Diynes intramolecular reactions

The same type of bis-functionalization has been reported for the palladium-catalyzed borylstannylative carbocy-cyclization of 1,6-, 1,5-, 1,7-diynes, bis-propargylamine, and ether.377 It should be noted that even 1,2-dialkylidene cyclobutane can be obtained in reasonable yield. Ito has proposed the related silaborative reaction involving nickel(O) catalysis.378 This reaction has been performed in an intra- and intermolecular fashion. The intramolecular reaction allows the formation of cyclic dienes and the intermolecular process proceeds through a dimerization of alkynes to give acyclic dienes. 

The reactions of Fischer carbene complexes with alkynes can under certain conditions lead to products that result from the incorporation of two alkynes, the carbene ligand and a carbon monoxide. In inter-molecular reactions, this is most commonly observed for acetylene itself or for sterically unhindered al-kynes. °2 As can be anticipated by the mechanism in Scheme 36, two-alkyne incorporated products of the type (258) are also favored for high alkyne concentration. Synthetically, the two-alkyne reactions are most useful in intramolecular reactions, two of which have been reported and are exemplified by the reactions in Scheme 43. The typical product from the reaction of a Fischer carbene complex with a diyne, such as (308), is a bicyclic phenol of the type (309). ° These products are apparently the result of the assembly of pieces indicated by (311). Under some conditions, dienones of the type (310) and (314) can be isolated, and it is thought they are the immediate precursors of the phenol products via an in situ reduction by a chromium(O) species. This reaction is completely regioselective with diyne (308) and the phenol (309) results from incorporation of the terminal alkyne of (308) before the disubstituted alkyne. Phenols of the type (309) have also been observed from the reaction of diynes with carbyne complexes. ... 

Intramolecular Reaction of 1,6-Dienes, -Enynes, and -Diynes Cycloisomerization, Tandem Addition-Cyclization, and Cycloaddition... 

The attachment of 148 to the appropriate diyne 155 led to an intramolecular reaction, which ensured the required regiochemistry of the substituents of rings A and D [159] (Scheme 32). Diyne 154 was obtained in foiu steps from 3-methoxybenzamide (149) (Scheme 32). Ortho hthiation of 149 and subsequent transmetalation with ZnCU-CuCN [160] followed by the reac-... 

Partially intramolecular reactions have the advantage of using readily accessible diynes and monoalkynes as substrates. However, problems with chemo- and regios-electivity remain. Facile dimerization of the diynes is a serious obstacle that must be overcome by using a large excess of the monoalkyne component. In 20(X), Yamamoto... 

Patterns of [2 - - 2 - - 2] cycloaddition for the synthesis of cyclophane are depicted in Scheme 8.1. Intermolecular reaction of diyne and monoyne can provide ortho, meta, and para isomers as dipodal cyclophanes (pattern A). Linear triyne can be transformed into ortho-ortho and ortho-meta isomers by an intramolecular reaction (pattern B). In the reaction of branched triyne, symmetrical 1,3,5- and unsymmetrical 1,2,4-isomers can be obtained as tripodal cyclophanes (pattern C). The choice of catalyst and tether is very important for induction of the aforementioned regioselectivities. 

Enantioselective reaction was achieved by cationic rhodium/chiral diphosphine complexes. The intramolecular reaction of linear triynes gave planar-chiral meta-cyclophanes in excellent ee. The intermolecular reaction of diynes with alkyne afforded planar-chiral para-cyclophanes with strained benzene ring in moderate to excellent ee. The intramolecular reaction of branched triynes gave planar-chiral tripodal-cyclophanes in excellent ee. 

In addition, microwave irradiation accelerated this transformation by at least 8-fold. Additives, in particular a quinolinium salt, were found to facilitate the intramolecular reaction of diynes that would not otherwise macrocyclize, apparently through an intermolecular noncovalent 7t-cation/arene inter-action. " It is noteworthy that RCM also can be assisted with such additives. These studies have positioned the Glaser-Hay reaction for investigation in the preparation of macrocycles from more complex substrates. 

Among the known methodologies for the synthesis of benzofuran derivatives, a favorable recent alternative to obtain 2-alkynylbenzofurans was represented by the intramolecular reaction of the ortho diyne phenols and aryl halides. This procedure may be performed with success in one or two steps in the presence of Pd(PPh3)4 [112] (Scheme 62). 

