Ni(II)-catalyzed enantioselective Nazarov cyclizations

Nazarov cyclizations are catalyzed by a dicationic Ni(ii) complex containing the chiral tridentate phosphine Pigiphos; the catalyst exerts a high degree of torquoselectivity and affords the products in up to 88% ee.     

Gold(I)-catalyzed propargyl Claisen rearrangement

Homoallenic alcohols are prepared from propargyl vinyl ethers using a trinuclear gold(I)-oxo complex, [(Ph3PAu)3O]BF4, as a catalyst for propargyl Claisen rearrangement at room temperature. The gold(I)-catalyzed reaction is effective for a diverse collection of propargyl vinyl ethers, including substrates containing aryl and alkyl groups at the propargylic position, and hydrogen, aryl, and alkyl substituents at the alkyne terminus. Tertiary propargyl vinyl ethers can be employed in the reaction, at slightly elevated temperatures, to afford tetrasubstituted allenes. Importantly, the rearrangement of 1,2-disubstituted vinyl ethers proceeds with excellent diastereoselectivity, and the rearrangement of chiral nonracemic propargyl vinyl ethers proceeds with excellent chirality transfer to furnish enantioenriched allenes.     

Aminosulf(ox)ides as ligands for Iridium(I)-catalyzed asymmetric transfer hydrogenation

A new class of efficient catalysts was developed for the asymmetric transfer hydrogenation of unsymmetrical ketones. A series of chiral N,S-chelates (6-22) was synthesized to serve as ligands in the iridium(I)-catalyzed reduction of ketones. Both formic acid and 2-propanol proved to be suitable as hydrogen donors. Sulfoxidation of an (R)-cysteine-based aminosulfide provided a diastereomeric ligand family containing a chiral sulfur atom. The two chiral centers of these ligands showed a clear effect of chiral cooperativity. In addition, aminosulfides containing two asymmetric carbon atoms in the backbone were synthesized. Both the sulfoxide-containing beta-amino alcohols and the aminosulfides derived from 1,2-disubstituted amino alcohols gave rise to high reaction rates and moderate to excellent enantioselectivities in the reduction of various ketones. The enantioselective outcome of the reaction was favorably affected by selecting the most appropriate hydrogen donor. Enantioselectivities of up to 97% were reached in the reduction of aryl-alkyl ketones.     

Au(I)-catalyzed ring expanding cycloisomerizations: total synthesis of ventricosene

The gold(I)-catalyzed cycloisomerization of enynes containing an embedded cyclopropane unit leads selectively to the formation of ring systems containing the cyclopropylmethyl cation. A subsequent Wagner-Merwein shift provides diastereomerically pure fused cyclobutanes. The utility of this methodology for the rapid assembly of polycyclic ring systems is illustrated by the total synthesis of the angular triquinane ventricosene.     

Dendronized diruthenium compounds via the copper(I)-catalyzed click reaction

Novel Ru2-containing dendritic compounds were prepared from the CuI-catalyzed 1,3-dipolar cycloaddition between Ru2 compounds containing one or two ethynes, Ru2(D(3,5-Cl2Ph)F)4-n(DMBA-4-C2H)n with n=1 and 2, and azidopoly(benzyl ether) dendrons. These new compounds were also characterized with X-ray diffraction and voltammetric techniques.     

Scope of enantioselective palladium(II)-catalyzed aerobic alcohol oxidations with (-)-sparteine

Evaluation of the substrate scope for Pd(II)/ (-)-sparteine catalyzed aerobic oxidative kinetic resolution of secondary alcohols is disclosed. An improved system is found with use of tert-butyl alcohol solvent in which benzylic and aliphatic alcohols as well as alcohols containing olefins are effectively oxidatively resolved. For substrates that successfully undergo oxidative kinetic resolution, k(rel) values are generally between 10 and 20. Successful scale-up of various substrates to 10-mmol scale is described. Extension to oxidative desymmetrization of 1,3-meso-diols is successful with enantiomeric excesses ranging from 78 to 85%.     

