Organocatalytic Synthesis Of Chiral 3-Nitro-1,2-dihydroquinolines And 3-Nitro-2H-thiochromene

With the potential for savings in cost,an easier experimental procedure and reductions in waste,the field of organocatalysis grew quickly since it had been publicly defined.Chiral 1,2-dihydroquinolines and 2H-thiochromenes can be used as structural motifs and synthetic intermediates in natural product synthesis.And they can be converted into chiral 1,2,3,4-tetrahydroquinolines and thiochromanes,which also have immense importance in the design new compounds for pharmaceutical use.Inspired by the previous studies,and based on our understanding of corresponding reaction mechanisms,we envisioned that a domino aza-Michael-Henry reaction between N-protected-2-aminobenzaldehyde and trans-?-nitroolefin might take place to afford chiral 3-nitro-1,2-dihydroquinolines.And chiral 1,2-dihydroquinoline was achieved with high yield and enantioselectivity.Based on the literatures,we proposed an “iminium-deprotonation activation” mode,and experiment was designed with the help of this mode.After that,the optimized reaction condition has been established.Then we found this domino aza-Michael-Henry reaction is applicable to different 2-sulfonamidebenzaldehydes with trans-?-nitroolefins.Corresponding chiral 3-nitro-1,2-dihydroquinolines were obtained in 62-99% yields and with up to 88% ee.In addition,a preliminary study showed that 2-mercaptobenzaldehyde derivatives could participate in a thia-Michael-Henry reaction with trans-nitroolefins to yield chiral 3-nitro-2H-thiochromenes.Although the yield is very high,the enantioselectivity of chiral 2H-thiochromene is moderate.Consequently,we explained reasons for the decrease of enantioselectivity compared to the chiral 2H-chromene resulted from the “iminium-deprotonation activation” mode.