Total Synthesis Highlights

To complete the synthesis of 3, it was necessary to construct the strained paracyclophane. The
authors took advantage of the facile cyclization of the thiolate liberated from 19, then installed the
ring-contracted alkene with a Ramburg-Bäcklund rearrangement. They completed the synthesis of
(+)-Hirsutellone B (3) by exposing the ketone 22 to NH 3 in CH 3 OH/H 2 O.
D. F. Taber, Org. Chem. Highlights 2010, July 5.
URL: http://www.organic-chemistry.org/Highlights/2010/05July.shtm
11. The Magnus Synthesis of (±)-Codeine
Although there have been many synthetic approaches to morphine and its methyl ether codeine (3),
the pentacyclic structure of these Papaver alkaloids continues to intrigue organic chemists. Philip
Magnus of the University of Texas devised (J. Am. Chem. Soc. 2009, 131, 16045.) an elegant
route to 3 based on the conversion of 1 to 2 by way of an intramolecular Michael addition.
The starting point for the synthesis was the commercial bromoaldehyde 4. Coupling with 5
delivered the substituted biphenyl 6, that was carried on to the mixed bromo acetal 8. On exposure
to fluoride ion, 8 was desilylated, and the intermediate phenoxide cyclized with impressive facility
to give 1. Exposure of 1 to nitromethane delivered the tetracyclic 2. This reaction apparently was
initiated by Henry addition of the nitromethane to the aldehyde. The intramolecular Michael
addition of the intermediate Henry adduct then proceeded to give the desired cis diastereomer of
the newly formed ring. Finally, loss of water gave 2.
Conjugate reduction of the nitroalkene 2 led to 9 with remarkable diastereocontrol. Exposure of 9
to LiAlH 4 converted the nitro group to the amine, and the enone to the allylic alcohol. On
exposure to acid, the hemiacetal was hydrolyzed. The liberated aldehyde underwent reductive