Alkynes iodo, cyclization

An organophosphine-mediated cyclization of alkyl 3-aroyloxy-2-butynoates gives rise to the formation of 2,3- and 2,4-disubstituted as well as 2,3,5-trisubstituted furans (Equation 25) <2004JA4118>. 3-Alkyne-l,2-diols undergo iodo-cyclization to give 3-iodofurans after subsequent dehydration <2001TL5945>. 

A facile route for the synthesis of novel benzo[ ]furanyl benzimidazole derivatives was reported involving iodo-cyclization of 3-(benzimidazol-2-yl)phenyl alkynes (14JHC1491). 

In the last two decades transition metal catalyzed cyclization/annulation reactions have also been reported. In most cases alkynes are cyclized within a biphenyl-containing substrate. Different modes of action for the transition metal can be distinguished. In the first case the metal undergoes an oxidative addition into an aryl-halogen bond and then performs the carbometallation of the alkyne. Here, an example by Larock and coworkers is presented, in which an in situ formed aryne species is cyclized with an iodo biaryl substrate 136 (Scheme 34) [89]. 

The first example of a cyclization of fluorine-containing 5-hexenyl radicals was the study of the radical-iniOated cyclodimenzation reaction of 3,3,4,4-tetra-fluoro-4-iodo-1-butene. In this reaction, the intermediate free radical adds either to more of the butene or to an added unsaturated species [54, 55] (equation 56). Electron-deficient alkenes are not as effective trapping agents as electron-nch alkenes and alkynes [55]. 

In addition, 2,6-dimethyl-5-iodo-4(3//)-pyrimidone (89) was allowed to react with phenylacetylene to give internal alkyne 90, which underwent a spontaneous cyclization to furnish 2,4-dimethyl-6-phenylfuro[2,3-[Pg.393]

Radical intermediates are also trapped by intramolecular reaction with an alkene or alkyne bond. At a mercury cathode this process competes with formation of the dialkylmercury [51], At a reticulated vitreous carbon cathode, this intramolecular cyclization of radicals generated by reduction of iodo compounds is an important process. Reduction of l-iododec-5-yne 5 at vitreous carbon gives the cyclopentane... 

Halogen shifts have been found for tungsten, with assumed formation of iodovinylidenes in reactions of 1-iodo-l-alkynes with W(CO)5(thf) en route to cyclization of 2-(iodoethynyl)styrenes to naphthalenes and of iodo-alkynyl silyl enol ethers [147], while more substantial confirmation is found in Mn =C=C(I)CH (OR)2 (CO)2Cp [R = Me, Et (OR)2 = 0(CH2)30], of which the XRD structure of Mn =C=C(I)CH(OMe)2 (CO)2Cp was determined [148]. 

The palladium/copper-catalyzed coupling reaction of 2-iodo-3-methoxy-6-methylpyridine and terminal alkynes leads to the formation of o-methoxyalkynylpyridines which undergo electrophilic cyclization reactions to afford furo[3,2-3]pyridines in moderate yields <2005JOC10292>. A similar Pd/Cu-catalyzed reaction with hydroxypyridines and trimethylsilyl (TMS)-acetylene leads to the formation of alkynyl pyridines which cyclize to form furo[2,3- ]-pyridines in good yields <1998JME1357>. 

The radical intermediates from Cr(II) reduction of alkyl halides can in principle be used synthetically, but have only seen limited attention to this point. co-Haloalkynes (bromides, iodides), in the presence of excess Cr(C104)2, undergo cyclization reactions to form exo-alkylidene cycloalkanes (equation 176)347. These reactions proceed by the radical cyclization of intermediate 42 onto the alkyne unit, which undergoes subsequent reduction by Cr(II) to give a hydrolytically unstable vinylchromium(III). Rings of four, five and six members can be formed. Alternatively, a-iodo esters undergo intramolecular atom transfer radical cyclizations onto alkynes or alkenes with catalytic or stoichiometric amounts of... 

