Amino alcohol B is an important intermediate in the synthesis of Crixivan® that is a potent HIV prot — Physical Chemistry Chemistry Question
Crixivan®
Amino alcohol B is an important intermediate in the synthesis of Crixivan® that is a potent HIV protease inhibitor. Chemists from Merck wanted to use the epoxide A as a starting material of the synthesis process.
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Upon treatment of A with benzyl amine in the presence of a weak acidic catalyst, they obtained mainly the undesired amino alcohol C along with some of the desired product D that could serve as a precursor of B. Draw the structure of C and a mechanism leading to this compound. Take into account stereochemical and regiochemical issues.
Model Answer
Formation of C (SN2 pathway): back side attack on benzylic position; the positive charge in the transition state at the reaction centre is stabilized by the phenyl group.
Formation of C and D (SN1 pathway): regioselective opening at the benzylic position due to resonance stabilization of the resulting carbocation by the phenyl group.
After the treatment of A with concentrated H2SO4 and acetonitrile under thermodynamic conditions, only E formed that was subsequently hydrolyzed to B. Draw the structure of E and a mechanism leading to this compound. Take into account stereochemical and regiochemical issues.
Model Answer
Only the cis–anellated product E can form. The trans–anellated compound F can not form from two five membered rings because of severe ring strain.