Allyl halide-alkyne cyclization

Evidence based on product mixtures now suggests, at least in the cases of a-halocarbonyl and perhaloalkyl starting marterials, that these reactions are in fact atom transfer radical cyclizations (equation 166)324,325. In them, the palladium catalyst is proposed to have roles both as the radical initiator and as a trap for iodine, similar to the more commonly used hexabutylditin. Intramolecular allyl halide-alkyne cyclizations proceed with trans-addition to the triple bond this is evidence that a still different mechanism may be operating in these cases (equation 167)1,326. 

Indium trichloride was identified as an efficient catalyst for the atom-transfer cyclization of allylic halides with an alkyne pendant [(42) (43)]. Mechanistic evidence... 

Moreto and coworkers have made improvements to the Chiusoli reaction, the Ni(CO)4-mediated carbonylation cyclization of allyl halides and alkynes, by conducting it in methanol403. It has subsequently been applied in the synthesis of methylenomycin B, in an intramolecular sense to provide bicyclo[3.3.0]octenones, and in intermolecular cases to form both fused bicyclic cyclopentenones and spirocyclopentenones (equations 203 and 204)403-405. 

In a mechanistically quite different process Ni(CO>4 is the catalyst precursor and the double bond of an allylic halide serves as the alkene component in another cyclopentenone synthesis. Sequential insertion of the alkyne and CO into an initially formed allyl-Ni complex leads to the primary cyclization product, a (2-oxo-3-cyclopenten-l-yl)methylnickel complex (Scheme 4). The final product of the sequence depends on which of several possible reactions of the latter take place. Important features of this reaction have been described in several reviews. " ... 

Intramolecular allylation of alkynes with allylsilanes is catalyzed by a variety of electrophilic transition metal halides and complexes (e.g. Pt(II), Pd(II), Ru(II), Au(III), and Ag(I)) (Scheme 10.196) [518]. Unlike the EtAlCl2- or HfCL,-catalyzed reaction, alkyriylaled allylsilanes are cyclized in an exo mode by these catalysts. The proposed reaction mechanism involves nucleophihc addition of an allylsilane to a metal-coordinated alkyne. 

The common methods for the S5mthesis of p-lactams are cycloaddition reactions such as the Staudinger s ketene-imine cycloadditions, ester enolate-imine cycloadditions, alkyne-nitrone cycloadditions (Kinugasa reaction), alkene-isocyanate cycloadditions, and Torii s cyclocarbonylation of allyl halides with imines. Several cyclizahon reactions of p-amino esters, p-amino acids, p-hydroxamate esters, and a-diazocarbonyls have been developed for the formation of p-lactam ring. N,N-Disubstituted a-haloamides cyclize by C3-C4 bond formation leading to the formation of P-lactam ring. 

A formal 13+2 -cycloaddi lion can be accomplished by adding bis(2-carbethoxyethyl) zinc to acetylenic esters . This reaction allows the construction of complex cyclopen-tenones, such as 388, which is a precursor of ( )-bilobalide (Scheme 101) . The allylzincation of tiimethylsilylacetylenes can be performed intramolecularly providing a functionalized alkenylzinc which cyclizes in the presence of Pd(PPh3)4 at 25 "C within 3.5 h, leading to the bicyclic product 389 in 84% yield (Scheme 102). The addition of allylic zinc halides to various alkynes occurs in the absence of copper salts. The related... 

Vinyl halides add to allylic amines in the presence of Ni(cod)2 where cod=l, 5-cyclooctodine, followed by reduction with sodium borohydride. Aryl iodides add to alkynes using a platinum complex in conjunction with a palladium catalyst. A palladium catalyst has been used alone for the same purpose, and the intramolecular addition of a arene to an aUcene was accomplished with a palladium or a GaCl3 catalyst, " AUcyl iodides add intramolecularly to aUcenes with a titanium catalyst, or to alkynes using indium metal and additives. The latter cyclization of aryl iodides to alkenes was accomplished with indium and iodine or with Sml2. " ... 

While this cyclization method does not allow the incorporation of substituents into the 3-position, as is available with internal alkynes, in analogous chemistry to that in Section 6.2.2, the palladium bound intermediate of cyclization can be intercepted with a range of external reagents to functionalize this site. These include aryl or vinyl halides, allylic substrates, carbonylation, and Heck coupling with alkenes [72]. 

The reaction takes advantage of the ease with which the functionalized alkynes used as starting material can be prepared and of the fact that a number of aryl and alkenyl halides or triflates, alkyl halides, and allyl esters can successfully be used as carbon donors. In the presence of carbon monoxide, a three-component process can take place, widening the scope of the reaction and providing a useful, straightforward entry into cyclization products incorporating a molecule of carbon monoxide. 

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