A cycloisomerization

The high-valent metal species required for activation of an alkyne has also been generated by the oxidative addition to an allylic or propargylic system. For example, with an allyl aryl ether as the substrate, this type of reaction achieves a cycloisomerization that occurs through an 0- to C-allyl migration (Equation (92)) 323,324 similarly, (9-propargyl derivatives lead to a mixture of allenyl and propargyl products (Equation (93)).325,326... 

R = H) 1 could selectively undergo a cycloisomerization reaction to produce various furan rings 2 under mild conditions with rhodium(I) or silver(I) catalysts. 

Belmont s group87 reported a cycloisomerization reaction on quinolines 77 (Scheme 5.34) bearing a silyl enol ether group on position 3 and an alkynyl group on position 2, leading to acridine derivatives 78. 

The cycloisomerization of allenyl ketones was initially described as being catalyzed by rhodium(I) or silver(I) by Marshall et al.21 The activity of copper, silver, and gold for this reaction was first compared in two papers published later (Scheme 12.7).22 In the case of copper and silver, only a cycloisomerization was observed (Table 12.4, entries 1 and 2) with gold, a dimer is obtained as well (entry 3). 

Copper(I) catalysis is very well established to promote intramolecular [2+2] photocycloaddition reactions of l,n-dienes (review [351]). The methodology recently enjoyed a number of applications [352-354], It is assumed that CuOTf, which is commonly applied as the catalyst, coordinates the diene and in this way mediates a preorganization. The Ghosh group recently reported a number of CuOTf-catalyzed photochemical [2+2] cycloaddition reactions, in which an organocopper radical complex was proposed as a cyclization intermediate (which should, however, have a formal Cu(II) oxidation state) (selected references [355-357]). A radical complex must, however, not be invoked, since the process may either proceed by a [2+2] photocycloaddition in the coordination sphere of copper without changing the oxidation state or according to a cycloisomerization/reductive elimination process. 

Intramolecular variants of the Alder-ene type couplings between alkynes and alkenes have been extensively explored by means of palladium catalysis [73]. Recently, such a cycloisomerization of enynes was also accomplished with ruthenium catalysis (Scheme 4.32) [74]. 

Scheme 15. Synthesis of Heterocycles from 1,6-Dienes, Enynes, and Diynes via (a) Cycloisomerization, (b) Tandem Addition—Cyclization, and (c) Cycloaddition...

As 1,/2-alkenes, 1,6-derivatives are used very frequently leading to five-membered heterocycles, while the use of 1,7-derivatives, which produce six-mem-bered heterocycles, is very rare. The reactions of 1,6-dienes, -enynes, and -diynes are classified into three groups (a) cycloisomerization, (b) tandem addition— cyclization, and (c) cycloaddition, such as the Pau-son—Khand reaction, cyclotrimerization, and the Diels—Alder reaction (Scheme 15).97 In these reactions five-membered heterocycles are constructed upon the carbon—carbon bond-forming processes. 

When the reaction of c/s-cyclohexyl carboxylates 101 and 107 was conducted in the presence of maleic anhydride (1 equiv) in toluene, a cycloisomerization affording c/s-fused bicyclic alkyl carboxylates 106 and 108 was observed (Scheme 50) [31]. 

A double cyclization of an aldehyde enol to the methylene malonate, followed by a cycloisomerization onto the triple bond, leads to a bicyclo[5.3.0] decane of a tris-norguaiane (Scheme 10) [45]. 

Trost has developed a cycloisomerization of enjmes involving a nickel-chromium catalyst system (Scheme 45).P 1 High yields among a broad range of substrates are noted. 

Dixneuf et al. first reported that various 2,3,5-trisubstituted furans 114 could be synthesized via a cycloisomerization of (Z)-pent-2-en-4-yn-l-ols 113 in the presence of Ru(II)-catalyst (Scheme 8.45) [162-164]. The corresponding furans were obtained generally in good to high yields, though this reaction was specific to terminal alkynes only. The authors proposed a mechanism based on the electrophilic activation of the alkyne moiety followed by intramolecular addition of the hydroxy function at the internal carbon atom of alkyne. A subsequent protiodemetalation-isomerization sequence furnished the furan 114 (Scheme 8.46). 

Recently, Iwasawa established a set of transition metal-catalyzed protocols for an efficient construction of N l-C2-fused polycydic indole skeletons via a cycloisomerization-cycloaddition domino reaction of alkynyl imines 172 [222-224]. It was shown that the latter substrates, upon activation with transition metal catalysts, such as W(0), Pt(II), and Au(III), generate reactive azomethine ylide intermediates 174 similar to 166 (Scheme 9.64). Interception of such yUdes with a variety of suitably substituted alkenes 17S via a [3 - - 2]-cydoaddition affords fused indole products 177 through a transient formation of the corresponding metallocarbenoids 176. Transformation of terminal alkynyl imines proceeds with a 1,2-H shift in the 176, whereas... 

Scheme 8.68 Synthesis of natural products applying a cycloisomerization step [403]. reaction as a key...

Cyclization of 2-benzylpent-4-enoic acid (a-benzyl-a-allylacetic acid) and related compounds 1 to corresponding 1,2,3,4-tetrahydronaphthalene (tetralin) derivatives 2, catalyzed by a strong acid, has been called Darzens synthesis of tetralin derivatives. The reaction formally falls into the category of a cycloisomerization reaction of alkenyl-substituted arenes. 

In 2005, Yamamoto et al. reported the synthesis of polycyclic pyrrole-2-carboxylates 76 via a CuBr -catalyzed three-component coupling of A-benzylallylamine, ethyl gly-oxalate, and terminal alkynes, and subsequent ttansforma-tion of the glycine-tethered 1,6-enynes 75 thus obtained through a cycloisomerization/Diels-Alder cycloaddition/ dehydrogenation sequence under iridium-catalyzed conditions (Scheme 3.43) [108]. 

The ene reaction, or Alder-ene reaction, is a cycloisomerization involving the migration of an atom, typically hydrogen, across two nonconjugated double or triple bonds (Scheme 11.70). The reaction often requires high temperatures or the addition of strong Lewis acids. 

Qiatani et al. reported a cycloisomerization of l-alkyl-2-ethynylbenzenes catalyzed by PtCU, PtCLt, and [RuCl2(CO)3]2 for preparing substituted indenes... 

A cycloisomerization cascade from alkynylcyclopropanecarboxylic acid derivatives to oxepinones and azepinones has been reported to involve nucleophilic addition followed by a cyclopropane ring opening, where both donor and acceptor groups are required as substituents of the cyclopropane ring (Scheme 133). ... 

Application of a cycloisomerization strategy to the synthesis of icetexane and cortistatin natural products and structural analogs... 

In a similar way, iminoalkynes containing aryl, alkenyl, and alkyl substituents undergoes Cul-catalyzed cyclization in excellent yields and short reaction times to give isoquinolines, pyridines, and pyrroles via a cycloisomerization (eq 18)4 Copper chloride is preferred, however, for the conversion of cyclic alkynyl imines to pyrrole-containing heterocycles. Copper iodide catalyzes the formation of furans from alkynyl ketones. ... 

SCHEME 747 (a) Cycloisomerization of 1,6-dienes using cationic platinum pincer complexes and (b) mechanism of platinum pincer complexes. 

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