Synthesis of tyrosine-derived tetrahydroisoquinolines by lewis acid catalyzed cyclization of N-(Phenyisulfonyl)alkyloxazolidinones

N-Boc-protected tyrosine esters 5a,b were converted into tetrahydroisoquinolines 13 and 14 in four steps by reduction and ring closure to oxazolidinones 9 and 10, addition of benzenesulfinic acid and aldehydes to sulfones 11 and 12 and subsequent Lewis acid catalyzed cyclization. In the case of m-tyrosine derivative 5a, selective protection with bromine prevented the formation of undesired regioisomers. Debromination of target compounds 13 was readily achieved under radical reduction conditions by using Bu3SnH/AIBN. Tetrahydroisoquinolines 13 and 14 were isolated as single diastereomers whose trans configuration was confirmed by Xray crystal structure analysis. Partial epimerization of trans-13i and trans-21 to the corresponding cis diastereomers was achieved under basic conditions.