Chiral Auxiliary Approach for Gold(I)-Catalyzed Cyclizations.

Two different classes of stereoselective cyclizations have been developed using a chiral auxiliary approach with commercially available [JohnPhosAu(MeCN)SbF6 ] as catalyst. First, a stereoselective cascade cyclization of 1,5-enynes was achieved using the Oppolzer camphorsultam as chiral auxiliary. In this case, a one-pot cyclization-hydrolysis sequence was developed to directly afford enantioenriched spirocyclic ketones. Then, the stereoselective alkoxycyclization of 1,6-enynes was mediated by an Evans-type oxazolidinone. A reduction-hydrolysis sequence was selected to remove the auxiliary to give enantioenriched ß-tetralones. DFT studies confirmed that the steric clash between the chiral auxiliary and alkene accounts for the experimentally observed diastereoselective cyclization through the Si face.

Hydrogen autotransfer and related dehydrogenative coupling reactions using a rhenium(i) pincer catalyst.

A novel rhenium complex bearing a non-innocent PNP pincer ligand was prepared. This novel catalyst is active in hydrogen autotransfer reactions to form new C-C and C-N bonds. More specifically, valuable alkylations of ketones and sulfonamides with primary alcohols are herein presented. In addition, the first examples of rhenium-catalysed synthesis of pyrroles are described by dehydrogenative coupling of diols, amines and ketones.

Functionalization of Unactivated C(sp3 )-H Bonds Using Metal-Carbene Insertion Reactions.

Versatile C-H insertions: Novel protocols for metal-carbene insertions using diazo compounds have been recently developed. Application of the respective rhodium and palladium catalytic systems allows formation of new carbon-carbon bonds in very good yields and selectivities.

Manganese-Catalyzed Hydrogen-Autotransfer C-C Bond Formation: α-Alkylation of Ketones with Primary Alcohols.

A novel catalytic hydrogen-autotransfer protocol for the atom-efficient α-alkylation of ketones with readily available alcohols is presented. The use of manganese complexes bearing non-innocent PNP pincer ligands enabled the functionalization of a broad range of valuable ketones, including 2-oxindole, estrone 3-methyl ether, and testosterone. Mechanistic investigations suggest the participation of an intramolecular amidate-assisted alcohol-dehydrogenation process.

Iron-Catalyzed Reaction of Urea with Alcohols and Amines: A Safe Alternative for the Synthesis of Primary Carbamates.

A general study of the iron-catalyzed reaction of urea with nucleophiles is here presented. The carbamoylation of alcohols allows for the synthesis of N-unsubstituted (primary) carbamates, including present drugs (Felbamate and Meprobamate), without the necessity to apply phosgene and related derivatives. Using amines as nucleophiles gave rise to the respective mono- and disubstituted ureas via selective transamidation reaction. These atom-economical transformations provide a direct and selective access to valuable compounds from cheap and readily available urea using a simple Lewis-acidic iron(II) catalyst.

(Enantio)selective Hydrogen Autotransfer: Ruthenium-Catalyzed Synthesis of Oxazolidin-2-ones from Urea and Diols.

A novel strategy for the synthesis of oxazolidin-2-ones from vicinal diols and urea is described. In this heterocycle synthesis, two different C-O and C-N bonds are sequentially formed in a domino process consisting of nucleophilic substitution and alcohol amination. The use of readily available starting materials and the good atom economy render this process environmentally benign. While this transformation is already highly chemo- and regioselective, we also developed the first asymmetric version of this method using (R)-(+)-MeO-BIPHEP as the chiral ligand.

Ruthenium pincer-catalyzed synthesis of substituted γ-butyrolactones using hydrogen autotransfer methodology.

The ruthenium pincer-catalyzed synthesis of γ-butyrolactones from 1,2-diols and malonates using borrowing-hydrogen methodology is reported. This regioselective domino-process takes place through catalytic C-C bond formation, followed by intramolecular transesterification. Herein, we show the Ru-MACHO-BH complex as a valuable catalyst in hydrogen autotransfer reactions.

Progress on all ends for carbon-carbon bond formation through photoredox catalysis.

Dual role for catalysts: Novel routes for the generation of asymmetric stereocenters using photoredox catalysis were recently developed. Different chiral catalytic systems allowed new CC bonds to form in good yields and enantioselectivities using a mild methodology in which light is used as the energy source.

Benign synthesis of indoles from anilines and epoxides: new application for ruthenium pincer catalysts.

For the first time, ruthenium pincer complexes such as Ru-MACHO-BH were successfully used as catalysts in the domino-synthesis of indoles from anilines and epoxides. Following previously optimised procedures, a variety of indoles were produced in an atom-efficient manner with water and hydrogen as the only stoichiometric side-products. The ß-amino alcohol, resulting from the ring-opening of the epoxide with the aniline derivative, undergoes dehydrogenation, followed by condensation with excess aniline and the final intramolecular cyclisation affords the desired indole. Ru-MACHO-BH showed similar catalytic activity than our previously reported in situ prepared catalyst (Ru3(CO)12/dppf) without further optimisation of the reaction conditions.

