P.Moran

We herein report a computational study of the bonding in gold(I) vinylidene complexes and compare them to their carbene and CO analogues. The relevance of these intermediates is analysed for the intramolecular cyclisation leading to vinyl sulfonates.

Tight ion pair gold vinylidene complexes are studied as intermediates in the formation of vinyl sulfonates using computational methods (see scheme). The role of π-backbonding in gold vinylidene complexes, such as the aforementioned tight ion pair, is analysed by using the intrinsic bond orbital method.

The hydroxylation of vitamin D₃ (VD₃, cholecalciferol) side chains to give 25-hydroxyvitamin D₃ (25OHVD₃) is a crucial reaction in the formation of the circulating and biologically active forms of VD₃. It is usually catalyzed by cytochrome P450 monooxygenases that depend on complex electron donor systems. Cell-free extracts and a purified Mo enzyme from a bacterium anaerobically grown with cholesterol were employed for the regioselective, ferricyanide-dependent hydroxylation of VD₃ and proVD₃ (7-dehydrocholesterol) into the corresponding tertiary alcohols with greater than 99 % yield. Hydroxylation of VD₃ strictly depends on a cyclodextrin-assisted isomerization of VD₃ into preVD₃, the actual enzymatic substrate. This facile and robust method developed for 25OHVD₃ synthesis is a novel example for the concept of substrate-engineered catalysis and offers an attractive alternative to chemical or O₂ /electron-donor-dependent enzymatic procedures.

Well PrepareD: Oxygen-independent, regioselective, and complete hydroxylation of the tertiary C25 of vitamin D₃ to its circulating 25-hydroxy form was catalyzed by a Mo-containing dehydrogenase from a denitrifying bacterium grown with cholesterol. This electron-donor-independent system can be used for the enzymatic synthesis of the clinically most relevant form of vitamin D.

The gold-catalyzed CH annulation of anthranil derivatives with alkynes offers a facile, flexible, and atom-economical one-step route to unprotected 7-acylindoles. An intermediate α-imino gold carbene, generated by an intermolecular reaction, promotes ortho-aryl CH functionalization to afford the target products. The transformation proceeds with a broad range of substrates under mild conditions. Moreover, the obtained functionalized indole products represent a versatile platform for the construction of diverse indolyl frameworks.

Good as gold: The gold-catalyzed CH annulation of anthranil derivatives with alkynes offers a facile, flexible, and atom-economical one-step route to unprotected 7-acylindoles. The reaction proceeds via an α-imino gold carbene intermediate, which promotes ortho-aryl CH functionalization to afford the product. The transformation proceeds with a broad range of substrates under mild conditions.

The rhodium(III)-catalyzed [3+2] CH cyclization of aniline derivatives and internal alkynes represents a useful contribution to straightforward synthesis of indoles. However, there is no report on the more challenging synthesis of pharmaceutically important N-hydroxyindoles and 3H-indole-N-oxides. Reported herein is the first rhodium(III)-catalyzed [4+1] CH oxidative cyclization of nitrones with diazo compounds to access 3H-indole-N-oxides. More significantly, this reaction proceeds at room temperature and has been extended to the synthesis of N-hydroxyindoles and N-hydroxyindolines.

A flurry diazo of activity: Reported herein is the first rhodium(III)-catalyzed [4+1] CH oxidative cyclization of nitrones with diazo compounds to access 3H-indole-N-oxides. More significantly, this reaction proceeds at room temperature and has been extended to the synthesis of N-hydroxyindoles and N-hydroxyindolines. Piv=pivaloyl.

An operationally simple and economical method for the direct alkylation of heteroaromatic bases employing readily available aldehydes as alkyl radical precursors and molecular oxygen as a reagent is presented. This simple transformation demonstrates a broad substrate scope with respect to aldehydes and nitrogen heterocycles, enabling the introduction of several medicinally important yet challenging alkyl moieties, such as ethyl, isopropyl, tert-butyl, and cyclohexyl to the different classes of heterocyclic bases in good to excellent yields.

A simple method for the direct alkylation of heteroaromatic bases with aldehydes as inexpensive alkyl radical precursors and molecular oxygen as a reagent is presented. This transformation demonstrates a broad substrate scope with respect to aldehydes and nitrogen heterocycles, enabling the introduction of various alkyl moieties to heterocyclic bases (>40 examples) in good to excellent yields.

A gold(I)-catalyzed enantioselective desymmetrization of 1,3-diols was achieved by intramolecular hydroalkoxylation of allenes. The catalyst system 3-F-dppe(AuCl)₂ /(R)-C₈-TRIPAg proved to be specifically efficient to promote the desymmetrizing cyclization of 2-aryl-1,3-diols, which have proven challenging substrates in previous reports. Multisubstituted tetrahydrofurans were prepared in good yield with good enantioselectivity and diastereoselectivity by this method.

A chiral anion-mediated enantioselective gold(I)-catalyzed desymmetrization of 1,3-diols by intramolecular allene hydroalkoxylation was developed. Subtle tuning of the both the chiral phosphate (X*) and the achiral phosphine ligand (L) components of the catalyst system allowed for the preparation of oxygen heterocycles containing two stereocenters in high enantio- and diastereoselectivity.

The first iron(III) chloride-catalyzed decarboxylative–deaminative functionalization of phenylglycine with o-substituted nitroarenes was achieved for the synthesis of 4(3H)-quinazolinones and benzimidazoles. The reaction of 2-nitrobenzonitrile/2-nitro-N,N-diphenylamine with phenylglycine at 120 °C in the presence of potassium carbonate as a base in toluene generated the products in 45–87% yields. Various functional groups like nitro, fluoride, chloride and trifluoromethyl were well tolerated under the present reaction conditions. In this tandem approach, involvement of transfer hydrogenation of the nitro functionality with in situ generated ammonia, imination, nitrile hydration to amide and oxidative cyclization sequences have been established. The process avoids the use of an external hydrogen source, costly catalysts as well as the isolation of amine and amide intermediates.

The first asymmetric regio- and diastereodivergent γ-allylation of cyclic α,β-unsaturated aldehydes based on combined organocatalysis and transition-metal catalysis is disclosed. By combining an aminocatalyst with an iridium catalyst, both diastereomers of branched allylated products can be achieved in moderate to good yields and excellent regio- and stereoselectivities. Furthermore, by replacing the iridium catalyst with a palladium catalyst, the linear allylated products are formed in good yields and excellent regio- and enantioselectivities. The developed method thus provides selective access to all six isomers of the γ-allylated product in a divergent fashion by choosing the appropriate combination of organocatalyst, transition-metal catalyst, and ligand.

Catalyst combo: By combining an aminocatalyst with an iridium catalyst, both diastereomers of branched allylated products can be achieved in good yields and excellent regio- and stereoselectivities. By replacing the iridium catalyst with a palladium catalyst, the linear allylated products are formed in good yields and excellent regio- and enantioselectivities. Thus, all six isomers of the γ-allylated product can be accessed.