Chemistry Reference
In-Depth Information
Scheme 1.2
As expected, compound
89
underwent C-14 chlorination and
90
underwent C-17
chlorination. Other chlorinating agents could also be used. In particular, SO
2
Cl
2
was able to selectively chlorinate
88-90
by transferring a Cl atom from a ClSO
2
inter-
mediate radical (liberating SO
2
), and then generating this radical after Cl transfer to the
steroid radical.
Why does this work? Why does an externally generated reagent not directly attack the
substrate but instead transfer an atom to the template, which then leads to attack on the
C-H bond with geometric control of the attack position? The reason is the same as that
which causes many hydrolytic enzymes to cleave a peptide bond in two steps by first
forming an ester intermediate with a serine hydroxyl group and then later using water
to hydrolyze that ester. By the time the water attacks, with loss of translational entropy,
the amine component of the original peptide bond is freely moving and has gained
translational entropy. In our radical relay mechanism, the PhI molecule - formed by
chlorine atom transfer to the large accessible iodine atom of the template - is freely
