Hai-Ying He

Stereoselective syntheses of chiral (3S,9bS)-1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones

Abstract Chiral (3S,9bS)-1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones 11a–11f, 14b,14c and 17a,b were prepared in 78–93% yields with high stereoselectivities (d.e. >99%) by the intermolecular condensations of 2-formylbenzoic acids 10 or 13 or 2-acetylbenzoic acid 15 with chiral diamines 9a–9f and 9h. Compounds 9a–9f and 9h were readily prepared in three steps from optically active N-Boc-α-amino acids 5a–5d.

Convenient syntheses of dihydropyrrolo[2′,1′:3,4]pyrazino- and dihydropyrrolo[2′,1′:3,4][1,4]diazepino-[2,1-a]isoindolones

Abstract Dihydropyrrolo[2′,1′:3,4]pyrazino[2,1-a]isoindolones 10a–10c were obtained in 76–81% yields by the reaction of 2-(1H-pyrrol-1-yl)ethylamine 8 with 2-formylbenzoic acids 9a , 9b or 2-acetylbenzoic acid 9c via N-acyliminium cation aromatic cyclizations. Similarly, dihydropyrrolo[2′,1′:3,4][1,4]diazepino[2,1-a]isoindolones 12a , 12b were prepared in one-pot reactions from 3-(1H-pyrrol-1-yl)propylamine 11 and 2-formylbenzoic acids 9a , 9b .

2-Substituted-1,2,3,4-tetrahydroisoquinolines and chiral 3-carboxyl analogues from N-benzotriazolylmethyl-N-phenethylamines

Abstract N- Benzotriazolylmethyl- N -phenethylamines 5a – 5c and 11a – 11c cyclize in the presence of aluminum chloride to produce 1,2,3,4-tetrahydroisoquinolines 6a – 6c and 12a – 12c (70–89%) via electrophilic attack of a transient iminium cation X on the tethered phenyl ring. The Bt group in 2 - benzotriazolylmethyl-1,2,3,4-tetrahydroisoquinolines 6a – 6b was replaced (i) with hydrogen by sodium borohydride to afford N -methyl-1,2,3,4-tetrahydroisoquinolines 7a – 7b or (ii) by nucleophiles, such as Grignard reagents, a silyl enol ether or triethyl phosphite, to furnish novel N -substituted-1,2,3,4-tetrahydroisoquinolines 13a – 13c , 14 or 15 , respectively. Optically active 3-substituted-1,2,3,4-tetrahydroisoquinolines 12a – 12c were similarly prepared in high yields without racemization.

Convenient syntheses of 2,3,4,5-tetrahydro-1,4-benzothiazepines, -1,4-benzoxazepines and -1,4-benzodiazepines

4-Benzotriazolylmethyl-2,3,4,5-tetrahydro-1,4-benzothiazepines 5a,b, -1,4-benzoxazepine (12) and -1,4-benzodiazepine (20) are obtained via aluminium chloride mediated intramolecular cyclizations of N,N-bis(1H-1,2,3-benzotriazol-1-ylmethyl)-2-(arylthio)ethan-1-amines 4a,b, -2-(phenoxy)ethan-1-amine (11) and -N-[2-(N′-methylanilino)ethyl]amine (19), respectively. Subsequent nucleophilic substitutions of the benzotriazolyl group in 5a,b, 12 and 20 succeeded with Grignard reagents, triethyl phosphite, sodium borohydride, and a silyl enol ether to give novel 2,3,4,5-tetrahydro-1,4-benzothiazepines 6–9, -1,4-benzoxazepines 13 and 14, and -1,4-benzodiazepines 21–23 in good yields.

Stereoselective syntheses of 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones

1H-Imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones 6a–i are synthesized in 67–96% yields with high stereoselectivities (de 88–99%, except 6e with a 58% de value) via intermolecular condensation of 2-formylbenzoic acid (5) and α-amino amides 4a–i in the presence of a catalytic amount of toluene-p-sulfonic acid. Intermediates 4 are obtained in two steps from easily available chiral N-Boc-α-amino acids 1.