Cyclotrimerization regioselectivity

The metathesis of ene-ynamides has been investigated by Mori et al. and Hsung et al. [80]. Second-generation ruthenium catalysts and elevated temperatures were required to obtain preparatively useful yields. Witulski et al. published a highly regioselective cyclotrimerization of 1,6-diynes such as 98 and terminal alkynes using the first-generation ruthenium metathesis catalyst 9... 

A few further general examples of zinc catalytic activity or reactivity include the following. Other zinc-containing systems include a zinc phenoxide/nickel(0) catalytic system that can be used to carry out the chemo- and regioselective cyclotrimerization of monoynes.934 Zinc homoenolates have been used as novel nucleophiles in acylation and addition reactions and shown to have general utility.935,936 Iron/zinc species have been used in the oxidation of hydrocarbons, and the selectivity and conditions examined.362 There are implications for the mechanism of metal-catalyzed iodosylbenzene reactions with olefins from the observation that zinc triflate and a dizinc complex catalyze these reactions.937... 

Witulski introduced a novel protocol for crossed alkyne cyclotrimerizations of systems such as 87 mediated by Grubb s catalyst to produce 4,6-disubstituted indolines 88 <00CC1965>. Interestingly, use of Wilkinson s catalyst [RhCl(PPhj)3] allows for the regioselective synthesis of the corresponding 4,5-substituted isomers. 

The rhodium-catalyzed cyclization/hydrosilylation of internal diyne proceeds efficiently with high stereoselectivity (Scheme 106). However, terminal diynes show low reactivity to rhodium cationic complexes. Tolerance of functionalities seems to be equivalent between the rhodium and platinum catalysts. The bulkiness of the hydrosilane used is very important for the regioselectivity of the rhodium-catalyzed cyclization/hydrosilylation. For example, less-hindered dimethylethylsilane gives disilylated diene without cyclization (resulting in the double hydrosilylation of the two alkynes), and /-butyldimethylsilane leads to the formation of cyclotrimerization compound. 

Ir-complexes also demonstrate catalyhc achvity in the intermolecular [2+2+2] cycloaddition of three monoalkynes, when Takeuchi examined the mixed cyclotrimerization of two alkynes. In this situation the choice of ligand was shown to determine the excellent chemoselechvity for example, when the Ir-dppe complex was used, 2 1 cycloadducts of DM AD and mono- or disubstituted alkynes were obtained, but when Ir-F-dppe (l,2-bis[bis(pentafluorophenyl)phosphino]eth ane) one was used, a 1 2 cycloadduct of DMAD and l,4-dimethoxybut-2-yne was obtained (Schemes 11.7 and 11.8) [15]. A regioselective cyclotrimerizahon of three alkynes was achieved by [lrH(cod)(dppm)] (bis(diphenylphosphino)methane), and 1,2,4-triarylbenzenes were obtained exclusively (Scheme 11.9) [16]. 

Transition metal-catalyzed intermolecular [2 + 2 + 2] cyclotrimerization of alkynes to benzene derivatives has been extensively studied. In this section, the focus is on the cyclo-trimerizations of the substrates bearing three independent unsaturated bond components. The key issue with this type of process usually involves the challenge of controlling regioselectivity [1—1]. However, 1,3,5-trisubstituted benzene 44 can be obtained as the sole product in good yield when 3-butyn-2-one 43 is used as the substrate for the cyclotrimerization catalyzed by Rh2(pfb)4 (pfb=perfluorobutyrate) in the presence of EtsSiH under a CO atmosphere (Eq. 11) [30]. 

It is possible to carry out the [2+2+2] cyclotrimerization reaction in a regioselective manner by using a partially or completely intramolecular approach. Rhodium-catalyzed intramolecular cyclotrimerization of 1,6,11-triynes, which construct fused 5-6-5 ring-systems, has been studied extensively [33-36]. Cyclization of 1,6,11-triyne 47 catalyzed by RhCl(PPh3)3, gives the tricyclic benzene 48 in good yield (Eq. 14) [33a]. 

Intermolecular cyclotrimerization of alkynes using Wilkinson s catalyst has also afforded substituted carbazole derivatives. This reaction was extended to an intramolecular version by offering the possibility for a six-membered ring annotation that cannot be achieved easily in the corresponding intermolecular version. Intramolecular cyclotrimerization is completely regioselective due to an additional tether. 

Cyclotrimerization of acetylenes to form benzene derivatives is studied intensively mainly because of the challenge of chemo- and regioselectivities. A regiose-lective and highly chemoselective method for preparing substituted benzenes was described via PdCl2-catalyzed cyclotrimerization in the presence of CuCl2 537... 

