2-Chlorobicyclo[2.2.1]hept-5-ene-2-carboxamide and 2-chlorobicyclo[2.2.1]heptane-2-carboxamide as precursors of bicyclo[2.2.1]hept-5-en-2-one and bicyclo[2.2.1]heptan-2-one: resolution, absolute configuration and hydrogen-bonding properties

The absolute configuration of bicyclo[2.2.1]heptan-2-one has not been correlated with a crystal structure of a chemical precursor. The only chemical correlation available had an ambiguity, which could have reversed the assignment. Herein, we report the resolution of 2-chlorobicyclo[2.2.1]hept-5-en-2-exo-carboxamide on a cellulose triacetate column and the crystal structures of the enantiomerically pure and racemic α-chloroamide. We found the absolute configuration (1R,2R,4R) for the (+)-enantiomer of the α-chloroamide. This compound was converted to (+)-bicyclo[2.2.1]hept-5-ene-2-one by base hydrolysis, and the 5,6-unsaturated compounds converted to the saturated congeners. This is the first unambiguous experimental determination of the absolute configuration of bicyclo[2.2.1]heptan-2-one and of bicyclo[2.2.1]hept-5-ene-2-one. The three crystal structures of 2-chlorobicyclo[2.2.1]hept-5-en-2-exo-carboxamide reported herein reveal H-bonded dimers, with two distinct orientations of the bicyclic portion relative to the carboxamide dimer. In the racemic crystal, each dimer is composed of two enantiomers, and the bicyclic portions have their bridge carbon atom (C-7) on opposite sides of the H-bonded carboxamide dimer moiety. In the enantiomerically pure crystals, the major dimer had both C-7 atoms on the same side of the carboxamide dimer moiety while the minor dimer had the C-7 atoms on opposite sides. The dimers are present in solution, and can be easily monitored.

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(−)-Bicyclo[2.2.1]hept-5-en-2-oneC7H8O[α]D20=-1067 (c 0.9, CHCl3)Absolute configuration: (1S,4S)

(−)-2-Chlorobicyclo[2.2.1]heptane-exo-2-carboxamideC8H12ClNO[α]D20=-25 (c 1.0, CHCl3)Absolute configuration: (1R,2S,4S)

(−)-Bicyclo[2.2.1]heptan-2-oneC7H10O[α]D20=-27 (c 1.1, CHCl3)Absolute configuration: (1R,4S)

(−)-2-Chloro[2.2.1]hept-5-ene-exo-2-carboxamideC8H10ClNO[α]D20=-60 (c 0.6, CHCl3)Absolute configuration: (1S,2S,4S)