Synthesis And Asymmetric Hydrogenation Of Novel Cyclic Enamides: (Z)-3-Arylidene-4-acyl-3, 4-dihydro-2H-benzoxazines

A series of 3-arylidene-4-acetyl-3,4-dihydro-2H-1,4-benzoxazines weresynthesized, and detailed optimization studies on asymmetric hydrogenation ofthese substrates were outlined. The absolute configuration of chiral products wasestablished by NOE experiment and X-ray crystallographic analysis. Alkaloids(-)-Galipinine and (-)-Galipeine were synthesized using Ir-catalyzed asymmetrichydrogenation of quinoline derivatives as a key step.i) Synthesis and Studies on Asymmetric Hydrogenation of Novel CyclicEnamidesOptically active 3-alkyl-3,4-dihydro-2H-1,4-benzoxazines are the integralpart of many naturally occurring substances, chiral drugs and syntheticintermediates of a wide range of biologically active molecules. Asymmetrichydrogenation of 3-arylidene-4-acetyl-3,4-dihydro-2H-1,4-benzoxazines, whichcan be easily synthesized from commercially available o-nitrophenols in five steps,is a convenient route. 3-Benzylidene-4-acetyl-3,4-dihydro-2H-1,4-benzoxazinewas chosen as a typical substrate, the reaction conditions, such as the solvents,catalyst precursors, reaction pressure, were investigated in details. Up to 98.6% eehas been achieved with Rh-Me-DuPhos complex under the optimized conditions. The feature of the H and 1 13C NMR spectra of the hydrogenation productsmeasured at ambient temperature is broadening, high-resolution spectra can beobtained on heating in DMSO-d6 at 100oC. The absolute configuration of chiralproduct 12a was established by NOE experiment and X-ray crystallographicanalysis. ii) The Total Synthesis of Alkaloids (-)-Galipinine and (-)-Galipeine andDetermination of the Absolute Configuration The total synthesis of (-)-Galipinine was achieved in four steps with anoverall 56% yield from piperonyl alcohol using the asymmetric hydrogenation ofthe quinoline derivatives as a key step, and its absolute configuration is assignedto be S. Likewise, (-)-galipeine was achieved in seven steps with an overall 54%yield from commercially available isovanillin, and its absolute configuration isassigned to be S.