Palladium-Catalyzed Cross-Coupling of Benzyl Chlorides with Cyclopropanol-Derived Ketone Homoenolates

The palladium-catalyzed cross-coupling reaction of cyclopropanol-derived ketone homoenolates with benzyl chlorides is reported. This reaction proceeds in high yields with electron-neutral and electron-rich benzyl chlorides; however, yields are low with electron-poor benzyl chlorides. In addition, a range of cyclopropanols can be coupled in good yields. The reaction can be conducted with a low catalyst loading (1% Pd) and on a gram scale without reduction in yield

The Acid-Free Cyclopropanol-Minisci Reaction Reveals the Catalytic Role of Silver–Pyridine Complexes

A well-defined homogeneous silver precatalyst can be utilized for the direct C–H functionalization of a wide range of aromatic nitrogen heterocycles with cyclopropanols under acid-free conditions. This reaction can be conducted on gram-scale and with low catalyst loadings (as low as 1%), which is rare for silver-catalyzed Minisci-type reactions. Moreover, reactivity trends, as well as steric and calculated electronic properties of the heterocycles, strongly suggest that silver–heterocycle complexes formed in situ behave as redox active catalysts and as Lewis acid activators of the heterocycle and that the electronic nature of the heterocyclic substrates tunes the reactivity of the resulting complexes

Measuring Kinetic Isotope Effects in Enzyme Reactions Using Time-Resolved Electrospray Mass Spectrometry

Kinetic isotope effect (KIE) measurements are a powerful tool for studying enzyme mechanisms; they can provide insights into microscopic catalytic processes and even structural constraints for transition states. However, KIEs have not come into widespread use in enzymology, due in large part to the requirement for prohibitively cumbersome experimental procedures and daunting analytical frameworks. In this work, we introduce time-resolved electrospray ionization mass spectrometry (TRESI-MS) as a straightforward, precise, and inexpensive method for measuring KIEs. Neither radioisotopes nor large amounts of material are needed and kinetic measurements for isotopically “labeled” and “unlabeled” species are acquired simultaneously in a single “competitive” assay. The approach is demonstrated first using a relatively large isotope effect associated with yeast alcohol dehydrogenase (YADH) catalyzed oxidation of ethanol. The measured macroscopic KIE of 2.19 ± 0.05 is consistent with comparable measurements in the literature but cannot be interpreted in a way that provides insights into isotope effects in individual microscopic steps. To demonstrate the ability of TRESI-MS to directly measure intrinsic KIEs and to characterize the precision of the technique, we measure a much smaller ¹²C/¹³C KIE associated specifically with presteady state acylation of chymotrypsin during hydrolysis of an ester substrate

Synthesis of Acyl Pyrroles via Palladium-Catalyzed Carbonylative Amination of Aryl and Alkenyl Iodides

A palladium-catalyzed synthesis of acyl pyrroles from aryl and alkenyl iodides is reported. This carbonylative amination requires only atmospheric (balloon) pressure of carbon monoxide and proceeds with Pd­(PPh₃)₄ and Pd-NHC catalysts. Aryl and heteroaryl iodides give the corresponding acyl pyrroles in good to excellent yields, while alkenyl iodides provide the corresponding acyl pyrroles in low to moderate yields

A Diels–Alder-Based Total Synthesis of (−)-Kainic Acid

An efficient synthesis of (−)-kainic acid, through a high-pressure-promoted Diels–Alder cycloaddition of a vinylogous malonate derived from 4-hydroxyproline, is described. The bicyclic adduct could be converted into the natural product with complete stereocontrol