Enantiomerically pure dihydroimidazoisoquinolinones by reaction of isoquinoline with amino acid fluorides

Asymmetric Synthesis of Isoquinoline Derivatives from Amino Acids

“…As could be shown with the tosyl-substituted tetrahydroisoquinoline 5e deprotection is possible by reaction with Na-naphthalide. [16] Since the resulting N-unsubstituted product 7a readily decomposed during the aqueous work-up in the presence of NH 4 Cl, it was preferably N-methylated or N-boc-protected to 7b and 7c, respectively (see Scheme 2). The structure of the tetrahydroimidazol[2.1-a]isoquinoline 7c was proved by X-ray crystal analysis (see Figure 3).…”

“…satd. NH 4 Cl solution (50 mL) was added and the mixture was extracted with AcOEt (4 × 20 mL). After drying of the combined organic layers with MgSO 4 , evaporation of solvent and column chromatography (hexane/AcOEt, 7:3 Ǟ AcOEt) 0.288 g (83 %) of the product 7c was obtained as colorless solidifying oil, which could be recrystallized from EtOH.…”

“…Recently, we investigated the stereoselective reaction of isoquinolines with α-aminoacyl fluorides [1,2] in the presence of AlCl 3 and trimethylsilyl chloride or trimethylsilyl cyanide affording either Reissert compounds (2-acyl-1-cyano-1,2-dihydroisoquinolines) [3] or novel dihydroimidazo[2,1-a]isoquinolin-3-ones 5 [4] via intermediate N-acyliminium salts. Remarkably the outcome of the reaction with trimethylsilyl cyanide depended on the type of protective group attached to the amino acid fluoride.…”

Diastereoselective synthesis of 3-substituted acylamino-3,4-dihydro-1,2,4-triazinones

“…1,2 Amino acid fluorides can also be used as chiral auxiliaries in reactions of this type. [3][4][5] We reported previously that 3-aryl-1,2,4-triazin-5(4H)-ones can give asymmetric products with high diastereoselectivity in reactions with C-nucleophiles in the presence of DCC-activated amino acids. 6 6-Phenyl-1,2,4-triazin-5(4H)-one 1 was acylated by N-substituted L-amino acids in the presence of ethyl chloroformate and reacted with C-nucleophiles yielding 3-substituted 2-(2-acylamino)acyl-6-aryl-3,4-dihydro-1,2,4-triazin-5(4H)-ones 2-6 in moderate yields but with high diastereoselectivity (Scheme 1, Table 1).…”

Efficient Asymmetric Synthesis of Reissert Compounds

“…4 Obviously, the N-acylisoquinolinium salts 3 primarily formed did not add cyanide but cyclised by intramolecular nucleophilic attack of the deprotonated tosylamino group at position 1 of the isoquinoline ring. Interestingly, N-arylsulfonylamino acid chlorides could be used by Ohsawa et al for asymmetric 1,2-addition of silylenol ethers or allylstannane to isoquinolines.…”