Asymmetric triple cascade organocatalytic reaction in water: construction of polyfunctional cyclohexene building blocks having multiple stereocenters

An asymmetric triple cascade organocatalytic reaction was carried out in water, which led to the construction of polyfunctional cyclohexene building blocks with multiple stereocenters with good diastereoselectivity and excellent enantioselectivity. This asymmetric triple cascade process was found to be quite effective for various nitroalkenes, including those with aliphatic substituents.

Figure optionsDownload as PowerPoint slide

(3S,4S,5R,6R)-3-Ethyl-5-nitro-4,6-diphenylcyclohex-1-enecarbaldehydeC21H21NO3[α]D20=-51 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4S,5S,6R)-3-Ethyl-5-nitro-4,6-diphenylcyclohex-1-enecarbaldehydeC21H21NO3[α]D20=-186 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5S,6R)

(3S,4S,5R,6R)-3-Methyl-5-nitro-4,6-diphenylcyclohex-1-enecarbaldehydeC20H19NO3[α]D20=-56 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4S,5R,6R)-5-Nitro-4,6-diphenyl-3-propylcyclohex-1-enecarbaldehydeC22H23NO3[α]D20=-36 (c 1.0 CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4S,5R,6R)-3-Benzyl-5-nitro-4,6-diphenylcyclohex-1-enecarbaldehydeC26H23NO3[α]D20=-16 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4S,5R,6R)-3-Isopropyl-5-nitro-4,6-diphenylcyclohex-1-enecarbaldehydeC22H23NO3[α]D20=-47 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4S,5R,6S)-6-(2-Chlorophenyl)-3-isopropyl-5-nitro-4-phenylcyclohex-1-enecarbaldehydeC22H22ClNO3[α]D20=+39 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6S)

(3S,4S,5R,6S)-6-(2-Bromophenyl)-3-isopropyl-5-nitro-4-phenylcyclohex-1-enecarbaldehydeC22H22BrNO3[α]D20=+51 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6S)

(3S,4S,5S)-3-Isopropyl-5-nitro-4-phenylcyclohex-1-enecarbaldehydeC16H19NO3[α]D20=+101 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5S)

(3S,4S,5R,6R)-3-Isopropyl-5-nitro-4-phenyl-6-m-tolylcyclohex-1-enecarbaldehydeC23H25NO3[α]D20=-51 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4S,5R,6R)-3-Isopropyl-6-(2-methoxyphenyl)-5-nitro-4-phenylcyclohex-1-enecarbaldehydeC23H25NO4[α]D20=+43 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4S,5R,6R)-4-(2-Chlorophenyl)-3-isopropyl-5-nitro-6-phenylcyclohex-1-enecarbaldehydeC22H22ClNO3[α]D20=+35 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4S,5R,6R)-4-(4-Bromophenyl)-3-isopropyl-5-nitro-6-phenylcyclohex-1-enecarbaldehydeC22H22BrNO3[α]D20=-58 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4S,5R,6R)-3-Isopropyl-4-(naphthalen-2-yl)-5-nitro-6-phenylcyclohex-1-enecarbaldehydeC26H25NO3[α]D20=-40 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4S,5R,6R)-3-Isopropyl-4-(3-methoxyphenyl)-5-nitro-6-phenylcyclohex-1-enecarbaldehydeC23H25NO4[α]D20=-32 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4R,5S,6R)-4-(Furan-2-yl)-3-isopropyl-5-nitro-6-phenylcyclohex-1-enecarbaldehydeC20H21NO4[α]D20=-73 (c 1.0, CHCl3)Absolute configuration: (3S,4R,5S,6R)

(3S,4S,5R,6R)-4-(2-Bromophenyl)-3-isopropyl-5-nitro-6-phenylcyclohex-1-enecarbaldehydeC22H22BrNO3[α]D20=+52 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4S,5R,6R)-4-(4-Chlorophenyl)-3-isopropyl-5-nitro-6-phenylcyclohex-1-enecarbaldehydeC22H22ClNO3[α]D20=-58 (c 1.0, CHCl3)Absolute configuration: (3S,4S,5R,6R)

(3S,4R,5R,6R)-4-Butyl-3-isopropyl-5-nitro-6-phenylcyclohex-1-enecarbaldehydeC20H27NO3[α]D20=-175 (c 0.5, CHCl3)Absolute configuration: (3S,4R,5R,6R)

(3S,4R,5R,6R)-4-(3-(tert-Butyldimethylsilyloxy)propyl)-3-isopropyl-5-nitro-6-phenylcyclohex-1-enecarbaldehydeC25H39NO4Si[α]D20=-98 (c 1.0, CHCl3)Absolute configuration: (3S,4R,5R,6R)