Importance of the CH/π hydrogen bond in the enhancement of CD amplitude of exomethylene steroids

Introduction of an axial methyl group to a bridgehead carbon has been known to enhance the circular dichroism (CD) amplitude of exomethylene steroids such as 4- and 6-methylene-5 alpha-estrane, at ca. 200 nm (pi/pi* transition). To investigate the effect of a methyl group on the rotational strength of these steroids, time-dependent density functional theory (DFT) calculations were carried out at the M06-2X/6-311++G(d,p)//MP2/6-31G(d, p) level. It has been shown that the replacement of the bridgehead hydrogen atom at position 10 of these steroids by a methyl group influenced the CD amplitude at the pi/pi* transition. Analysis of natural bonding orbital (NBO) charges of relevant atoms has provided data consistent with this finding. In view of this, we suggest that the enhancement of the CD amplitude by methyl substitution beta to the carbon-carbon double bond originates from the CH/pi hydrogen bond occurring between CH groups and the pi-system.