Ethers, acid cleavage from alkenes

In 2009, Marco et al. reported the synthesis of hyacinthacine A2 7 and A3 8 and unnatural isomer 5- p/-hyacinthacine A3 118 from the intermediate 119, issued from the (/ )-Gamer s aldehyde, a derivative of L-serine [38]. Alcohol 119, obtained in six steps from Gamer s aldehyde [39], was first protected as a TES ether, then submitted to an oxidative cleavage of the terminal alkene to provide the alcohol 121 after subsequent reducticm step. Desilylation followed by mesylation afforded the compound 123, which underwent a one-pot acidic cleavage of the Boc and aminoketal protective groups. Standard hydrogenoly-sis of benzyl ethers and cyclization under basic conditions achieved this linear but efficient synthesis of hyacinthacine A2 (14 steps from Gamer s aldehyde, 22% overall yield) (Scheme 34). 

The mechanism of the formation of the tetrahydropyranyl ether (see Figure 23.1) is an acid-catalyzed addition of the alcohol to the double bond of the dihydropyran and is quite similar to the acid-catalyzed hydration of an alkene described in Section 11.3. Dihydropyran is especially reactive toward such an addition because the oxygen helps stabilize the carbocation that is initially produced in the reaction. The tetrahydropyranyl ether is inert toward bases and nucleophiles and serves to protect the alcohol from reagents with these properties. Although normal ethers are difficult to cleave, a tetrahydropyranyl ether is actually an acetal, and as such, it is readily cleaved under acidic conditions. (The mechanism for this cleavage is the reverse of that for acetal formation, shown in Figure 18.5 on page 776.)... 

Using Hydrohalic Acids When an epoxide reacts with a hydrohalic acid (HC1, HBr, or HI), a halide ion attacks the protonated epoxide. This reaction is analogous to the cleavage of ethers by HBr or HI. The halohydrin initially formed reacts further with HX to give a 1,2-dihalide. This is rarely a useful synthetic reaction, because the 1,2-dihalide can be made directly from the alkene by electrophilic addition of X2. 

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