Efficient lipase-catalysed route for the kinetic resolution of salsolidine and its ß-carboline analogue

Racemic 1-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 1 and 1-methyl-1,2,3,4-tetrahydro-s-carboline 3 were resolved through lipase-catalysed asymmetric acylation on the secondary amino group. High enantioselectivities (E >200) were observed when the acylation of racemic 1 was performed with phenyl allyl carbonate in the presence of Candida rugosa lipase in toluene at 40 °C or with Candida antarctica lipase B in tert-butyl methyl ether at 50 °C. Excellent enantioselectivity (E >200) characterised the CAL-B-catalysed acylation of racemic 3 with phenyl allyl carbonate in the presence of triethylamine in tert-butyl methyl ether at 50 °C. The product (R)-carbamates (ee >97%) were hydrolysed into the corresponding (R)-enantiomers of the free amines 1 and 3 (ee = 99%) with the use of Pd2(dba)3·CHCl3 catalyst.