Cyclization allyl halides

Limited work has revealed that vinyl and allyl halides cyclize only in low yield, and the products suffer halogen loss in the process. Also, unlike allyl ethers, vinyl ethers and esters are only marginally... 

A two-step cyclization of an enamine with an electrophilic olefin has been reported in which the first step is alkylation by an allyl halide and the second step is alkylation by the electrophilic olefin (50). The reaction... 

Nickel carbonyl effects coupling of allylic halides when the reaction is carried out in very polar solvents such as DMF or DMSO. This coupling reaction has been used intramolecularly to bring about cyclization of to-allylic halides and was found useful in the preparation of large rings. 

When the electrophile contains two allyl halide moieties, two carbon—carbon bonds are formed, resulting in cyclized compounds 47 and 48, as shown in Eq. 2.34 [7f]. 

Interestingly, if the cyclization was carried out in the presence of an aryl or allyl halide and a palladium(O) catalyst, an additional C-C coupling step via presumed intermediate 210 led to the formation of tetrasubstituted furans of type 211 (Scheme 2.64) [101]. 

With the ready availability of 2-fluoro-allylic halides and a-fluoroacrylic acid derivatives, incorporation of a pendant fluorovinyl unit is easier than ever. The utility of these products is markedly enhanced by the reactivity of the fluorovinyl unit in olefin metathesis reactions. Some success has been found in cyclization reactions as shown below [83] (Scheme 36). 

If an allyl halide is used as the quaternizing agent, an intramolecular 1,5-cyclization of the ylid may take place. In this way, various dihydro-indolizines, which are prone to oxidation and thus difficult to prepare, have been made.67 The probable mechanism is shown in Scheme 9. 

The cyclofunctionalization of 4-alkynoic and 5-alkynoic acids generates y-alkylidene-y-lactones and 5-alkylidene-S-lactones, respectively (equation 76 and Table 22). The initial products from the reactions catalyzed by mercury or silver salts undergo protiodemetallation under the reaction conditions. The vi-nylpalladium intermediates undergo either protiodemetallation or coupling with an added allyl halide. The palladium(II)-catalyzed cyclization of 3-alkynoic acids proceeds by 5-endo closure to give 3-buten-4-olides (Table 22, entry 2).50 190... 

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

Jt-allyl complex can be generated after cyclization, as suggested by Takacs in a Fe(0)-catalyzed cyclization of polyenes. It also can be preformed if an active functional group is present in the allylic position. The palladium-catalyzed intramolecular cycloisomerization reaction of allylic acetates is an efficient method for constructing five- or six-membered rings [56, 57]. An asymmetric approach to this transformation has been studied and so far only poor enantioselectivity has been achieved (0-20% ee) [58]. Very recently, Zhang et al. also reported a Rh-catalyzed cycloisomerization involving a Jt-allylrhodium intermediate formed from an allylic halide [59]. 

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. 

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. 

When Me3SiSnBu3 is treated with CsF, the fluoride anion should coordinate to the silyl group and not the stannyl group to produce a hypervalent silicate, and as a result, a stannyl anion would be generated.282 The stannyl anion reacts with vinyl iodide to produce a vinyl anion via a halogen-metal exchange and it reacts with the carbonyl group intramolecularly (Equation (113)). Aryl halides or allyl halides are also used in similar cyclizations.283,284... 

The cycloisomerization of allenyl ketones can be exploited for the synthesis of 2,3,4- or 2,3,5-trisubstituted and tetrasubstituted furans, when the Pd(0)-catalyzed cyclization of a,7-disubstituted substrates is combined with the coupling of an aryl halide or substituted allyl halide, as has been reported by Ma et al. (Equation 14) <20000L941, 2000CC117, 2003CEJ2447>. 

Stereoselective synthesis of the 1,3-amino alcohol moiety is possible starting from N-tert-butyldimethylsilyloxycarbonyl derivatives of allylic halides 5 through a ScN cyclization. Thus, methyl ( )-2-tm-butyldimethylsilyloxycarboiiylamino-6-chloro-4-hexenoatc (5, R = COOCH3), treated with 2 equivalents of silver fluoride in acetonitrile, gives a mixture of the cis- and trans-tetrahydro-2//-l,3-oxazin-2-oncs 6 in 65% yield, although in moderate diastereoselectivity,9c. 

An interesting Darzens-like formal cycloaddition of azirines has also been reported <2004EJ02421>. While this is not a true cycloaddition reaction, two bonds are formed in the same reaction sequence. Reaction of sulfone 114 with lithium diisopropylamide (LDA) generates a carbanion which then adds to the azirine to generate intermediate 115. Cyclization of this intermediate with the allyl halide provides the product aziridine 116. This reaction proceeds in only 13% yield but is nonetheless an interesting route to fused-ring aziridines (Equation 27). 

Cycloaddition reactions of 18-electron transition metal ti -allyl complexes with unsaturated electrophiles to form five-membered rings have been extensively investigated. These transformations constituted a family of metal-assisted cycloaddition reactions in which the metal functions as an electron-donor center. These are typically two-step processes that involve the initial formation of a dipolar metal r) -alkene intermediate (2) and subsequent internal cyclization (equation 2). The most extensively investigated application of this methodology has been with dicarbonyl-ii -cyclopentadienyliron (Fp) complexes from the laboratory of Rosenblum. These (ri -allyl)Fp complexes are available either by metallation of allyl halides or tosylates with a Fp anion, or by deprotonation of (alkene)Fp cations. ... 

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. " ... 

Synthesis of maerolides. The intramolecular coupling reaction of allylic halides (I, 722-723 2, 290-292 3, 211) has now been shown to be applicable to the synthesis of maCrocyclic lactones. Thus addition of the dibromo ester (1) to 6 eq. of nickel carbonyl in N-methylpyrrolidone effects cyclization to the macrolide (2) as the major product. 

Allylic halide substrates in the P-keto ester series cyclize well, and convenient routes to five-, six- and seven-membered rings have been described (equations 50 and 51). Unfortunately, the dia-stereoselectivity in these examples again is highly dependent on the substitution patterns about the dicarbonyl substrate. 

This section covers the formation of cyclopropanes via cyclization of reactive allylic intermediates (cations, anions, radicals). Included are those transformations of allylic functional derivatives (e.g. allylic halides, alcohols, aldehydes, ketones, acids, esters, boronates, Grignard reagents) to cyclopropyl derivatives that do not actually proceed via allylic reactive intermediates, but which are not covered by other sections of this volume. Additionally, this section will cover methods for the formation of cyclopropanes by pericyclic reactions. 

---