Cascade rings

The 3 + 2-cycloaddition of pyrroline A-oxide to 2-chloro-2-cyclopropylidene acetate and its spiropentane analogues (60) yields spiro [cyclopropane-1,5 -isoxazolidinejs (61) which undergo a novel cascade ring enlargement to yield indolizinones (62) in high yield (Scheme 21). ... 

A new selective thermal cascade ring-enlargement process of 4-chloro-substituted spiro[cyclopropane-l,5 -isoxazolidines], leading to a new method for the synthesis of the indolizine skeleton, has been reported (see Scheme 17). Apparently, the process is made possible by the presence of a chlorine substituent on the carbon a to the spirocyclopropane ring which facilitates a cyclopropyl-to-cyclobutyl ring enlargement mediated by a polar solvent. 

The water-soluble complex [RuCl(triphenylphosphine monosulfonate) (=C=CHPh)][Na]2 (L3) made possible the following cascade ring-opening/ cross-metathesis reaction (Eq.9) [72]. 

Illustrating the high potential of these reactions, cascade ring-closing metathesis of dienynes or trienynes have also provided access to fused 6,8,6-tricarbocyclic systems [14], and to a highly functionalized 5,7,6-tricyclic ring system related to the terpenoid guanacastepene A structure [15]. 

Enynes without the cycloalkene moiety can also react with electron-deficient alkenes by a cascade ring-closing metathesis-cross metathesis (RCM-CM) process [23] (Scheme 10). The use of Hoveyda s catalyst is necessary, not to stop the reaction at the RCM step, but to perform the subsequent CM step. Indeed, the organic product arising from the RCM is first formed and then reacts with the alkene in the presence of the ruthenium complex to give the CM reaction. 

Intramolecular cyclisation following halogen-metal exchange in the benzonitrile derivatives 25 provides a route to xanthones and thioxanthones. Incorporation of a second aryl halide function into the benzonitrile substrate allows an anionic cascade ring-closing sequence and the formation of pentacyclic xanthene derivatives 26 <03JOC4091>. 

In 2012, You and co-workers developed a cascade ring-closing metathesis/ isomerization/asymmetric Pictet-Spengler reaction, employing ruthenium complex (Hoveyda-Grubbs II catalyst) and chiral phosphoric acid as the... 

The characteristic feature in the mechanism of cyclization reactions is the reductive cascade ring closure. The mechanisms of silylcarbocyclizations (SiCaC, SiCaT,f CO-SiCaC, = CO-SiCaB, and CO-SiCaT reductive... 

Nemeto, H., Yoshida, M., Fukumoto, K. and lhara, M. (1999) A novel strategy for the enantioselective synthesis of the steroidal framework using cascade ring expansion reactions of small ring systems - asymmetric total synthesis of (-l-)-equilenin. Tetrahedron Lett., 40, 907-10. 

Ligand 29 (Table 15.1, entry 9) was also nsed in intramolecular Mizoroki-Heck reactions [72]. In combination with Pd(OAc)2, it catalysed a cascade ring-closing metathesis (RCM)/Mizoroki-Heck reaction. The RCM step was conducted at room temperature on (bromo or iodo) iV-alkenyl-A-allyl-2-halo-benzenesnlfonamides and the Mizoroki-Heck reaction was run at 110°C for 16 h in a perflnorons solvent system. The overall yield with fluorous conditions (0-67%) was significantly lower than a reference system with polymer-bound palladinm catalyst (58-80%). 

Grigg, R. and York, M. (2000) Bimetallic catalytic cascade ring-closing metathesis-intramolecular Heck reactions using a fluorous biphasic solvent system or a polymer-supported palladium catalyst. Tetrahedron Lett., 41, 7255-8. 

Yoshida M, Ismail MAH, Nemoto H, Ihara M (2000) Asymmetric Total Synthesis of (+)-Equilenin Utilizing Two Types of Cascade Ring Expansion Reactions of Small Ring Systems. J. Chem Soc Perkin Trans I 2629... 

Table 4. Examples of cascade ring closing metathesis reactions using Grubbs catalysts.

In chapter entitled Synthesis of Substituted Tetrahydrofurans, J. D. Rainier outlines the advances that have been made during the last 10 years in the synthesis of tetrahydrofurans such as nucleophilic additions to acetals and hemiacetals, cycloadditions, oxidative cyclizations, furan reductions, Prins-pinacol cascades, ring-opening of bicyclic substrates, and nucleophilic substitutions. 

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