Unimolecular cyclization

Based on a unimolecular cyclization rate constant of 5 x 105s" 1 for A5-hexenyl radical at 318 K (cf. Reference 34). 

The overall reactivities of these radicals in their ummolecular 5-hexenyl cyclization processes reflects those same factors which affect the reactivity of partially-fluorinated radicals in their bimolecular addition reactions with alkenes, such as styrene. Table 17 indicates this clearly, and it also reflects the general leveling effect which would be expected for the more facile unimolecular cyclization processes which have log A s about 1-2 units larger than those for the bimolecular additions. 

Our earlier studies of the bimolecular alkene addition reactivity of a,a-difluoro alkyl radicals indicated that they exhibited little philicity , reacting with styrene and pentafluorostyrene (IPs 8.43 and 9.20, respectively) at virtually the same rate [70]. Their significantly greater reactivity in bimolecular additions, hydrogen-abstraction reactions and unimolecular cyclizations can therefore be largely attributed to their pyramidal nature, with some possible thermodynamic con-... 

The proposed mechanism for this reaction involves the initial coordination of styrene oxide to Tbt(Tip)Sn=Se followed by nucleophilic attack of a second Tbt(Tip)Sn=Se molecule on the less substituted carbon with the formation of cis- and trans-195. Alternatively, the unimolecular cyclization of the initial styrene oxide-Tbt(Tip)Sn=Se complex leads to the formation of compound 196 as a minor product (Scheme 10). 

Unimolecular cyclizations essentially deal with the synthesis of purine-fused diazocines and the corresponding aza- or deaza-analogues. Such cyclizations occur very often with good yields. Other ring constmctions reported are generally... 

Among the unimolecular cyclizations, the synthesis yielding a single product with excellent yields was the cyclization of allyloxy alcohols brought about by a ruthenium complex. The other unimolecular processes exhibited very low yields and/or mixture of products. The most popular synthesis of 1,3-dioxocins involved the cyclization of 1,5-alcohols with the insertion of a carbon unit. Such acetalization of both acyclic dialcohols or hydroxyl groups bound to rings is particularly efficient and the cyclization of methane-diphenols or dihydroxybenzophenones with dihalomethanes was of wide applications. Palladium-promoted cyclization of chloromercurio compounds showed to be certainly less effective even if it presented some cases in reasonable yields. The sole example synthesis of 1,3-dioxocins by transformation of another ring has no preparative interest. 

In Scheme 139, three examples of unimolecular cyclization leading to uncondensed dioxocins by nucleophilic attack of an hydroxyl group at a carbonyl, a masked carbonyl or a carboxy acid are reported. 2-Hydroxy-l,5-dioxocin 708 was accidentally obtained in the attempt to oxidize the ether diol 707 to the corresponding dialdehyde derivative. Rather, oxidation occurred at one end of the molecule followed by intramolecular hemiacetal formation to yield 708 <2003JOC9166>. 

Unimolecular cyclizations involving C-N bond formation include intramolecular alkylations and acylations were applied for a variety of azocines, while macrocyclic O-alkylations and ketalizations are the most reliable methods for oxocine core synthesis through C-O bond formation. Other types of unimolecular cyclizations are scarce and erratic, and they usually depend on stereochemistry of the open-chain precursors and require tuning of the functional groups involved. 

Unimolecular cyclization is an important method of heteronine ring system formation. It is reviewed in this section in the order of the bond types formed. Taking into account the synthetic value of the RCM strategy and its extensive development over recent years, it is excluded from general discussion of C-C bond-formation reactions in Section... 

Polymer molecular weights were lower than those obtained by bulk polymerization. This might have been expected, rapid initiation and favouring of cyclization over chain extension would be consequences of the low dielectric constant of the solvent. As well as energetic considerations, the rate of chain extension, a bimolecular process, will be influenced more by reduced monomer concentration than unimolecular cyclization. Despite an increased rate of formation of cyclics, a termination reaction here, the lower stability of zwitterions in this solvent results in faster polymerization rates. 

The thermal unimolecular cyclization of 3-diazoalkenes to pyrazoles appears to be an intramolecular 1,3-dipolar cycloaddition and the first-order rate coefficients of four substituted // art5-3-diazo-l-phenylpropenes fit the Hammett equation (p = — 0.40). The small value of p, indicating a lack of sensitivity of the cyclization rate to the electronic nature of the substituents supports the belief that the reaction involves a synchronous, cyclic electron shift. Table 11 lists the measured rate coefficients. 

In 1965, the American chemists Robert B. Woodward (1917-1979, 1965 Nobel laureate in Chemistry) and Roald HofEcnann (1937-, 1981 Nobel laureate in Chemistry) (ref. 151), well aware of the stereospecificity of many unimolecular cyclization reactions of open conjugated molecules, e.g. cis-1,3-butadiene, developed a vast application of frontier orbitals to this and similar types of reactions. 

Most of the unimolecular cyclizations discussed in this section can be treated as syntheses of... 

These results indicate that the rate of polymerization is higher at lower conversions than the rate of 1,4-dioxane formation from the polymer. At certain conversions, i.e. at a certain polymerization degree, these rates become equal to each other and only the formation of 1,4-dioxane is observed. This is illustrated in Scheme (4-9) as a competition between bimolecular growth and unimolecular cyclization. Depletion of monomer decreases the rate of propagation, however, the rate of cyclization remains invariant. 

A simple example of the formation of a six-membered ring by unimolecular cyclization is provided by an alternative synthesis of the chloride of compound (93) from the pyrrolidine (95) (Equation (39)) <44JOC359>, while bimolecular reaction of piperidine (96) gives the diazoniadispiro derivative (4) (Equation (40)) <65JOC82l>. A seven-membered ring can be formed if the stereochemistry of the starting material is suitable, as in compound (97) (Equation (41)) <63JOC2843> there is no obvious reason for the difference in yield between pyrrolidine and piperidine derivatives. 

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