Resolution approaches to enantiomers of 4-formyl[2.2]paracyclophane

Three techniques for the resolution of 4-formyl[2.2]paracyclophane were examined with the separation of the diastereomeric derivatives with (R)- and (S)-2-hydrazino-2-oxo-N-(1-phenylethyl)acetamide followed by their hydrolysis being found to be the most efficient, allowing (Rp)- and (Sp)-4-formyl[2.2]paracyclophanes to be obtained with 99.5% and 98.7% ee, respectively.

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(Sp)-[2.2]paracyclophane-4-carbaldehydeC17H16OEe = 98.7%[α]54625=+245 (c 0.41, CHCl3)[α]D25=+184 (c 0.41, CHCl3)[α]D25=+184 (c 0.44, CH2Cl2)[α]D25=+140 (c 0.43, toluene)Source of chirality: (S)-2-(2-((Sp)-[2.2]paracyclophane-4-ylmethylene)hydrazinyl)-2-oxo-N-(1-phenylethyl)acetamideAbsolute configuration: (Sp)

(Sp)-4-[(1S)-phenyl-ethylamino]methyl[2.2]paracyclophaneC25H25NEe = 88%[α]D25=+276 (c 0.44, C6H6)Source of chirality: (S)-(α-phenylethyl)amineAbsolute configuration: (Sp,S)

(R)-2-(2-((Sp)-[2.2]paracyclophane-4-ylmethylene)hydrazinyl)-2-oxo-N-(1-phenylethyl)acetamideC27H27N3O2Ee 86%[α]D25=+318 (c 0.38, CH2Cl2)Source of chirality: (R)-(+)-2-hydrazino-2-oxo-N-(1-phenylethyl)acetamideAbsolute configuration: (Sp,R)

(Rp)-4-[(1S)-phenyl-ethylamino]methyl[2.2]paracyclophaneC25H25NEe >98%[α]D25=-174 (c 0.50, C6H6)Source of chirality: (S)-(α-phenylethyl)amineAbsolute configuration: (Rp,S)

(R)-2-(2-((Rp)-[2.2]paracyclophane-4-ylmethylene)hydrazinyl)-2-oxo-N-(1-phenylethyl)acetamideC27H27N3O2Ee = 99%[α]D25=-281 (c 0.43, CH2Cl2)Source of chirality: (R)-(+)-2-hydrazino-2-oxo-N-(1-phenylethyl)acetamideAbsolute configuration: (Rp,R)