Effect of meso-substituents on the osmium tetraoxide reaction and pinacol-pinacolone rearrangement of the corresponding vic-dihydroxyporphyrins.
To investigate the effects of electron-donating and electron-withdrawing substituents upon the reaction of porphyrins with osmium tetraoxide, and the pinacol-pinacolone rearrangement of the resulting diols, a series of meso-substituted porphyrins were prepared by total synthesis. Porphyrins with electron-donating substitutents at the meso-positions gave vic-dihydroxychlorins in which the adjacent pyrrole subunit was predominantly oxidized. No such selectivity was observed in a porphyrin containing a methoxycarbonyl as the electron-withdrawing group, whereas a formyl substituent again resulted in oxidation at the pyrrole unit adjacent to the meso-substituent. Under pinacol-pinacolone conditions, vic-dihydroxy chlorins containing 4-methoxyphenyl or 3,5-dimethoxyphenyl groups at the meso-position showed preferential migration of the ethyl group over the methyl group to give 8-ketochlorins, whereas the diol with an n-heptyl substituent under similar reaction conditions gave both 7- and 8-ketochlorins. In contrast, the diol containing a meso-formyl substituent produced the corresponding 7-ketochlorin exclusively. These results indicate that it is not possible to predict the reactivity of meso-substituted porphyrins in the osmium tetraoxide reaction nor the general substituent migratory aptitudes in the pinacol-pinacolone rearrangement based on simple electronic arguments, most likely because many parameters (e.g., meso-beta-pyrrolic steric crowding and long-range electronic effects) ultimately determine the reactivity. The structural assignments of the porphyrin diols and the keto-analogues were confirmed by extensive (1)H NMR studies; some of the dihydroxychlorins and ketochlorins were found to display unusual features in their (1)H NMR spectra.
Chen
Y
Y
Chemistry Division, Photodynamic Therapy Center, NMR Facility, Molecular and Cellular Biophysics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Medforth
C J
CJ
Smith
K M
KM
Alderfer
J
J
Dougherty
T J
TJ
Pandey
R K
RK
D000478:Alkylation; D002074:Butanones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009993:Osmium Tetroxide / Q000737:chemistry*; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry*
D002074:Butanones; D011166:Porphyrins; C084935:pinacolone; D009993:Osmium Tetroxide