Polycyclization Reactions

Polycyclization reactions involving attack on an aromatic ring by unstabilized carbon-centered radicals in the last step have also been described by Pines and by Walling  

In the same way the vinylic analog of 411 at low tributylstannane concoi-tration affords a mixture of exo- and endo-2-methylnorbomane (71%) as the result of a double 1,5-cyclization in a Cy5/Cy6 case. The obtainment of good yields of bicyclic compounds from radicals such as 411 results from the stereoselective initial cyclization to the cis radical 412 as expected from the behavior of 3-substituted 5-hexenyl radicals, while the corresponding 2-substituted 3-hexenyl radicals, cyclizing as they do mainly to the tram radicals, give poor yields of bicyclic compounds.  

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A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

Intramolecular reaction can be used for polycyclization reaction[275]. In the so-called Pd-catalyzed cascade carbopalladation of the polyalkenyne 392, the first step is the oxidative addition to alkenyl iodide. Then the intramolecular alkyne insertion takes place twice, followed by the alkene insertion twice. The last step is the elimination of/3-hydrogen. In this way, the steroid skeleton 393 is constructed from the linear diynetriene 392(276]. 

The stage is now set for the crucial polycyclization event. Tertiary carbinol 8, derived from the action of methyllithium on enone 9, is a rather unstable substance, and it was submitted to the polycyclization reaction without purification. When intermediate 8 is treated with trifluoroacetic acid (TFA) and the vinyl cation trapping agent ethylene carbonate in 1,2-dichloroethane at 0°C, the desired... 

Polycyclization reactions to give polymers possessing heterocyclic fragments 92UK1864. 

An application of the RCM strategy features polycyclization reactions, wherein for instance the substrate 176 could be converted in good yield into the 3-pyrroline trimer 177 using the catalyst 178 (Equation 55) <1998JOC4291>. 

Exercise 8-11 Propose a stepwise mechanism for the polycyclization reaction shown in... 

Porphyrins and phthalocyanines are representative examples of cyclic ligands and their metal complexes. They are prepared either by polycyclization reactions of bifunctional/higher-functional ligand precursors or polyreactions of bifunctional/higher-functional porphyrins and phthalocyanines. 

A difTerent approach to polycyclization reactions has been reported with acetylenic compounds such as 421 (Scheme ISO). By stannane reduction one obtains compound 425 in low yield. The reaction involves formation of the radical 422, which cyclizes to the (Cy 5) radical, which then gives 423, and this, on further reduction, gives 424, which cyclizes to the (Cy S ) radical and finally gives 425. 

C. Polycyclization Reactions Involving Addition to a Polar Bond... 

The first step of a polycyclization reaction involving free radical addition to the oxygen atom of a carbonyl group has been described in Section X.l.B.b, Scheme 83. The second step proposed involved cyclization of the radical 190 to the (Cy 4) radical in a Cy4/Cy5 case. According to the discussion in Section V.2.B, this is unlikely and, in fact, this proposal was later rejected. 

In the meantime, other intramolecular additions were studied, which afforded new preparative methods and which are probably involved in biogenetic schemes. Much less is known at this time of the scope and the quantitative aspect of these reactions. Among the many problems not satisfactorily solved at this time one may cite the origin of the stereospecificity observed in mono- and polycyclization reactions, the scope of polycyclizations reactions and of intramolecular additions to acetylenic and polar bonds, a better knowledge of intramolecular additions of heteroatomic radicals and radicals bearing heteroatoms in the chain, and the limits of the cyclization processes applied to higher homologs than the Cy5/Cy6 case. 

This approach has been extended to the enantioselective construction of multiple C—C bonds and contiguous stereocenters. In this way, an oxidative organocatalytic polycyclization reaction of suitable functionalized aldehydes such as 127 afforded di- to hexacyclization products in good yields and useful enantioselectivities (Eq. 9.26) [102] ... 

Similar shifts occur in polycyclics (reaction 38) and another type of transannular interaction is responsible for the loss of all... 

Furthermore, Jacobsen s group reported the development of a new thiourea catalyst for the enantioselective bicycliza-tion of hydroxylactams [54]. The enantioselective cationic polycyclization reactions catalyzed by bifunctional thiourea derivatives appear to engage stabilizing jt-cadon interactions as a principal element of enantioselectivity (Scheme 9.41). 

The anion-binding thiourea catalysis was applied further in asymmetric polycyclization of hydroxylactam derivatives 296 (Scheme 2.81). It was found that larger aromatic groups on the pyrrolidine ring of thiomea catalyst produced better results in terms of reactivity and enantioselectivity. The 4-pyrenyl-substituted thiourea 289c was found to be an optimal catalyst to promote polycyclization reactions which involved stabilizing cation-ji interactions to indnce the enantioselectivity [112]. 

Formation of cationic T -dienyliron complexes by proton addition to (Ti -diene)iron complexes with an additional conjugated double bond can also be applied to acyclic systems. Monocyclization and polycyclization reactions proceed by nucleophilic addition of pendent double bonds to the complexes. " - " ... 

Zuercher WJ, Scholl M, Grubbs RH. Ruthenium-catalyzed polycyclization reactions. J. Org. Chem. 1998 63 4291-4298. 

Koh JH, Gagn6 MR (2004) Pd(II)- and Pt(U)-mediated polycyclization reactions of 1,5-and 1,6-dienes evidence in support of carbocation intermediates. Angew Chem Int Ed Engl 43 3459-3461... 

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