Cyclizations ring-size selectivity

An equally high ring-size selectivity is observed in the cyclization of 1,4-diketones such as 282 (Scheme 2.109). Here again an intramolecular crotonic condensation may yield two products, containing either a three- or a five-membered ring. The reaction, however, invariably follows the latter pathway and serves as a reliable method to synthesize cyclopentenone derivatives. A similar reaction for 1,6-diketones, for example 283, ultimately yields acylcyclo-pentenones. The competing pathway leading to the cycloheptenone derivative is virtually blocked. 

Electrophilic cyclizations are useful for closure of a variety of oxygen-, nitrogen-, and sulfur-containing rings. The product structure depends on the ring size and the exo-endo selectivity. The most common cases are formation of five- and six-membered... 

Tandem radical additions have been used in the preparation of piperidines. Substituted nitrogen containing heterocycles with ring sizes ranging from 5-8 have been synthesized by radical methods [95JCS(P1)19]. Addition of sulfur radicals to 225 occurs selectively at the enamide portion followed by an intramolecular 6-exo cyclization to produce a diastereomeric mixture of 226 in good yield. 

The regioselectivity in diene addition reactions can also be influenced by ring strain effects in cyclization reactions. The regioselectivity is highly predictable in those cases, in which addition to the preferred diene center forms the preferred ring size. Thus, the cyclization of radical 15 proceeds readily to form the ct s-disubstituted cyclopentyhnethyl radical 16 with high selectivity. Similarly, cyclization of 17 affords exclusively bicyclic radical 18, in which the additional cyclopentane ring has been formed by addition to the terminal position of the butadiene subunit. This preference for 5-exo cyclizations onto dienes is not even dismpted by substiments at the C1 or C4 positions of the diene system, as seen for radical 19, which cyclizes to 20 (equation lO). This is in contrast to alkyl radical cyclizations to alkenes, in which major amounts of 6-endo cyclization is observed for 5-substituted systems. ... 

Another approach to the study of the cyclic units formed in these cyclopolymerizations is through the study of the radical cyclization reaction of selected model compounds. Thus, extensive studies have shown that the five-membered ring is predominant, while new evidence indicates that radical stability exerts a marked influence on the ring size. These conflicting aspects of cyclopolymerization have been discussed in detail by Butler(L7) he has pointed out that considerably more investigations will be necessary before definite conclusions can be drawn with respect to the ratio of five- to six-membered rings in the many cyclopolymers already synthesized, and a satisfactory explanation for these extensive variations from one system to another is available. 

Finally cyclization reactions can be noted as providing preferential ring-size regiospecificity for a number of these otherwise ambiguous substrates. All of the considerations are capable of mechanical application to the process of sequence selection, i.e., of eliminating sequences (step 5d) and so pruning the list offered, but without resorting to yield prediction. 

An examination of the data reported in the table indicates that excellent results can be obtained in most cases and that the nature of the nucleophile and the ring size of the formed heterocyclic compoimd have little influence on the facial selectivity observed. The last example reported in Table 4 refers to the interesting case of a 1,1-disubstituted alkene. The cyclization reaction proceeds with a good asymmetric induction to give a tetrasubstituted chiral carbon atom, which is not easily accessible by other methods [80]. 

Although a variety of reactions need to be catalyzed, a single gallium-modified zeotype catalyst is used in the aromatization process developed by BP and UOP. The aromatization unit is operated in conjunction with UOP s CCR system. Acidic sites catalyze dehydrogenation, oligomerization, and cyclization. The shape selectivity of the cavities promotes the cycli-zation reactions and limits the size of the rings. Reportedly, an improved, second generation Ga-MFI catalyst is employed in this process. 

For the common ring sizes (n = 5-7), the selected representative examples are subdivided into sections according to the specific (formal) cyclization mode those leading to larger cycles are summarized in a single paragraph. 

Selectivity in aldol cyclizations is influenced by carbonyl type and ring size. 

The effect of substitution on the aryl ring in this system was also studied by the same authors [140] (Scheme 67). The retention spiroacetals 268 were obtained under spontaneous cyclization conditions with good selectivity across most ring sizes, except for the electron-poor N02-substituted analogue. The selectivity could be completely reversed, in some cases, using the previously developed methanol-induced spirocyclization conditions to give the inversion spiroacetals 269 predominantly. 

The second group of saturated 5(47/)-oxazolones used as intermediates for polymer synthesis are the 2,2 -bis(oxazolones) with 2,2 -bis[4,4-dimethyl-5(47/)-oxazolone] 329 being the simplest member of the series (Fig. 7.33). These compounds, are prepared by cyclization of the corresponding bis(amino acids) and give a wide variety of polymers after ring opening with diamines, dialcohols or other nucleophiles. The physical chemical properties of these polymers depend on the nature of the substituents and the size of the chain. Some selected references describe representative examples. 

An equivalent reaction has been achieved via the treatment of hydroborated bisalkenes with alkaline silver nitrate solution (Table 1.4).22,23 This method has been used to synthesize a number of small and medium-size carbocyclic rings in moderate to good yield. The selectivity for terminal cyclization observed for 1,6-heptadiene and 1,7-octadiene indicates that, in these cases, hydroboration of each of the alkenes occurs independently to yield acyclic boranes. It has, however, been found that both cyclic and acyclic boranes react under these conditions to yield the ring-closed products (Scheme 1.3). 

The formation of bi- and tricyclic compounds by transannular photochemical cyclization of monocyclic reactants mostly follows special rules that are caused by the molecular rigidity, equilibria of ring conformers and distinct stereoelectronic effects and, therefore, will be discussed in a separate section. Naturally, it is no longer possible to strictly structure the reactions according to the size and the type of the ring and, furthermore, vastly different examples are known. Therefore, only some representative examples will be discussed in this section and the selection does not claim to be complete. 

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