An efficient methodology for the synthesis of α-Kdo glycosidic bonds has been developed with 5,7-O-di-tert-butylsilylene (DTBS) protected Kdo ethyl thioglycosides as glycosyl donors. The approach permits a wide scope of acceptors to be used, thus affording biologically significant Kdo glycosides in good to excellent chemical yields with complete α-selectivity. The synthetic utility of an orthogonally protected Kdo donor has been demonstrated by concise preparation of two α-Kdo-containing oligosaccharides.

β-Thiolactones have enabled the sterically demanding peptidyl ligations of Val–Leu, Val–Val and Val–Pro using a one-pot NCL and desulfurization protocol.

The first total synthesis of a major component of marine glycolipid vesparioside B ( Scheme 1 , 1, R1 = n-C22H45, R2 = n-C14H29) has been accomplished through a convergent [4 + 3] coupling strategy. Key steps included stereoselective installment of a set of challenging 1,2-cis-glycoside bonds. A 2-quinolinecarbonyl-assisted α-galactosylation and a novel β-arabinosylation were developed, respectively, to synthesize the α-galactofuranosidic and the β-arabinopyranosidic linkages. Furthermore, a 4,6-O-benzylidene-controlled α-galactopyranosylation reaction allowed the efficient connection of the left tetrasaccharide donor 2 with the right disaccharide lipid acceptor 3, hence leading to the total synthesis of 1.

Ground-state destabilization of the N−C(O) linkage represents a powerful tool to functionalize the historically inert amide bond. This burgeoning reaction manifold relies on the availability of amide bond precursors that participate in weakening of the n N → π* C=O conjugation through N−C twisting, N pyramidalization, and n N electronic delocalization. Since 2015, acyl N−C amide bond activation through ground-state destabilization of the amide bond has been achieved by transition-metal-catalyzed oxidative addition of the N−C(O) bond, generation of acyl radicals, and transition-metal-free acyl addition. This Perspective summarizes contributions of our laboratory in the development of new ground-state-destabilized amide precursors enabled by twist and electronic activation of the amide bond and synthetic utility of ground-state-destabilized amides in cross-coupling reactions and acyl addition reactions. The use of ground-state-destabilized amides as electrophiles enables a plethora of previously unknown transformations of the amide bond, such as acyl coupling, decarbonylative coupling, radical coupling, and transition-metal-free coupling to forge new

We report the synthesis, characterization, and reactivity of [(NHC)PdCl 2 (aniline)] complexes. These well-defined, air-and moisture-stable catalysts are highly active in the Suzuki−Miyaura cross-coupling of amides by N−C(O) activation as well as in the Suzuki−Miyaura cross-coupling of esters, aryl chlorides, and Buchwald−Hartwig amination. Most crucially, this study introduces broadly available anilines as stabilizing ligands for well-defined Pd(II)−NHC catalysts. The availability of various aniline scaffolds, including structural and electronic diversity, has a significant potential in fine-tuning of challenging cross-couplings by Pd− NHCs. The parent catalyst in this class, [Pd(IPr)(AN)Cl 2 ], has been commercialized in collaboration with Millipore Sigma, offering broad access for reaction screening and optimization.

Herein, we demonstrate that amides can be readily coupled with nonactivated arenes via sequential Ir-catalyzed C–H borylation/N–C­(O) activation. This methodology provides facile access to biaryl ketones and biaryls by the sterically controlled Ir-catalyzed C–H borylation and divergent acyl and decarbonylative amide N–C­(O) and C–C activation. The methodology diverts the traditional acylation and arylation regioselectivity, allowing us to directly utilize readily available arenes and amides to produce valuable ketone and biaryl motifs.

We describe the development of [(NHC)Pd(cinnamyl)Cl] complexes of ImPy (ImPy = imidazo[1,5-a]pyridin-3-ylidene) as a versatile class of precatalysts for cross-coupling reactions. These precatalysts feature fast activation to monoligated Pd(0) with...

In the last decade, major advances have been made in homogeneous gold catalysis. However, AuI/AuIII catalytic cycle remains much less explored due to the reluctance of AuI to undergo oxidative addition and the stability of the AuIII intermediate. Herein, we report activation of aryl halides at gold(I) enabled by NHC (NHC=N‐heterocyclic carbene) ligands through the development of a new class of L‐shaped heterobidentate ImPy (ImPy=imidazo[1,5‐a]pyridin‐3‐ylidene) N,C ligands that feature hemilabile character of the amino group in combination with strong σ‐donation of the carbene center in a rigid conformation, imposed by the ligand architecture. Detailed characterization and control studies reveal key ligand features for AuI/AuIII redox cycle, wherein the hemilabile nitrogen is placed at the coordinating position of a rigid framework. Given the tremendous significance of homogeneous gold catalysis, we anticipate that this ligand platform will find widespread application.