[RaZ]

Hi, I'm looking through the synthesis of 6S-Cephalosporin (see attached) but I can't seem to figure out the mechanism.  Within scheme 2 (of page 6054 in the attached file), I can't figure out how the mechanism to change the stereochemistry works...for example going from 11 to 12, how does adding NaH change the stereochemistry?  Also, in the middle steps, how does adding O3 (ozone) and Me2CO change the sulfer into the sulfoxy.  Any help will be greatly appreciated.

Thanks.

[movies]

The epimerization from 11 to 12 is pretty straightforward.  The base just deprotonates the alpha-position of the ketone to make an enolate and then the protonation is selective to form the thermodynamically more favorable product with the two alkyl substituents on the 4-membered ring anti to one another.

As for the ozone step, this is an oxidation reaction using a powerful oxidant (O₃).  Think of it like a peroxide.  You have an electron rich atom but also a weak O-O bond.  So you can transfer one of the oxygen to the sulfur and release O₂.  The sulfure atom has lone pairs which are nucleophilic enough to attack O and break the O-O bond.

[RaZ]

hey, thanks a lot.

another question tho, when the oxidation occurs why is it selective for the cis diastereomer (wouldn't this be the more unstable one?).  It says in the article 'when the mixture of the two diastereomers were oxidised with ozone in cold ethanol, selective formation of the desired sulfoxide occured' and also 'the high reactivity of the cis diastereomer may be attributed to the relative accessibility of the pro-(S) lone electron pair of the sulphur.'  By this does this mean that the ozone can approach from "above" the molecule in the cis configuration since there is no steric hinderance?  Thanks.

[movies]

You mean compound 49?  That's probably because the molecule has a convex face.  If you were to make a model of the compound you would find that one of those lone pairs points pretty much right into the center of the compound and the other points out to the outer, exposed face of the molecule.