Grubbs catalyst enyne metathesis

Diels-AIder reactions were utilized to prepare isoquinoline derivatives. Various tetrahydroisoquinoline-3-carboxylic acid derivatives were prepared by an enyne metathesis followed by a Diels-AIder reaction. For example the enyne 71 was treated with Grubb s catalyst to afford diene 72 in 65% yield. Subsequent Diels-AIder reaction and oxidation gave tetrahydroisoquinoline 73 in 93% yield <0OCC5O3>. Dihydrosoquinoline 75 was prepared... 

Enyne metathesis using ruthenium catalyst 52a was developed by Mori and Kinoshita [18]. When enyne 62a was treated with Grubbs s ruthenium catalyst 52a in benzene at room temperature for 22 h, the cyclized product 63a was obtained in only 13% yield (Eq. 29). It seems that the catalyst was coordinated by the diene generated in this reaction. This problem was overcome by the study of... 

Enyne metathesis can also be used with highly substituted substrates. Catherine Lievre of the Univcrsite de Picardie reports (J. Org. Chem. 2004,69, 3400) that enynes such as 11, readily prepared from carbohydrate precursors, are cyclized by the second generation Grubbs catalyst 2 to the enantiomerically-pure cyclic dienes, exemplified by 12. 

Metathesis of enynes 63 with Grubbs catalyst (Scheme 23) affords 3-vinyl-2,5-dihydrobenzo[/)]oxepines 64. Subsequent dienophile addition gives Diels-Alder adducts 65-67 in 50-80% yields <2001SL1784>. 

It should be noted that while enyne metathesis is considered incompatible with molybdenum catalyst 1, ruthenium catalysts other than the Grubbs type also promote the reaction. Semeril et al. [103] reported efficient enyne RCM with a catalyst conveniently generated in situ from [RuCl2(p-cymene)]2,1,3-bis(mesityl)imidazolium chloride and caesium carbonate. Interestingly the authors found that the in situ derived system gave better results than the isolated catalyst. One of the most impressive examples of the use of enyne RCM is the total synthesis of (-)-longithorone by Layton et al. [104]. Inspired by a pro-... 

An efficient method for the preparation of highly functionalized conjugated dienes with the use of silicon-tethered ring-closing enyne metathesis in the presence of first- and second-generation Grubbs catalysts has been described... 

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>. 

An enyne metathesis approach to pyrrole-2-phosphonates was reported <07CEJ203>. Treatment of enyne amine 10 with a second-generation Grubbs ruthenium catalyst in the presence of the oxidant tetrachloroquinone (TCQ) gave pyrrole-2-phosphonate 11. 

The short total synthesis of (+)-differolide based on a tandem enyne metathesis / [4+2] cycloaddition was accomplished by T.R. Hoye et al." The enyne metathesis was carried out on ally propynoate using Grubbs s first-generation metathesis catalyst. The catalyst was added to the substrate slowly to maintain high substrate and low ruthenium carbene concentrations. The initially formed 2-vinylbutenolide readily dimerized via a Diels-Alder cycloaddition in which the vinyl group participated as the dienophile to afford the natural product. 

M. Shair and co-workers were the first to apply the enyne metathesis for macrocyclization during the biomimetic synthesis of (-)-longithorone A." The two 16-membered paracyclophane building blocks, one diene and one dienophile component, were prepared using 50 mol% Grubbs s first-generation catalyst under 1 atm ethylene gas pressure. These components, after several additional steps, underwent two facile Diels-Alder cycloaddition reactions to afford the natural product. 

Scheme 43. (a) Enyne metathesis using first generation Grubbs Ru-caibene catalyst. 

Scheme 69. Second-generation Grubbs catalyst applied to intermolecular enyne cross-metathesis for the preparation of anoUgnan. (Mes = Mesityl Cy = cyclohexyl Ms = mesylate.)...

Scheme 74. Tandem ring-closing enyne metathesis using first generation Grubbs catalyst to form...

Transition metal catalysis is playing an ever increasing role in the synthesis of heterocyclic ring systems. Grubb s ruthenium catalyst is very effective in enyne metathesis of (10) in which the azepine (11) is formed in high yield <94SLI020> and molybdenum metathesis is used in the preparation of pyrroloazepine derivatives <94TL6005>. Palladium catalysis of the cyclisation of N,N-dimethyl-2-(r-acetoxy-2 -propenyl) benzylamines yields 2,3-dihydro-l//-2-benzazepinium (12) salts (Scheme... 

Perez-Castells and coworkers devised a tandem enyne methathesis Diels-Alder reaction strategy for the assembly of polycyclic indole structures [109]. The enyne metathesis reaction using Grubbs s catalyst (311) with the 2-alkynylaniline 310 in the absence of a dienophile proceeded to form the mono- and bis-indole derivatives 313 and 314 (Scheme 66). Testing the hypothesis that a Diels-Alder cycloaddition with an activated diene might be faster than the undesired cross-metathesis reaction which led to the formation of 314, a one-pot reaction with maleic anhydride (312) as the dienophile was conducted. Disappointingly, the above reaction resulted in a... 

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