Epoxidation with m-CPBA

Next, the double bond is made into an epoxide with m-CPBA. Epoxides react with nucleophiles, and this is the way that the four-membered ring of grandisol was formed the nitrile still has a proton next to it, and a strong base will remove this proton as before to give an enolate . The enolate reacts with the epoxide to give a four-membered ring. 

If a suitable (1,3-di-f-butyl) allene is epoxidized with m-CPBA the unstable allene oxide can actually be isolated. On heating, this epoxide gives a stable fra s-di-f-butylcycl6propanone. It is very difficult to see how this reaction could happen except via the oxyallyl cation intermediate. 

In this three-step sequence, alkene 16 is first epoxidized with m-CPBA providing the a-epoxide in 87 % yield along with only minor amounts of the (3-isomer (10 %). As the aminal fragment... 

Work has been done with salen catalysts to enable enantioselective epoxidations with m-CPBA. Highly enantioselective K.ochi-Jacobsen-K.atsuki epoxidation of unfunctionalized olefins with Mn(III)-(salen)-based chiral catalyst provides an efficient route to optically active epoxides. It has been noted that m-CPBA in the presence of JV-methylmorpholine N-oxide at low temperature (e.g., -78 °C) suppresses bond rotation leading to high enantioselectivity even when the substrate is acyclic.10,15... 

Martin and co-workers utilized the Prilezhaev reactions to synthesize epoxides 32 and 33. Epoxidation with m-CPBA gave in 96% yield an inseparable mixture of epoxides 32/33 in a 2 3 ratio.20... 

Using osmium tetroxide to add two hydroxyl groups to the second alkene will give the diastereoisomer on the left, because the mechanism ensures both O atoms add to the same side of the alkene (p. 442 of the textbook). To get the trans diol, we can make an epoxide with m-CPBA and then open it with water, an Sn2 reaction that proceeds with inversion of configuration. 

With the two methyl stereocenters successfully set, we next focused on installing the secondary C4-hydroxyl group. Using selenium dioxide, we were able to convert the allylic methyl ether in one step into an enal (174), which we then reduced with diisobutylaluminum hydride (175, Scheme 32). This allylic alcohol could be epoxidized with /m-CPBA, thus ensuring installation of the desired C4-hydroxyl group stereocenter under substrate-controlled conditions... 

Of course epoxidation reactions form rings, and you have seen examples of epoxidations with m-CPBA even in this chapter (p. 848) of alkenes such as cyclohexene. We pointed out in Chapter 19 that epoxidation is stereospecific because both new C-O bonds form to the same face of the alkene. 

MBH adduct 842 has subjected to epoxidation with m-CPBA followed by a Swern oxidation to afford aldehyde 844 (Scheme 4.244). Wittig methodology using (iodomethylene)triphenylphosphorane gave iodide 845 in 34% overall yield. Iodide 845 was subsequently treated with sodium benzylselenoate to afford 846 and then free-radical mediated ring closure as well as ester hydrolysis afforded selenophene-3-carboxylic acid 847 in 26% yield within two steps. Acid... 

To introduce an epoxy group on the terminal double bond, the other alkene function was protected by bromoetherification to produce the bromo ether, which was desilylated and compound 452 provided. In the final two steps, olefin 453 was epoxidized with m-CPBA and deprotected with a zinc-silver complex to obtain ( )-verrucarol (454) (Scheme 8.13). 

The Grubbs catalyst was recycled in a cascade sequence as shown in eq 11. The Grubbs catalyst was recycled as described before, but in these reactions the extracted product was epoxidized with m-CPBA after removal from the reaction vessel containing the PDMS thimble. The isolated 3delds of the product ranged from 60 to 86% through five cycles. 

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