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 -(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 -2-bromophenylalanine affords the chiral tetrahydroisoquinoline in 54% overall yield.
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