ChemInform Abstract: Syn-Selective Michael Addition of Amines to Bis-enones: Synthesis of 1, 3,4,7-Tetrasubstituted (4R,5S,6S,7R)-Hexahydro-5,6-dihydroxy-2H-1,3- diazepin-2-ones.

✍ Scribed by E. P. SCHREINER; A. PRUCKNER

• Publisher: John Wiley and Sons
• Year: 2010
• Weight: 37 KB
• Volume: 28
• Category: Article
• ISSN: 0931-7597
• DOI: 10.1002/chin.199752177

✦ Synopsis

Syn-Selective Michael Addition of Amines to Bis-enones: Synthesis of 1, 3,4,7-Tetrasubstituted (4R,5S,6S,7R)-Hexahydro-5,6-dihydroxy-2H-1,3-diazepin-2-ones.

-The O-protected title compounds (IX), seven-membered cyclic ureas, are useful as intermediates in the synthesis of HIV-proteinase inhibitors. Their preparation was achieved in a three-step sequence starting with diethyl isopropylidene-L-tartrate (I). The bis-enones (III) are produced as a mixture of their E,E-, E,Z-and Z,Z-stereoisomers, which on treatment with amines give predominantly the desired C2-symmetric derivates (V) together with the asymmetric (VI) and in the case of (Vc) in addition 16% of the monoadduct. The diastereoselectivity depends on the reaction temperature and the configuration of the starting olefin. This approach could be extended to asymmetric substituted cyclic ureas (XI) by controlled monoaddition of (IVa) to (IIIa), providing the monoaddition product (X), which is reacted with a second amine followed by cyclization.

-(SCHREINER, E. P.; PRUCKNER, A.;