Substituted Dihydroisoquinolinones by Iodide-Promoted Cyclocarbonylation of Aromatic α-Amino Acids

Abstract

Imidazolidinone derivatives of a range of aromatic -amino acids, on treatment with phosgene and potassium iodide, undergo a mild Bischler-Napieralski-style cyclocarbonylation reaction that generates a tricyclic lactam by insertion of a C=O group between amino acid nitrogen and the ortho position of the aryl substituent. Regio-and diastereoselective functionalization of the lactam generates a library of substituted dihydroisoquinolinones and their congeners in enantioenriched form.

N-Chloroformylimidazolidinone Enolates as 1,3-Dipolar Reagents for the Stereoselective Synthesis of 3,4-Dihydroisoquinolones

“…23 The differences in reactivity under the two sets of reaction conditions suggest that different intermediates are generated. We propose that KI leads to a transient carbamoyl iodide, 16,24 whereas AlCl3 promotes formation of an N-acylium ion, with the carbamoyl iodide being more sensitive to the geometry of imidazolidinone substituents.…”

“…We previously reported that an intramolecular KI-promoted Friedel-Crafts cyclization of N-chloroformylimidazolidinones derived from aromatic amino acids such as L-phenylalanine, provides an efficient synthesis of certain substituted 3,4dihydroisoquinolones (Scheme 1). 16…”

Asymmetric and Geometry‐Selective α‐Alkenylation of α‐Amino Acids

“…N ′‐Alkenylureas 3 may be made by isomerization of their N ′‐allyl congeners, so we began by preparing N ′‐allylureido imidazolidinones 2 (Scheme ) from l ‐alanine. Either the syn or the anti diastereoisomer of 2 a could be made selectively from a common imine intermediate 1 a by choice of conditions, with acylation of the imine with a carbamoyl chloride at elevated temperatures giving syn ‐ 2 a , and anti ‐ 2 a being obtained by acylating N ‐methylallylamine with the anti carbamoyl chloride generated using phosgene and pyridine …”

Recent Advances in Synthesis of 3,4‐Dihydroisoquinolin‐1(2H)‐one

“…The cyclized product (3S,10aS)-3-(tert-butyl)-2-methyl-2,3,10,10a-tetrahydroimidazo [1,5-b]isoquinoline-1,5-dione can be used to get the functionalized dihydroisoquinolinones via the by regio-and diastereose- lective alkylation followed by the acidic hydrolysis of the imidazolidinones to get enantiopure dihydroisoquinolinones carboxylic acids (Scheme 74). [91] S. Cui et al demonstrated the silver catalyzed cascade phosphorylation/cyclization of propene having N-cyanamide to dihydroisoquinolinones. The propene containing N-acylcyanamides on treatment with diphenylphosphineoxide in presence of the 1 equivalent of silver nitrate cyclized to phosphorous incorporated dihydroisoquinolinones.…”