Synthesis of eight-membered carbocycle

Recognizing that intermediates in the [4 + 2]-reaction of dienes and alkynes could be intercepted with components in addition to CO as in the [4 + 2 + l]-reaction, Gilbertson and Evans independently published two new methods for the synthesis of eight-membered carbocycles involving [4 + 2 + 2]-cycloadditions. Saa and co-workers report a... 

A method for the synthesis of eight-membered carbocycles based on a new tandem tungsten-catalysed cycloisomerization-cyclopropanation reaction has been reported (Scheme 99).143 This is a catalytic reaction in which a heteroatom-stabilized Fischer... 

Scheme 16.65 Gold-mediated synthesis of eight-membered carbocycles.

Based on previous success in the Pauson-Khand reaction [43], Evans demonstrated a sequential approach to the synthesis of eight-membered rings, which involved a rhodium-catalyzed aUyhc amination reaction followed by carbocyclization, to effect a three-component couphng (Scheme 12.11). To date, this transformation is only the second example of a sequential rhodium-catalyzed reaction in which only temperature is used to modulate catalytic activity. 

Unlike carbocyclic and oxygen-containing heterocyclic systems, catalytic enantioselective synthesis of eight-membered ring amines proceeds efficiently and with excellent enantioselectivity. These catalytic ARCM reactions can be carried out in the absence of solvent as well. Representative data regarding cat-... 

The secondary marine metabolite (+)-acetoxycrenulide has unprecedented structural features which prompted L.A. Paquette et al. to embark on its total synthesis. The eight-membered carbocycle of the target was constructed via a Claisen rearrangement. The bicyclic p,y-unsaturated lactone was subjected to Simmons-Smith conditions, that delivered the cyclopropyl ring exclusively from the p-face of the molecule as a result of the predominant ground-state conformation. 

The Cope rearrangement is of great importance as a synthetic method e.g. for the construction of seven- and eight-membered carbocycles from 1,2-divinylcyclopropanes and 1,2-divinylcyclobutanes respectively (e.g. 11 12), and has found wide application in the synthesis of natural products. The second step of the para-Claisen rearrangement is also a Cope rearrangement reaction. 

Let s now consider concerted skeletal rearrangements which allow the direct transformation of a sugar structure into a carbocyde. The Claisen rearrangement has been used for the direct conversion of sugar C-glycosides to eight membered carbocycles, respectively. The reaction has precedents in the transformation of 2-methylene-6-vinyl-tetrahydropyrans to cyclooctenone derivatives, a transformation that has been applied in the synthesis of several natural products [54],... 

Vinylogous modes of this rearrangement are also possible. Complex systems can be attained by utilizing a built-in electrophile in an intramolecular ring expansion/alkylation, as shown in equation (35). This kind of cyclization is applicable to seven- and eight-membered carbocyclic ring synthesis and proceeds with approximately 12 1 stereoselectivity, which is due to the more stable, parallel conformation depicted in equation (35). ... 

In the laboratory of S.L. Schreiber, the total synthesis of (+)-epoxydictymene was accomplished by the tandem use of cobalt-mediated reactions as key steps. The eight-membered carbocycle was formed via a Nicholas reaction, while the five-membered ring was annulated by the Pauson-Khand reaction. Several P.-K. conditions were explored and the best diastereoselectivity was observed when NMO was used as a promoter. The annulated product was isolated as an 11 1 mixture of diastereomers. 

The next synthesis by Wender (Scheme 11.22) [29] is method-oriented. It demonstrates a metal-mediated 4 + 4 -cycloaddition to generate the eight-membered carbocycle. This renders the synthetie sequenee short, allowing the preparation of the cyclization precursor to use traditional steps of open-chain synthesis. Note that all branches are generated by bond-formation. 

Clark and co-workers used the olefin metathesis strategy pioneered by Rodriquez and co-workers for the synthesis of eight and nine-membered ring carbocycles, in their synthesis of the nine-membered carbocyclic core of a class of herbicidial nonadrides known as the comextins. Treatment of diene 381 with either catalytic 3 in refluxing dichloromethane, or 4 in... 

Yu s group reported the first Rh-catalyzed [7-1-1] cycloaddition of buta-1,3-dienylcyclopropanes and CO for the synthesis of cyclooctadienones (see (51)) [125], This reaction showed good compatibility with different functional groups, providing an efficient entry to the eight-membered carbocyclic rings. 

The foregoing methods have been successfully applied to the synthesis of carbocyclic cytochalasans and the macrolide methynolide (191 equation 22). Iterative ring expansion of the five- and eight-mem-bered ring sulfonium salts (187) and (189) leads to the 11-membered ring sulfur heterocycle (190). Sulfonium salt (189) is a 1 1 mixture of stereoisomers that gives (190) with 16 1 selectivity in 76% yield. 

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