450375-12-9

Upstream product

• 450375-10-7 N-benzyl-N-methyl-P,P-di-1-naphthylphosphinamine 
• 450375-09-4 dichloro-N-benzyl-N-methylphosphinamine 
• 103-67-3 benzyl-methyl-amine 

Downstream Products

• 28170-21-0 bis(naphthalen-1-yl)phosphinic acid 

Relevant academic research and scientific papers

Dearomatizing anionic cyclization of N-alkyl-N-benzyl(dinaphthyl) phosphinamides. A facile route to γ-(amino)dihydronaphthalenylphosphinic acids

(Chemical Equation Presented) The dearomatizing anionic cyclization of N-alkyl-N-benzyldi(n-naphthyl)phosphinamides (n = 1, 2) and subsequent trapping with a series of electrophiles (MeOH, MeI, CF3SO3Me, Me3O+BF4-, AllylBr, and PhCH 2Br) have been accomplished. Optimized reaction conditions (base, temperature, reaction time) allow for synthesizing tetrahydro-1H-naphtho[1,2-c] [1,2]-azaphosphole 1-oxides 13 and 18 and tetrahydro1H-naphtho[2,1-c][1,2] azaphosphole 3-oxides 16 and 27-29 in high yield and diastereoselectivity. Appropriate selection of the base proved to be critical for promoting anionic cyclization of 2-naphthyl derivatives. The dearomatized heterocycles are transformed quantitatively into γ-(N-alkylamino)phosphinic acids by acid hydrolysis of the P-N linkage. Bioactivity assays on five human tumor cell lines for one of these amino acids revealed growth inhibition factors (GI 50) at a micromolar scale. Additionally, evidence for the feasibility of intermolecular nucleophilic dearomatization and sequential nucleophilic attack to both aromatic rings of dinaphthylphosphinamides have been obtained.

Nucleophilic Naphthalene Dearomatization of N-Alkyl-N-benzyl(dinaphthyl)phosphinamides. Application to the Synthesis of γ-(N-Alkylamino)(dihydronaphthalenyl)phosphinic Acids

Lithiation of N-alkyl-N-benzyl(dinaphthyl)phosphinamides with s-BuLi at -90 deg C in THF promoted the dearomatization of one naphthalene ring through anionic cyclization. The intermediate lithium compounds were trapped with MeOH, MeI and allyl bromide affording benzo[e]-1-phosphaisoindoles with excellent stereoselectivities. Acid hydrolysis of the P-N linkage allowed to obtain γ-(N-alkylamino)phosphinic acids containing a dihydronaphthalene system. This structural fragment proved to be an element of conformational restriction.