Ring-closing metathesis strategy

A sophisticated exploitation of a ring closing metathesis strategy was delivered by Hanna (Eq. 5) [135] ... 

An elegant traceless linker variation on the ring-closing metathesis strategy resulted in the preparation of the tetrahydroazepine 201 from the immobilized diene 200, although the yield of 201 was only moderate (Equation 26) <1998EJ02583>. 

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. 

Ring-closing metathesis (RCM) has also been employed in the synthesis of substituted furans. Donohoe and co-workers used a ring-closing metathesis strategy to form the furan moiety of (-)-(Z)-deoxypukalide, a compound from the family cembranolides, which have been shown to exhibit neurotoxicity and anti-inflammatory properties. Treatment of a mixed acetal with Grubbs II catalyst, followed by in situ aromatization with PPTS, yielded the disubstituted furan in 85% yield over two steps. Seven additional steps were required to reach of (-)-(Z)-deoxypukalide. 

Application of Ring-Closing Metathesis Strategy to the Synthesis of Vaniprevir (MK-7009), a 20-Membered Macrocyclic HCV Protease Inhibitor... 

Application of Ring-Closing Metathesis Strategy to the Synthesis of Vaniprevir... 

Scheme 12 Synthesis of indoles using an isomerization/ring-closing metathesis strategy.

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. 

A ring-closing metathesis strategy was also employed by Srikrishna and workers in the first total synthesis of ( )-lagopodin A, a fungal sesquiterpene. The authors found the sterically congested 1-aryl-1,2,2-trimethylcyclopentane component especially challenging to construct. Olefin metathesis of heptadiene 64 in the presence of 5 mol % of 3 in... 

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... 

Clive and Liu used a ring-closing metathesis strategy to access the six-member ring carbocyclic components of the anticancer agent s ottelione A and Olefin metathesis of 158 or 160 with catalytic amount of 3 in the presence of dichloromethane provided the corresponding carbocycles 159 and 161 in 93 and 86% yields, respectively. The authors also attempted this... 

Frejd and co-workers used a ring-closing metathesis strategy as the key transformation in their synthesis of several novel spiro-cyclohexene bicyclo[2.2.2]octane derivatives. Spiro-cyclohexene bicyclo[2.2.2]octane derivatives are rare molecular frameworks, with only a few examples reported to date. Olefin metathesis of diastereomeric homoallylic alcohols 200 and 202 using 10 mol % of 3 in refluxing dichloromethane provided the corresponding spirocyclic carbocycles 201 and 203 in 84 and 85% yields, respectively. 

Dysinosin A is a highly oxygenated novel inhibitor of thrombin and factor Vila. Hanessian and co-workers employed a ring-closing metathesis strategy in their preparation of the 6,5-fused core of dysinosin A." Olefin metathesis of 206 and 208 using only 1 mol % of 4 gave quantitative yields... 

Dudley and co-workers used a relay ring-closing metathesis strategy in the synthesis of (+)-dihydro-e/ /-deoxyarteannuin B, a key biogenic... 

Castle and co-workers used a ring-closing metathesis strategy in their synthesis of the carbocyclic core of ( )-hasubanonine, a member of the hasubanan alkaloid family." Hasubanan alkaloids are of interest due to their structural similarity to morphine alkaloids. Treatment of diene 220 with a catalytic amount of 4 in refluxing dichloromethane furnished the desired phenanthrene core 221 in quantitative yield. Six additional steps were required to obtain the desired natural product. 

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