ALKYLATION OF THE ISOQUINOLINE SKELETON IN THE 1-POSITION: LITHIATED 2-PIVALOYL- AND 2-BIS(DIMETHYLAMINO)-PHOSPHINOYL-1,2,3,4-TETRAHYDROISOQUINOLINES

Article abstract of DOI:10.1016/S0040-4020(01)91914-3

Nucleophilic reactivity in the 1-position of 1,2,3,4-tetrahydroisoquinoline is generated by lithiation of the N-pivaloyl- (16a) and N-phosphinoyl-derivatives (17a).The organolithium compounds (16b, 17b) thus obtained are highly nucleophilic and can be alkylated even with poor alkylating reagents such as secondary halides, neopentyl bromide and cyclopentanone.Hydrolysis of the phosphorylamide products with hydrochloric acid leads to 1-substituted tetrahydroisoquinolines in excellent yields (Table 2).