Ring-closing metathesis/isomerization

Tandem ring closing metathesis - isomerization Scheme 24... 

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 ring-closing metathesis approach was used beneficially to prepare isomeric seven-membered oxepine derivatives by Schmidt and Biernat. Thus, with the use of Grubbs first-generation catalyst, the metathesis of 33 afforded oxepine 34, whereas a tandem ring-closing metathesis-isomerization of the same substrate afforded glycal 35 (Scheme 13.9) [22]. 

A synthesis of enantioenriched tetrahydro- -carbolines has been reported using chiral phosphoric acid in conjunction with Hoveyda-Grubbs II catalyst through a ring-closing metathesis/isomerization/Pictet-Spengler cascade reaction (Scheme 93). ... 

Three novel stereo- and regioselective schemes for the total synthesis of (+ )-brefeldin A 440 have been accomplished. Each of them exploit intermolec-ular nitrile oxide cycloaddition for constructing the open chain and introducing substituents, but differ in subsequent stages. The first (480) and the second (481) use intramolecular cycloaddition for the macrocycle closure. However, in the second scheme INOC is followed by C=C bond cis-trans-isomerization. In the third scheme (481) intermolecular cycloaddition is followed by ring closing metathesis as the key step. 

The ruthenium-catalyzed isomerization of aryl allyl ethers or amines followed by ring-closing metathesis with ruthenium catalyst 1 furnishes fused benzo-heterocycles in good yield (Scheme 40).66 67... 

Six-membered ring-closing metathesis is based on azepine derivatives bearing terminal alkenyl groups at both N-1 and C-2 positions. Such reactions form (isomeric to 94 and 98, respectively) lactams 114 (01JOM9056) and 115 (99SL1127). 

A conceptually neat ruthenium-mediated isomerization and ring-closing metathesis was used in the synthesis of the l/f-2-benzazepine derivative 210 in moderate yield from 207 via 208 and 209 (Scheme 27) <2003SL1859>. 

With the same catalyst precursor, attempts to synthesize seven-membered cyclic enamides via ring closing metathesis of N-protected 5-hexenyl enam-ines failed, and selectively led to the formation of six-membered cyclic enamides resulting from initial isomerization of the 5-hexenyl into a 4-hexenyl group followed by cyclization [47]. 

Several examples of sequential isomerization/ring-closing metathesis for the preparation of heterocycles have also been performed by using two successive catalytic reactions catalyzed by two different ruthenium catalysts, but the second catalyst was introduced after completion of the first catalytic reaction. The isomerization was usually catalyzed by RuHCl(CO)(PPh3)3 [48], or RuCl2(= CHPh)(PCy3)(bis(mesityl)imidazolylidene) in the presence of trimethylsilyl vinyl ether [49], whereas a classical metathesis catalyst was subsequently introduced for the cyclization [48,49]. 

Interestingly, when RuCl2(= CHPh)(PCy3)(bis(mesityl)imidazolylidene) was used as the catalyst in dichloromethane under a N2 H2 (95 5) atmosphere, the ring-closing metathesis of allyl homoallyl ethers and to-sylamide was performed but a subsequent ruthenium-catalyzed double bond isomerization took place and very little hydrogenation was observed (Scheme 24) [50]. 

It has been shown that the simultaneous use of the metathesis catalyst RuCl2(PCy3)(IMes)(= CHPh) and the isomerization catalyst RuClH(CO) (PPh3)3 promoted the selective ring-closing metathesis of the diene resulting from initial isomerization of congested 1,9-dienes [71]. 

Schmidt and co-workers have also independently developed the self-cleavable diene linker 14 and solid-phase synthesis of the branched hexasaccharide 16 has been achieved (O Scheme 6) [12], The ring-closing metathesis of 15 provided the allyl glycoside 16 from which the allyl protecting group was readily removed by Ir-mediated isomerization followed by hydrolysis. 

Fustero, S. Sanchez-Rosello, M. Jimenez, D. Sanz-Cervera,J.F. DelPozo,C. Acena,J. L. Role of the gem-difluoro moiety in the tandem ring-closing metathesis-olefin isomerization regioselective preparation ofunsaturated lactams. 7. Org. Chem. 2006, 77(7), 2706-2714. 

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

A review of olefin metathesis has included the application of Claisen rearrangement and olefin metathesis to prepare intricate targets. " Isomerization issues during the ring-closing metathesis step of a new approach towards pentalenene have been reported (Scheme 74). " ... 

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