Starting from plain tropinone, Grignard addition of p-fluorophenylmagnesium bromide to tropinone in THF gives the tertiary alcohol pictured in the top center. This is dehydrated with KHSO4 to the alkene in the top right.
Then the alkene is hydroborated to get anti-Markovnikov addition, which is reacted with N-chlorodiethylamine in one pot to get the anti-Markovnikov chloroalkane, which is then subjected to reaction with potassium cyanide to get the nitrile.
Alcoholysis is performed on the nitrile in methanol to get the methyl ester, WIN-35,428.
Questions that are important:
My book on organometallics says that hydroboration is stereoselective to "cis addition" I assume this is important since we need to get the correct stereoisomer of WIN-35,428 for it to be worth a damn.
Also, by what mechanism does the reaction with N-chlorodiethylamine proceed? Does it switch the chirality of the stereocenter, or does it cause racemization? (yuk)
And again, would addition of -CN be SN1 or SN2? We may be switching the chiral center back and forth a couple times, and Im not familiar (yet) with this kind of stuff, so I'd rather ask for help than risk an incorrect guess as to which isomers are formed and how they survive the reactions.
So, what is the consensus?
PrimoPyro
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