Ruthenium-catalyzed synthesis of indoles from anilines and epoxides.

A general synthetic route to indoles from readily available anilines and epoxides by using ruthenium catalysis is described. This straightforward transformation allows a variety of indoles to be obtained in good yields by using [Ru3(CO)12]/1,1'-bis(diphenylphosphino)ferrocene as the catalytic system. Water and hydrogen are formed as the only stoichiometric by-products, making this process highly atom efficient.

Synthesis of 4,6-disubstituted 2-(4-morpholinyl)pyrimidines by cross-coupling reactions using triorganoindium compounds.

4,6-Disubstituted-2-(4-morpholinyl)pyrimidines, an important class of bioactive compounds, have been synthesized from 4,6-dichloro-2-(4-morpholinyl)pyrimidine by selective and sequential palladium-catalyzed cross-coupling reactions using triorganoindium reagents. This methodology, being efficient and versatile, allowed the synthesis of a variety of non-symmetrical pyrimidines functionalized at C-4 and C-6 positions.

Synthesis of functionalized thiophenes and oligothiophenes by selective and iterative cross-coupling reactions using indium organometallics.

The synthesis of unsymmetrical 2,5-disubstituted thiophenes by selective and sequential palladium-catalyzed cross-coupling reactions of indium organometallics with 2,5-dibromothiophene is reported. Following an iterative coupling sequence, α-oligothiophenes were synthesized in good yields and with high atom economy.

Flow synthesis using gaseous ammonia in a Teflon AF-2400 tube-in-tube reactor: Paal-Knorr pyrrole formation and gas concentration measurement by inline flow titration.

Using a simple and accessible Teflon AF-2400 based tube-in-tube reactor, a series of pyrroles were synthesised in flow using the Paal-Knorr reaction of 1,4-diketones with gaseous ammonia. An inline flow titration technique allowed measurement of the ammonia concentration and its relationship to residence time and temperature.

Palladium-catalyzed cross-coupling reactions of organogold(I) phosphanes with allylic electrophiles.

Aryl and alkenylgold(I) phosphanes react regioselectively with allylic electrophiles such as cinnamyl and geranyl halides (bromide, chloride and acetates) under palladium catalysis in THF at 80 °C to afford the α-substitution product with moderate to high yields. When the reaction is performed with a chiral enantiopure secondary acetate, the α-substituted cross-coupling product is obtained with complete inversion of the stereochemistry.

A versatile synthesis of fumaquinone.

Fumaquinone, a novel prenylated naphthoquinone antibiotic, was synthetized from ethyl acetoacetate in three steps (58% overall yield). The key step of the synthesis is the construction of the naphthoquinone skeleton by a regioselective Diels-Alder reaction between a 2-alkyl 1,3-bis(trimethylsilyloxy)-1,3-diene derivative and a bromoquinone. This short and versatile approach confirms the structure of fumaquinone and allows the synthesis of derivatives at the C-6 position.

Palladium-catalyzed cross-coupling reactions of organogold(I) reagents with organic electrophiles.

The palladium-catalyzed cross-coupling reaction of organogold(I) reagents (alkyl, alkenyl, aryl, and alkynyl) with organic electrophiles, such as aryl and alkenyl halides, aryl triflates, benzyl bromide, and benzoyl chloride is reported. The reaction takes place, under palladium catalysis, at room temperature with short reaction times to give the corresponding cross-coupling products in high yields.

A versatile enantioselective synthesis of barrenazines.

A versatile enantioselective total synthesis of barrenazines A and B has been accomplished from 1,4-butanediol. The key steps of the synthesis are a sequential allylboration/ring-closing metathesis for the construction of the tetrahydropyridine ring and the preparation of a functionalized 4-azidopiperidin-5-one through a stereoselective epoxidation and regioselective ring-opening reaction. The C(2)-symmetrical pyrazine skeleton of barrenazines was prepared by dimerization of the azidopiperidinone, and the carbon side chain was completed by copper-catalyzed reactions using Grignard reagents.

Total synthesis of (+)-neomarinone.

The first total synthesis of (+)-neomarinone has been achieved by following a concise and convergent route using methyl (R)-lactate and (R)-3-methylcyclohexanone as chiral building blocks. Key steps of the synthesis are the stereocontrolled formation of the two quaternary stereocenters by diastereoselective 1,4-conjugate addition and enolate alkylation reactions, and the construction of the furanonaphthoquinone skeleton by regioselective Diels-Alder reaction between a 1,3-bis(trimethylsilyloxy)-1,3-diene and a bromoquinone. The synthesis proves the relative and absolute stereochemistry of natural neomarinone.