Styrenyl ethers, rearrangement

There is much more left to be done in the area of catalytic RCM. It is likely that many elegant and creative uses of catalytic RCM are in the making. Judging by the related developments in recent years, it is also likely that catalytic RCM will influence positively the development of numerous other ongoing metal-catalyzed or uncatalyzed reactions. The advent and utility of complexes la, lb and 2 will undoubtedly inspire organic chemists to devise new and useful transformations, where these transition metal systems are effectively utilized (e.g., styrenyl ether rearrangements) [40]. 

Scheme 8. Zr-catalyzed kinetic resolution of allylic styrenyl ethers may be followed by a Ru-or Mo-catalyzed rearrangement to afford 2-substituted chromenes...

Catalytic Ru-Catalyzed Rearrangements of Terminal Styrenyl Ethers... 

Scheme 9. Ru-catalyzed rearrangement of styrenyl ethers proceeds efficiently under 1 atm ethylene to afford a range of 2-substituted chromenes...

Scheme 10. Mechanism proposed for the Ru-catalyzed rearrangement of terminal styrenyl ethers...

As mentioned above, we planned to obtain optically pure styrenyl ethers through Zr-catalyzed kinetic resolution [5] subsequent metal-catalyzed rearrangement would afford optically pure chromenes. However, as shown in Scheme 11, the recovered starting material (40) was obtained with <10% ee (at 60% conversion) upon treatment with 10 mol% (,R)-(EBTHI)Zr-binol (3b) and five equivalents of EtMgCl (70°C, THF). We conjectured that, since the (EBT-HI)Zr-catalyzed reaction provides efficient resolution only when asymmetric alkylation occurs at the cyclic alkene site, competitive reaction at the styrenyl terminal olefin renders the resolution process ineffective. Analysis of the H NMR spectrum of the unpurified reaction mixture supported this contention. Indeed, as shown in Scheme 11, catalytic resolution of disubstituted styrene 49... 

Catalytic transformations of both terminal and disubstituted styrenyl ethers will be discussed in this article. In the former case, since the starting material and the product are isomeric, the Ru-catalyzed process constitutes a catalytic rearrangement. 

The synthetic versatility and significance of the Zr-catalyzed kinetic resolution of exocyc-lic allylic ethers is demonstrated by the example provided in Scheme 6.9. The optically pure starting allylic ether, obtained by the aforementioned catalytic kinetic resolution, undergoes a facile Ru-catalyzed rearrangement to afford the desired chromene in >99% ee [20], Unlike the unsaturated pyrans discussed above, chiral 2-substituted chromenes are not readily resolved by the Zr-catalyzed protocol. Optically pure styrenyl ethers, such as that shown in Scheme 6.9, are obtained by means of the Zr-catalyzed kinetic resolution, allowing for the efficient and enantioselective preparation of these important chromene heterocycles by a sequential catalytic protocol. 

Alternatively, as shown in Scheme 8, we envisioned that styrenyl allylic ethers, in the presence of an appropriate catalyst, might undergo a net skeletal rearrangement to yield the desired isomeric heterocyclic products [14]. Rearrangement substrates would be synthesized in the non-racemic form by the Zr-catalyzed kinetic resolution [5c]. 

Several factors and observations support the route proposed in Scheme 10 (1) Due to steric factors, the styrenyl alkene is expected to react preferentially (versus the neighboring disubstituted cyclic olefin see below for further discussion). (2) Involvement of tetracyclic intermediates such as 43 provides a plausible rationale for the reluctance of six-membered ring ethers [46 in Eq. 4] to participate in the catalytic rearrangement and for the lack of reactivity of cyclopen-tenyl substrates [48 in Eq. 5] because of the attendant angle strain, the generation of the tetracyclic intermediate is not favored. (3) Reactions under ethylene atmosphere inhibit dimer formation, since 44 is intercepted with H2CCH2, rather than 41 [19]. 

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