5911-60-4

Upstream product

• 612-35-1 2-Benzylbenzoic acid 
• 7111-66-2 1-phenyl-1,3-dihydro-2-benzofuran 
• 124-38-9 carbon dioxide 
• 1586-00-1 2-(benzyl)benzyl alcohol 
• 79-22-1 methyl chloroformate 

Downstream Products

• 290347-03-4 (4S*)-N-[(R)-2-hydroxy-1-phenylethyl]-4-phenyl-1,4-dihydroisoquinolin-3-one 
• 290347-00-1 (4S*)-N-[(R)-2-hydroxy-1-phenylethyl]-4-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 290346-99-5 N-[(R)-2-hydroxy-1-phenylethyl]-4-phenyl-1,4-dihydroisoquinolin-3-one 
• 153218-97-4 (4S)-(-)-4-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 28102-51-4 (4S*)-N-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline 

Relevant academic research and scientific papers

Diastereoselective protonation of lactam enolates derived from (R)-phenylglycinol. A novel asymmetric route to 4-phenyl-1,2,3,4-tetrahydroisoquinolines

(equation presented) Highly diastereoselective protonation of chiral lactam enolates of 4-substituted-1,4-dihydroisoquinolin-3-ones is reported. Protonation and alkylation processes of these lactam enolates derived from phenylglycinol occur with opposite diastereofacial selectivity. This diastereoselective protonation has been applied to the asymmetric synthesis of (4S)-N-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline 9 obtained in up to 97% ee.

Electron-transfer-induced reductive cleavage of phthalans: Reactivity and synthetic applications

The behavior of phthalan (1a) was investigated under conditions of electron transfer from alkali metals in aprotic solvents. Reaction with lithium in the presence of a catalytic amount of naphthalene in THF led to the reductive cleavage of an arylmethyl carbon-oxygen bond, with formation of a stable dilithium compound. Trapping of this intermediate with several electrophiles (alkyl halides, carbonyl derivatives, CO2) was successful. The extension of this procedure to several substituted phthalans (1b-i) was investigated, and the regiochemistry as well as the synthetic usefulness of these reactions are discussed.

Reductive electrophilic substitution of phthalans and ring expansion to isochroman derivatives

Reductive cleavage of phthalan, 1a, with Li metal in the presence of a catalytic amount of naphthalene leads to the formation of a stable aromatic dilithium compound. The adducts of the latter with CO2, aldehydes or ketones undergo ring closure to isochroman derivatives, leading to ring expansion of the original heterocycle. The reductive electrophilic substitution procedure was successfully extended to the substituted phthalans 1b and 1c, to afford the corresponding isochroman-3-ones in satisfactory yields.