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1. Highly-chemoselective step-down reduction of carboxylic acids to aromatic hydrocarbons via palladium catalysis

   https://doi.org/10.1039/c9sc00892f  

   Liu, Chengwei; Qin, Zhi-Xin; Ji, Chong-Lei; Hong, Xin; Szostak, Michal (June 2019, Chemical Science)

   Aryl carboxylic acids are among the most abundant substrates in chemical synthesis and represent a perfect example of a traceless directing group that is central to many processes in the preparation of pharmaceuticals, natural products and polymers. Herein, we describe a highly selective method for the direct step-down reduction of carboxylic acids to arenes, proceeding via well-defined Pd(0)/( ii ) catalytic cycle. The method shows a remarkably broad substrate scope, enabling to direct the classical acyl reduction towards selective decarbonylation by a redox-neutral mechanism. The utility of this reaction is highlighted in the direct defunctionalization of pharmaceuticals and natural products, and further emphasized in a range of traceless processes using removable carboxylic acids under mild, redox-neutral conditions orthogonal to protodecarboxylation. Extensive DFT computations were conducted to demonstrate preferred selectivity for the reversible oxidative addition and indicated that a versatile hydrogen atom transfer (HAT) pathway is operable. 

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2. Non-Classical Amide Bond Formation: Transamidation and Amidation of Activated Amides and Esters by Selective N–C/O–C Cleavage

   https://doi.org/10.1055/s-0040-1707101  

   Li, Guangchen; Szostak, Michal (January 2020, Synthesis)

   In the past several years, tremendous advances have been made in non-classical routes for amide bond formation that involve transamidation and amidation reactions of activated amides and esters. These new methods enable the formation of extremely valuable amide bonds via transition-metal- catalyzed, transition-metal-free or metal-free pathways by exploiting chemoselective acyl C–X (X = N, O) cleavage under mild conditions. In a broadest sense, these reactions overcome the formidable challenge of activating C–N/C–O bonds of amides or esters by rationally tackling nN→π*C=O delocalization in amides and nO→π*C=O donation in esters. In this account, we summarize the recent remarkable advances in the development of new methods for the synthesis of amides with a focus on (1) transition-metal/NHC- catalyzed C–N/C–O bond activation, (2) transition-metal-free highly selective cleavage of C–N/C–O bonds, (3) the development of new acyl-transfer reagents, and (4) other emerging methods. 

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3. Decarbonylative Sonogashira cross-coupling: a fruitful marriage of alkynes with carboxylic acid electrophiles

   https://doi.org/10.1039/D1QO01539G  

   Liu, Chengwei; Szostak, Michal (December 2021, Organic Chemistry Frontiers)

   The Sonogashira cross-coupling is one of the most fundamental C–C bond-forming reactions, wherein the strategic value of an alkyne moiety has found widespread applications at the frontiers of organic chemistry, materials science and drug discovery as the cornerstone building block of chemical synthesis. Although traditional variants of Sonogashira cross-coupling involve aryl halides and pseudohalides as electrophiles, recently, tremendous advances have been made in the unconventional disconnection exploiting common carboxylic acids by a decarbonylation/transmetalation pathway. This manifold (1) permits one to take advantage of carboxylic acids as a ubiquitous class of substrates in organic synthesis that are derived from an orthogonal pool of precursors to aryl halides and pseudohalides and (2) combines the benefits of the palladium-catalyzed C(sp 2 )–C(sp) coupling of terminal alkynes with the inherent presence of the carboxylic acid moiety in pharmaceuticals, natural products and organic materials. In this highlight article, we summarize the recent progress in the decarbonylative Sonogashira cross-coupling of carboxylic acid electrophiles to produce arylalkynes and conjugated enynes as a novel avenue for chemical synthesis, whereby a large number of chemical reactions critically rely on transformations of alkynes. 

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4. Decarbonylative sulfide synthesis from carboxylic acids and thioesters via cross-over C–S activation and acyl capture

   https://doi.org/10.1039/D1QO00824B  

   Liu, Chengwei; Szostak, Michal (August 2021, Organic Chemistry Frontiers)

   A method for the synthesis of sulfides from carboxylic acids via thioester C–S activation and acyl capture has been developed, wherein thioesters serve as dual electrophilic activators of carboxylic acids and S-nucleophiles through the merger of decarbonylative palladium catalysis and sulfur coupling. This new concept employs readily available carboxylic acids as coupling partners to directly intercept sulfur reagents via redox-neutral thioester-enabled cross-over thioetherification. The scope of this platform is demonstrated in the highly selective decarbonylative thioetherification of a variety of carboxylic acids and thioesters, including late-stage derivatization of pharmaceuticals and natural products. This method operates under mild, external base-free, and operationally practical conditions, providing a powerful new framework to unlock aryl electrophiles from carboxylic acids and increase the reactivity by employing common building blocks in organic synthesis. 

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5. Synthesis of Amides by Transamidation and Amidation of Activated Amides and Esters

   Li, Guangchen; Szostak, Michal (January 2020, Science of synthesis)

   This chapter provides a summary of the recent advances in direct transamidation and amidation reactions of activated amides and esters via transition- metal-catalyzed and transition-metal-free C(acyl)–N and C(acyl)–O bond cleavage as a new disconnection for the synthesis of amide bonds. 

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