Eight-membered rings, ring-closing metathesis

Related microwave-assisted ring-closing metathesis reactions, leading to seven-[154] and eight-membered aza-heterocyclic products [49], are depicted in Scheme 6.74. 

Scheme 6.74 Formation of seven- and eight-membered rings by ring-closing metathesis reactions.

Furstner succeeded in the synthesis of dactylol using ring-closing metathesis of 9d. Crimmins synthesized enantioselectively diene 9e, and RCM of 9e gave eight-membered ring compound lOe, which is an intermediate for the synthesis of laurencin [Eq. (6.12)] ... 

Ru and Os tetranuclear clusters, 6, 874 in transition metal complex electron counting, 1, 2-3 Eight-membered rings, via ring-closing diene metathesis,... 

Dienes are cyclized by intramolecular metathesis. In particular, cyclic alkenes 43 and ethylene are formed by the ring-closing metathesis of the a,co-diene 46. This is the reverse reaction of ethenolysis. Alkene metathesis is reversible, and usually an equilibrium mixture of alkenes is formed. However, the metathesis of a,co-dienes 46 generates ethylene as one product, which can be removed easily from reaction mixtures to afford cyclic compounds 43 nearly quantitatively. This is a most useful reaction, because from not only five to eight membered rings, but also macrocycles can be prepared by RCM under high-dilution conditions. However, it should be noted that RCM is an intramolecular reaction and competitive with acyclic diene metathesis polymerization (ADMET), which is intermolecular to form the polymer 47. In addition, the polymer 47 may be formed by ROMP of the cyclic compounds 43. 

An eight-membered ring is formed in a ring-closing metathesis. 

The synthesis of polycyclic ethers with variable ring sizes can be conducted by two-directional double ring-closing metathesis. This methodology was used to prepare, in one-step, the tricyclic ether 73, which has a six-, seven-, and eight-membered ring (Scheme 9) <2000AGE372>. 

For manzamine A, Martin et al. developed a strategy for the construction of the eight-membered ring E [15], Pandit et al. succeeded in the formation of the 13-membered ring D [18]. The efforts culminated recently in the total synthesis of manzamine A and related manzamine alkaloids, employing the ring-closing metathesis reaction as a key step [16]. Thus, 49 is converted into 50 with a yield of 67 % (Scheme 8). 

The very complex natural product ircinal A Z-196 has difficult Z-alkenes in the eight-membered ring and in the frill round the molecule s waist. Both have been inserted by metathesis with good Z-selectivity.42 The starting material 193 has three alkenes but only two metathesise to give the 13-membered cyclic frill 194. The final metathesis to close the eight-membered ring is obviously difficult and the yield is poor. 

L 9. Kraffit, M.E. Cheung, Y.Y. Capucao, A.J. Synthesis of the First Inside-Outside Eight-Membered Ring via Ring-Closing Metathesis A Total synthesis of (+/-)- Asteriscanolide Synthesis 2000, 7, 1020-1026... 

Ring-closing metathesis of diallyl dipeptide (52), using a ruthenium catalyst, affords diazocine (53) in 51% yield (Equation (13)) <95JA2108>. Other metathesis-type catalysts were ineffective for closure of eight-membered rings, and the present catalyst fails in the case of acyclic precursors to 1,4-oxazocines or dioxocins. 

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