Pd0‐Catalyzed Intramolecular α‐Arylation of Sulfones: Domino Reactions in the Synthesis of Functionalized Tetrahydroisoquinolines

A new strategy for the synthesis of tetrahydroisoquinolines based on the Pd⁰‐catalyzed intramolecular α‐arylation of sulfones is reported. The combination of this Pd‐catalyzed reaction with intermolecular Michael and aza‐Michael reactions allows the development of two‐ and three‐step domino processes to synthesize diversely functionalized scaffolds from readily available starting materials.     

Condensation of 4-aryl-4-oxobutanoic acids with benzylamines: Synthetic and structural studies on 1-arylmethyl-3-[(<Emphasis Type="Italic">E</Emphasis>)-1-arylmethylidene]-5-phenyl-2,3-dihydro-1H-2-pyrrolones

The microwave-mediated reaction of 4-aryl-4-oxobutanoic acids with benzylamines furnished 1-arylmethyl-3-[(E)-1-arylmethylidene]-5-phenyl-2,3-dihydro-1H-pyrrolones. This result is in contract to the earlier report on this reaction conducted under neat conditions. Structures for the products were assigned on the basis of spectral data and confirmed by independent synthesis. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 368–373, March, 2007.     

Ring‐Rearrangement Metathesis

Ring‐rearrangement metathesis (RRM) refers to the combination of several metathesis transformations into a domino process, in which an endocyclic double bond of a cycloolefin reacts with an exocyclic alkene. RRM has proven to be a powerful method for the rapid construction of complex structures. The extension of the basic ring‐opening–ring‐closing metathesis process by further metathesis steps as well as an examination of the driving forces, limits, scope, recent advantages, and future perspectives of these domino sequences is presented with various examples, thus reflecting the high efficiency and utility of RRM in organic synthesis.     

Multicomponent coupling reactions for organic synthesis: chemoselective reactions with amide-aldehyde mixtures

The acid-catalyzed condensation chemistry of simple amides and aldehydes provides a highly prolific source of diverse reactants for irreversible follow-up reactions. Amide-aldehyde mixtures have been successfully employed in multicomponent syntheses of N-acyl alpha-amino acids (via palladium-catalyzed amidocarbonylation) and various cyclohexene, cyclohexadiene, and benzene derivatives (via the amide-aldehyde-dienophile (AAD) reaction).     

Titanocene-catalyzed cascade cyclization of epoxypolyprenes: straightforward synthesis of terpenoids by free-radical chemistry

The titanocene-catalyzed cascade cyclization of epoxypolyenes, which are easily prepared from commercially available polyprenoids, has proven to be a useful procedure for the synthesis of C(10), C(15), C(20), and C(30) terpenoids, including monocyclic, bicyclic, and tricyclic natural products. Both theoretical and experimental evidence suggests that this cyclization takes place in a nonconcerted fashion via discrete carbon-centered radicals. Nevertheless, the termination step of the process seems to be subjected to a kind of water-dependent control, which is unusual in free-radical chemistry. The catalytic cycle is based on the use of the novel combination Me(3)SiCl/2,4,6-collidine to regenerate the titanocene catalyst. In practice this procedure has several advantages: it takes place at room temperature under mild conditions compatible with different functional groups, uses inexpensive reagents, and its end step can easily be controlled to give exocyclic double bonds by simply excluding water from the medium.     

Enantioselective Synthesis of 3,4‐Dihydropyran‐2‐ones by Domino Michael Addition and Lactonization with New Asymmetric Organocatalysts: Cinchona‐Alkaloid‐Derived Chiral Quaternary Ammonium Phenoxides

Chiral quaternary ammonium phenoxides were readily prepared from commercially available cinchona alkaloids and proved to be useful new asymmetric organocatalysts. Among various chiral quaternary ammonium phenoxides, a cinchonidine‐derived catalyst that bears both a sterically hindered N1‐9‐anthracenylmethyl group and a strongly electron withdrawing 9‐O‐3,5‐bis(trifluoromethyl)benzyl group were found to be highly effective for the Michael addition of ketene silyl acetals (derived from phenyl carboxylates) and α,β‐unsaturated ketones followed by lactonization. Optically active 3,4‐dihydropyran‐2‐one derivatives were obtained in high yields with excellent control of enantio‐ and diastereoselectivity. This catalyst can be handled in air and stored at room temperature in a sealed bottle without decomposition for at least one month.     

Palladium-catalyzed cascade reaction of alpha,beta-unsaturated sulfones with aryl iodides

Unlike traditionally used acyclic 1,2-disubstituted alkenes, the reaction of alpha,beta-unsaturated phenyl sulfones with aryl iodides under Heck reaction conditions (Pd(OAc)(2) as catalyst, Ag(2)CO(3) as base in DMF at 120 (0)C) takes place mainly by a cascade process, involving one unit of the alkene and three units of the aryl iodide, to afford a substituted 9-phenylsulfonyl-9,10-dihydrophenanthrene. The dominant formation of this 3:1 coupling product, instead of the Heck trisubstituted olefin, shows that aromatic C-H bond activation processes can compete with the usually fast syn beta-hydrogen elimination step in the Heck arylation of an acyclic olefin. The structural scope of this palladium-catalyzed cascade arylation of alpha,beta-unsaturated sulfones has proved to be wide with regard to substitution at the beta-position (alkyl, aryl, or alkenyl substitution), substitution at the sulfone unit (alkyl or phenyl sulfones), and configuration at the CdoublebondC bond (trans or cis). Moreover, although less favored than in the case of the arylation of alpha,beta-unsaturated sulfones, similarly substituted 9,10-dihydrophenanthrenes have also been obtained in the case of alpha,beta-unsaturated phosphine oxides and alpha,beta-unsaturated phosphonate esters. A Pd(0)-Pd(II)-Pd(IV) mechanistic pathway involving the successive formation of highly electrophilic sigma-alkylpalladium intermediates and palladacycles is proposed for this multicomponent arylation.     

Pd-catalyzed cross-coupling reactions of arenediazonium salts with arylsilanes and aryltrifluoroborates in water

Pd-catalyzed cross-coupling reactions of various arenediazonium salts with ArSi(OR)₃ and KArBF₃ have been achieved in good to excellent yields under simple aerobic conditions in water at room temperature. The functional group tolerance makes these transformations as attractive alternatives to the traditional cross-coupling approaches. Furthermore, the sequence can also be performed in a one-pot domino process, omitting the isolation of the intermediate arenediazonium salt.