1-octyne 1 + 2 4- 2 cycloaddition

Cycloadditions with ynamines proceed readily at room temperature in carbon tetrachloride solution to yield a-pyrones (106) <77S252>. Likewise, a-pyrones (107) are also formed with cyclo-octyne <83TL1481>, whereas with benzyne the a-benzopyrone (108), produced initially, enters into a second [4 + 2] cycloaddition with benzyne to give ultimately the 9,10-disubstituted anthracene (109) (Scheme 12) <77S252>. 

Although stoichiometric amounts of transition metal complexes were employed, the cross-[2+2+2] cycloaddition of three different alkynes has been achieved using zirconium and nickel complexes. The reaction of 2-butyne, 4-octyne, and Cp ZrEt selectively afforded unsymmetrical zirconacyclopentadiene. Subsequently, it reacted with 3-hexyne in the presence of NiBr fPPhjlj to give the desired hexasubstituted benzene (Scheme 21.6) [9]. 

With Ni° as a catalyst, an intermolecular [4+2] cycloaddition [45] reaction with cyclobutanone 52 and 4-octyne 53a produced cyclohexenone 54a in 95% yield. The proposed reaction mechanism is illustrated in Scheme 9. Presumably the reaction of 52 and 53a with Ni° would proceed through oxidative cyclization to give oxanicke-lacyclopentene (55). P-C elimination cleaves the cyclobutane ring to generate 56 and leads to formation of product 54a after reductive elimination. Overall, a formal [4+2] cycloaddition was accomplished with Ni° via p-C elimination. In contrast, Rh was not an effective catalyst for this transformation. 

Here, the [2 + 2 + 2] cycloaddition of alkenyl isocyanate 202 and 1-octyne was promoted efficiently by the rhodium/(/ )-203 catalyst to give indolizinone 204 in 59% yield (91% ee). Thereafter, a highly diastereoselective hydrogenation followed by Barton-McCombie deoxygenation provided (—)-209D (205). Considering that... 

In 2011, Nakai et al. found that acyclic compounds also participated in cycloaddition through carbon-carbon bond activation (Scheme 12.22). Reaction of o-arylcarboxybenzonitrile 56 and 4-octyne in the presence of a nickel catalyst, prepared in situ from Ni(cod)2 and PMes, and MAD in toluene at 120 °C for 12 h resulted in the formation of coumarin 58 in 80% yield. Sequential inter- and intramolecular carbon-carbon cleavage in the presence of a nickel catalyst has been used to construct flve-membered oxanickelacycle 57, which reacts with alkynes to furnish cycloadducts [27]. Detailed observations revealed that the catalytic reaction proceeded with the elimination of aryl cyanide. A similar sequence has been utilized for the synthesis of quinolone derivative 59 (Scheme 12.23). These reaction outcomes suggest an unusual mechanistic aspect cleavage of two independent C—CN and C—CO bonds via the formation of a heteronickelacycle intermediate. 

Nickel-catalyzed [4 + 2] cycloaddition using C—H bond activation was also developed by Nakao et al. (Scheme 12.27) [31], Formamide 66 reacted with 4-octyne in the presence of nickel catalyst gave substituted dihydropyridone 67 in good yield. Shiota et al. reported that chelation-assisted C—H bond activation enables [4 + 2] cycloaddition of amide 68 with alkynes to provide isoquinolone (Scheme 12.28) [32]. The key azanickelacycle intermediate 69 was generated in situ via N—H bond and C—H bond activation with chelation assistance by a 2-pyridinylmethylamine moiety. 

In 2011, Yoshida, Fukutani, and co-workers reported the first example of a nickel-catalyzed N—O/C—H bond cleavage tandem process for the constmction of isoquinolines with the cycloaddition of aromatic (O-benzyl)ketoximes and alkynes via elimination of benzyl alcohol (Scheme 12.31) [35,36]. The process does not require an external oxidant. The cycloaddition of 6>-benzylketoxime 73 and 4-octyne was treated in the presence of a nickel catalyst, which was prepared in sim from Ni(cod)2 and DPPF in toluene at 110 °C for 6 h, and isoquinoline 75 was obtained in 80% isolated yield. 

Kurahashi and Matsubara have used an isocyanate as both a nitrogen source and CO equivalent in a [24-2+1] cycloaddition to give 3-pyrrolin-2-ones (Scheme 110 2010CC8055). Mixing methyl acrylate (415), 2-octyne (416), and phenyl isocyanate (417) with a Ni catalyst and carbene hgand gives a 5 1 mixture of the 3-pyrrolin-2-ones 418 and 419, respectively. 

A [4 + 2] cycloaddition reaction of the strained cyclo-octyne (14) with substituted furans was used by Tochtermann and Weidner for the preparation of 7,7-disubstituted 7-lactones of type 16. The initial cycloadducts 15 were subjected to a sequence of reduction/oxidation to arrive at the desired lactone 16 (Scheme 13.6) [17]. 

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