Iron‐Catalyzed Decarboxylation of Trifluoroacetate and Its Application to the Synthesis of Trifluoromethyl Thioethers

Nucleophilic CF₃ has been generated by decarboxylation of potassium trifluoroacetate, arguably the most easy‐to‐handle, inexpensive, and sustainable source of trifluoromethyl groups. Simple iron(II) chloride catalyzes the decarboxylation as well as a subsequent trifluoromethylation of organothiocyanates, resulting in a straightforward synthesis of trifluoromethyl thioethers. The KCN byproduct is absorbed by iron(II) with formation of nontoxic potassium hexacyanoferrate. An analogous trifluoromethylation of aldehydes with trifluoroacetate underlines the synthetic potential of such iron‐catalyzed decarboxylative trifluoromethylations.     

Palladium‐Catalyzed Oxidative Synthesis of Highly Functionalized Ortholactones

A palladium‐catalyzed oxidative reaction is reported which converts dihydropyrans to their corresponding ortholactone. The products are formed in good to excellent yields with a very high level of chemoselectivity and functional group tolerance. Mechanistic studies confirm that the reaction proceeds by a Wacker‐type mechanism.     

Silver‐Catalyzed Arylation of (Hetero)arenes by Oxidative Decarboxylation of Aromatic Carboxylic Acids

A long‐standing challenge in Minisci reactions is achieving the arylation of heteroarenes by oxidative decarboxylation of aromatic carboxylic acids. To address this challenge, the silver‐catalyzed intermolecular Minisci reaction of aromatic carboxylic acids was developed. With an inexpensive silver salt as a catalyst, this new reaction enables a variety of aromatic carboxylic acids to undergo decarboxylative coupling with electron‐deficient arenes or heteroarenes regardless of the position of the substituents on the aromatic carboxylic acid, thus eliminating the need for ortho‐substituted aromatic carboxylic acids, which were a limitation of previously reported methods.     

Copper‐Catalyzed Oxidative Dearomatization of 2‐Naphthols via Etherification

Copper‐catalyzed intermolecular oxidative‐etherification type dearomatization reaction of 2‐naphthols was developed. With air as the terminal oxidant, the reaction proceeded in excellent yields under mild conditions. In addition, the reaction between two different naphthol substrates occurred smoothly. A series of multifunctionalized β‐naphthalenones, important scaffold existed widely in natural products and biologically active molecules, were synthesized efficiently.     

Copper‐Catalyzed Aerobic Decarboxylation/Ketooxygenation of Electron‐Deficient Alkenes

A copper‐catalyzed ketooxygenation of electron‐deficient alkenes was developed. This approach combines O?H alkylation, aerobic decarboxylation, and oxygenation in one transformation. Mechanistic investigation of this reaction showed that the copper salt is responsible for both generating the amidoxyl radical and promoting aerobic decarboxylation.     

A Convenient Synthesis of N‐Aryl Benzamides by Rhodium‐Catalyzed ortho‐Amidation and Decarboxylation of Benzoic Acids

The rhodium‐catalyzed amidation of substituted benzoic acids with isocyanates by directed C?H functionalization followed by decarboxylation to afford the corresponding N‐aryl benzamides is demonstrated, in which the carboxylate serves as a unique, removable directing group. Notably, less common meta‐substituted N‐aryl benzamides are generated readily from more accessible para‐ or ortho‐substituted groups by employing this strategy.     

Synthesis of Quinolines via a Metal‐Catalyzed Dehydrogenative N‐Heterocyclization

Efficient ruthenium‐, rhodium‐, palladium‐, copper‐ and iridium‐catalysed methodologies have been recently developed for the synthesis of quinolines by the reaction of 2‐aminobenzyl alcohols with carbonyl compounds (aldehydes and ketones) or the related alcohols. The reaction is assumed to proceed via a sequence involving initial metal‐catalysed oxidation of 2‐aminobenzyl alcohols to the related 2‐aminobenzaldehydes, followed by cross aldol reaction with a carbonyl compound under basic conditions to afford α,β‐unsaturated carbonyl compounds. These aldehydes or ketones can be also generated in situ via dehydrogenation of the related primary and secondary alcohols. In the final step cyclodehydration of the α,β‐unsaturated carbonyl compound intermediates gives quinolines. Good yields of quinolines were also obtained by reacting 2‐nitrobenzyl alcohols and secondary alcohols in the presence of a ruthenium catalyst. Finally, aniline derivatives afforded also a useful access to quinolines by the reaction with 1,3‐propanediol or 3‐amino‐1‐propanol, or in a three‐component reaction with benzyl alcohol and aliphatic alcohols.     

