Approaches to Seven-Membered Rings

In this chapter we provide an overview of studies originating from the above work and directed at the design and development of three new metal-catalyzed cycloaddition reactions, namely the [5+2] cycloaddition of vinylcyclopropanes (VCPs) and rc-systems, the [6+2] cycloaddition of vinylcyclobutanones and re-systems, and the three-component, [5+2+1] cycloaddition of VCPs, rc-systems, and CO. These new reactions provide fundamentally new approaches to a range of problems in seven- and eight-membered ring synthesis. 

Complementing these purely thermal processes, transition metal-catalyzed reactions have also been used for the synthesis of seven-membered rings. For example, palla- 

Design of a Transition Metal-Catalyzed [5-t2] Cycioaddition of Vinylcyciopropanes and 7r-Systems 

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Two approaches to seven-membered rings have been realized with the aid of transition metal catalysts ... 

Research by Dowd illustrates another approach to seven-membered rings based on expansion of a cyclobutanone (Eq. 23) mediated by... 

Figure 2. Cycloaddition approaches to seven-membered ring synthesis that are isoelectronic with the Diels-Alder reaction.

Stryker recently reported a metal-catalyzed [3+2+2] cycloaddition leading to a seven-membered ring (Eq. 51)7 This is a fundamentally new development in this area and suggests that multicomponent approaches to seven-membered rings akin to those developed for five-and six-membered rings (e.g., Pauson-Khand, [2+2+2]) are on the horizon. 

In a related study, Evans et al. (88S862) introduced a useful approach for the synthesis of three- to seven-membered ring iodo ethers generally... 

A New Improved Synthesis of Tricycle Thienobenzazepines Apphcation of chemistry recently developed by Knochel" combined with the well-described halogen dance (HD) reaction, allowed preparation of our key intermediate A in only three synthetic transformations (Scheme 6.4). In this respect, treatment of 2-bromo-5-methylthiophene with hthium diisopropylamide followed by dimethylformamide afforded aldehyde 11 in good yield, lodo-magnesium exchange with conunercial 4-iodo-3-nitro anisole followed by reaction with 11 afforded the thiophene catbinol 12. Dehydroxylation of 12 provided our key intermediate A which presented the requisite functionality to examine our approach to the construction of the seven-member ring system. 

Heterocyclic seven-membered ring systems are present in various natural and synthetic bioactive compounds and pharmaceuticals. Therefore, the development of new approaches to these heterocycles with total regio- and stereocontrol is of great importance to both medicinal and synthetic chemists, and still constitutes an exciting synthetic challenge. For this purpose, we recently invented a base-induced... 

A flexible approach to the synthesis of substituted benzazepines 403 was devised (equation 166). As before, the seven-membered ring was made by the use of a ring-expansion reaction and exclusive migration of the aromatic ring was observed. 

The intramolecular nitrone cyclization approach has been used to produce cycloadducts containing a central seven-membered ring in a manner analogous to that described in Section 10.21.9.3.2(ii) <1996T11265>. 

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