Synthesis of seven-membered carbocycle

Two strategies are available for the synthesis of seven-membered carbocycles starting with methylenecyclopropanes ... 

Furans in synthesis of seven-membered carbocycles 84AG29. 

The present [3 + 4] annulation methodology for the synthesis of seven-membered carbocycles involves a straightforward procedure that also provides the product functionalities (e.g., masked and unmasked ketone carbonyl and trimethylsilyl groups) that can be transformed to hitherto inaccessible or difficult-to-prepare cycloheptane structures. The prior approach,7-9 based on Cope rearrangement of cis-1,2-divinylcyclopropane, bears an intrinsic drawback in that there exist a limited number of methods for stereoselective preparation of the substrate. 

Transition Metal Catalyzed Synthesis of Seven-Membered Carbocyclic Rings... 

As we have described recently, the possibilities for the synthesis of pharmacologically important molecules from monoterpenes obtained from essential oils are enormous, but we will not repeat this discussion here [36]. However, specific examples of the use of monoterpenes for the synthesis of seven-membered carbocyclic natural products will be included in the following section. 

Ovaska TV, Sullivan JA, Ovaska SI, Winegrad JB, Fair JD (2009) Asymmetric Synthesis of Seven-Membered Carbocyclic Rings via a Sequential Oxyanionic 5- xo-Dig Cyclization/ Claisen Rearrangement Process. Total Synthesis of (-)-Frondosin B. Org Lett 11 2715... 

Scheme 18.3) [3], The GaCb-catalyzed reaction was employed in the synthesis of seven-membered carbocycles. For example, the same reaction of 6-aryl-l-hexyne with a GaCls catalyst afforded dihydrobenzocycloheptenes in good yield. 

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. 

Aggarawa and co-workers applied their strategy for the synthesis of five- and six- membered ring carbocyclic silyl enol ethers to the the synthesis of seven-membered ring carbocyclic silyl enol ether bearing a phenyl substituent. Substrate 230 required upward of 20 mol % of 4 in refluxing benzene to achieve modest yields of the desired product 231. 

Singh and co-workers applied their methodology for the synthesis of embellished spiro-fused bicyclo[2.2.2]octane systems to the synthesis of seven-membered ring carbocyclic derivatives. Treatment of diene 299 with 10 mol % of 3 in dichloromethane gave the corresponding spirocyclic carbocycle 300 in 86% yield. 

The cobalt-catalyzed cooligomerization of diynes with nitriles allows a simple one-step synthesis222 of condensed pyridine derivatives including difficultly accessible 5,6,7,8-tetrahydroisoquinolines223 The synthesis is a versatile one in that pyridines condensed with five- and seven-membered carbocyclic rings can also be achieved in moderate yield in similar fashion. Additional attractive features of this simple synthesis are the formation of condensed isoquinolines by the use of functionalized nitriles and the pronounced regioselectivity observed when dissymmetrical diacetylenes are employed (Scheme 148).222... 

A variety of functionalities, tether lengths, and alkene substitution patterns were tolerated (Equation (35)).52,53 Of particular significance is the synthesis of a-methylene-y-butyrolactone 55, as only Zhang had reported successfully using Alder-ene chemistry to gain access to this novel system (see Section 10.12.4.3). The reaction was sensitive to the length of the tether, since there was a marked decrease in yield for the formation of the six- and seven-membered carbocycles (53 and 54, respectively) compared to the five-membered case 52. 

Synthesis of 2-amino-4H-pyrans, annulated with five- 201 to seven-membered carbocycles... 

A RCM-ROM-RCM strategy was employed as the key step to the synthesis of these alkaloids (Scheme 10). Both alkaloids can be derived from the protected bis-hydropyrrole 31 which is the ring rearranged product from the seven-membered carbocycle 32. Compound 32 can be obtained from the enantiomerically pure triol derivative 33, which in turn can be obtained from commercially available tropone 34.34... 

The functionalized oxazofine fused with the seven-membered carbocycle 36 has been found to be a key precursor for the synthesis of calystegines (Scheme 4). It has been obtained from methyl a-D-glucopyranoside (29) by conversion to 30 in 65% overall yield. Compound 30 was oxidized, and reacted with Ph3P=CHC02Et to give the ethyleiuc ester... 

Another example from the Spanish authors [14, 35] is especially interesting, as the cycloaddition leads to the formation of a compound with a seven-membered ring (Scheme 9). The literature shows that in recent years a tremendous amount of effort has been expended in trying to prepare carbocyclic five-membered rings by a route as simple and elegant as the Diels-Alder reaction for the synthesis of six-membered rings. [4c] Is a counterpart for... 

The synthesis of natural products containing seven-membered carbocycles is a healthy and rapidly growing area of research, as can be testified by the increasing number of publications that have appeared in this century. It can readily be envisioned that the presence of a seven-membered ring will now be treated in the same fashion that six-membered rings have always been appraised, and that combinations of the most common ring sizes will encounter domino solutions. 

Shibasaki and co-workers used a ring-closing metathesis approach to prepare a number of five-, six-, and seven-membered rings from electron-deficient olefins. Treatment of acyclic enol ether 18 with 7 mol % of 3 in refluxing benzene provided the corresponding cyclic enol ether 19 in 94% yield. Deprotection of the silyl ether 19 (not shown) resulted in the corresponding cyclic ketone, a valuable synthetic intermediate in natural products synthesis and a number of industrial processes. The authors reported additional examples of the synthesis of five-membered ring carbocycles as part of this study. 

The iron carbonyl-promoted cyclocoupling reaction of polybromo-ketones and unsaturated substrates provides a powerful tool for the synthesis of five- and seven-membered carbocycles. The intramolecular version of this reaction has now been reported for the synthesis of polycyclic terpenes. Reaction of the dibromo-ketone (54), obtained from geraniol, with [Fe2(CO)9] in benzene under pressure gives, in 70% yield, a Cio fraction, the major component (54%) of which is camphor. The other major component (20%) is dihydrocarvone (56). Other cyclic terpenes can be synthesized by similar reactions. 

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