Remote meta-C-H olefination of phenylacetic acids directed by a versatile U-shaped template.

meta-C-H olefination of phenylacetic acid derivatives has been achieved using a commercially available nitrile-containing template. The identification of N-formyl-protected glycine as the ligand (Formyl-Gly-OH) was crucial for the development of this reaction. Versatility of the template approach in accommodating macrocyclopalladation processes with different ring sizes is demonstrated.

Ligand-enabled triple C-H activation reactions: one-pot synthesis of diverse 4-aryl-2-quinolinones from propionamides.

Diverse 4-aryl-2-quinolinones are prepared from propionamides in one pot by ligand-promoted triple sequential C-H activation reactions and a stereospecific Heck reaction. In these cascade reactions, three new C-C bonds and one C-N bond are formed to rapidly build molecular complexity from propionic acid.

Palladium-catalyzed oxidative arylating carbocyclization of allenynes: control of selectivity and role of H2O.

Highly selective protocols for the carbocyclization/arylation of allenynes using arylboronic acids are reported. Arylated vinylallenes are obtained with the use of BF3⋅Et2O as an additive, whereas addition of water leads to arylated trienes. These conditions provide the respective products with excellent selectivities (generally >97:3) for a range of boronic acids and different allenynes. It has been revealed that water plays a crucial role for the product distribution.

Palladium-catalyzed oxidative carbocyclizations.

Palladium-catalyzed oxidative carbon-carbon bond-forming annulations, that is, carbocyclization reactions, have recently emerged as efficient and atom-economical routes to carbo- and heterocycles, whereby less functionalized substrates and fewer synthetic steps are needed to obtain a target molecule compared with traditional non-oxidative carbon-carbon bond-forming reactions. In this review, the synthetic efforts in palladium-catalyzed oxidative carbocyclization reactions are summarized.

Palladium-catalyzed oxidative arylating carbocyclization of allenynes.

Vinylallenes or cross-conjugated trienes are obtained selectively in the title reaction. Two possible mechanisms are suggested to rationalize the formation of the different types of products. Control experiments indicate that p-benzoquinone (BQ) plays an important role as a ligand in addition to its role as an oxidant. E=CO(2)Me.

From allene to allene: a palladium-catalyzed approach to beta-allenyl butenolides and their application to the synthesis of polysubstituted benzene derivatives.

An allene to allene protocol for the synthesis of beta-allenyl butenolides in moderate to high yields from 2,3-allenoic acids and propargylic carbonates catalyzed by Pd(OAc)2-TFP has been developed; the products were applied successfully to the Diels-Alder reaction with electron-deficient alkynes to afford polysubstituted benzene derivatives with an excellent regioselectivity.

Cu- and Pd-catalyzed asymmetric one-pot tandem addition-cyclization reaction of 2-(2',3'-alkadienyl)-beta-keto esters, organic halides, and dibenzyl azodicarboxylate: an effective protocol for the enantioselective synthesis of pyrazolidine derivatives.

[reaction: see text] Optically active pyrazolidine derivatives have been constructed by the Cu- and Pd-catalyzed asymmetric one-pot tandem addition-cyclization reaction of 2-(2',3'-dienyl)-beta-ketoesters, organic halides, and dibenzyl azodicarboxylate. The absolute configurations of the final products depend on the structure of the ligand.

Ligand-controlled C(sp³)-H arylation and olefination in synthesis of unnatural chiral α-amino acids.

The use of ligands to tune the reactivity and selectivity of transition metal catalysts for C(sp(3))-H bond functionalization is a central challenge in synthetic organic chemistry. Herein, we report a rare example of catalyst-controlled C(sp(3))-H arylation using pyridine and quinoline derivatives: The former promotes exclusive monoarylation, whereas the latter activates the catalyst further to achieve diarylation. Successive application of these ligands enables the sequential diarylation of a methyl group in an alanine derivative with two different aryl iodides, affording a wide range of ß-Ar-ß-Ar'-α-amino acids with excellent levels of diastereoselectivity (diastereomeric ratio > 20:1). Both configurations of the ß-chiral center can be accessed by choosing the order in which the aryl groups are installed. The use of a quinoline derivative as a ligand also enables C(sp(3))-H olefination of a protected alanine.

An efficient synthesis of 2,5-dihydrofuran-fused bicyclic skeletons via the Pd(II)-catalyzed tandem-cyclization reaction of 1,omega-bisallenols.

A palladium(II)-catalyzed tandem double-cyclization reaction of 1,omega-bisallenols was developed to form 2,5-dihydrofuran-fused bicyclic skeletons. With "unsymmetric" substrates, the reaction may also be realized with one hydroxyl group being protected as the acetate. Optically active bicyclic products were prepared by applying the Novozym-435 catalyzed kinetic resolution and the tandem double cyclization of these optically active allenol-allenyl acetates. The reaction may proceed via an oxypalladation, insertion, and elimination process.

Efficient highly selective synthesis of methyl 2-(ethynyl)alk-2(E)-enoates and 2-(1'-chlorovinyl)alk-2(Z)-enoates from 2-(methoxycarbonyl)-2,3-allenols.

Highly regio- and stereoselective reactions of readily available 2-(methoxycarbonyl)-2,3-allenols 1 with oxalyl chloride in the presence of Et(3)N or DMSO afforded methyl 2-(ethynyl)alk-2(E)-enoates (E)-2 and 2-(1'-chlorovinyl)alk-2(Z)-enoates (Z)-3, respectively, in moderate to good yields.

PdCl2/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols: an efficient synthesis of 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives.

A PdCl2/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols was observed to provide an efficient route to 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives. By using the easily available optically active starting materials, 2,5-dihydrofurans with high enantiopurity may be prepared. A Pd(II)-catalyzed mechanism was also discussed.

PdI2-catalyzed coupling-cyclization reactions involving two different 2,3-allenols: an efficient synthesis of 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives.

Transition-metal-catalyzed dimeric coupling-cyclization reactions of two different 2,3-allenols afforded 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives 3. 2-Substituted 2,3-allenols 1 cyclized to form the 2,5-dihydrofuran ring, whereas the 2-unsubstituted 2,3-allenols 2 provided the 1,3-diene unit at the 4-position. The reaction is proposed to proceed through an oxypalladation, insertion, and beta-hydroxide elimination process. The C=C double bond was formed with high E stereoselectivity by beta-hydroxide elimination.

Studies on highly stereoselective addition-elimination reactions of 3-(methoxycarbonyl)-1,2-allen-4-ols with MX. An efficient synthesis of 3-(methoxycarbonyl)-2-halo-1,3(Z)-dienes.

3-(Methoxycarbonyl)-2-halo-1,3(Z)-dienes were prepared highly stereoselectively via SN2'-type addition-elimination reactions of 3-(methoxycarbonyl)-1,2-allen-4-ols with MX. These products may easily undergo Negishi or Sonogashira coupling reactions to yield a series of stereodefined polysubstituted (E)-1,3-dienes.