Cyclooctyne

Apparatus 1-1 round-bottomed, three-necked flask with a dropping funnel, a mechanical stirrer and a thermometer, combined with a vent, for the addition of bromine and the dehydrobromination to 1-bromocyclooctene 1-1 flask (see Fig. 1) for the preparation of cyclooctyne. 

Cycloaddition with cyclooctyne proceeds in a similar manner, but in this case the initial cycloadduct corresponding to 2 is isolable in 25 % yield. 

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... 

The behavior of the Si—P 7r-bond toward a G=C triple bond was examined in the case of 15a by employing differently substituted alkynes.14 It appeared that 15a does not react with dialkyl, diaryl-, or disilyl-substi-tuted alkynes at 110°C even cyclooctyne, usually a very reactive alkyne, does not react. However, when 15a was stirred with phenylacetylene at 80°C in toluene, the C—H insertion product 24 was isolated as colorless crystals (Eq. 9).14 Its molecular structure has been elucidated by singlecrystal X-ray diffraction (Fig. 9). 

Figure 17.16 Cyclooctyne derivatives can be used as alternative click chemistry reactants, as they are capable of reacting with an azide group without the presence of Cu1+ to form a cycloaddition product. This reaction proceeds at a slower rate than the Cu1+-catalyzed process, but it avoids the cytotoxic effects that copper addition can have on cells.

Due to molecular strain, cyclooctyne is a very reactive species. Its reactions with azides proceed rapidly even at room temperature making it a convenient tool for probing structures of unstable azides. Thus, the reaction of cyclooctyne with diazide 1061 carried out in GH2CI2 at room temperature is accomplished within 2h and provides ditriazolyl derivative 1060 in 76% yield. A similar reaction of cyclooctyne with diazide 1062 leads to ditriazolyl derivative 1063 in 90% yield (Scheme 175) <2005T8904>. 

Cyclic stannanes can be generated by reaction of stannylenes with alkynes112. For example, bis[bis(trimethylsilyl)methyl]tin reacts with cyclooctyne to provide A1,18-9,10-(distanna-9,9,10,10-tetrakis[bis(trimethylsilyl)methyl])bicyclo[6,2,0]-decene, 69. This reaction is a typical oxidative addition on stannylenes. 

Reaction of cyclooctyne with (I2B)2CHMe formed a 4,5-cyclooctadiiododiborole, which was methylated with AlMe3 and the product treated with nickel or cobalt reagents to give complexes of type 26.31... 

Other ROMPs include the polymerizations of 1,3,5,7-cyclooctatetraene and cyclooctyne ... 

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. 

Cyclooctyne has a reasonable thermostability. It can be stored for at least one month at -20 C with only slight polymerization. 

Cyclooctyne has a very strong, unpleasant odour. The odour of the aqueous layers disappears upon shaking with a small amouni of bromine. 

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

Dichlorocyclooctane Cyclooctyne 1,2.Cyclooctadiene (major) (minor), an allene... 

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