Au(I)-catalyzed cyclization of enynes bearing an olefinic cycle

Gold(I)-catalyzed cyclization of enynes containing an olefinic cycle has been studied. The introduction of an olefinic ring instead of a terminal alkene in enynes dramatically increased the yield of the reaction. Enynes having an olefinic cycle were prepared by a rhodium-catalyzed intermolecular [4 + 2] cycloaddition of diynes with butadiene. Consecutive rhodium-catalyzed Diels-Alder/gold(I)-catalyzed cycloisomerization reactions were integrated in a one-pot reaction.     

Evaluation of disaccharide-based ligands for Pd(0)-catalyzed asymmetric allylations

A series of phosphines based on disaccharides containing a d-glucosamine framework were prepared and tested for their abilities as ligands for the palladium(0)-catalyzed asymmetric allylic allylation of racemic 1,3-diphenyl-2-propenyl acetate with various nucleophiles. In contrast to previous results exploiting monosaccharides, the iminophosphines generally afforded higher enantiomeric excesses, up to 99%.     

Preparation of benzolactams by Pd(OAc)2-catalyzed direct aromatic carbonylation

We developed a new method for Pd(II)-catalyzed direct aromatic carbonylation in a phosphine-free catalytic system using Pd(OAc)2 and Cu(OAc)2 in an atmosphere of CO gas containing air. The carbonylation proceeded with ortho-palladation, inducing a remarkable site selectivity to afford a variety of five- or six-membered benzolactams from secondary omega-arylalkylamines, such as N-alkylbenzylamines or N-alkylphenethylamines.     

Polarographic study of the Co(II)-catalyzed reduction of nitrite

In the potential region corresponding to the reduction of Co(OH)⁺ to the metal, a catalytic polarographic current is observed in an ammoniacal buffer solution containing nitrite ion. In neutral unbuffered media, the catalytic current appears even on the limiting plateau of aquacobalt(II) reduction wave. The catalytic current is due to the reoxidation of an electrodeposited metallic cobalt to Co(II) by nitrite ion. The condition necessary for the catalytic reaction to proceed is the increase in pH at the electrode surface. It is shown that the hydroxide ion is produced as a result of the catalytic reaction.     

Assembly of digitoxin by gold(I)-catalyzed glycosidation of glycosyl o-alkynylbenzoates

Digitoxin, a clinically important cardiac trisaccharide, was assembled efficiently from digitoxigenin and 3,4-di-O-tert-butyldiphenylsilyl-d-digitoxosyl o-cyclopropylethynylbenzoate in 9 steps and 52% overall yield via alternate glycosylation and protecting group manipulation. The present synthesis showcases the advantage of the gold(I)-catalyzed glycosylation protocol in the synthesis of glycoconjugates containing acid-labile 2-deoxysugar linkages.     

Palladium(0)-catalyzed phenylation of imidazo[4,5-b]pyridines

The tetrakis(triphenylphosphine)palladium(O)-catalyzed coupling of benzeneboronic acid with 2-chloro, 6-bromo and 6-bromo-2-chloro derivatives of 1- and 3-methylimidazo[4,5-b]pyridines to novel 2-phenyl-, 6-phenyl- and 2,6-diphenylimidazo[4,5-b]pyridines is described. The phenylation of imidazo[4,5-b]-pyridines containing labile hydrogens was not successful.     

Flexible synthesis of phenanthrenes by a PtCl(2)-catalyzed cycloisomerization reaction

Readily available biphenyl derivatives containing an alkyne unit at one of their ortho positions are converted into substituted phenanthrenes upon exposure to catalytic amounts of either PtCl(2), AuCl(3), GaCl(3), or InCl(3) in toluene. This 6-endo-dig cyclization likely proceeds through initial pi-coordination of the alkyne unit followed by interception of the resulting eta(2)-metal complex by the adjacent arene ring. The reaction is inherently modular, allowing for substantial structural variations and for the incorporation of substituents at any site of the phenanthrene product except C-9. Moreover, the reaction is readily applied to the heterocyclic series as exemplified by the preparation of benzoindoles, naphthothiophenes as well as bridgehead nitrogen heterocycles.     

Enantioselective synthesis of highly substituted furans by a copper(II)-catalyzed cycloisomerization-indole addition reaction

A catalytic enantioselective reaction based on a copper(II) catalyst strictly containing chiral anionic ligands is described. In the present work, copper(II)-phosphate catalyst promotes the intramolecular heterocyclization of 2-(1-alkynyl)-2-alkene-1-ones and facilitates high levels of enantioselectivity in the subsequent nucleophile attack. Mechanistic studies suggest that formation of a copper(II)-indole species is important for catalysis.     

