A wild-type Baeyer-Villiger monooxygenase was engineered to overcome numerous liabilities in order to mediate a commercial oxidation of pyrmetazole to esomeprazole, using air as the terminal oxidant in an almost exclusively aqueous reaction matrix. The developed enzyme and process compares favorably to the incumbent Kagan inspired chemocatalytic oxidation, as esomeprazole was isolated in 87% yield, in >99% purity, with an enantiomeric excess of >99%.

Terminal and internal acetylenes were obtained in good to excellent isolated yields from carbonyl compounds by converting the carbonyl functionality into the enol nonaflate intermediate followed by elimination to give the C-C triple bond. The one-pot transformations were uniformly induced by phosphazene bases combined with mildly electrophilic nonafluorobutane-1-sulfonyl fluoride. The method is the most general among those reported to date as it applies to both acyclic ketones and aldehydes. Only moderate kinetic regioselectivity in favour of alk-1-yne achieved from methyl n-alkyl ketone represents a limitation of the method. In all the other instances, individual acetylenic products were obtained.

A mechanistic study on the ligand-free room-temperature Heck reaction of alkenyl nonafluorobutanesulfonates (nonaflates) is described. Kinetic data obtained from poisoning experiments, centrifugation and variation of catalyst loading consistently provide evidence for a homogeneous palladium catalysis unprecedented in Heck chemistry. The Heck reaction of alkenyl perfluorobutanesulfonates represents a remarkably robust, active and efficient catalytic system generally applicable to the coupling with a broad range of terminal olefins including non-activated ones under ambient conditions. It features insensitivity towards atmospheric oxygen and moisture, furnishing uniformly high yields of the anticipated coupling products without the necessity to purify commercial reagents and solvents.Keywords: alkenyl nonaflates; catalyst poisoning; Heck reaction; homogeneous catalysis; kinetics; ligand-free catalysis Coupling of olefins with aryl/alkenyl halides, commonly known as the Heck reaction, represents one of the basic tools in contemporary organic synthesis.[1]The existing vast realm of the Heck chemistry can conventionally be subdivided to ligand-assisted and ligand-free catalysis. Ligands at palladium play a different role depending on the application. While the ligation is crucially important for enantioselective variants of the Heck reaction [2] or activation of otherwise unreactive aryl chlorides, [3] it often tends to deteriorate the desired coupling, causes side reactions and deactivates the catalyst, [4] in particular, when aryl iodides are used as substrates.[5] From this standpoint, it is of no surprise that the fastest versions of Heck reaction known so far are described for ligand-free systems containing free halides (Cl À or Br À added as quaternary ammonium salts) which are believed to stabilize Pd(0)-species.[1d]Later on, it was shown that intermediary Pd nanoparticles as colloids are likely to be the true catalytic species in such systems. [6] Owing to the recent advancements in the mechanistic study and design of robust and efficient low Pd-loading systems, [7] the ligand-free Heck reaction became an emerging trend with particular promise for industrial applications. [8] On the other hand, it was demonstrated in a number of well-documented cases that palladacycles [7a,9] and pincer Pd(II) complexes [10] are pre-catalysts and not the actual active species catalyzing the Heck reaction of aryl halides as it was believed earlier.[11] Compelling evidence based on kinetic studies [10,12] and quantitative poisoning experiments [10] was obtained that the above complexes decompose under the reaction conditions to generate the actual catalytic species, Pd nanoparticles.The above breakthroughs in understanding the nature of catalysis in the Heck chemistry of aryl halides [13] and a lack of mechanistic insight in the underligated Heck reaction of aryl and alkenyl perfluoroalkanesulfonates [14] prompted us to investigate the nature of Pd-catalysis for the latter substrates.Herein, we report on the nat...

In light of the pivotal role of the carbonyl group in organic synthesis, [1] new general transformations of the carbonyl compounds are always of particular importance. This is why the relatively recent discovery of transition-metal-catalyzed reactions of alkenyl triflates, readily available from enolizable carbonyl precursors, immediately found widespread application.[2] Following this line of research, alkenyl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonates (hereinafter referred to alkenyl nonaflates) were introduced and advantageously employed as a useful alternative to the triflates in Heck, [3] Negishi, [4] Stille, [5] and Sonogashira [6] coupling reactions. Routinely, the coupling protocols consist of two steps that include O-sulfonylation of the starting carbonyl compounds, followed by Pd-catalyzed CÀC cross-coupling of the isolated alkenyl perfluoroalkanesulfonate leading to the desired products. Alternatively, Reissig and co-workers established that isolation and purification of the alkenyl nonaflates is not necessary for the subsequent coupling reaction provided that the nonaflates are generated from trimethylsilyl enol ethers and the mild sulfonylating reagent nonafluorobutane-1-sulfonyl fluoride (NfF) [7] under catalysis by fluoride ion. This resulted in the development of a general, one-pot transformation of trimethylsilyl enol ethers into 1,3-dienes by in situ generation of alkenyl nonaflates followed by Heck reactions.[8] However, it requires an extra step to obtain the requisite trimethylsilyl enolates from the ultimate precursors, ketones or aldehydes. This requirement serves to highlight a major challenge in the development of general and straightforward coupling methods, namely, the conversion of carbon-[*] Dr.

Biocatalytic asymmetric reductions have been key steps in the synthesis of 1,1-dimethoxy-2-propanone, catalyzed by suitable ketoreductases to (S)- and (R)-1,1-dimethoxy-2-propanol, obtained in ≥99.9% ee and excellent yield. Removal of the protecting group gave the (S)- and (R)-lactaldehydes in excellent yield and purity.