Diynes, tandem cycloadditions

In previous works this group had observed a competition between the PKR and a [2 + 2 + 2] cyclization in the second reaction step of three triple bonds. Thus, when reacting linear triynes 174 under catalytic, high CO pressure, cobalt mediated PKR conditions, they obtained mixtures of products 175 coming from two [2 + 2 + 1] cycloadditions, and 176 from a [2 + 2 + 1]/ [2 + 2 + 2] tandem reaction. When the triple bonds were ether linked, the latter was the favored reaction, while with substrates lacking oxygen atoms, the iterative PKRs was the major pathway (Scheme 51) [166]. When the reaction was performed intramolecularly between a diyne and an alkyne, the only reaction products were the result of a [2 + 2 + 1 ]/[2 + 2 + 2] tandem cycloaddition [167,168]. 

Itoh and coworkers111 carried out tandem [2 + 2 + 2]/[4 + 2] cycloadditions catalyzed by a ruthenium catalyst. The reaction of diyne 147 with excess norbomene 148 in the presence of ruthenium catalyst 153, for example, afforded 149. Adduct 150 either dissociated from the catalyst or reacted with another equivalent of norbornene. In the latter case, a ruthenium catalyzed Diels-Alder reaction occurred, affording hexacyclic adduct 152 via 151 (equation 43). Compounds 150 and 152 were obtained in yields of 78% and 10%, respectively. Both cycloaddition reactions proceeded with complete stereoselectivity. When 1,6-heptadiyne was used instead of 147, only trace amounts of a cycloadduct were obtained. Replacing norbornene by norbornadiene, which was expected to result in polymer formation, did not afford any adduct at all. 

Scheme 54 Cycloaddition of diynes with dienes in the synthesis of triquinanes. Tandem [2 + 2 + l]/[4 + 2] cycloadditions...

It is also worthy of note that the construction of tetracyclic compounds 44 by cobalt-catalyzed tandem Pauson-Khand/[2 + 2 + 2] cycloaddition reactions of 1,6-diynes 43 was also reported by Chung et al. [45,46]. It was experimentally shown that the [2 + 2 + 2] cycloaddition reaction occurs after the [2 + 2 + 1] cycloaddition between CO and the substrate (Scheme 22). 

Intramolecular Reaction of 1,6-Dienes, -Enynes, and -Diynes Cycloisomerization, Tandem Addition-Cyclization, and Cycloaddition... 

Scheme 15. Synthesis of Heterocycles from 1,6-Dienes, Enynes, and Diynes via (a) Cycloisomerization, (b) Tandem Addition—Cyclization, and (c) Cycloaddition...

As 1,/2-alkenes, 1,6-derivatives are used very frequently leading to five-membered heterocycles, while the use of 1,7-derivatives, which produce six-mem-bered heterocycles, is very rare. The reactions of 1,6-dienes, -enynes, and -diynes are classified into three groups (a) cycloisomerization, (b) tandem addition— cyclization, and (c) cycloaddition, such as the Pau-son—Khand reaction, cyclotrimerization, and the Diels—Alder reaction (Scheme 15).97 In these reactions five-membered heterocycles are constructed upon the carbon—carbon bond-forming processes. 

Triazole Derivatives. Triazole derivatives are known to possess tumor necrosis factor-a (TNF-a) production inhibitor activity. The synthesis of triazole derivatives can be achieved from alkynes or diynes by a tandem cascade reaction involving 1,3-dipolar cycloaddition, anionic cyclization and sigmatropic rearrangement on reaction with sodium azide. Some of the benzoyl triazole derivatives were considered to be potent local anaesthetics and are comparable with Lidocaine. The triazoles can also be prepared from benzoyl acetylenes,triazoloquina-zoline derivatives, 2-trifluoromethyl chromones, aliphatic alkynes, 2-nitroazobenzenes, ring opening of [ 1,2,4]triazolo [5,1-c] [2,4]benzothiazepin-10 (5//)-one, alkenyl esters and dendrimers. A number of these reactions are outlined in eqs 44 8. 

The highly chemoselective and stereoselective tandem Pauson-Khand/4 + 2-cycloaddition of the diene-diyne substrate (3) produced the spirotricyclic core analogue (4) of the sesquiterpene polyol, mangicol (Scheme 2)J... 

The Co2(CO)8-catalysed tandem 2- -2- -1/2- -2-f 2-cycloaddition reaction of terminal diynes (180) provides a simple one-pot synthesis of novel tetracyclic compounds (181) (Scheme 69). A computational study of the thermal nl + ct2 -I- a 2-cycloaddition of quadricyclane with acetylene, ethylene, DCE, and DMAD... 

Various cyclohexadienes can be obtained through the rhodium-catalyzed cyclotrimerization of 1,6-diynes with alkenes [12] or 1,6-enynes with alkynes [13], Valorization of these cyclohexadienes was reported with the development of original tandem [2-I-2-I-2] cycloaddition/[4-l-2] Diels-Alder cascades. For example, Tanaka and coworkers recently achieved the construction of bridged polycyclic lactam products, by performing a [2-1-2-1-2] cycloaddition/[4-l-2] Diels-Alder cascade between... 

The Huisgen azide-alkyne 1,3-dipolar cycloaddition (AAC) [75] and later developed Cu-catalyzed azide-alkyne cycloadditions (CuAAC) [76-80], which are the most commonly utilized methods for the synthesis of N-substituted 1,2,3-triazoles, will not covered here. Very recently, Bi and co-workers [81] developed an elegant silver-catalyzed tandem hydroazidation/alkyne-azide cycloaddition of diynes with TMSN3 providing an easy access to 1,5-fused 1,2,3-triazole frameworks [82, 83]. 

The ruthenium-catalyzed cycloaddition of 1,6-diynes to 1,3-dienes forming 1,3,5-cyclooctatrienes and vinylcyclohexadienes can formally be assigned to [4+2+2] cycloaddition. This reaction is actually a tandem process catalyzed by Ru(II) resulted in the formation of Z-tetraenes or vinyl-Z-trienes, followed by the ring closure in pure thermal conrotatory Sir- or disrotatory 6ir-electrocyclization processes, respectively (Scheme 2.88 and Table 2.13) [141]. 

---