Alkyne cyclooctyne

Dihydrazones can be oxidized to alkynes with O2 (CuCl as a catalyst), HgO, ° " FsCCOaAg and Pb(OAc)4 (Scheme 61). 1-Amino-1,2,3-triazoles, which are sometimes observed as by-products in the HgO oxidation of 1,2-dihydrazones, can be oxidized with Pb(OAc)4 to give alkynes. Cyclooctyne" has been prepared and cycloheptyne and cyclohexyne" have been generated by this method (Scheme 62). The 1-tosylamino-1,2,3-triazoles can also be used as educts for alkyne synthesis the anions are decomposed to yield the corresponding alkyne, N2 and toluenesulfmate (Scheme 63). ... 

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). 

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]. 

The endoperoxide transfers a sulfur atom to alkenes forming thiiranes (episulfides) the process is made more efficient in the presence of the tetraphenylporphyrinato cobalt(ll) complex <1996CC177>. With cyclic alkynes such as cyclooctyne, an interesting thiirenium ion intermediate could be observed <2002JA8316>. 

In a variation of the reactions in Scheme 44, Rudler has reported that the alkene which intercq)ts the vinyl carbene complex leading to cyclopropane products can be tethered onto the starting carbene complex.This was extensively studied for the reaction of the carbene complex (334) with a number of alkynes leading to bicycloheptanones of the type (336). ° This reaction is quite general (14 examples, 44-95%) and is regioselective with terminal alkynes, i.e. it occurs in the same sense that has been observed for the benzannuladon reaction (R = H in 336). Acetylene fails and cyclooctyne gives a reduced... 

The Huisgen [3+2] cycloaddition between azides and alkynes is another bioorthognal ligation reaction for incorporation of probes into protein and peptide scaffolds. Two variants of this reaction have been developed using either copper(I) [218] or strained cyclooctyne molecules [219] to promote the reaction. As with the Staudinger ligation this method has found extensive use in protein and peptide labeling studies. 

The formation of the allene, sometimes a serious complication in alkyne synthesis, is not a problem in this case, because 1,2-cyclooctadiene, once formed, dimerizes readily and can therefore be easily removed from cyclooctyne by distillation. 

A wide range of 3,3-disubstituted cyclopropenes, e.g. the dimethyl and diphenyl derivatives, as well as spiro[2.4]hept-l-ene or 6,6-dimethyl-4,8-dioxaspiro[2.5]oct-l-ene, can thus be reacted with a variety of mono- and disubstituted alkynes. Usually, the chemoselectivity of this cy-clocotrimerization reaction is remarkably high. The norcaradiene derivatives initially obtained are in equilibrium with the valence tautomeric cycloheptatrienes. The equilibrium ratio of the valence tautomers is strongly dependent on the position and kind of substituents, especially those in the 7-position of the newly formed norcaradienes and cycloheptatrienes. When one or two phenyl groups are present in this position, only norcaradiene products can be detected by and NMR spectroscopy at room temperature, whereas in the case of methyl substituents, both valence tautomers are formed in almost equal amounts. When cyclic alkynes, such as cyclooctyne, are employed in the reaction, only norcaradienes are formed regardless of the substituents present in the cyclopropene cosubstrate. ... 

The 1,3-diiodo compounds can be transformed into 1,3-dialkyl derivatives by alkylations using AIR3. In a corresponding reaction with cyclooctyne instead of the alkynes mentioned above, a bicyclic system is generated in 84% yield (Equation (9)) <94ZN(B)3I5>. 

Cycloaddition of thiophene 1,1-dioxides with alkynic dienophiles leads to the formation of benzene derivatives with elimination of sulfur dioxide. Thus, the unstable parent thiophene 1,1-dioxide 1 reacts with diethyl acetylenedicar-boxylate and cyclooctyne to give diethyl phthalate and benzocyclooctene, although in low yields (Scheme 53) [132, 175]. Cycloadditions with alkenic and alkynic dienophiles had been used as evidence for the generation of 1 until spectroscopic evidence became available [46]. Tetrachlorothiophene dioxide 53 reacts with phenylacetylene [35] and a cyclic alkyne 92 [176] to give 1,2,3,4-tetrachloro-5-phenylbenzene and compound 93, respectively (Scheme 54). 

Adducts of the marginally stable cyclooctyne and cyclooctenyne with the Pt[PPh3l2 [48] and - Co2(CO)5 [49, 50] fragments have been prepared by direct complexation. Reaction of 1,2-dibromocycloalkenes with sodium amalgam in the presence of Pt(PPh3)3 has produced complexes 27-29 of the unisolable cycloheptyne, cyclohexyne [51], and even cyclopentyne [47] (Scheme 4-10) the free alkynes apparently are not intermediates in these reactions. 

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