nan Jahangir

Preparation of N-Arylated Heterocycles by Nucleophilic Aromatic Substitution

Abstract Nucleophilic aromatic substitution of fluorobenzoates and fluorophenylnitriles with weakly basic heterocycles readily occur. This synthetic methodology is utillized to produce potent angiotensin-II antagonists.

Effects of remote N-(tert-butoxycarbonyl) groups on heteroatom directed lithiation at benzylic positions☆

Abstract Lithiation of N-BOC-2-methylphenethylamine (6) occurs exclusively at the methyl group whereas lithiation of the phenylpropyl congener (11) is less regioselective. N-BOC-phenylpropylamine (17) is efficiently lithiated at the benzylic position while N-BOC-2-methylphenylbutylamine (23) undergoes lithiation of the methyl group but with low conversion. The results are discussed from the general perspective of heteroatom-directed metalation. Several of the lithio derivatives can be converted to heterocycles, e.g., tetrahydro-3-benzazepin-2-one (10), hexahydro-3-benzazocin-2-one (16) and 3-phenylpyrrolidines (19–22).

The Activation of Imines to Nucleophilic Attack by Grignard Reagents

Abstract The reaction of trimethylsilyl trifluoromethanesulfonate (trimethylsilyl triflate, TMSOTf) with imines leads to the formation of N-trimethylsilyliminium salts which react efficiently with soft nucleophiles to form secondary amines.

Synthesis of naucléfine, angustidine, angustine, (±)-13b,14-dihydro-angustine and naulafine

Abstract The lithio derivatives of 3-cyano-4-methylpyridines and 6,7-dihydro-5H-2-pyrindine-4-carbonitrile react with 2,9-bis-(trimethylsilyl)-3,4-dihydropyrido[3,4-b]indolium trifluoromethanesulfonate to form cyclic amidines which, upon hydrolysis and oxidation, produce the title alkaloids.

Preparation of Tetrahydroisoquinolines from N-(tert-Butoxycarbonyl)-2-methylbenzylamines

Dilithiation of N-(tert-butoxycarbonyl)-2-methylbenzylamine (1a) followed by treatment with N,N-dimethylformamide affords 2-(tert-butoxycarbonyl)-3-hydroxy-ltetrahydroisoquinoline (3a). Dehydration and reduction of 3a afford BOC-tetrahydro-isoquinoline (5a). The methodology is also applicable to synthesis of chloro and fluoro substituted tetrahydroisoquinolines (5b,c), 3 and 4 substituted derivatives (8, 10), and the hexahydro-2H-benzoquinolizine ring system (13)

Synthesis of naucléfine, angustidine, angustine, and (±)-13b, 14-dihydroangustine

2,9-Bis-(trimethylsilyl)-3,4-dihydropyrido[3,4-b]indolium trifluoromethanesulphonate reacts with the lithio derivatives of 3-cyano-4-methylpyridines to generate pentacyclic amidines which, upon hydrolysis and oxidation, produce nauclefine, angustine, and angustidine.

Diastereoselective addition of lithiated N,N-diethyl-o-toluamide to chiral isopropylidine glyceraldehyde lmines. Asymmetric synthesis of 3-substituted 3,4-dihydro-1(2H)-isoquinolones

The lithio derivative of N,N-diethyl-o-toluamide adds regiospecifically to (R)-and (S)-glyceraldehyde acetonide p-methoxybenzyl imines to afford the Cram-chelation controlled products (3S,1′R)-(3) and (3R,1′S)-(3),respectively.

Activated imines as carbon electrophiles: applications in alkaloid synthesis

3,4-Dihydroisoquinolines and 3,4-dihydro-β-carbolines react with trimethylsilyl trifluoromethanesulphonate to form complexes that react readily with the lithio derivatives of 3-cyano-4-methylpyridines; the method has been applied to the synthesis of the Alangium alkaloids, (±)-alangimaridine and alangimarine.