Lanthanide(III)-catalyzed multi-component aza-Diels-Alder reaction of aliphatic N-arylaldimines with cyclopentadiene

The Ln(OTf)₃-catalyzed formal aza-Diels-Alder (or Povarov) reaction of cyclopentadiene with in situ generated N-arylimines containing enolizable protons is described. This three-component Povarov reaction generates highly functionalized C-2 aliphatic substituted tetrahydroquinolines, heterocycles that were previously inaccessible using the Povarov reaction, because of the instability of the intermediate aliphatic N-arylaldimine.     

Synthesis of 6-amino-5-cyano-1,4-disubstituted-2(1H)-pyrimidinones via copper-(I)-catalyzed alkyne-azide 'click chemistry' and their reactivity

In this paper we present the room temperature synthesis of a novel serie of 1,4-disubstituted-1,2,3-triazoles 4a-l by employing the (3+2) cycloaddition reaction of pyrimidinones containing alkyne functions with different model azides in the presence of copper sulphate and sodium ascorbate. To obtain the final triazoles, we also synthesized the major precursors 6-amino-5-cyano-1,4-disubstituted-2(1H)-pyrimidinones 3a-r from ethyl 2,2-dicyanovinylcarbamate derivatives 2a-c and various primary aromatic amines containing an alkyne group. The triazoles were prepared in good to very good yields.     

Cu(II)-aza(bisoxazoline)-catalyzed asymmetric benzoylations

[reaction: see text] Racemic 1,2-diols and alpha-hydroxy carbonyl compounds can be asymmetrically benzoylated in a kinetic resolution in the presence of various Cu(II)-aza(bisoxazoline) catalysts. A novel bisbenzyl-substituted aza(bisoxazoline) ligand proved to be especially effective when immobilized on MeOPEG(5000), giving from 91 to > or = 99% ee in 37-49% yield for each of five sequential reactions.     

Computational elucidation of the internal oxidant-controlled reaction pathways in Rh(III)-catalyzed aromatic C-H functionalization

The Rh(III)-catalyzed C-H functionalizations of benzamide derivatives with olefin were studied by DFT calculations to elucidate the divergent pathways controlled by the N-OR internal oxidants. For substrates of N-OMe and N-OPiv internal oxidants, the energy profiles for consecutive N-H deprotonation/C-H activation/olefin insertion sequences were similar, and different properties and reactivities of the generated 7-membered rhodacycles were predicted. When N-OMe is involved, this intermediate is generally unstable, and the olefination occurs easily via a β-H elimination/reductive elimination (RE) sequence to generate the Rh(I) intermediate, which is then oxidized to the active Rh(III) via MeOH elimination from the N-OMe reduction in the presence of a HOAc. However, for a 7-membered rhodacycle containing a N-OPiv moiety, the coordination of the acyloxy carbonyl oxygen stabilizes this intermediate and increases the barrier of the olefination pathway. Instead, the migration of the acyloxy from N to Rh(III) via a 5-membered ring TS to form a cyclic Rh(V) nitrene intermediate is more kinetically favorable, then the facile RE of this Rh(V) species forms the heterocycle product and regenerates Rh(III). Notably, for both reactions, the direct C-N formation from intermediates containing a C(sp(3))-Rh(III)-N(sp(3)) unit would be very difficult with barriers over 40 kcal/mol.     

Rh(II)-catalyzed Sommelet-Hauser rearrangement

Catalytic Sommelet-Hauser rearrangement is reported. The Rh(II)-catalyzed reaction of aryldiazoacetates with ethyl benzylthioacetate affords Sommelet-Hauser rearrangement products in good to excellent yields. This reaction provides a reliable and efficient way to introduce a substituent to the ortho position of arylacetates.     

Gold(I)-catalyzed stereoselective olefin cyclopropanation

A triphenylphosphinegold(I)-catalyzed cyclopropanation of olefins using propargyl esters as gold(I)-carbene precursors is reported. This reaction provided the basis for the use of a DTBM-SEGPHOS gold(I) complex as a catalyst in the enantioselective (up to 94% ee) preparation of vinyl cyclopropanes with high cis-selectivity.