Cleft molecules as organocatalysts in an asymmetric hetero-Diels–Alder reaction

The synthesis and application of chiral carbocyclic cleft molecules derived from 2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-dione in the hetero-Diels–Alder reaction of benzaldehydes and aminodiene 14 is presented. Catalysis by single hydrogen-bond activation gave up to 52% ee.

Figure optionsDownload as PowerPoint slide

(+)-(1R,4S,5R,8S)-4-Amino-8-(1-naphthyl)-2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-8-olC27H23NOEe >99%[α]D20=+8.9 (c 0.9, CHCl3)Absolute configuration:(1R,4S,5R,8S)

(−)-(1R,4S,5R,8S)-4,8-Di(1-naphthyl)-8-methoxy-2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4-olC38H30O2Ee >99%[α]D20=-125 (c 0.27, CHCl3)Absolute configuration:(1R,4S,5R,8S)

(+)-(1R,4S,5R,8S)-4-Benzylamino-8-(1-naphthyl)-2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-8-olC34H29NOEe >99%[α]D20=+66 (c 0.79, CHCl3)Absolute configuration:(1R,4S,5R,8S)

(+)-(1R,5R,8S)-8-Hydroxy-8-(1-naphthyl)-2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4-oneC27H20O2Ee >99%[α]D20=+208 (c 1.19, CHCl3)Absolute configuration:(1R,5R,8S)

(+)-(1R,5R,8S)-8-Methoxy-8-(1-naphthyl)-2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4-oneC28H22O2Ee >99%[α]D20=+126 (c 1.03, CHCl3)Absolute configuration:(1R,5R,8S)

(−)-(1S,4S,5S,8S)-4,8-Di(2-naphthyl)-2,3:6,7dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-diolC37H28O2Ee >99%[α]D20=-228 (c 1.07, CHCl3)Absolute configuration:(1S,4S,5S,8S)

(−)-(1S,4R,5S,8R)-4,8-Di(2-methoxyphenyl)-2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-diolC31H28O4Ee >99%[α]D20=-84 (c 0.96, CHCl3)Absolute configuration: (1S,4R,5S,8R)

(−)-(1S,4S,5S,8S)-4,8-Diphenyl-2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-diolC29H24O2Ee >99%[α]D20=-75 (c 1.3, CHCl3)Absolute configuration: (1S,4S,5S,8S)

(−)-(1S,4R,5S,8R)-4,8-Di(1-naphthyl)-2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-diolC37H28O2Ee >99%[α]D20=-101 (c 1.00, CHCl3)Absolute configuration: (1S,4R,5S,8R)