Science of Synthesis

Zeh, J.; Hiersemann, M., Science of Synthesis: Stereoselective Synthesis, (2011) 3, 368.

The aromatic Claisen rearrangement of aryl allyl ethers to ortho-substituted phenols is rarely used to construct stereogenic benzylic carbon atoms. However, an example that demonstrates the potential of this transformation is illustrated in ‌Scheme 24‌.[‌35‌] High temperatures are required to effect rearrangement of the allyl aryl ether ‌87‌. The transition-state structure ‌88‌ implies a suprafacial sigmatropic shift on the convex face of the bicyclic ring system, which represents another example of a synthetically useful substrate-induced diastereoselective reaction that is not self-immolative in nature. Since the resulting hydroquinone monomethyl ether is sensitive to acids, bases, and oxygen, it is directly converted into the dimethyl ether ‌89‌, which can be isolated as a single diastereomer. The hydroxy group is subsequently oxidized to afford the corresponding ketone, which undergoes a Lewis acid catalyzed ring expansion with diazo(trimethylsilyl)methane followed by desilylation to yield the α,β-unsaturated ketone ‌90‌ that is converted into (+)-frondosin A (‌15‌).

‌Meeeee 88‌ Mee Meeeeeee Meeeeee Meeeeeeeeeeee ee eee Meeee Meeeeeeee ee (+)-Meeeeeeee M[‌88‌]

References