Intermediates cycloalkynes

Reaction of 1 with semicarbazide hydrochloride gives the semicarbazone 4, in 74 % yield, which can be oxidized by selenium(IV) oxide to provide dibenzo[2,3 6,7]thiepino[4,5-rf][l,2,3]selenadi-azole (5) in 80 % yield. Thermolysis of selenadiazole 5 leads, with subsequent release of nitrogen, to diradical 6, which can either dimerize to 7 or lose selenium to give the intermediate cycloalkyne. The latter can be trapped by dienes as cycloadducts.93 Thus, the thermolysis of 5 in the presence of 2,3,4,5-tetraphenylcyclopenta-2,4-dienone gives the cycloadduct 1,2,3,4-tetraphenyltribenzo-[/ ,<7,/]thiepin (8) in 14% yield. 

Cycloalkene (Section 5 1) A cyclic hydrocarbon characterized by a double bond between two of the nng carbons Cycloalkyne (Section 9 4) A cyclic hydrocarbon characterized by a tnple bond between two of the nng carbons Cyclohexadienyl anion (Section 23 6) The key intermediate in nucleophilic aromatic substitution by the addition-elimination mechanism It is represented by the general structure shown where Y is the nucleophile and X is the leaving group... 

In previous experiments, Bald et al. [2] had tried to liberate 131 from 3-bromo-6,7-benzobicyclo[3.2.1]octa-2,6-diene (134) by /3-elimination of hydrogen bromide with KOtBu. Both the trapping products 140 of the intermediate with DPIBF and the enol ether 138 appeared to provide evidence in favor of 131, but did not exclude the cycloalkyne 136 [94]. The generation of 136 in the presence of DPIBF by two routes that cannot lead to 131 gave rise to cycloadducts different from 140, which were converted into 140 on treatment with KOtBu, however [95, 96], On the basis of these results and further investigations [97, 98], the formation of 131 from 134 is considered unlikely. Instead of 131, 136 seems to arise and to be the source of the products observed. In contrast, the phenyl derivative 137 of 131 is the obvious intermediate in the reaction of 135 with KOtBu, which furnished the enol ether 139 [2]. 

An exo-type cyclization, proceeding through a cycloalkylidene carbene (49 n = 1, 3, 4), was proposed to explain the formation of enynes (50) and (52) from alkynyl lithium species (48). The proposed carbene (49) could be trapped by addition to cyclohexene and the cycloalkyne intermediate (51) was trapped by Diels-Alder reaction with 1,3-diphenylisobenzofiiran. 

In order to further investigate the possibility of cycloalkyne 4b formed as a transient intermediate in the reaction of 3 with n-BuLi, specifically labeled 3 — CBr2 was synthesized and subsequently was reacted with n-BuLi. The reactive intermediate (s) thereby generated were trapped in situ by cyclohexene. Careful integration of the gated-decoupled C NMR spectrum of 5 — C obtained indicated that no scrambling of the C label had occurred in the... 

No experimental evidence was found that products formed as a result of alkene trapping of a putative cycloalkyne intermediate in either of these reac-... 

The alternative /3,y-elim [nation-addition route, forming the cyclo-allenic intermediate (161, n = 2, 3) could not be dismissed, since the equilibrium between a cycloallene and the corresponding cycloalkyne... 

The bis(triphenylphosphine)platinum(0) complex of cyclopentyne (240) [Eq. (32)] is the only complex of a five-membered cycloalkyne that is discussed in an earlier review.2 The mechanism of its preparation is significant because 239 was isolated and shown to react with Na/Hg to give 240, thus suggesting that 7r-complexes may play a role in the formation of dw complexes of larger cycloalkynes2 36 82 and, possibly, cyclic allenes (Section IV)82 where trapping of the free intermediate had often been presumed. 

It is also possible to prove the occurrence of cycloheptyne (IS) and cyclohexyne (20) in solution. Here, as in the isolation of very reactive cycloalkynes, it is essential to generate the intermediate in a fast reaction at low temperatures in the absence of a reactive reagent which could add to the cycloalkyne. Again, an oxidative decomposition with lead tetraacetate, here of the corresponding 1-aminotriazoles (22) resp (27), is used for the generation of (16) and (20)14). 

In Tables 1 and 2 the methods of generation and experimental evidence for the intermediate occurrence of unstable cycloalkynes and methods of synthesis of isolable angle strained cycloalkynes, resp. are given. 

Table 1. Unstable Angle Strained Cycloalkyne Intermediates ...