Control of the regioselectivity in Co-catalysed cross-cyclization has been solved in an ingenious way utilizing 1,5-hexadiyne (116) as one component and bis(trimethyl-silyl)acetylene (118) as the other. Although bulky bis(trimethylsilyl)acetylene (118) itself cannot cyclotrimerize to hexasilylbenzene due to steric hindrance, it reacts with the cobaltacyclopentadiene 117 formed from the less bulky diyne 116 to produce the... 

The 1,3-diyne 160 undergoes an interesting regioselective cyclotrimerization to afford unsymmetrically 1,3,5-substituted benzene 162. In this reaction the enetriyne 161 is formed at first by the Pd-catalysed dimerization of 160, and the reaction... 

Again, with the help of spectral analyses, the hyperbranched structures of the poly(aroylarylene)s were confirmed. Thanks to the 1,3,5-regioselectivity of the cyclotrimerization reaction, the NMR spectra of the hb-PAAs were... 

Diederich and co-workers have synthesized a triscluster complex 47 of the unusual Cjg molecule via oxidative cyclotrimerization of the hexatriyne complex 48 (Scheme 4-17) [72]. The cyclocoupling efficiency benefits from the bent geometry of the coordinated triyne (a = 138°). Other noteworthy features include (1) the regioselective complexation of the silylated triyne (2) efficient desilylation of the complexed triyne. 

The use of precursors of asymmetrically substituted arynes introduces the question of regioselectivity, since two products of cyclotrimerization are possible. However, the cyclotrimerization of asymmetrically substituted aryne 2, generated from 3-methoxy-2-(trimethylsilyl)phenyl triflate (64), proceeds in good yield and with high regioselectivity, affording a 93 7 mixture of regioiso-mers 65 and 66 (Scheme 14) [39]. 

Regarding the regioselectivity of the cyclotrimerization of the asymmetrically substituted aryne 2, further experimental work and/or calculations are needed to find a rational explanation. It is not a trivial problem. If the cyclotrimerization of 2 proceeds via the mechanism of Scheme 15, intermediates 69,70 and 71 might be formed (Scheme 16). All three can be transformed into 65, but 66 can only be formed from 69. 

Scheme 35) [70]. As in the cyclotrimerizations of arynes, there is no clear explanation for the regioselectivity of this reaction. 

Yokota et al. reported quantitative cyclotrimerization of symmetrie internal alkynes using a complieated eatalyst system of Pd(II)/chlorohydroquinone/NPMoV under oxygen [54]. In addition, regiocontrol to produce a single isomer is one problem inherent in cyclotrimerization of substituted alkynes, and many attempts to achieve regioselective cyclization have been carried out with partial success. 

The 1,3,5-unsymmetrically substituted benzene 224 was prepared in 64% yield by intermolecular cyclotrimerization of 1,3-decadiyne (223). The reaction was surprisingly regioselective to give 224 as a single product [68]. 

Another type of benzannulation, which might be related to the benzannulation of conjugated enynes, is the Pd-catalyzed cyclotrimerization of 1,3-diynes (Scheme 1,3-Diynes cyclotrimerize in the presence of a Pd catalyst to give 1,3.5-trisubstituted benzene derivatives. In this reaction, too, the regioselectivity is perfectly controlled as shown in Scheme 4, and other products were never isolated. The reaction of various diynes is summarized in Table 7. Some functional groups such as olefins and ether linkages may be present in the side chain. An example for the cross-cyclotrimerization of a diyne and an aUcyne has also been reported (Scheme... 

Transition-metal-catalyzed intermolecular [2+2+2] cyclotrimerization of alkynes to benzenes has been extensively studied with several catalyst systems involving palladium, cobalt, nickel, rhodium, and other transition metals. This methodology can be applied to the preparation of polysubstituted benzenes. The major challenge of this transformation is control of regioselectivity of unsymmetrical alkynes, particularly in the cross-cyclotrimerization of two or three alkynes. 

In 1996, Garcia et al. reported cyclotrimerization of (trifluoromethyl)acetylene 390a using a bimetallic rhodium complex at room temperature to afford l,3,5-/ra (trifluoromethyl) benzene 391 in high yield (Scheme 2-33). Recently, Tanaka et al. reported a chemoselective and regioselective intermolecular cross-cyclotrimerization of two different alkynes using a cationic Rh complex as catalyst (Scheme 2-34). ° ... 

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