An alternative pathway utilizes the palladium-catalyzed replacement of an iodo group at 05 of the pyrimidines (266 R2 = I) to give alkynes (266 R2 = C=C-TMS) (Equation (92)) <86CPB2719>. Replacement of the chlorine by sodium hydrogen sulfide is followed by immediate cyclization to the thienopyrimidines (267) in yields of 53-95%. 

In addition to cationic cyclizations, other conditions for the cyclization of polyenes and of ene-ynes to steroids have been investigated. Oxidative free-radical cyclizations of polyenes produce steroid nuclei with exquisite stereocontrol. For example, treatment of (259) and (260) with Mn(III) and Cu(II) afford the D-homo-5a-androstane-3-ones (261) and (262), respectively, in approximately 30% yield. In this cyclization, seven asymmetric centers are established in one chemical step (226,227). Another intramolecular cyclization reaction of iodo-ene poly-ynes was reported using a carbopaUadation cascade terminated by carbonylation. This carbometalation—carbonylation cascade using CO at 111 kPa (1.1 atm) at 70°C converted an acycHc iodo—tetra-yne (263) to a D-homo-steroid nucleus (264) [162878-44-6] in approximately 80% yield in one chemical step (228). Intramolecular aimulations between two alkynes and a chromium or tungsten carbene complex have been examined for the formation of a variety of different fiised-ring systems. A tandem Diels-Alder—two-alkyne annulation of a triynylcarbene complex demonstrated the feasibiHty of this strategy for the synthesis of steroid nuclei. Complex (265) was prepared in two steps from commercially available materials. Treatment of (265) with Danishefsky s diene in CH CN at room temperature under an atmosphere of carbon monoxide (101.3 kPa = 1 atm), followed by heating the reaction mixture to 110°C, provided (266) in 62% yield (TBS = tert — butyldimethylsilyl). In a second experiment, a sequential Diels-Alder—two-alkyne annulation of triynylcarbene complex (267) afforded a nonaromatic steroid nucleus (269) in approximately 50% overall yield from the acycHc precursors (229). 

Aryl radicals participate in radical cyclization reactions when the aromatic ring has an alkene or alkyne substituent. o-Iodo aryl allyl ethers cyclize to benzofuran derivatives, for example, when treated with AIBN, aqueous H3PO2 and NaHCOs in ethanol. Cyclization of an o-bromo-A-acyl aniline (a methacrylic acid derivative) with AIBN/BusSnH gave an indolone under the typical conditions used for cyclization of alkenes. 

In 1989 Curran and co-workers reported on a photocatalytically induced free-radical cyclization leading to various cyclic, bi-, or polycyclic carbocycles (fused and spiro) via isomerization of unsaturated iodides (alkenes, alkynes) [63]. This corresponds to the nonreductive variant of the tin hydride method. Under sunlight irradiation and in the presence of 10 mol% hexabutylditin, a-iodo esters, ketones, and malonates are efficiently transformed via an iodide atom transfer chain mechanism (eq. (4)). 

Palladium-catalysed cyclization of suitable iodo-alkynes (39.1) is improved by the presence of thallium(I) carbonate to give the aminovinylisoquinoline (39.2) otherwise, a poor yield of the vinylisoquinoiine (39.3) is obtained. 

Chromones and flavones 16 are formed by Pd(0)-catalyzed carbonylative cyclization of o-hydroxy- or o-acetoxy iodo arenes with terminal alkynes in the presence of Et2NH. Intermediates are the corresponding or /zo-functionalyzed aryl alkynyl ketones 15, which can be synthesized separately and cyclized by Et2NH [37]. 

A general cyclization reaction of 6-lithiated (trimethylsilyl)alkynes is exemplified by the conversion of the iodo compound 499 into the methylenecyclopentane 500 by treatment with -butyllithium . Heating a mixture of the acetylenic silane 501 and 2-(benzyloxymethyl)allylzinc bromide 502 resulted in the diene 503, which cyclized to the methylenecyclopentene 504 in the presence of tetrakis(triphenylphosphine)palladium ... 

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