Synthesis of Seven-Membered Rings

The [4 + 3]-cycloaddition is a commonly used method for the synthesis of seven-membered rings.9 Many of these reactions involve metals, principally in the role of a Lewis acid as exemplified in Equation (10). These Lewis acid-catalyzed [4 + 3]-cycloadditions have been reviewed by Rigby,62 Sarhan,63 Harmata,64,65 and Hoffmann,66 and will not be reviewed here due to the role of the metal as a Lewis acid. Several computational papers on this subject have also been published.67-71... 

The first metal-catalyzed [4 +2]-reaction of tethered dienes with 7r-systems was reported by Wender and Jenkins using alkynes initially as the two-carbon component.21 This study was based on the earlier observation by Wender and Ihle that in the [4 + 4]-cycloaddition of bis-dienes a competing side-reaction is the [4 + 2]-cycloaddition of the diene with a mono-ene portion of a second diene. The extension of this reaction to the synthesis of seven-membered rings by trapping the metallacycloheptadiene with CO, a formal [4 + 2 + l]-cycloaddition, has been shown in preliminary studies to be feasible. For example, tethered diene-yne 160 can be converted to cycloheptadienone 163 in an Rh(l)-catalyzed [4 + 2 + l]-reaction with CO, albeit the [4 + 2]- and [2 + 2 + l]-reaction products dominate (Equation (29)). The mechanistic scheme (Scheme 44) illustrates the possible metallacyclic intermediates leading to the observed products and provided the conceptual basis for the realization of three novel reaction types ([4 + 2], [2 + 2 + 1], and [4 + 2 + 1 ]).1... 

Metal-mediated and -catalyzed [3 + 2 + 2]-higher-order cycloaddition reactions have also proved to be viable and mechanistically novel methods for the synthesis of seven-membered rings. The reported [3 + 2 + 2]-cycloadditions of allyliridium (Equation (30)),139 -allylcobalt (Scheme 47),140 and allylmanganese (Equation (31 ))141 complexes with alkynes involve the reaction of preformed allylmetal complexes with two separate alkynes, leading to a cycloheptadiene-metal complex. 

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

Coquerel Y, Eilippini MH, Bensa D, Rodriguez J (2008) The MARDi cascade a Michael-initiated domino-multicomponent approach for the stereoselective synthesis of seven-membered rings. Chem Eur J 14 3078-3092... 

E. Alcazar, J. M. Pletcher, and F. E. McDonald, Synthesis of seven-membered ring glycals via endo-selective alkynol cyclo-isomerization, Org. Lett., 6 (2004) 3877-3880. 

Synthesis of Seven-Membered Rings with Four and More Heteroatoms 546... 

CONTENTS The Synthesis of Seven-Membered-Rings General Strategies and the Design and Development of a New Class of Cycloaddition Reactions, Paul A. Wender and Jennifer A. Love. Recent Advances in Diels -Alder Cycloadditions of 2-Pyrones, Benjamin T. Woodard and Gary H. Posner. The Inter- and Intramolecular [4 + 4] Photocycloaddition of 2-Pyridones and Its Application to Natural Product Synthesis, Scott McN. Sieburth. 3 + 4 Annulations Between Rhodi- J s... 

However, we are not surprised that an enolate ion is formed from a ketone in basic solution. The oxyallyl cation is much more surprising. How can we be convinced that it really is an intermediate There are several alternative ways to make the same intermediate. If basic nucleophiles such as the methoxide ion are avoided and reaction of zinc with an a,a -dibromoketone in a nonnucleophilic solvent like diglyme is used instead, the oxyallyl cation can be trapped in a Diels-Alder reaction. This is tile basis for a good synthesis of seven-membered rings. 

On the other hand, the intramolecular allenic PKR has allowed the efficient synthesis of seven membered rings. Mukai has synthesized bicy-clo[5.3.0]decenones (19) from allenynes 18, using several rhodium catalysts. The process tolerates hydroxy and silyloxy groups and generally reaches good yields (Scheme 7) [40,41],... 

Diazocarbonyl precursors of Rh(II) carbenoids proved to be of particular efficiency in the synthesis of seven-membered rings. Thus, thermocatalytic... 

Otherwise difficult to obtain using other methods. Hence, the scope of 4+3 cycloaddition reactions has been extended beyond the synthesis of seven-membered ring carbocycles. 

At the end of this section, it may be said that even though most five- and six-membered heterocyclic rings can now be readily prepared, the synthesis of seven-membered rings is not straightforward. 1,7-Cyclizations of conjugated 1,5-dipoles and related reactions may be a subject for more work in the future. 

The synthesis of seven-membered rings from furans and a,a -dibromoketones via oxyallyl intermediates is well known. It was reported that this reaction occurs quite easily when water is used as solvent <97TL8031>. In a study on the influence of steric and electronic effects on a function attached at C-2 of furans in the yield and diastereoselectivity of [4 + 3] cycloaddition reactions with oxyallyl cations it was found that in almost all cases a c/x-diastereospecificity and a high endo diastereoselectivity is obtained <97T11669>. A tandem Peterson olefination-[4 + 3] cycloaddition reaction with furans has been reported <97JOC1578 97TL386l>. For an intramolecular [4 -t- 3] cycloaddition see <97JOC6051>. The first asymmetric [4 + 3]... 

A further application of 1,3-dipolar additions to the synthesis of seven-membered rings is cycloaddition to the C=N double bond of 1,5-benzothiazepines. In an extension of their investigations into the cyclofunctionalisation of heterocyclic imine systems, Chimirri et al. have demonstrated that the cycloaddition of benzonitriloxide to 1,5-benzothiazepines affords 3a,4-dihydro-l-phenyl-5//-... 

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