The reaction of hexa-2,4-diyn-l-al (64) with mercaptoacetaldehyde leads to 2-formyl-5-(prop-l-ynyl)thiophene (65). The addition direction is governed by the aldehyde group via intramolecular aldol condensation in the intermediate (77HOU947). 

In this method, one alkyne is treated with Schwartz s reagent (see 15-17) to produce a vinylic zirconium intermediate. Addition of MeLi or MeMgBr, followed by the second alkyne, gives another intermediate, which, when treated with aqueous acid, gives the diene in moderate-to-good yields. The stereoisomer shown is the one formed in usually close to 100% purity. If the second intermediate is treated with I2 instead of aqueous acid, the 1,4-diiodo-1,3-diene is obtained instead, in comparable yield and isomeric purity. This reaction can also be done intramolecularly Diynes 56 can be cyclized to ( , E) exocychc dienes 57 by treatment with a zirconium complex. 

When colorless crystals of rac-s-trans-3,8-di-tert-butyl-l,5,6,10-tetraphenyl-deca-3,4,6,7-tetraene-l,9-diyne (123) were heated at 140 °C for 2 h, the ben-zodicylobutadiene derivative (126) was produced as green crystals. As shown in the sequence (Scheme 20), 123 is first isomerized to its s-ds-isomer (124), and intramolecular thermal reaction of the two allene moieties through a [2+2] conrotatory cyclization gives the intermediate 125, which upon further thermal reaction between acetylene moieties gives the final product 126 [19,22].This is another example of the crystal-to-crystal reaction. 

In Section 9.2, intermolecular reactions of titanium—acetylene complexes with acetylenes, allenes, alkenes, and allylic compounds were discussed. This section describes the intramolecular coupling of bis-unsaturated compounds, including dienes, enynes, and diynes, as formulated in Eq. 9.49. As the titanium alkoxide is very inexpensive, the reactions in Eq. 9.49 represent one of the most economical methods for accomplishing the formation of metallacycles of this type [1,2]. Moreover, the titanium alkoxide based method enables several new synthetic transformations that are not viable by conventional metallocene-mediated methods. 

The Sonogashira reaction is of considerable value in heterocyclic synthesis. It has been conducted on the pyrazine ring of quinoxaline and the resulting alkynyl- and dialkynyl-quinoxalines were subsequently utilized to synthesize condensed quinoxalines [52-55], Ames et al. prepared unsymmetrical diynes from 2,3-dichloroquinoxalines. Thus, condensation of 2-chloroquinoxaline (93) with an excess of phenylacetylene furnished 2-phenylethynylquinoxaline (94). Displacement of the chloride with the amine also occurred when the condensation was carried out in the presence of diethylamine. Treatment of 94 with a large excess of aqueous dimethylamine led to ketone 95 that exists predominantly in the intramolecularly hydrogen-bonded enol form 96. 

When the terminal alkynes 96 are treated with the trimethylsilylalkyne 97 in the presence of HfCl4 as a Lewis acid, the silylated vinylallenes 98 are produced in acceptable yields. In an intramolecular variant of this process, 100 was obtained from the diyne 99 [32]. Vinylallenes, incorporated into a cyclic framework and hence of restricted conformational mobility, are of interest for photochemical studies [33] and are among the photoproducts in ring-enlargement reactions of polycyclic allenes [34]. 

In addition to the Hopf cydization of 176, there is a second pericydic reaction leading to 162, that is, the dehydro Diels-Alder reaction of butenyne with acetylene (Scheme 6.47). The theoretical treatment of this process by Johnson et al. [59] predicted a free reaction enthalpy and a free activation enthalpy, both at 25 °C, of -13.4and 42.0kcalmol-1, respectively. Ananikov [116] arrived at a similar result for the intramolecular case of non-l-en-3,8-diyne (202) and calculated the same quantities to be -15.3 and 30.9 kcal mol-1 for the formation of the isoindane 203. As already discussed regarding Scheme 6.40, the conversion of 162 into benzene and likewise that of 203 into indane have to be considered as a sequence of two [1,2]-H shifts 116, 117], whose highest transition state has a significantly lower energy than that for the formation of 162 and 203 by the dehydro Diels-Alder reaction. 

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. 

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