Cascade alkene metathesis

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-... 

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. 

The enantioselective synthesis of azabicyclic y-lactams starting from 2-azanorbornenones after treatment of a catalytic amount of RuCl2(PCy3)2 (= CHPh) in the presence of ethylene or allyl acetate proceeds also via ring rearrangement—alkene metathesis (ROM-CM-RCM) [41] (Scheme 19). If n = 0 or 3, no RCM occurs and a cyclic dialkenyl compound is formed by cascade ROM-CM reactions. 

Alkene metathesis catalysts are also capable of undergoing reaction with aUene and alkyne functionality, which can lead to the synthesis of polyene compounds. For example. Diver has explored the use of alkene/alkyne CM, which leads to 2-substituted 1,3-dienes (Scheme 2.11). Prunet has recently disclosed an elegant metathesis cascade sequence towards the synthesis of Taxol, involving two alkenes and one alkyne functional group (Scheme 2.12) the desired product was accompanied by small quantities of a side product that resulted from metathesis of the two alkenes. 

In a different approach, Lebel and co-workers designed a multicatalytic process combining the [(IPr)Pd(OAc)2]-catalyzed alcohol oxidation and their [RhCl(PPh3)3]-catalyzed carbonyl methylenation. They were able to perform both reactions sequentially in one pot, effectively converting alcohols into terminal alkenes (Equation (12.3)). To further highlight this approach, they performed a three-reaction cascade comprised of the two former reactions, which resulted in the formation of a diene, followed by an alkene metathesis in... 

Keywords Alkene metathesis Cascade reaction Stereoselective synthesis Total synthesis... 

Cascade Reaction Involving Selective Alkene Metathesis. 183... 

In the previous section we have shown that tandem ene-yne-ene RCM has been broadly used for the rapid and efficient construction of complex frameworks. In principle, selective alkene metathesis can be combined with other types of transformation to achieve a cascade reaction, which will provide a tremendous increase in molecular complexity [77]. Therefore, in this section, we highlight several recent examples of cascade reaction involving selective alkene metathesis for natural product synthesis. 

In 2009, Lee and coworkers reported the concise total syntheses of epoxyquinoid namral products (+)-asperpentyn (103), (-)-harveynone (104), and (—)-tricholo-menyn A (105) via cascade enyne metathesis and metallotropic [l,3]-shift (Fig. 29) [78]. In order to initiate the cascade effectively, arelay metathesis strategy was also adopted. By treatment of the polyenyne precursor (106) with Grubbs II catalyst, a mixture of epimers (107) and (108) was isolated in 62% yield. This cascade process selectively commenced from the terminal alkene of the allyl ether (106) to form the relay intermediate (109), which then underwent sequential relay metathesis and enyne metathesis to form alkynyl Ru-alkylidene (111). Subsequent facile metallotropic [1,3]-shift took place to provide the conjugated alkyhdene product (112), which would ultimately deliver the final products (107) and (108) through termination at the less hindered carbon. 

In summary, the aforementioned examples have demonstrated the versatile utilities of the cascade reaction involving selective alkene metathesis and have... 

In the presence of diazo compounds 9, enynes 10 containing a fluorinated amino acid moiety could be transformed into fluorinated alkenyl bicyclo[4.1.0]heptane amino acid derivatives 11 using Cp (Cl)Ru(COD) as the precatalyst (Scheme 5.5) [12], In this process, the in situ-generated catalyst from ruthenium complex and diazo compound completely inhibits RCM of enyne to the profit of cascade alkenyl-ation/cyclopropanation. The Cp (Cl)Ru moiety in ruthenacyclobutane is believed to favor reductive elimination versus expected alkene metathesis. 

Using the catalyst system described above in combination with a rhodium phosphine catalyst Lebel reported the de novo synthesis of alkenes from alcohols [100]. They developed a one-pot process, avoiding the isolation and purification of the potentially instable aldehyde intermediate. They combined the oxidation of alcohols developed by Sigman [89] with their rhodium-catalyzed methylenation of carbonyl derivatives. The cascade process is compatible with primary and secondary aliphatic as well as benzyUc alcohols in good yields. They even added another reaction catalyzed by a NHC complex, the metathesis reaction, which has not been addressed in this review as there are many good reviews, which exclusively and in great depth describe all aspects of the reaction. 

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. 

The intermolecular enyne cross metathesis, and consecutive RCM, between a terminal alkyne and 1,5-hexadiene produces cyclohexadienes, by cascade CM-RCM reaction, and trienes, formed during the sole CM step. Studies of various parameters of the reaction conditions did not show any improvement of the ratio of desired cyclohexadiene product [25] (Scheme 12). The reaction with cyclopentene instead of hexadiene as the alkene leads to 2-substituted-l,3-cycloheptadienes [26]. After the first cyclopentene ROM, the enyne metathesis is favored rather than ROMP by an appropriate balance between cycloalkene ring strain and reactivity of the alkyne. 

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