In most cases reactivity in addition reactions to the triple bond increases with increasing angle deformation. For transient cycloalkynes comparative studies of the reactivity, e.g. competition experiments, are one of the few experimental methods to assess ring strain in these reactive intermediates. 

Although there is ample evidence for nucleophilic additions to benzyne la> and some other unstable angle strained cycloalkyne intermediates 15,27,31,205 207), only a few addition reactions to isolable angle strained cycloalkynes are known which can be classified as nucleophilic. Hydroxylamine and hydrazine add to (31) to yield the corresponding oxime and hydrazone, resp. 208). 

A reaction typical of angle strained cycloalkynes is the addition of CS2 leading to tetrathiafulvalenes 8,7° 85 87 102 65,107). The formation of the tetrathiafulvalenes is explained by the intermediate occurrence of the carbene (70), which has been trapped by reaction with methanol in the case of (10) and (31)85,219>. 

Curci et al. subjected cyclodecyne 125 to epoxidation with methyl(trifluoromethyl)dioxirane and observed a mixture (7 1) of m-bicyclo[5.3.0]decan-2-one 126 and m-bicyclo[4.4.0]decan-2-one 127, these products presumably arising via respective 1,5- and 1,6-transannular insertion pathways into the intermediate oxirene (Scheme 62) <1992TL7929, 1996CHEC-II(1)145>. Prior to this report, Concannon and Ciabattoni had observed the product profiles arising from the oxidation of several cycloalkynes with MCPBA (Table 18) <1973JA3284>. 

Inspection of molecular models reveals that cyclononyne should be slightly strained, while all smaller cycloalkynes should be strongly strained. In fact up to the present time, cycloheptyne is the smallest cycloalkyne to have been isolated -Since the reactivity of medium-sized cycloalkynes increases with decreasing ring size (see Section III), one may expect the formation of smaller cycloalkynes as highly reactive reaction intermediates. 

Decrease of the yields of adducts in various trapping reactions with decreasing ring size offers further support for the intermediate occurrence of cycloalkynes, since if the trapping reagent were to add to the intermediate precursor of the cycloalkyne, for instance 25 or 26, such a significant difference in product yield would not be expected. 

Trapping is usually a strong indication for the intermediacy of cycloalkyne, but adducts may be formed without their intermediate occurrence. Thus, the reaction of 1,2-dibromocyclobutene (27)- and 1,2-bromoacenaphthylene (29) with magnesium yielded the corresponding cycloalkyne adducts, 28 and 30, in 8% and 4% yield, respectively. However, it was shown that the reactions proceeded via addition of 16 to 27 and 29 followed by bromine elimination by magnesium to give 28 and 30. 

Owing to the rapid decomposition of the intermediate precursor of the unstable cycloalkyne, such as 26 or 27, kinetic investigations to confirm the intermediacy of cyclic acetylenes could not be performed. However, l-Iithio-2-bromocyclopentene (48) was found to be fairly stable at room temperature. The kinetic measurements indicate that 48 loses lithium bromide in a first-order reaction (k = 2 x lO" s at 20 °C in ether), and the Arrhenius energy of activation for this reaction was estimated... 

An alternative method whereby a fused-ring oxirene may be generated is the epoxidation of a cycloalkyne. Curci et al. have employed methyl(trifluoromethyl)dioxirane (TFD) toward that end, and obtained (215) and c -bicyclo[4.4.0]decan-2-one in ca. 7 1 ratio from cyclodecayne (213) <92TL7929>. These products obviously stem from stereoselective 1,5- and 1,6-transannular insertion pathways. The authors conclude that the products of cycloalkyne oxidations may arise directly from trapping of the oxirene intermediates by transannular hydrogen transfer, as shown in Scheme 46. 

Benzyne is another cycloalkyne that has been proposed as an intermediate for elimination-addition reactions ofbenzene. 

Stable platinum(O) complexes of a number of strained cycloalkyne and even aryne intermediates have also been reported [79]. Upon generating the [2.2]paracyclophane-l-yne by debromination of l,2-dibromo[2.2]para-cyclophane-l-ene (6) with sodium amalgam in the presence of Pt(PPh3)4 the platinum complex 122 was obtained. The compound is stable in air and its constitution has been confirmed by an X-ray crystal structure analysis [82]. 

The isolation and characterization of the complexes 119,121 and 122 makes the [2.2]paracyclophane-l-yne a likely intermediate in elimination reactions, but direct spectroscopic evidence for the free cycloalkyne would certainly be even more convincing. 

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