Aerobic Double Dehydrogenative Cross Coupling between Cyclic Saturated Ketones and Simple Arenes

Abstract

The major limitation in the synthetic application of two-component Baeyer-Villiger monooxygenases was addressed by identifying the 28 kDa flavin-reductase Fre from E. coli as a suitable supplier of reduced FMN for these enzymes. Coexpression of Fre with either 2,5-or 3,6-DKCMO from P. putida NCIMB 10007 significantly enhanced the conversion of camphor and norcamphor serving as representative ketones. With purified enzymes full conversion was achieved while only slight amounts of product were formed in the absence of this flavin reductase. Fusion of the genes of Fre and DKCMOs into single open reading frame constructs resulted in unstable proteins exhibiting flavin reducing, but poor oxygenating activity, which led to overall decreased conversion of camphor.

A Straightforward Synthesis of Trideuterated α‐Terpinene for Mechanistic Studies

“…To avoid cleavage of the ketal, the deuteration reaction was changed to basic conditions using K 2 CO 3 , following a modified procedure which has already been reported. [33] As outlined above, twofold cross-coupling reactions of the triflates 22c and 17d with chloromagnesium cyano(isopropyl)cuprate and lithium dimethylcuprate, respectively, furnished the targeted trideuterated α-terpinene 6c with a deuterium incorporation >99 %, according to NMR (no residual proton signals were detected at deuterated positions).…”

“…[40] (7,7,9,9-2 H 4 )-1,4-Dioxaspiro[4.5]decan-8-one (21b). According to a slightly modified procedure reported previously in the literature, [33] K 2 CO 3 (1.33 g, 9.61 mmol, 0.5 equiv.) was added to a solution of 1,4-dioxaspiro [4.5]decan-8-one (21a, 3.00 g, 19.2 mmol) in D 2 O (25 mL) and the mixture was stirred at 130°C overnight.…”

Ligand‐Enabled Triple CH Activation Reactions: One‐Pot Synthesis of Diverse 4‐Aryl‐2‐quinolinones from Propionamides

“…However, as illustrated in Table 3, incorporation of the second aryl is exclusively selective for the 4position of the 2-quinolinone ring. Pdinsertion into the secondary C(sp 3 )ÀH bond followed by bhydride elimination would then yield cinnamide intermediate 7, [13] which allows for subsequent Heck coupling with a second aryl iodide. These observed results are inconsistent with a mechanism involving consecutive b-arylations followed by Pd-mediated dehydrogenation.…”

“…[12] As such, we present the following mechanism: b-arylation of the primary C(sp 3 )ÀH bond affords hydrocinnamide 2. Pdinsertion into the secondary C(sp 3 )ÀH bond followed by bhydride elimination would then yield cinnamide intermediate 7, [13] which allows for subsequent Heck coupling with a second aryl iodide. Intramolecular C À H amidation [14] would then provide the 4-aryl-2-quinolinone product 3 (Scheme 3).…”

Ubiquitous Benzoquinones, Multitalented Compounds for Palladium‐Catalyzed Oxidative Reactions

“…These last conditions, well known from the case of copper salts, thanks to the Wacker process,48 have been developed with various co‐oxidants 49. BQ could act as an electron‐transfer mediator (ETM) between the catalyst and the oxidant, thereby increasing the efficiency of the oxidation 49a,49b. The direct regeneration of BQ by molecular oxygen is a slow reaction, and has usually required oxygen pressure (5–10 atm) 50.…”