Palladium(II)-catalyzed cycloisomerization of functionalized 1,5-hexadienes

Scope and limitations of the Pd(II)-catalyzed cycloisomerization of functionalized 1,5-hexadienes have been studied. In situ NMR experiments indicate a challenging competition between various reaction pathways. A careful balance between substrate structure, nature of the precatalyst, and reaction conditions was required to gain access to a useful building block for sesquiterpene total synthesis.     

Substituent effect on the reaction pathway of Au(I)-catalyzed ene-yne cycloisomerization

The Au(I)-catalyzed ene-yne cycloisomerization pathway which is highly dependent on the substrate structures is described. The steric and electronic effects of substrate substituents could be important factors inducing the formation of the desired and undesired products. Comparison between the Au(I)-catalyzed reactions of substrates bearing the substituted phenyl moiety with and without methoxy group suggests that the methoxy group would direct the formation of undesired products through a cationic intermediate. This intermediate could be formed via aryl moiety attack presumably induced by the methoxy group at the para position. The use of nitrile groups instead of ester groups in the substrate effectively leads to the preferential formation of the desired product. This is probably because 1,3-diaxial interactions in the transition state of the Au(I)-catalyzed ene-yne cycloisomerization would be reduced by the use of the relatively small nitrile group. This steric effect is different from the electronic effect of the methoxy group of the aryl moiety, which makes the undesired reaction pathway favorable.     

Research on Au(I)-catalyzed ene-yne cycloisomerization for construction of quassinoid scaffold

Compounds that undergo Au(I)-catalyzed cycloisomerizations affording tetracyclic products that can be converted into compounds with the skeleton of bruceantin are described. The Au(I)-catalyzed cycloisomerizations reported herein are hindered by a 1,3-diaxial interaction between the substituent and the methyl group in the transition state. The use of small substituents was found to increase the yield of the desired product, while the reaction of substrates with large substituents afford undesired constitutional isomers.     

Gold(I)-catalyzed intramolecular acetylenic Schmidt reaction

Substituted pyrroles were prepared by a gold(I)-catalyzed acetylenic Schmidt reaction of homopropargyl azides. The reaction allows for regiospecific substitution at each position of the pyrrole ring under mild conditions. A mechanism in which azides serve as nucleophiles toward gold(I)-activated alkynes with subsequent gold(I)-aided expulsion of dinitrogen is proposed.     

Au(I)-catalyzed efficient synthesis of functionalized bicyclo[3.2.0]heptanes

An efficient Au(I)-catalyzed synthesis of highly strained and functionalized bicyclo[3.2.0]heptanes is developed. Subsequent couplings with various nucleophiles offer additional structural features/complexity. These one-pot, three-component reactions are proposed to proceed via a key 1,3-dipolar cycloaddition between a Au carbenoid-containing carbonyl ylide and ethyl vinyl ether.     

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.     

A Rh(I)-catalyzed cycloisomerization of homo- and bis-homopropargylic alcohols

The ability to form rhodium-vinylidene complexes in situ from terminal alkynes has led to the development of a catalytic process, the cycloisomerization of homopropargylic and bis-homopropargylic alcohols to dihydrofurans and dihydropyrans. Among the transition metals that perform similar reactions, rhodium catalysts demonstrate the best chemoselectivity and turnover numbers to date. Both secondary and tertiary alcohols participate equally well. The presence of proparylic oxygen and nitrogen functionality, which potentially can be induced to ionize via formation of allenylidene metal complexes, is compatible with this catalyst. The formation of a 5-amino-dihydropyran which is not compatible with some of the previous catalysts proceeds in good yield with the rhodium catalysts. A substrate bearing a benzylic hydroxyl group adjacent to an electron-rich aromatic ring also participates without complications of ionization. The method provides access to useful aminosugars. A mechanism to account for the different selectivity of this catalyst as compared to others is proposed.     

Au(I)-catalyzed cycloisomerization of 1,5-enynes bearing a propargylic acetate: formation of unexpected bicyclo[3.1.0]hexene

The use of N-heterocyclic carbene (NHC) as a ligand in the gold(I)-catalyzed cycloisomerization of enyne results in the assembly of a new carbocyclic product.     

Palladium(0)-catalyzed cycloisomerization of enallenes

A novel palladium(0)-catalyzed cycloisomerization of enallenes has been developed. This reaction, catalyzed by [Pd(dba)2] (dba=dibenzylideneacetone) in acetic acid, results in the formation of cyclopentene derivatives and [n.3.0]bicyclic systems (n=3, 4) in good to high yields. The carbon-carbon bond-forming step is highly stereoselective to give cis-fused bicyclic systems. The presence of acetic acid as solvent and dba as ligand for palladium(0) turned out to be essential for the reaction in order to provide good reactivity and regioselectivity.     

Tetrasubstituted 2-imidazolones via Ag(I)-catalyzed cycloisomerization of propargylic ureas

A one-pot protocol based on a Ag(I)-catalyzed cycloisomerization of propargylic ureas, derived from secondary propargylamines and isocyanates, was developed for the generation of the 2-imidazolone core.     

Rh(I)-catalyzed hydroacylation/cycloisomerization cascade: synthesis of (±)-epiglobulol

A novel Rh(I)-catalyzed cascade reaction was developed by combination of a hydroacylation of 4,6-dienal and a cycloisomerization of the resultant triene, giving the bicyclo[5.3.0]decenone derivative 8b in a stereoselective manner. It was found that the Thorpe-Ingold effect played an important role in the second cycloisomerization step of this cascade cyclization. From the cascade cyclization product, (±)-epiglobulol could be synthesized.     

Synthesis of functionalized oxazolones by a sequence of Cu(II)- and Au(I)-catalyzed transformations

A study concerning a two-step sequence leading to the formation of diversely 1,5-disubstituted oxazolones is described. The mild conditions employed allow the efficient and rapid synthesis of a variety of such compounds via an initial Cu(II)-catalyzed coupling of a bromoalkyne with a secondary tert-butyloxycarbamate followed by a Au(I)-catalyzed cycloisomerization of the N-alkynyl tert-butyloxycarbamates thus obtained.     

Bi(OTf)3-catalyzed cycloisomerization of aryl-allenes

Intramolecular hydroarylation of allenes was achieved under very mild conditions using bismuth(III) triflate as the catalyst. Efficient functionalization of activated and nonactivated aromatic nuclei led to C-C bond formation through a formal Ar-H activation. A tandem bis-hydroarylation of the allene moiety was also developed giving access to various interesting polycyclic structures.