Synthetic methods ring expansion

Although the merits of the synthetic method described in the preceding section are apparent, the limited applicability of this method prompted the search for alternative synthetic routes. During our work in this field we have found that a well known ring expansion via a carbene intermediate 45) does indeed proceed remarkably well with a variety of precursors. 

A sequential process of carbopalladation and ring expansion of allenylcyclobuta-nols provides five-membered rings (Scheme 16.19) [24], The intramolecular version of this approach offers a facile synthetic method for 5,7- and 5,8-fused ring frameworks (Scheme 16.20) [24]. 

Abstract Development in the field of transition metal-catalyzed carbonylation of epoxides is reviewed. The reaction is an efficient method to synthesize a wide range of / -hydroxy carbonyl compounds such as small synthetic synthons and polymeric materials. The reaction modes featured in this chapter are ring-expansion carbonylation, alternating copolymerization, formylation, alkoxycarbonylation, and aminocarbonylation. 

H-Azepines are more rare than 1H- or 3H-azepines and only a few synthetic approaches have been developed. Of these the two main methods involve the ring expansion of six-membered heterocycles. Early studies revealed that highly substituted 4f/-azepines (269) result from the base-catalyzed ring expansion of 4-(chloromethyl)-l,4-dihydro-pyridines (267 Scheme 37). The reaction was found to be temperature and solvent sensitive, and azepines (268)-(270) have been isolated and characterized. However, later studies (68JCS(C)1675) on cyano derivatives (267 E = CN) show the reaction to be even more... 

After many years of investigation a great number of quinuclidine derivatives have been synthesized. Synthetic methods described in the literature for the preparation of quinuclidine and its derivatives and methods for building up quinuclidine bicyclic systems are separated in this review from those for substituent introduction into preformed quinuclidine rings. Reactions involving quinuclidine ring expansion with formation of derivatives of other 1-azabicycloalkanes are gathered into a special section. 

If the moeity adding to the aryne carries a suitably placed electrophilic center, cyclization with the initially formed anion can occur as observed in the synthesis of dibenzothiophene (60).92 Of wider synthetic import in this context is enolate addition to arynes. Here, after the initial ring closure many types of products can be formed (Scheme ll).35 However, with some substrates, a particular reaction course can predominate 93 94 for example, reaction of cyclodecanone with bromobenzene provides an efficient method for benzo-annulation and ring expansion. Similarly, high yields of benzocyclobutenols can be obtained from the monoketals of ot-diketones.9s... 

This homologous Baeyer-Villiger type oxidative ring expansion represents a conceptually new protocol illustrating the substantial value of one-pot, four-component annulations as a flexible and simple new synthetic method. 

All the optically active terpenes mentioned in this chapter are commercially available in bulk (>kg) quantities and are fairly inexpensive. Although many of them are isolated from natural sources, they can also be produced economically by synthetic methods. Actually, two thirds of these monoterpenes sold in the market today are manufactured by synthetic or semi-synthetic routes. These optically active molecules usually possess simple carbocyclic rings with one or two stereo-genic centers and have modest functionality for convenient structural manipulations. These unique features render them attractive as chiral pool materials for synthesis of optically active fine chemicals or pharmaceuticals. Industrial applications of these terpenes as chiral auxiliaries, chiral synthons, and chiral reagents have increased significantly in recent years. The expansion of the chiral pool into terpenes will continue with the increase in complexity and chirality of new drug candidates in the research and development pipeline of pharmaceutical companies. 

The Eschenmoser fragmentation does not have to be a ring expansion, and it is a useful synthetic method for making keto-alkynes. The following reaction, which we will use to discuss the fragmentation s mechanism, was used to make an intermediate in the synthesis of an insect pheromone, exo-brevicoinin. 

Three highly useful synthetic transformations are presented in this section the synthesis of isoflavones from chalcones, the synthesis of a-arylalkanones fmm arylalkenes, and the synthesis of a-arylalkanoic acids from aryl ketones. Two others are potentially useful methods, but are not as yet widely used the preparation of a-branched carboxylic acids from a ynes, and the ring expansion and ring contraction of cyclic alkenes and ketones. 

In summary then, the oxyanion-accelerated rearrangement of 2-vinylcyclobutanol derivatives is now established as an attractive method for achieving two-carbon ring expansion under relatively mild conditions. In conjunction with the efficient synthetic routes to vinylcyclobutanones outlined in Scheme 21, this version of the VCB rearrangement provides several strategically novel annulation methods for the construction of six-membered carbocycles. ... 

An improved method of thermal ring expansion employs silyl enol ethers as starting materials. The synthetic sequence begins with a cycloalkanone which is converted, via dihalo-cyclopropanation of the silyl enol ether, to a dihalo-1-trimethylsiloxybicyclo[n. 1.0]alkane. Thermolysis of the latter in refluxing benzene affords ring-expanded 2-halocycloalken-2-ones, after elimination of halotrimethylsilane. Alternatively, the same product can be obtained by treatment of the dihalo-l-(trimethylsiloxy)bicyclo[n. 1,0]alkane with hydrochloric acid at room temperature (Table 4).3°.3i... 

There are several significant preparative procedures for dioxazines, oxathiazines and diathiazines that are based on transformation of other heterocyclic systems. Most, but not all, involve ring expansion of five- or, less frequently, four-membered systems. The synthetic methods employed in the preparation of the precursor heterocycles are not covered in this section as they are dealt with in the appropriate chapters elsewhere in this edition. 

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