature, green solvents). This method was applied with good efficiency on a wide range of substrates, without epimerization of chiral stereocenters and on SPPS.

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Solvent-free amide bond formation using a variety of methoxysilanes as coupling agent

Abstract: A solvent-free procedure for forming amide bonds without exclusion of air and moisture is described. Using tetramethoxysilane 1, hexamethoxydisilane 2 and dodecamethoxy-neopentasilane 3 as coupling agent carboxylic acids and amines...

Cited by 15 publications

References 32 publications

Silyl Esters as Reactive Intermediates in Organic Synthesis

Silyl Esters as Reactive Intermediates in Organic Synthesis

On the Use of Triarylsilanols as Catalysts for Direct Amidation of Carboxylic Acids

Catalytic and Sustainable Amide Bond Formation using a DABCO/Dichlorotriazine System

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