Cycloalkynes

Thermal electrocyclizations of perhalogenated 1,3-butadienes yield perhalogenated cyclobutenes which can be solvolysed to 3,4-dihydroxy-3-cydobutene-l,2-dione ( squaric acid") and its derivatives (G. Maahs, 1966 H. Knorr, 1978 A.H. Schmidt, 1978). Double CO extrusion from fused cyclobutenediones has been used to produce cycloalkynes, e.g., benzyne from benzocyclobutenedione by irradiation in an argon matrix (O.L. Chapman, 1973) and cyc/o-Ci8, cyclo-Cn, etc. by laser desorption mass spectroscopy of appropriate precursors (see section 4.9.8). 

The reduction of medium-size cycloalkynes, however, always yields considerable amounts of the less strained cis-cycloalkenes (A.C. Cope, 1960 A M. Svoboda, 1965). Cyclo-decyne, for example, is reduced almost exclusively to cis-cyclodecene. 

MolTmann, R. W. 1967, Dehydrobenzene and Cycloalkynes, Verlag Chemie Weinheim, Ger. and Academic Press New York London... 

Because of the linear geometry required of cumulated dienes cyclic allenes like cycloalkynes are strained unless the rings are fairly large 1 2 Cyclononadiene is the smallest cyclic allene that is sufficiently stable to be isolated and stored conveniently... 

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... 

R. W. Hofl nann, Dehydrobenzene and Cycloalkynes, Academic Press, New brk, 1967. 

In spite of the fact that few cycloalkynes occur naturally, they gained recent attention when it was discovered that some of them hold promise as anticancer drugs. (See the boxed essay Natural and Designed Enediyne Antibiotics following this section.)... 

Cycloalkyne (Section 9.4) A cyclic hydrocarbon characterized by a triple bond between two of the ring carbons. 

Alicyclic Hydrocarbons. These refer to cyclic analogues of aliphatic hydrocarbons and are named accordingly, using the piefix cyclo-." Their properties are similar to their open-chain aliphatic counterparts. Alicyclic hydrocarbons are subdivided into monocyclic (cycloalkanes, cycloalkenes, cycloalkynes, cycloalkadienes, etc.) and polycyclic aliphatic compounds. Monocyclic aliphatic structures having more than 30 carbon atoms in the ring are known, but those containing 5 or 6 carbon atoms are more commonly found in nature [47, p. 28]. 

Cycloalkynes. These structures have one triple bond in the carbon ring, as shown in the following example ... 

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. 

In a more recent and improved approach to cyclopropa-radicicol (228) [ 110], also outlined in Scheme 48, the synthesis was achieved via ynolide 231 which was transformed to the stable cobalt complex 232. RCM of 232 mediated by catalyst C led to cyclization product 233 as a 2 1 mixture of isomers in 57% yield. Oxidative removal of cobalt from this mixture followed by cycloaddition of the resulting cycloalkyne 234 with the cyclic diene 235 led to the benzofused macrolactone 236, which was converted to cyclopropa-radicicol (228). 

This type of alkyne dimerization is also catalyzed by certain nickel complexes, as well as other catalysts and has been carried out internally to convert diynes to large-ring cycloalkynes with an exocyclic double bond. ... 

Scheme 23 Stereospecific [2+2] cycloaddition reaction of a benzyne 3.2.2 Reactions of Cycloalkynes...

Friedel-Crafts reaction remains unexplored, possibly due to the difficulty of the cycloalkyne formation. A mild, versatile, and efficient method for the one-step synthesis of substituted dihydro- and tetrahydroisoquinolines has been developed by the FeCl3-6H20-catalyzed intramolecular allenylation/cyclization reaction of benzylamino-substituted propargylic alcohols, representing the first example of the intramolecular Friedel-Crafts reaction of propargylic alcohols (Scheme 8) [24, 25]. FeCls, InCls, and Yb(OTf)3 also exhibit good catalytic activity for the reaction. 

Hoffmann, R. W. Dehydrobenzene and Cycloalkynes. Weinheim Verlag Chemie, G.m.b.H. New York Academic Press 1967. 

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