Oxidative Decarboxylation of Short‐Chain Fatty Acids to 1‐Alkenes

The enzymatic oxidative decarboxylation of linear short‐chain fatty acids (C4:0–C9:0) employing the P450 monooxygenase OleT, O₂ as the oxidant, and NAD(P)H as the electron donor gave the corresponding terminal C₃ to C₈ alkenes with product titers of up to 0.93 g L^?1 and TTNs of >2000. Key to this process was the construction of an efficient electron‐transfer chain employing putidaredoxin CamAB in combination with NAD(P)H recycling at the expense of glucose, formate, or phosphite. This system allows for the biocatalytic production of industrially important 1‐alkenes, such as propene and 1‐octene, from renewable resources for the first time.     

Biomimetic Hydrogenation Catalyzed by a Manganese Model of [Fe]‐Hydrogenase

[Fe]‐hydrogenase is an efficient biological hydrogenation catalyst. Despite intense research, Fe complexes mimicking the active site of [Fe]‐hydrogenase have not achieved turnovers in hydrogenation reactions. Herein, we describe the design and development of a manganese(I) mimic of [Fe]‐hydrogenase. This complex exhibits the highest activity and broadest scope in catalytic hydrogenation among known mimics. Thanks to its biomimetic nature, the complex exhibits unique activity in the hydrogenation of compounds analogous to methenyl‐H₄MPT⁺, the natural substrate of [Fe]‐hydrogenase. This activity enables asymmetric relay hydrogenation of benzoxazinones and benzoxazines, involving the hydrogenation of a chiral hydride transfer agent using our catalyst coupled to Lewis acid‐catalyzed hydride transfer from this agent to the substrates.     

Synthetic Studies toward C‐Glucosidic Ellagitannins: A Biomimetic Total Synthesis of 5‐O‐Desgalloylepipunicacortein A

C‐glucosidic ellagitannins constitute a subclass of bioactive polyphenolic natural products with strong antioxidant properties, as well as promising antitumoral and antiviral activities that are related to their capacity to interact with both functional and structural proteins. To date, most synthetic efforts toward ellagitannins have concerned glucopyranosic species. The development of a synthetic strategy to access C‐glucosidic ellagitannins, whose characteristic structural feature includes an atropoisomeric hexahydroxydiphenoyl (HHDP) or a nonahydroxyterphenoyl (NHTP) unit that is linked to an open‐chain glucose core by a C‐aryl glucosidic bond, is described herein. The total synthesis of the biarylic HHDP‐containing 5‐O‐desgalloylepipunicacortein A ( 1 β ) was achieved by either using the natural ellagic acid bis‐lactone as a precursor of the requested HHDP unit or by implementing an atroposelective intramolecular oxidative biarylic coupling to forge this HHDP unit. Both routes converged in the penultimate step of this synthesis to enable a biomimetic formation of the key C‐aryl glucosidic bond in the title compound.     

Laccase‐Catalyzed Oxidative Polymerization of Phenols

Laccase‐catalyzed oxidative polymerization of phenol and its derivatives has been performed in aqueous organic solvents at room temperature in air. Laccase derived from Pycnoporus coccineus efficiently induced the polymerization to produce polyphenols consisting of a mixture of phenylene and oxyphenylene units. The unit ratio of the polymer could be precisely controlled by selection of the solvent and the monomer substituent.

     

Biomimetic Total Synthesis of Cyanosporaside Aglycons from a Single Enediyne Precursor through Site‐Selective p‐Benzyne Hydrochlorination

The cyanosporasides A–F are a collection of monochlorinated benzenoid derivatives isolated from the marine actinomycetes Salinispora and Streptomyces sp. All derivatives feature one of two types of cyanocyclopenta[a]indene frameworks, which are regioisomeric in the position of a single chlorine atom. It is proposed that these chloro‐substituted benzenoids are formed biosynthetically through the cycloaromatization of a bicyclic nine‐membered enediyne precursor. Herein, we report the synthesis of such a bicyclic precursor, its spontaneous transannulation into a p‐benzyne, and its differential 1,4 hydrochlorination reactivity under either organochlorine or chloride‐salt conditions. Our bioinspired approach culminated in the first regiodivergent total synthesis of the aglycons A/F and B/C, as well as cyanosporasides D and E. In addition, empirical insights into the site selectivity of a natural‐like p‐benzyne, calculated to be a ground‐state triplet diradical, to hydrogen, chlorine, and chloride sources are revealed.     

Synthesis of Substituted 2‐Amino‐1,3‐oxazoles via Copper‐Catalyzed Oxidative Cyclization of Enamines and N,N‐Dialkyl Formamides

A facile synthesis of 2‐amino‐1,3‐oxazoles via Cu^I‐catalyzed oxidative cyclization of enamines and N ,N ‐dialkyl formamides has been developed. The reaction proceeds through an oxidative C−N bond formation, followed by an intramolecular C(sp²)−H bond functionalization/C−O cyclization in one pot. This protocol provides direct access to useful 2‐amino‐1,3‐oxazoles and features protecting‐group‐free nitrogen sources, readily available starting materials, a broad substrate scope and mild reaction conditions.