Novel stereoselective synthesis of 2,3-dihydro-1H-benzo[f]chromen-3-amine derivatives through a one-pot three-component reaction

A short and stereoselective novel synthesis of benzo[f]chromen-3-amine derivatives in good yields, through a three-component aromatic Betti type reaction under solvent free conditions is reported. The spontaneous reaction occurs in the absence of acid catalysts. The use of chiral 1-phenylethylamine or α,β-unsaturated aldehydes allowed us to prepare enantiopure benzo[f]chromen-3-amine derivatives with good stereoselectivity. Conformational analysis compared with the 1H NMR data of the products obtained, allowed us to the determine the absolute configuration, which was also confirmed by X-ray analysis.

Figure optionsDownload as PowerPoint slide

(1S,3R)-2,3-Dihydro-1-methyl-N-((R)-1-phenylethyl)-1H-benzo[f]chromen-3-amineC22H23NOEe = 98%[α]D20=+54.5 (c 2.4, CHCl3)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: (S,R,R)

(1R,3R)-2,3-Dihydro-1-phenyl-N-((R)-1-phenylethyl)-1H-benzo[f]chromen-3-amineC27H25NOEe = 98%[α]D20=+178.0 (c 0.31, CHCl3)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: (R,R,R)

(1S,3S)-2,3-Dihydro-1-phenyl-N-((R)-1-phenylethyl)-1H-benzo[f]chromen-3-amineC27H25NOEe = 98%[α]D20=-67.8 (c 0.42, CHCl3)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: (S,S,R)

(1R,2S,3R)-2,3-Dihydro-2-methyl-1-phenyl-N-((R)-1-phenylethyl)-1H-benzo[f]chromen-3-amineC28H27NOEe = 98%[α]D20=+126.4 (c 0.41, CHCl3)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: (R,S,R,R)

(1R,2R,3S)-2,3-Dihydro-2-benzylamino-5,5-dimethyl-benzo[10,15-f]chromen[3,8-c]norpineneC27H29NOEe = 98%[α]D20=+31.2 (c 1.4, CHCl3)Source of chirality: (1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carbaldehydeAbsolute configuration: (R,R,S,S,S)

(1R,2R,3S)-2,3-Dihydro-2-[N(R)-1-phenylethyl]amino-5,5-dimethylbenzo[10,15-f]chromen[3,8-c]norpineneC28H31NOEe = 98%[α]D20=+38.3 (c 1.6, CHCl3)Source of chirality: (1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carbaldehydeAbsolute configuration: (R,R,S,R,S,S)