Carbocyclic ring-closing metathesis

Evans and Kennedy later combined the regioselective rhodium-catalyzed allylic alkylation, using a-substituted malonates, with ring-closing metathesis for the construction of five-, six-, and seven-membered carbocycles (Scheme 10.2) [13]. The combination of these methodologies allowed for the rapid and flexible assembly of carbocycles possessing vicinal ternary-quaternary or quaternary-quaternary stereogenic centers. 

Scheme 10.2 The allylic alkylation/ring-closing metathesis approach to vicinally substituted carbocycles.

S.S. Salim, R.K. Bellingham, V. Satcharoen, R.C.D. Brown, Synthesis of heterocyclic and carbocyclic fluoro-olefins by ring-closing metathesis, Org. Lett. 5 (2003) 3403-3406. 

A common procedure used to forge carbocyclic systems is represented by the ring-closing metathesis reactions exploiting various Grubbs-type carbene catalysts. Based on this cyclization technology, Skaanderup and Madsen [71], on the way to polyhydroxy-nortropane calystegines, reported the asymmetric synthesis of aminated 6a-carbahexoseptanose derivatives 311. 

Quite recently, Marco-Contelles [73] has made use of free radical cyclization and ring-closing metathesis in order to develop useful synthetic protocols to access a number of chiral non-racemic, densely oxygenated medium-sized carbocycles from carbohydrate precursors. 

Ring-closing metathesis (RCM), a powerful method used to synthesize carbocycles, has been used for preparing 4a-carba-furanosides. An example is shown in Scheme 8.26, starting from D-mannose, which was transformed into the alkene 93 via the protected hemiacetal 92. The hydroxyl of 93 was then oxidized, and the ketone was transformed into diene 94 through a second... 

Synthesis of carbocyclic systems intramolecular free-radical cyclization, the Diels-Alder reaction, and ring-closing metathesis... 

Carbohydrates have been starting materials for the synthesis of functionalized carbocycles for a long time [47 9]. More recently, ring-closing metathesis... 

M. T. Crimmins, B. W. King, W. J. Zuercher, and A. L. Choy, An efficient general asymmetric synthesis of carbocyclic nucleosides application of an asymmetric aldol/ring-closing metathesis strategy, J. Org. Chem., 65 (2000) 8499-8509. 

Many other types of heterocyclic and carbocyclic ring systems, with different substitution patterns, can be prepared by using ring-closing metathesis. Metathesis catalysts are also effective for ring-opening metathesis polymerization (ROMP), in which cyclic alkenes can be polymerized. 

There have been several reports of the use of ring-closing metathesis applied to sugar-derived compounds for the preparation of cycloheptene and cyclooctene derivatives. The mannose-derived dienes 42 (R = H, Ac) were converted in high yields to the carbocycles 43 using Grubbs ruthenium-based catalyst, and the... 

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. 

Davies and co-workers also applied a ring-closing metathesis strategy in their preparation of constrained p-amino acid derivatives. Their work employed a chiral auxiliary, S -(l-phenyl-ethyl)-carbamic acid benzyl ester, to achieve the desired P-amino acid derivatives in a stereoselective fashion. Treatment of diene precursors 46 and 48 with 4 mol % of 3 in refluxing dichloromethane provided the corresponding carbocyclic P-amino acid derivatives 47 and 49 in 85 and 35% yield, respectively, with greater than 95% diastereoselectivity in both cases. The diminished yield in the case of 49 is presumably due to sterics effects. 

Martin and co-workers applied a ring-closing metathesis strategy in the synthesis of medium-size carbocycles fused to butyrolactones/ Fused butyrolactones are ubiquitous in nature and play an important role in the... 

A number of research groups have used ring-closing metathesis to prepare conformationally constrained a- and P-amino acids containing six-membered ring carbocycles. Several key examples are discussed in the paragraphs below. 

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