Cyclization reactions alkynes

Dimethyl acetylenedicarboxylate (DMAD) (125) is a very special alkyne and undergoes interesting cyclotrimerization and co-cyclization reactions of its own using the poorly soluble polymeric palladacyclopentadiene complex (TCPC) 75 and its diazadiene stabilized complex 123 as precursors of Pd(0) catalysts, Cyclotrimerization of DMAD is catalyzed by 123[60], In addition to the hexa-substituted benzene 126, the cyclooctatetraene derivative 127 was obtained by the co-cyclization of trimethylsilylpropargyl alcohol with an excess of DMAD (125)[6l], Co-cyclization is possible with various alkenes. The naphthalene-tetracarboxylate 129 was obtained by the reaction of methoxyallene (128) with an excess of DMAD using the catalyst 123[62],... 

The von Richter cinnoline process was further extended to solid-phase synthesis. The route began from benzylaminomethyl polystyrene and the required diverse o-haloaryl resins represented by 21 were prepared from substituted o-haloanilines. A Pd-mediated cross-coupling reaction with 21 and the alkynes provided the alkynylaryl derivatives represented by alkyne 22. The von Richter cyclization reaction with hydrobromic or hydrochloric acid in acetone/HaO and cleavage from the resin occurred in the same step to furnish the cinnoline derivatives 23 in 47-95% yield and 60-90% purity (no yield reported for each entry). 

Hexacarbonyldicobalt complexes of alkynes have served as substrates in a variety of olefin metathesis reactions. There are several reasons for complex-ing an alkyne functionality prior to the metathesis step [ 125] (a) the alkyne may chelate the ruthenium center, leading to inhibition of the catalytically active species [125d] (b) the alkyne may participate in the metathesis reaction, giving undesired enyne metathesis products [125f] (c) the linear structure of the alkyne may prevent cyclization reactions due to steric reasons [125a-d] and (d) the hexacarbonylcobalt moiety can be used for further transformations [125c,f]. 

The reaction can be done intramolecularly. N-Benzyl pent-4-ynamide reacted with tetrabutylammonium fluoride to an alkylidene lactam. Similar addition of a tosylamide-alkene, with a palladium catalyst, led to a vinyl Al-tosyl pyrrolidine. Similar cyclization reactions occur with tosylamide-alkynes. ... 

The benzoquinone 66 is similarly prepared by the regioselective cycloaddition of 64, derived from 63. The cyclization reaction is based on the electronic effect of the substituent of 65 [34]. The maleoylcobalt complex 67, substituted by PPh3, is unreactive towards terminal alkynes. The reaction course is altered... 

Aside from alcohols, other oxygen nucleophiles have also participated in hydroalkoxylation reactions with alkynes. The most common of these are 1,3-dicarbonyl compounds, whose enol oxygens are readily available to add to alkynes. Cyclization reactions of this type have been carried out under Pd(0) catalysis with various aryl or vinyl iodides or triflates, often in the presence of CO, affording the corresponding furan derivatives (Equation (95)).337-340 A similar approach employing cyclic 1,3-diketones has also been reported to prepare THFs and dihydropyrans under Pd, Pt, or W catalysis.341 Simple l-alkyn-5-ones have also been isomerized to furans under the influence of Hg(OTf)2.342... 

Alkoxides that arise from simple carbonyl additions have also functioned as excellent in situ nucleophiles for intramolecular hydroalkoxylation reactions. Garbinols derived from the addition of allyltin reagents have proved to be potent nucleophiles in reactions of this type (Equation (99)),349 and this approach has also been used for the combined addition-cyclization of alkynals under Pd(n)350 or Cu(i)351 catalysis, and alkynones under Pd(n) catalysis.352... 

Enyne metathesis is unique and interesting in synthetic organic chemistry. Since it is difficult to control intermolecular enyne metathesis, this reaction is used as intramolecular enyne metathesis. There are two types of enyne metathesis one is caused by [2+2] cycloaddition of a multiple bond and transition metal carbene complex, and the other is an oxidative cyclization reaction caused by low-valent transition metals. In these cases, the alkyli-dene part migrates from alkene to alkyne carbon. Thus, this reaction is called an alkylidene migration reaction or a skeletal reorganization reaction. Many cyclized products having a diene moiety were obtained using intramolecular enyne metathesis. Very recently, intermolecular enyne metathesis has been developed between alkyne and ethylene as novel diene synthesis. 

A wide variety of five-membered zirconacydes 8 may be formed by the formal co-cycliza-tion of two 7i-components (3 and 6 alkene, alkyne, allene, imine, carbonyl, nitrile) on zir-conocene ( Cp2Zr ) (Scheme 3.2) [2,3,8]. The co-cydization takes place via the r 2-complex 5 of one of the components, which is usually formed by complexation of 3 with a zircono-cene equivalent (path a) ( Cp2Zr itself is probably too unstable to be a true intermediate) or by oxidation on the metal (cyclometallation/p-hydrogen elimination) (path b). Two additional routes to zirconocene r 2-complexes are by the reverse of the co-cyclization reaction (i. e. 8 reverting to 5 or 9 via 7), and by rearrangement of iminoacyl complexes (see Section... 

