Cycloadditions seven-membered ring synthesis

Scheme 13.5 Representative thermal cycloadditions for seven-membered ring synthesis.

V. CYCLOADDITION STRATEGIES FOR SEVEN-MEMBERED RING SYNTHESIS... 

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

As an extension of his studies in the field of the skeletal rearrangement and cycloaddition involving carbon monoxide, Wender reported a new method for seven-membered ring synthesis through a carbonylative ring-expansion reaction of allenylcyclobutanes as a formal [6-H] cycloaddition (Scheme 8.12) [27]. The reaction is believed to proceed through the formation of rhodacycloheptene followed by CO insertion and reductive elimination of the metal species. 

The metal-catalyzed [5 + 2]-cycloaddition reaction of VCPs and 7t-systems provides a new concept for seven-membered ring construction that has been significantly advanced over the last decade in the areas of catalyst development, chemo-, diastereo-, and enantioselectivity, substrate scope, and applications to total synthesis. 

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. 

Monocyclic carbasugars. The 1,3-dipolar cycloaddition was used in the synthesis of polyhydroxylated compound with the seven-membered ring (Fig. 16).29... 

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. 

In a novel total synthesis of the tricyclic sesquiterpene (—)-longifolene, an intramolecular diazoalkane cycloaddition to a cyclohexadienone ring followed by thermal ring contraction of the resulting pyrazoline gave the tricychc vinylcyclo-propane 261 and this constitutes the key steps in this synthesis (314) (Scheme 8.63). The interesting features of this sequence are the separation of dipole and dipolarophile by five atoms and the formation of a seven-membered ring in the cycloaddition step. 

Another example is compound 214, which imitates the trombin-bound structure of the fibrin peptide A, and is an inhibitor of this protease. The first step of this synthesis, Scheme 63, involves opening of 208 to the seven-membered ring compound 209. Subsequent acylation with 210 to form 211 is followed by an intramolecular oxidative cycloaddition to provide tricyclic lactam 212. Nucleophilic ring opening proceeds readily with glycine methyl ester to afford lactam 213 in 88% yield, which was transformed into 214 using solid-phase protocols [161]. 

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... 

Irradiation of tetramethylcyclobutanedione (16) in furan gives an 8-oxabicyclo[3.2.1]oct-6-en-3-one derivative via oxyallyl cation (17). This reaction is the first example of the cycloaddition of cyclopropanones. Although the syntheses of a few seven-membered ring compounds have been subsequently carried out by means of this photoreaction, interest in cyclopropanone chemistry has been directed to structure and reactivity relationships, but not to organic synthesis. ... 

Intermolecular meta cycloadditions provide yet another option for the facile [SC -i- 2C] construction of seven-membered rings, as illustrated in Srinivasan s pioneering studies (Scheme 24). The availability of simple arenes and alkenes and of numerous methods as discussed above for the modification of meta cycloadducts makes this a particularly effective stategy for cycloheptanoid synthesis. 

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