Natural product synthesis five-membered ring compounds

Five- and six-membered heterocycles, containing either a nitrogen or oxygen atom, and in particular pyrrolidine rings, are very important in natural products synthesis. There are many methods by which all these compounds may be synthesized and new routes to this target are constantly being sought. 

Organic molecules in which one carbon atom is common to two rings are called spirocyclic compounds. The simplest spirocyclic hydrocarbon is spiropentane, a product of laboratory synthesis. More complicated spirocyclic hydrocarbons not only have been synthesized but also have been isolated from natural sources. a-Alaskene, for example, occurs in the fragrant oil given off by the needles of the Alaskan yellow cedar one of its carbon atoms is common to both the srx-membered ring and the five-membered ring. 

A (trimethylsilyl)cyclopentene annulation method has been developed that leads to a regiocontrolled approach to the synthesis of five-membered rings/ Thus, it was shown that (trimethylsilyl)allenes could be persuaded to react at -78 C with unsaturated carbonyl compounds in the presence of titanium tetrachloride (Scheme 16). The methodology is presently being applied to polyquin-ane natural product synthesis. 

Targets with one Heteroatom Five-membered heterocycles with one heteroatom, such as pyrrolidine and tetrahydrofiiran skeletons, exist widely in numerous natural products and bioactive compounds. Therefore, intense efforts have been devoted to the synthesis of these five-membered ring systems. Among the various methods existing for the synthesis of chiral pyrrolidine and proline derivatives, few can match the synthetic potential of 1,3-DC reactions of azomethine ylides with alkenes [3]. Generally, azomethine yhdes are unstable species, so they are normally generated in situ and trapped by unsaturated bonds (Scheme 2.1) [2b]. 

Sultones are the internal esters of hydroxy sulfonic acids and are the sulfur analogs of lactones. Sultones are demanded scaffolds in medicinal chemistry research. Biological studies on sultones are mainly concerned with their toxicological, skin sensitization, and antiviral activities [20]. Sultones are synthetically useful heterocycles which can react with a variety of compounds to introduce the alkylsulfonic acid function and therefore used as sulfoalkylating agents [21]. There have been several new developments for the synthesis of sultones which have also been applied in the total synthesis of natural products. In recent years, the palladium-catalyzed direct arylation of several aromatics via a C-H bond activation using aryl halides has led to successes. An intramolecular version of this reaction has allowed the synthesis of several biaryls via the formation of five- to seven-membered rings. Thus, the sultones should be synthesized by C-H activation via two pathways (Scheme 4.14). 

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