Organocatalytic Activation of Inert Hydrosilane for Peptide Bond Formation

Abstract

We describe the development of a reliable catalytic protocol for peptide bond formation that is generally applicable to natural and unnatural α-amino acids, β-amino acids, and peptides bearing various functional groups. A 10 mol % loading of HSi[OCH(CF 3 ) 2 ] 3 as a catalyst was sufficient to guarantee a consistently high yield of the resulting peptide. This method facilitates the sustainable utilization of natural resources by using a catalyst and an auxiliary based on earth-abundant silicon.

Silyl Esters as Reactive Intermediates in Organic Synthesis

“…Many amino esters were tolerated in this reaction with varying functional groups; however, lower yields were obtained with sterically challenging substrates. 70 Figure 29 Scope of 31-mediated peptide formation using 30 as a catalyst.…”

“…A mechanism was proposed for the tris(1,1,1,3,3,3-hexafluoropropan-2-yloxy)silane ( 30 ) catalyzed peptide bond formation using trimethoxysilane ( 31 ) (Scheme 53 ). 70 Silyl ester 79 is formed when tris(hexafluoropropan-2-yloxy)silane 30 reacts with a carboxylic acid. This silyl ester reacts with the amine to generate the amide, generating silanol 80 .…”

Concise Synthesis of 2,5-Diketopiperazines via Catalytic Hydroxy-Directed Peptide Bond Formations

“…In contrast, the ideal protocol for preparing dipeptides is direct dehydrative condensation reactions under catalytic conditions, since the only byproduct of the catalysis in principle is water, which is superior in terms of both atom economy and practicality of operations. Over the past decade, several successful examples of catalytic peptide bond formation reactions have been reported. − Recently, we developed diboronic acid anhydride (DBAA)-catalyzed direct peptide bond formation via dehydrative condensation of β-hydroxy-α-amino acids (Scheme A) . The designed DBAA, possessing a characteristic B–O–B motif, showed significant performance as a dehydrative condensation catalyst through a bidentate electrophilic activation of carboxylic acids via covalent bond formation with β-hydroxy groups of substrates, forming serine- or threonine-derived peptides in high to excellent yields with high functional group tolerance.…”

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

“…Two types of catalysts have been developed for amide synthesis: enzymes [28] and Lewis acids (boron‐based [23,29–31] and metal‐based catalysts [32,33] ). [34] These methods have demonstrated cost‐effectiveness and broad applicability.…”

“…[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] ). [34] These methods have demonstrated cost-effectiveness and broad applicability.…”