Cyclooctyne ring

The smallest unstrained cyclic triple bond is found in cyclononyne. Cyclooctyne has been isolated," but its heat of hydrogenation shows that it is considerably strained. There have been a few compounds isolated with triple bonds in seven-membered rings. 3,3,7,7-Tetramethylcycloheptyne (lOS) dimerizes within 1 h at room temperature,but the thia derivative 106, in which the C—S bonds are longer than the corresponding C—C bonds in 105, is indefinitely stable even at 140°C. ° Cycloheptyne itself has not been isolated, though its transient existence... 

Cycloadditions with other symmetrical acetylenes were carried out by using thiocarbonyl (5)-methylide (69) (159). Interestingly, no reaction was observed when acetylene dicarboxamide was used. The reaction of 69 with cyclooctyne resulted in the formation of cycloadduct 103 (Scheme 5.38). Interestingly, the spirocyclic 2,5-dihydrothiophenes of type 103 or 104 undergo acid-catalyzed ring opening upon treatment with silica gel or trifluoroacetic acid to give thiophenes 105 and 106, respectively. 

Problem 15.40 Show steps in the synthesis of cyclooctyne, the smallest ring with a triple bond, from C.H,OOC(CH,),COOC,H, ... 

The Cg ring in 172 has undergone dehydrogenation to form a cyclooctyne ligand that coordinates to a cluster face in the analogous bonding mode to that observed in the alkyne clusters 75-82. 

Cycloalkynes display a deshielding with increasingly strained rings, as reported for a series of cyclooctynes [250] an outstanding alkyne carbon shift is found in cyclooctadie-nyne. 

Coordination to alkynes distorts the triple bond character nearer to that of a double bond, decreasing the linearity. Utilization of the coordination effect makes it feasible to prepare cyclic alkynes whose synthesis is difficult to achieve. Highly strained cyclooctyne can be prepared by coordination. As an example, starting from (R)-pulegone, three of the four rings of the epoxydictymene skeleton 152 were constructed by the consecutive Lewis acid-promoted Nicholas reaction of allylic silane 149 to form 150, and the intramolecular Pauson-Khand reaction of 151. The total synthesis of (+)-epoxydictymene 153 from 152 has been achieved [38]. 

Since the Schrock carbyne is active in the transalkylidynation reaction, the possibility of ring-opening polymerisation of cycloalkynes by acetylene transalkylidynation catalysts (metal alkylidyne complexes) has been evaluated [151]. Unfortunately, cyclooctyne is one of the few relatively stable strained cyclic acetylenes, but it is not strained enough to react selectively with the catalyst and yield a polymer according to the scheme... 

Alkyncs can be prepared through the use of two basic procedures. Before these procedures are presented, it should be noted (hat the smallest ring in which an acetylene linkage is stable at room temperature for an extended period of time is cyclooctyne. 

The most important influence on the isolability is the ring size, i.e. the number of atoms in the ring. Cyclononyne (6) and cyclooctyne (14) are isolable compounds, but... 

Introduction of additional unsaturation in cyclooctyne leads to increasing ring strain and reactivity depending on the relative position and the number of double bonds, as is shown in the following scheme106,144). 

In the benzoannellated compounds two opposing effects on isolability are to be expected. Annellation of a benzene ring to cyclooctyne should increase ring strain as does introduction of an additional double bond. On the other hand, the size of the benzene ring should, like a bulky substituent, impede oligomerization reactions and thereby kinetically stabilize the angle strained cycloalkyne. 

Cyclooctyne (14) and the dibenzoannellated system (45) possess only C2-symmetry ioo.ii8,t8s) an(j are therefore chiral molecules. Models suggest that ring strain should increase the barrier to racemization compared to unstrained compounds. 

However, (46) exhibits only 3 singlets in the -NMR-spectrum at +35 °C for methyl, a- and y-methylene groups, resp. At lower temperatures (—70 °C, 60 MHz) the expected splitting is observed and from the coalescence temperatures a value AG = 12 kcal/mole can be obtained for the inversion process. Thus, ring strain increases the barrier for inversion in the cyclooctyne system, but the increase is not sufficiently large to allow separation of enantiomers at or near room temperature. 

Cyclooctyne (14) adds bromine to give l,2-dibromo-cis-cyclooctene93) this is presently the only route to prepare a pure 1,2-dihalocyclooctene. The addition of bromine and iodine to (31) leads to the unexpected products (54) apparently trans-annular attack of the cationic intermediate (55) by the nucleophilic sulfur produces a strained sulfonium ion which stabilizes itself by ring opening to (54)201). 

Phenylazide has often been used to trap unstable cycloalkynes 1S18 2S 62> and to characterize angle strained cycloalkynes 18,89). The addition of suitable diazoalkanes to cyclooctyne (14) was applied as the first step in the synthesis of threemembered ring spirenes 223,224>. 

Like trans cycloalkenes, cycloalkynes with small rings are unstable. The carbon chain must be long enough to connect the two ends of the triple bond without introducing too much strain. Cyclooctyne is the smallest isolated cycloalkyne, though it decomposes upon standing at room temperature after a short time. 

The enthalpies of hydrogenation of some medium-ring acetylenes to the corresponding cycloalkanes are summarized in Table 3 It has been suggested that the result for cyclooctyne (69-1 kcal/mole) may be somewhat in error. Cyclooctyne,... 

The medium-ring acetylenes show typical C C stretching vibration - at ca. 2210 cm. The fairly strong band in cyclooctyne in the same region suggests that an angle strain at the triple bond would render the C=C rtretching vibration more unsymmetric. This fact indicates that, in spite of an appreciable strain, the essential character of acetylenic bond is preserved in cyclooctyne. 

It was anticipated that 5,6-didehydro-l l,12-dihydrodibenzo[a.e]cyclooctene (85), having a large ring strain, should be less stable than cyclooctyne. However, 85 obtained from the dibromo compound 84 on treatment with potassium f-butoxide and n-methylpiperidine was found to be stable". 85a could be kept without... 

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