Alkynylation phenols

An alternative preparation of benzofurans was carried out via a microwave-assisted Mannich condensation of paraformaldehyde and a secondary amine followed by cyclization with an alkynyl phenol 185 mediated by alumina doped with Cul (Scheme 67). The reaction can be carried out in a single-step... 

The cyciization of o-alkynyl phenol derivatives under the influence of a base or copper or palladium catalysts is a simple and reliable route to benzo[3]furans (Equation 107) <1996H(43)101>, given that the substrates are easily... 

Fiirstner and co-workers have demonstrated the utility of the PtCl2-catalyzed carboalkoxylation of protected o-alkynyl phenols in the synthesis of the pterocarpene nucleus of erypoegin H <2007AGE4760>. Naphthalene fused 2,3-dihydrofurans have been shown to be available through a Pt- and Ru-catalyzed aromatization of enediynes with concomitant intramolecular nucleophilic additions <2007S2050>. 

From ortho-Halophenols From oitho-Alkynyl-phenols... 

A conformationally restricted 2,3-diarylbenzo[i)]furan library was built up on solid-phase by the palladium/bipyridy-catalyzed annulation of o-alkynyl phenols with aryl halides <04JOC2235>. 

Common model reactions for the title conversion include cyclizations of alkynoic acids to lactones, with variable degrees of regioselectivity [3-5]. Another model-reaction is the cyclization of ortho-alkynyl-phenols to benzofurans. The reaction is... 

An efficient synthetic methodology was developed in which the palladium-mediated intramolecular carbonylative annulation of o-alkynylphenols was employed to construct benzo[l>]furo[3,4-d]furan-l-ones by a tandem reaction. Several densely functionalized alkynyl- phenols were cyclized into their respective substituted benzo[fc]furo[3,4-d]furan-l-ones in good yields under conditions of a combination of PdCljfPPh,), dppp and CsOAc in acetonitrile at 55°C under a balloon pressure of CO. An example is depicted below <01OL1387>. 

Chemo- and regioselective synthesis of naphtho[2,3-c]chromenes result from the palladium-catalyzed reaction of 2-haloaryl aUenes with 2-alkynyl-phenols in refluxing 1,4-dioxane (Scheme 18) (14CC5891). Another palladium catalyst was involved in the intramolecular oxidative cyclization of 3-allyl-2 -hydroxyflavones to afford chromone[2,3-c]-2f/-chromenes in good... 

Rhodium-catalyzed-carbonylation of o-alkynyl phenols has resulted in the formation of 3-substituted coumarins and 3-substituted benzofuran-2-ones, under the water-gas shift reaction conditions (Takashi et al. 1998). Rhg(CO)ig was employed as the catalyst in the carbonylation. The reaction has been shown to involve oxidative addition and insertion of carbon monoxide followed by reductive elimination. Coumarins were obtained in low yield (20%-40%) (Scheme 10.4). 

Liao, Y., Reitman, M., Zhang, Y, Fatiii, R. and Yang, Z. (2002) Palladium(II)-mediated cascade carbonylative annnlation of o-alkynyl-phenols on sdyl bnker-based macrobeads a combinatorial synthesis of a 2,3-disubstituted benzo[b]furan library. Organic Letters, 4, 2607-2609. 

An intramolecular version of alkyne hydration was reported in 2006 by Belting and Krause [127] providing an efficient route to tetrahydrofuranyl ethers 32. This transformation consists in a tandem cycloisomerization-hydroalkoxylation of homopropargylic alcohols 31 in the presence of an alcohol in a dual catalyst system (a gold precatalyst and a Bronsted acid) under mild conditions (Scheme 13). The reaction proceeds satisfactorily with terminal and internal alkynes, with bis-homopropargylic alcohols and alkynyl phenols to provide cyclic acetal skeletons that occur in a variety of natural products. Substituted furanones can be obtained by gold(III)-catalyzed activation of alkynes by heterocyclization and subsequent 1,2-alkyl shift [128]. 

Scheme 6.20. This ruthenium catalyst (10 mol%) was active for the cydization of ds-1 -ethynyl-2-vinyloxiranes to afford various 2,6-disubstituted phenols in reasonable yields. Under similar conditions, 1,1,2,2,-tetrasubstituted oxiranes gave the 2,3,6-trisubstituted phenols with a skeleton reorganization [22]. The 1,2-deuterium shift of the alkynyl deuterium of d-Sle was indicative of mthenium vinylidene intermediates (Scheme 6.20).

In2000, Hashmi and coworkers reported that certain alkynyl furans (151) undergo rapid cycloisomerization to give bicyclic phenols (152) in the presence of AUCI3 at room temperature (Equation 9.16) [51]. A number of late-transition metal catalysts promote this transformation [52]. Echavarren and coworkers have studied the Pt-catalyzed variant [53], which is believed to proceed via a mechanism involving Pt-cydopropylcarbene intermediates [54]. 

The following phenol synthesis from easily accessible furyl alkynyl starting material was the first gold-catalysed reaction to proceed via car-benes and arene oxides (Ts = p-toluene sulfonate Cat = AUCI3 in... 

Addition of cyclohexyl isocyanide to enol ether 164 derived from addition of phenol to a (l-alkynyl)carbene complex la results in formation of a... 

A synthesis of [3]-fused furans involving a ring enlargement can be effected by the treatment of a-alkynyl-a-cyclopropylcycloalkanones with an electron-rich Au(l) catalyst in the presence of a suitable nucleophile (Equation 18) <2006AGE6704>. The nucleophiles that can be used include alcohols, phenols, carboxylic acids, indole, and 2-pyrrolidone. Open-chain ketones as well as other ring sizes react with comparable yields. Silver and lanthanide triflates are also effective catalysts for this transformation. 

Alkynyl complexes. These complexes, which are readily available by reaction of an alkynyllithium with chromium carbonyl followed by methylation with CH3OSO2F, undergo facile Diels-Alder reactions with dienes to provide a general route to ,p-un-saturated chromium carbene complexes. The latter undergo benzannelation or cyclo-hexadienone annelation on reaction with an alkyne. A (trimethylsilyl)ethynyl complex is useful because benzannelation results in migration of silicon from carbon to oxygen to provide a protected phenol. 

The degree of aggregation of organolithium compounds (alkyl-, aryl-, and alkynyl-lithium compounds as well as lithium enolates) in dilute tetrahydrofuran solution at —108 °C has been determined by means of cryoscopic [289] and NMR spectroscopic measurements [290] for a review on the solution structure of Hthium enolates and phenolates, see reference [406]. 

Phenol triflate Me, Ph, aryl, alkenyl, alkynyl B/L/LiCl [159]... 

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