Cascade reactions metathesis

Ru-catalysed enyne metathesis offers a short approach to chiral derivatives of 3-vinyl-5,6-dihydro-2//-pyrans. Some epimerisation can occur at the pyranyl C atom at elevated temperatures (Scheme 3) <02T5627>. The bispropargyloxynorbomene derivative 6 undergoes a cascade of metathesis reactions in the presence of alkenes and Grubbs catalyst incorporating an enyne-RCM that leads to fused cyclic dienes. A dienophile can be added to the reaction mixture, resulting in Diels-Alder reactions and the formation of functionalised polycyclic products <02TL1561>. 

Abstract Ruthenium holds a prominent position among the efficient transition metals involved in catalytic processes. Molecular ruthenium catalysts are able to perform unique transformations based on a variety of reaction mechanisms. They arise from easy to make complexes with versatile catalytic properties, and are ideal precursors for the performance of successive chemical transformations and catalytic reactions. This review provides examples of catalytic cascade reactions and sequential transformations initiated by ruthenium precursors present from the outset of the reaction and involving a common mechanism, such as in alkene metathesis, or in which the compound formed during the first step is used as a substrate for the second ruthenium-catalyzed reaction. Multimetallic sequential catalytic transformations promoted by ruthenium complexes first, and then by another metal precursor will also be illustrated. 

Norbornene derivatives bearing two alkynes undergo cascade enyne metathesis reactions when treated with a first generation ruthenium carbene and ethylene, giving heterocyclic dienes [28]. The ROM of the norbornene moiety initiates the cascade enyne RCM reactions (Scheme 14). When ethylene is replaced by a monosubstituted alkene, a single enyne RCM takes place, after the initial ROM of norbornene. 

A similar type of cascade reaction has been carried out with cyclic alkenes bearing only one olefinic side chain to obtain substituted heterocycles via ruthenium-catalyzed ring closing-ring opening metathesis (RCM-ROM) reactions. The preparation of enantiomerically pure cis- or trans-a,a -disubstituted piperidines has been achieved in the same yield for the two diastereoisomers [35] (Scheme 17). This reaction has also been used as a key step for the synthesis of natural products [36-39]. 

The cascade alkene metathesis processes described above result from the combination of ROM and RCM. The cascade alkene metathesis reaction involving ROM, RCM and CM reported in Scheme 18 leads to [n.3.0]bicycles in a stereo-controlled manner [40]. The reaction combines ring opening of... 

All the above cascade alkene metathesis reactions are based on the ROM of a cycloalkene moiety. Harrity and co-workers have described the synthesis of functionalized spiro cyclic systems by cascade selective olefin ringclosing metathesis reactions from an acyclic tetraalkene. The selectivity for five-membered ring closure over seven-membered ring closure would be the result of a kinetically favored cyclization process [42] (Scheme 20). The syn-... 

Scheme 6.58 Cross-metathesis/AFC cascade reaction of indolyl allyl ether or amine 135 and phenyl enone 136 reported by You.

Undheim K, Efskind J (2000) Ru(II)-catalyzed ring closing metathesis in stereoselective spiroatmulations and cascade reactions of cyclic dipeptide substrates. Tetrahedron 56 4847 4857.doi 10.1016/S0040-4020(00)00200-3... 

Site Isolation of the Grubbs Catalyst from the Sharpless Dihydroxylation Catalyst. The Grubbs catalyst was site isolated from AD-mix to complete cascade reactions as shown in eqs 13-15. The Grubbs catalyst was added to the interior of a thimble with CH2Cl2 [BMIM][PF6] and the metathesis reaction was run to completion. Next, the AD-mix was added to the exterior of a thimble with 1 1 (v/v) f-Bu0H H20 or 1 2 3 (v/v/v) [BMIM][PF6] H20 acetone. The product of the metathesis reaction fluxed to the exterior and reacted to yield the diol. 

This method was extended to substrates with intermediates that were challenging to isolate. For instance, a metathesis-dihydroxylation cascade reaction was completed on a challenging substrate (eq 16). The metathesis reaction of diallylamine yielded a molecule with an estimated boiling point of 55 °C this molecule was not isolated but rather converted to the diol and isolated as a high-boiling product (80% isolated yield). It was not necessary to isolate the volatile intermediate in this sequence. 

A second challenging metathesis-dihydroxylation cascade reaction was completed (eq 17). Diallyl sulfide (boiling point 138 °C) was reacted with the Grubbs catalyst to yield a cyclic intermediate with an estimated boiling point of 90 °C. The intermediate had an unpleasant odor, but it was not isolated in this sequence. Rather, the formation of the diol and oxidation of the... 

Conceptually similar palladium-catalyzed cascade reactions have been developed, involving molecular-queuing cycloaddition, cyclocondensation and Diels-Alder reactions [71], cydization-anion-capture-olefin metathesis [72], carbonylation-allene insertion [73], carbonylation/amination/Michael addition [74], sequential Petasis reaction/palladium-catalyzed process [75], supported allenes as substrates [76], and palladium-ruthenium catalysts [77]. 

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