Photo-Fries Rearrangement of Some 3-Acylestrones in Homogeneous Media: Preparative and Mechanistic Studies

Abstract

Irradiation of a series of 3-acylestrones under a nitrogen atmosphere in cyclohexane, acetonitrile (MeCN), and methanol (MeOH) was investigated under steady-state conditions. The molecules underwent the photo-Fries rearrangement, with concomitant homolytic fragmentation of the ester group and [1;3]-acyl migration. This pathway afforded the ortho-acyl estrone derivatives, the main photoproducts, together with estrone. During the irradiation of 3-benzoyl estrone, epimerization of estrone through the Norrish type I reaction occurred, providing lumiestrone as the photoproduct. This photoreaction involves the fragmentation of the C-α at the carbonyl group (C-17) of the steroid. On the other hand, epimerization of ortho-regioisomer 2-acetyl estrone occurred during the irradiation of 3-acetyl estrone. Photosensitization with acetone and chemical quenching with N,N,N,N-tetramethyldiazetinedioxide of the photo-Fries reaction confirmed that the photoreaction took place from the singlet excited state while the Norrish type I reaction proceeds efficiently from the triplet excited state. Solvent effects, as well as the nature of the acyl group on the photoreactions, were also studied.

Photochemical Behavior of Some Estrone Aryl and Methyl Sulfonates in Solution: Preparative and Mechanistic Studies

“…Therefore, the epimerization of the methyl group at C‐13 of compounds 1b , 2b and 3b , respectively, was not observed and no competition with deactivation pathways occurred. A similar behavior has been early observed for 3‐acyl estrone derivatives (39). On the other hand, epimerization of compounds 1a , 2a and 3a to photoproducts 1c , 2c and 3c , respectively, is due to the non‐planarity of the arylsulfonyl group with the benzene moiety disfavoring the intramolecular hydrogen bonding between the thionyl group and the hydroxyl group.…”

“…Oxidation of intermediate B by residual molecular oxygen and further reaction with methanol, affords compound 4b (see Scheme 5(b)). This photochemical behavior was also observed during irradiation of estrone methyl ether (39).…”

“…On the other hand, epimerization of compounds 1a , 2a and 3a to photoproducts 1c , 2c and 3c , respectively, is due to the non‐planarity of the arylsulfonyl group with the benzene moiety disfavoring the intramolecular hydrogen bonding between the thionyl group and the hydroxyl group. Therefore, in these cases, the ESIPT process is not a competitive pathway and the epimerization reaction of the carbonyl group proceeds smoothly because an intramolecular triplet photosensitization process occurs from the aryl moiety to the carbonyl group at C‐17 of compounds 1c , 2c and 3c accordingly which was previously reported in the literature for 3α‐dimethylphenylsilyloxy androstanone derivatives (16,42) and 3‐acylestrone derivatives (39).…”

“…The photoepimerization reaction of estrone 5 is in agreement with similar results reported in the literature such as the involvement of a triplet state in the photoepimerization reaction of cyclic ketones (16,42,45). Likewise, we have previously demonstrated that direct irradiation of estrone methyl ether furnished lumiestrone methyl ether involving the photoepimerization of methyl group at C‐13 through a Norrish Type‐I mechanism (39). Furthermore, we have also assessed that the photoepimerization reaction of estrone methyl ether was efficiently quenched by TMDO and was sensitized by acetone confirming that the triplet excited state is the photoreactive excited state of the photoreaction.…”

“…In addition, we have also contributed to show how important is the application of the photo‐Fries rearrangement reaction in the preparation of 2,2‐dimethyl‐4‐chromanone derivatives (33,34) and carbazole derivatives (35,36). Recently, we were able to show the selectivity and the effect of surfactant micelles on the photo‐Fries reaction of an assortment of substituted acetamides (37) as well as substituted aryl benzoates (38) and also, the photochemical behavior of 3‐aryloxy estrone derivatives in solution (39).…”