Seven-membered rings formation

The final cyclization manifold has been realized with a different ruthenium catalyst (Scheme 22). The cationic [Cp Ru(MeCN)3]PF6 induces exclusive endo-dig cyclization of both homopropargylic and bis-homopropargylic alcohols.29 73 The clean reaction to form a seven-membered ring is noteworthy for several reasons intramolecular exo-dig cyclization with bis-homopropargylic alcohols is not well established, the platinum-catalyzed case has been reported to be problematic,80 and the selectivity for seven-membered ring formation over the exo-dig cyclization to form a six-membered ring is likely not thermodynamic. The endo-dig cyclization manifold was thus significant evidence that a re-examination of alkyne hydrosilylation mechanisms is necessary (see Section 10.17.2). 

Now LDA is a very strong base, and it is also a large base. We deduce that it can only remove a proton from the less-hindered position, i.e. the COCH3, and this leads to seven-membered ring formation. 

Under optimized conditions, cycloisomerizations of a number of functionalized hept-l-en-6-ynes took place in good-to-excellent yields (Table 9.3). Heteroatom substitution was tolerated both within the tether and on its periphery. Alkynyl silanes and selenides underwent rearrangement to provide cyclized products in moderate yield (entries 6 and 7). One example of seven-membered ring formation was reported (entry 5). Surprisingly, though, substitution was not tolerated on the alkene moiety of the reacting enyne. The authors surmize that steric congestion retards the desired [2 + 2]-cycloaddition reaction to the point that side reactions, such as alkyne dimerization, become dominant. 

Type zinc-ene reactions seem to be more difficult to achieve compared to type I cyclizations even though successful examples of six- or seven-membered ring formations have been reported. Nevertheless, type I reactions constitute a particularly attractive strategy for the formation of five-membered rings that proceed smoothly compared to intermolecular additions to monosubstituted alkenes. However, allylic organozincs are able to add to substituted alkenylmetals under extremely mild conditions. 

K. Krohn, S. Grignard, and G. BSmer, From sugars to carbocycles. 4. Exclusive seven-membered ring formation from D-glucose, Tetrahedron Asymmetry 5 2485 (1994). 

In the preparation of cyclic ethers by diene-ene RCM, there is a competition between the formation of cyclic allyl ether with a smaller ring size and of cyclic pentadienyl ether with a larger ring size (Scheme 24). In particular, in the competition between five- and seven-membered ring formation, both dihydrofuran and dihydrooxepine derivatives are formed in comparable amounts, whereas in the competition between seven- and nine-membered rings, a dihydrooxepine forms exclusively <2006JOC3977>. 

Acid-catalyzed seven-membered ring formation to afford the first stable A-oxo-2,1 -benzoxazepinium ions has been reported, based on reaction of l-chloro-2-(2-nitrobenzyl)cyclopropane with H2S04 and FSO3H nitro group trapping of an intermediate carbocation was proposed in this process <1996ZOR852>. 

Seven-membered Ring Formation Using Sml2... 

Another example is the assembly of the complex [6-7-5]-fused tricyclic core 35 of guanacastepenes, obtained as a single diastereoisomer, as shown in Scheme 22 <2005OL3425>. The efficiency of this reaction is consistent with the gi OT-dialkyl effect that is required for the seven-membered ring formation in this type of electron-transfer reaction. 

C-C bond formation in inter- or intramolecular additions starting with olefin [ 199, 200], ketyl [201] (generated by PET [202], chemical or cathodic [24, 203] reduction) [204, 205] or imine radical anions [206] has become a versatile method. In general, the intramolecular addition is highly suitable for the construction of five membered rings, less so for six-, and not effective for seven-membered ring formation. 

Direct generation of a cyclopropoxy anion from a siloxycyclopropane and fluoride ion has been applied to seven-membered ring formation. Michael addition of the resulting allyl anion can account for the cyclization. An uncyclized i ,y-unsaturated ketone with the E configuration is also formed as a byproduct. 

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