Diastereoselective Pictet–Spengler Based Synthesis of a Chiral Tetrahydroisoquinoline D1 Potentiator

A practical synthesis
of a D1 potentiator chiral tetrahydroisoquinoline
has been accomplished employing diastereoselective Pictet–Spengler
methodology to access the required trans-stereochemistry. A dynamic
kinetic resolution by crystallization gives high yields of a N-(phenylsulfonyl)­alkyloxazolidinone that is converted to
an acyl iminium ion when exposed to a variety of Lewis acids resulting
in a highly diastereoselective Pictet–Spengler cyclization.
An eight-step linear synthesis that starts with commercially available R-2-bromophenylalanine affords the chiral tetrahydroisoquinoline 1 in 54% overall yield.