Asymmetric control in Diels–Alder cycloadditions of chiral 9-aminoanthracenes by relay of stereochemical information

Two approaches to the synthesis of chiral 9-amino anthracenes are described. The first, by nucleophilic addition of organolithium reagents to imines promoted by BF3·OEt2, unexpectedly provided stable aminoboranes as products. The second approach, using palladium catalysed cross coupling, was more successful for primary amines, and the key 9-(α-methylbenzylamino)anthracene subjected to cycloadditions with N-methyl maleimide and maleic anhydride. Excellent reactivity was achieved with good levels of diastereoselectivity, through a favourable combination of electrostatic and hydrogen bonding effects. Trial studies of the retro Diels–Alder reaction of these cycloadducts were also performed.

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(R)-9-(N-α-Methylbenzylamino)anthraceneC22H19NEe = 93%[α]D = +198 (c 0.5, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (R)

(R)-(+)-α-Methylbenzyl formamideC9H11NO[α]D = +168.6 (c 1, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (R)

(R)-(+)-N-Methyl-α-methylbenzylamineC9H13N[α]D = +77.7 (c 1, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (R)

9-[N-Methyl-N-(R)-α-methylbenzylamino]anthraceneC23H21N[α]D = +70 (c 1, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (R)

(3aS,9aS)-3a,4,9,9a-Tetrahydro-4-[(R)-α-methylbenzylamino]-2-methyl-4,9-[1′,2′]benzeno-1H-benzo[f]isoindole-1,3-(2H)-dioneC27H24N2O2[α]D = +50 (c 0.5, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (3S,9S,αR)

(11S,15S)-9,10,11,15-Tetrahydro-9-[(R)-α-methylbenzylamino]-9,10[3′,4′]-furanoanthracene-12,14-dioneC26H21NO3[α]D = +26 (c 1, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (3S,9S,αR)

1-Methyl-(3R)-(10-oxo-9,10-dihydroanthracen-9-yl) pyrrolidine-2,5-dioneC19H15NO3[α]D = +125 (c 0.08, CHCl3)Source of chirality: commercial (R)-α-methyl benzylamineAbsolute configuration: (R)