Cyclization Ring-closing metathesis

Diynes can be employed in intramolecular ring-closing metathesis. Several catalysts involving Mo and W have been investigated. These cyclizations can be combined with semihydrogenation to give macrocycles with Z-double bonds. 

A further application of ring-closing metathesis in seven-membered heterocyclic ring formation is in the synthesis of the trans-fused oxpane systems. This process involved tandem RCM/allylstannane-aldehyde cyclizations and interaction of the process provides access to trans-fused polyoxepanes <00S883>. 

The ring-closing metathesis (RCM) approach is useful for the synthesis of indolizidinone derivatives. The procedures published are based on the use of compound 103, an amide of a pyrrolidine derivative bearing on C-l the second unsaturated branch ready for the cyclization. The reaction proceeded smoothly with high yields in both examples (Scheme 27) <2001JOC9056, 2004JOC3968>. 

Ring-closing metathesis of an enyne, which has double and triple bonds in the molecule, is a remarkable reaction which is useful in synthetic organic chemistry. In enyne metathesis, the double bond is cleaved and carbon-carbon bond formation occurs between the double and triple bonds. The cleaved alkylidene part is moved to the alkyne carbon. Thus, the cyclized compound formed in this reaction has a diene moiety [Eq. (6.77)]. The reaction is also called skeletal rearrangement and is induced by Pt, Pd, Ga, and Ru catalysts ... 

The combination of allylic amination, ring-closing metathesis, and a free radical cyclization provides a convenient approach to the dihydrobenzo[b]indoline skeleton, as illustrated in Scheme 10.10. The rhodium-catalyzed aUylic amination of 43 with the lithium anion of 2-iodo-(N-4-methoxybenzenesulfonyl)arrihne furnished the corresponding N-(arylsulfonyl)aniline 44. The diene 44 was then subjected to ring-closing metathesis and subsequently treated with tris(trimethylsilyl)silane and triethylborane to afford the dihydrobenzojhjindole derivative 46a in 85% yield [14, 43]. 

Amino acids continue to be useful starting materials for the preparation of enantiomerically-pure heterocycles. Henk Hiemstra of the University of Amsterdam and Floris Ruljes of the University of Nijmegen report (J. Am. Chem. Soc. 2004,126,4100) that cyclization of the ally silane 9 followed by ring-closing metathesis leads to the highly-functionalized quinolizidine 11. 

The N-heterocyclic alkenes derived from ring-closing metathesis are useful substrates for further transformation. In a synthesis directed toward the insecticidal cripowellin 12, Dieter Enders of RWTH Aachen has shown (Angew. Chem. Int. Ed. 2005,44, 3766) that the tertiary amide 8 cyclizes efficiently to the nine-membered alkene 9. The vision was that an intramolecular Heck cyclization could then deliver the cripowellin skeleton. Indeed, the Heck did proceed, and, depending on conditions, could be directed toward either 10 or 11. Unfortunately, the conformation of 9 is such that the cyclization proceeded cleanly across the undesired face. Nevertheless, both 10 and 11 appear to be valuable intermediates for further transformation. 

Dihydropyrroles have recently become readily available by ring-closing metathesis. For this purpose, N-acylated or N-sulfonylated bis(allyl)amines are treated with catalytic amounts of a ruthenium carbene complex, whereupon cyclization to the dihydropyrrole occurs (Entries 6 and 7, Table 15.3 [30,31]). Catalysis by carbene complexes is most efficient in aprotic, non-nucleophilic solvents, and can also be conducted on hydrophobic supports such as cross-linked polystyrene. Free amines or other soft nucleophiles might, however, compete with the alkene for electrophilic attack by the catalyst, and should therefore be avoided. 

The cyclization of A-alkenyl derivatives of resin-bound peptides by ruthenium-catalyzed ring-closing metathesis has been investigated [426-428]. These reactions do not proceed well on insoluble supports, and cyclizations in solution are generally more successful. 

Treatment of enynes 35 and 36 with first generation Grubbs carbene under the above diene ring-closing metathesis conditions did not furnish the desired spiro-cycles. Next, trials of cyclization were attempted by using its imidazolidinylidene... 

A novel approach to enantiopure spirocyclic (3-lactams has been developed by Alcaide et al. [106] using different intramolecular metal catalyzed cyclization reactions with monocyclic unsaturated alcohols 142 (Scheme 35). Ring-closing metathesis is one of the most powerful and reliable methods to construct a ring system. Transformation of alcohols in diolefin precursors followed by ring-closing... 

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