The reaction of nBu2ZrCp2 with 2 equivalents of PhC CPh provides the novel bicyclic gem-dizirconium complex 140 [236] (Scheme 7.42). Protonolysis of complex 140 with 3 n HC1 gives bibenzyl in 88% yield, while its deuterolysis with D20 provides tetradeuterio-bibenzyl 141 with 92 % deuterium incorporation. The dual path nature (142 versus 140) of the reaction of Cp2Zr with alkynes is an important factor in designing Zr-promoted cyclizations of alkynes, enynes, and diynes. 

Alkynes are interesting radical acceptors for cyclization reactions because the products contain double bonds that can be subjected to further transformations. In the case of terminal alkynes, the desired products can be obtained in high yields as single isomers. With non-terminal alkynes as acceptors, the alkene products are generated as mixtures of ( )- and (Z)-isomers in high yields but with low selectivity [36],... 

The key features of the catalytic cycle are trapping of the radical generated after cycliza-tion by an a,P-unsaturated carbonyl compound, reduction of the enol radical to give an enolate, and subsequent protonation of the titanocene alkoxide and enolate. The diaster-eoselectivity observed is essentially the same as that achieved in the simple cyclization reaction. An important point is that the tandem reactions can be carried out with alkynes as radical acceptors. The trapping of the formed vinyl radical with unsaturated carbonyl compounds occurs with very high stereoselectivity, as shown in Scheme 12.21. 

Low-temperature photochemical cyclization of alkynes bearing a bulky substituent, mediated by CpCo(CO)2, proceeds with CO insertion to give cyclopentadienone complexes. Higher reaction temperatures lead to cyclotrimerization. The intramolecular variant of this reaction gives the bicyclic cyclopentadienones 139 and 139 (equation 19)142. Cyclization of unsymmetrically substituted diynes with the chiral R CpCo(CO)2 (R = 8-phenylmenthyl) leads to the formation of a mixture of diastereomers modest diastere-oselectivity was found. 

While one of the first preparations of a cyclobutadiene-metal complex involved the cyclodimerization of diphenylacetylene in the presence of Fe(CO)5 at high temperature212, the thermal reaction of alkynes with Fe(CO)s gives predominantly cyclopentadienone complexes (Section IV.E.l.b). The cyclization of alkynes by a wide variety of metal complexes has been reported (Scheme 59)l 5-21 A—222... 

As an extension of the Heck reaction, Pd-catalyzed hydroarylation of alkynes and alkenes continnes to attract high level of research interest in simple couphng processes and in cyclization reactions. The use of this type of transformation as part of a domino reaction will be of increasing interest. The research in the field of domino reactions is attracting considerable attention in synthetic organic chemistry since it enables the rapid assembly of complex molecirles in one-pot processes. Very elegant examples of palladium-catalyzed cascade processes where a single catalytic cycle entails several sequential bond transformations have been recently reported [la, b, 2a, b, c]. 

In addition to reactions characteristic of carbonyl compounds, Fischer-type carbene complexes undergo a series of transformations which are unique to this class of compounds. These include olefin metathesis [206,265-267] (for the use as metathesis catalysts, see Section 3.2.5.3), alkyne insertion, benzannulation and other types of cyclization reaction. Generally, in most of these reactions electron-rich substrates (e.g. ynamines, enol ethers) react more readily than electron-poor compounds. Because many preparations with this type of complex take place under mild conditions, Fischer-type carbene complexes are being increasingly used for the synthesis [268-272] and modification [103,140,148,273] of sensitive natural products. 

Although terminal alkynes can easily be converted into vinylidene complexes, vinylidene complexes have not yet been extensively used as intermediates in organic synthesis [150,546,576-578,944]. Some cyclization reactions, which might proceed by transient formation of vinylidenes, are listed in Table 3.23 (see also Sections 2.1.5.1 and 2.2.2). 

Finally, zinc-copper exchange by treatment of FG-RZnI with Me2Cu(CN)Li2 provides copper species that add smoothly to various alkynes and which can also be used to perform cyclization reactions (Scheme 2.48) [98]. 

The electrophile for the cyclization reaction of an a-amino-organolithium compound is not restricted to a terminal (or phenylthio-substituted) ahcene and examples have been reported using carboxylic amides, alkynes and allyhc ethers." " For example, Fautens and Kumanovic reported that treatment of the bicyclic stannane shown in Scheme 24... 

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>. 

Allyl sulfones offer the possibility to conduct cyclization reactions that are isomerizations, and investigations by Smith and Whitham indicate that this is a very promising technique for the preparation of functionalized products.118 The mechanism consists of reversible addition of a sulfonyl radical to a terminal alkene or alkyne, cyclization, and fragmentation of the resulting -sulfonyl radical. Two examples of these isomerizations are provided in Scheme 26. 

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