78702-72-4

Upstream product

• 100-44-7 benzyl chloride 
• 78702-55-3 2-bis(dimethylamino)phosphinoyl-1-methyl-1,2,3,4-tetrahydroisoquinoline 
• 91-21-4 1,2,3,4-tetrahydroisoquinoline 
• 76068-81-0 1-(3,4-dihydroisoquinolin-2(1H)-yl)-2,2-dimethylpropan-1-one 
• 78702-53-1 2-bis(dimethylamino)phosphinoyl-1,2,3,4-tetrahydroisoquinoline 

Downstream Products

• 81763-86-2 1-benzyl-1-methyl-1,2,3,4-tetrahydroisoquinoline 

Relevant academic research and scientific papers

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

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).

2-Bis(dimethylamino)phosphinoyl-1-lithio-1,2,3,4-tetrahydro-isoquinoline. A Highly Nucleophilic d1-Reagent for the Preparation of 1-Substituted Tetrahydroisoquinolines

The title compound 4 is generated from the phosphoric amide 5 in tetrahydrofuran with butyllithium.The lithium reagent 4 is stable at room temperature; its reactions with electrophiles furnish the products 6-22, 26,27, see Table 1 and the Scheme.A second alkylation is also possible, see 23-25.The cleavage to tetrahydroisoquinolines is accomplished in refluxing aqueous-methanolic hydrochloric acid, see Table 2.Phosphinoylation, lithiation, reaction with electrophiles and cleavage constitute an efficient sequence for 1-alkylation of the isoquinoline nucleus.