Cu(I)-catalyzed regioselective synthesis of polysubstituted furans from propargylic esters via postulated (2-furyl)carbene complexes

Polysubstituted furan derivatives are regioselective obtained from (bis-alkynyl)methyl carboxylates in the presence of catalytic amounts of copper(I) salts. This multistep process is consistent with the intermediacy of a copper(I) (2-furyl)carbene complex which is intercepted by suitable trapping reagents.     

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.     

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.     

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.     

Copper(I)-catalyzed regioselective propargylic substitution involving Si-B bond activation

The silicon nucleophile generated by copper(I)-catalyzed Si-B bond activation allows several γ-selective propargylic substitutions. The regioselectivity (γ:α ratio) is strongly dependent on the propargylic leaving group. Chloride is superior to oxygen leaving groups in linear substrates (γ:α > 99:1), and it is only the phosphate group that also shows promising regiocontrol (γ:α = 90:10). That leaving group produces superb γ-selectivity (γ:α > 99:1) in α-branched propargylic systems, and enantioenriched substrates react with excellent central-to-axial chirality transfer.     

Ligand-free Ag(I)-catalyzed carboxylation of terminal alkynes with CO2

A convenient approach to selectively prepare a wide range of functionalized propiolic acids was developed by AgI-catalyzed carboxylation of terminal alkynes using carbon dioxide as carboxylative agent under ligand-free conditions.     

Au(I)- and Pt(II)-catalyzed cycloetherification of omega-hydroxy propargylic esters

Depending on the nature of the metal catalyst, omega-hydroxy propargylic acetates choose between alternative cycloetherification manifolds to produce functionalized heterocycles in high yields. AuCl catalyzes the formation of oxacyclic enol acetates, whereas [Cl(2)Pt(CH(2)CH(2))]2 (Zeise's dimer) will induce a propargylic substitution via an unprecedented S(N)2'-type allenic substitution from within a chelated square planar cationic Pt(II) complex.     

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.     

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 formation of 4-alkylidene-1,3-dioxolan-2-ones from propargylic tert-butyl carbonates

[reaction: see text]. A study concerning the gold(I)-catalyzed rearrangement of propargylic tert-butyl carbonates into 4-alkylidene-1,3-dioxolan-2-ones is described. The mild reaction conditions employed allow the efficient synthesis of a variety of cyclic carbonates that would be less conveniently obtained using reported methods. Variability in the structure of the final product has been observed and is significantly dependent on the nature of the substituent attached to the alkyne moiety.     

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.     

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.     

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.     

Synthesis of 2,3-dihydroisoxazoles from propargylic N-hydroxylamines via Zn(II)-catalyzed ring-closure reaction

A novel cyclization reaction of propargylic N-hydroxylamines to 2,3, 5-trisubstituted 2,3-dihydroisoxazoles in the presence of catalytic amounts (10 mol %) of ZnI(2) and DMAP is reported. The methodology provides a mild new approach to this useful class of substituted heterocycles that complements extant methods. The unique reactivity of the propargylic N-hydroxylamine substrates in the presence of Zn(II) and DMAP may have additional applications in other, related alkyne cyclization reactions.     

PdCl2-catalyzed efficient transformation of propargylic amines to (E)-alpha-chloroalkylidene-beta-lactams

[reaction: see text] The PdCl2-catalyzed cyclocarbonylation reaction of propargylic amines with CuCl2 and benzoquinone afforded (E)-alpha-chloroalkylidene-beta-lactams in moderate to good yields. The formation of the corresponding Z-isomers or five-membered products was not observed. The reaction of the readily available optically active propargylic amines provides a convenient synthesis of the corresponding (E)-alpha-chloroalkylidene-beta-lactams with high ee values. The structure and the stereochemistry of the products were established by the X-ray single-crystal diffraction study of (E)-6d and (E)-6e, which indicates that the stereoselectivity in this reaction is different from what was observed with propargylic alcohols. A rationale for this reaction was proposed.     

Studies on the Cu(I)-catalyzed regioselective anti-carbometallation of secondary terminal propargylic alcohols

A highly regioselective Cu(I)-catalyzed anti-carbometallation of secondary terminal propargylic alcohols with 1 degrees alkyl or aryl Grignard reagents affording 2-substituted allylic alcohols was developed. By using this method, optically active allylic alcohols can be prepared from the optically active propargylic alcohols without obvious loss of the enantiopurity. The cyclic organometallic intermediate formed may undergo an iodination or a Pd(0)-catalyzed coupling reaction to afford stereo-defined allylic alcohols.