Synthesis and Stabilities of 3-Borylated Indoles

We report herein that 3-pinacol boronic esters undergo facile protodeborylation in the presence of palladium catalysts and base, and this contributes significantly to the generation of nonborylated indole byproducts in the B2Pin2-mediated palladium-catalysed borylative cyclization of 2-alkynylanilides. Suginome’s reagent provides an alternative method to access 3-borylated indoles as these compounds are less susceptible to protodeborylation

Metal Acetylides in Cycloaddition Reactions

This review highlights recent advances in the synthesis of (hetero)aromatic systems via cycloaddition reactions of alkynylmetals with dienes and dipoles. This methodology is advantageous when accessing complex molecules because it offers a short, atom-economic, and regioselective route to quickly access scaffolds of broad interest to the chemical sciences

Frontispiece: A Pd-Catalyzed Synthesis of Functionalized Piperidines

Pd Catalysis A readily available cyclic carbamate functions as a general precursor to a range of functionalized piperidine products using a new Pd-catalyzed annulation strategy. An asymmetric catalytic variant provides a rapid and efficient means to access these heterocycles with high to excellent levels of enantiocontrol. In addition, these richly functionalized compounds are amenable to further chemoselective elaboration. For more information, see the Communication by J. P. A. Harrity et al. on page 13000 ff

Exploiting synergistic catalysis for an ambient temperature photocycloaddition to pyrazoles

Sydnone based cycloaddition reactions are a versatile platform for pyrazole synthesis, however they operate under harsh conditions (high temperature and long reaction times). Herein we report a strategy that addresses this limitation utilizing the synergistic combination of organocatalysis and visible light photocatalysis. This new approach proceeds under ambient conditions and with excellent levels of regiocontrol. Mechanistic studies suggest that photoactivation of sydnones, rather than enamines, is key to the successful implementation of this process

Development of an amine-catalyzed regioselective synthesis of pyrroles

A regioselective synthesis of pyrroles has been devised through the cycloaddition of 1,3-oxazolium-5-olates and enamines. Product regiochemistry is controlled by the enamine substitution pattern. Moreover, an amine-catalyzed variant of this reaction allows aldehydes to be used directly as substrates for pyrrole synthesis

Expanding available pyrazole substitution patterns by sydnone cycloaddition reactions

We report the use of alkynylsilanes for the regiocontrolled synthesis of pyrazoles from functionalised sydnones. The strategies outlined herein allow a range of pyrazoles to be accessed with substitution patterns that are otherwise not directly obtained with high selectivity by alkyne cycloadditions. Moreover, this study serendipitously highlighted a simple and convenient procedure for the synthesis of aryl monofluoromethyl ethers through the combination of TBAF and dichloromethane

Pd-Catalyzed [4 + 1] annulation strategy to functionalized 4-methyleneproline derivatives

A Pd-catalyzed formal [4 + 1] cycloaddition reaction of sulfur ylides and in situ-generated Pd-stabilized zwitterions offers a convenient route to a series of functionalized proline derivatives. The utility of this method is demonstrated by a gram-scale synthesis and chemoselective functionalization of a proline-based derivative

Accounting for Different Reactivities of Sulfinate and Thiosulfate Salts in Regioselective Azetidine Coupling via C–H Sulfenylation of Indoles

The regioselective incorporation of azetidines into heteroaromatic compounds is reported via a formal C–H sulfenylation reaction. While sodium sulfinate salts undergo C3 sulfenylation of electron-rich indoles only, the corresponding thiosulfate salts have proved to be more generally useful. A mechanistic hypothesis for the different reactivities of sulfinate and thiosulfate salts is provided

Exploiting hydrazones to improve the efficiency of 6π-electrocyclization reactions of 1-azatrienes

The greater geometric lability of hydrazones compared to that of oxime ethers is used as a basis to overcome the reluctance of Z-oxime ether azatrienes to undergo electrocyclization toward the synthesis of borylated (heteroaromatic) pyridines and ring-fused analogues. Such hydrazones now allow access to previously inaccessible tri- and tetrasubstituted 3-borylpyridines in high yields

Design and synthesis of novel pyrazole based heterotricycles and their derivatization via automated library synthesis

Small molecule heterocycles bearing orthogonal functionality have the potential to deliver diverse structural motifs that aid the drug discovery effort. This work highlights how a readily assembled N ‐hydroxyethyl pyrazole trifluoroborate offers rapid access to architecturally distinct 5‐6‐6 and 5‐7‐6 fused tricyclic compounds. This chemistry is not only amenable to single compound synthesis, but also to high throughput experimentation. It enables easy access to diverse compound arrays with varying physchem and ADME profiles by fully automated library synthesis. The combination of the high throughput experimentation with rapid testing of the compounds in an integrated physchem and ADME profiling workflow allows accelerated design of novel lead compounds in drug discovery projects