Indian Journal of Chemistry Vol. 43B, June 2004, pp . 1275-1281 Ceric ammonium nitrate (CAN) catalyzed Baeyer-Villiger oxidation of carbonyl compounds, specially 20-oxosteroids Papori Goswami, Saroj Hazarika, Archana M Das & Pritish Chowdhury* Natural Products Chemistry Division, Regional Research Laboratory, Jorhat 785006, India e-mail: [email protected] Received 4 February 2003; accepted (revised) 10 December 2003 The role of ceric ammonium nitrate (CAN) as an effective catalyst in the peracid induced Baeyer-Villiger oxidation of carbonyl compounds with special reference to steroids has been demonstrated. IPC: Int.C1.7 C 07 K 1/00 Ceric ammonium nitrate (CAN) finds application in temperature even when kept for more than 48 hr. Fur­ synthetic organic chemistry for various chemical ther, GLC experiment confirmed 40-55% conversion 2 transformations, viz., nitration 1, nitroacetamidation , of benzophenone 12 to phenyl benzoate 12a in 5 hr complex formation with various alcohols3 etc. Its role when CAN was used as a catalyst along with peracid as single electron oxidant has been reported in a num­ whereas only 8% conversion was observed in the ab­ 4 8 ber of publications including some recent reviews - . sence of CAN when kept for more than 24 hr. During CAN-induced oxidative radical transformations of our investigation, we also found that for all the cases 9 steroids have also been reported . We too have re­ (substrates 5-8, 10, 11, 13-15) the oxidation furni shed ported lO the catalytic action of CAN in the esterifica­ only one isomer viz. 5a-8a, lOa, lla, 13a-15a as con­ tion of carboxylic acids in very high yield . This in firmed by TLC as well as analytical and spectral data. conjugation with our interest on steroid transforma­ The stereochemistry at C-17 position (17 Ha) in case ll 14 tions - persuaded us to study its role in 8aeyer­ of C-17 acetox y steroids fonned was confirmed by 1S 16 Villiger oxidation - of 20-oxopregnanes to 17- comparing the specific rotational value of products viz. l7 acetoxysteroids of potent sex hormones and also of 1a and 2a with those of the authentic compounds2112 the formation of the steroidal D-ring lactones many of when those were found to be completely identical. l8 2o which are biologically active . Earlier Mehta et al. reported the Baeyer-Villiger Thus several steroidal carbonyl compounds 1-11 oxidation of some carboxylic system by using slurry (Table I) which are available in our laboratory un­ of CAN in acetonitrile. However, no Baeyer-Villiger derwent Baeyer-Villiger oxidation to furnish their oxidation occurred in our hands when the carbonyl respective oxidation products 1a-lla (Table I) in compounds as listed in Table I were subjected to high yield, when treated with m-chloroperbenzoic similar reaction conditions. T herefore, the present acid (m-CPBA) in the presence of catalytic amount of CAN catalyzed Baeyer-Villiger oxidation provides a CAN in dichloromethane keeping just for 4-6 hr at useful way specially in the conversion of 20- room temperature. The method has been found to be oxopregnanes to 17-acetoxy steroids (C-19 steroids) effective for some non-steroidal carbonyl compounds of sex hormone series and synthesis of steroidal ring­ 12-15 also (Table II) which give respective esters A and ring-D lactones. 12a-15a Cfable II). Regarding this interesting observation about CAN It is pertinent to note that although Andre et all ~ . which can act both as a Lewis acid or as a SET ox i­ have earlier reported the Baeyer-Villiger oxidation of dant, it seems to be reasonable that CAN co-ordinates some 20-oxopregnanes lIsing peracid alone, the reac­ with the ketone carbonyl to facilitate nucleophilic tion mixture had to be kept for 3 weeks in dark for attack of the peracid to form a complex which breaks­ completion. In the present case we did not find Baeyer­ down to the products after the rearrangement steps. Villiger oxidation of 20-oxopregnanes 1-4 (Table I) Recently, a nice modification of the 8aeyer-Villiger when treated with either CAN or peracid alone at room oxidation of some non-reactive substrates through 1276 INDIAN 1. CHEM., SEC B, JUNE 2004 Table I - CAN catalyzed BV oxidation of carbonyl compounds in the presence of peracids. S.No. Substrate Product Yield a (% ) 80 376 1. AcO 1a 75 318 2. 2a o 91 352 354(M++2) 3. CI CI 80 334 4. HO 4a 77 290 5. Sa 78 348 6. AcO 6a --Col1ld GOSWAMI ('I a/.: CATALYZED BAEYER-VILLlGER OXIDATION OF 20-0XOSTEROIDS 1277 Table 1- CAN catalyzed BV oxidation of carbonyl compounds in th e presence of peracids-Collld a mlz(M +) S.No. Substrate Product Yield (%) 0 83 324 326(M++2) 7. CI H C H 7a b 0 79 306 8. 0 0 8a 0 78.8 390 9. Ac c 9a SH 17 82 402 10. 10a sH 17.;., " 78 388 11 . 11 a (a) Yi elds refer to th e isolated products which were fully characterised by spectral analysis. (b) The compounds shown has two molecular ion peak clu e to J5 C1 and ,17C1 isotopes. (c) The stereochemistry of the epoxide was tentatively confirmed as Sa, 6a, o n th e basis of the comparison of tr. ':! physical data of with that of authentic 5u, 6u-epoxy cholesterol: I nl D -9.20 (c2, EtOH) [lit 20 I a) D -10.40 (c2, EtOH)J, mp 132-36°C ll it 21l mp 136°C). their hemi ketals or ketals was reported~ l, wherein il dizes ketones as SET oxidant leading to radical was th e acti on of a Lewis acid that promoted the gen­ cations, which usually undergo fragme nta tion ~~. In eration of the reactive oxycarbonium ion to which the situ generation of nitric acid from CAN may also be peracid added smoothly. It is reported that CAN oxi- responsi ble for the observed BY oxidation reactions. 1278 INDIAN 1. CHEM., SEC B, JUNE 2004 Table II-CAN c<ltalysed BY oxid<ltion of non-steroid carbonyl compounds in the presence of peracids Yielda S .No. Substrate Product m/z(M+) (%) 12 . 56 198 o°-U12a d 13. ~o ~0'10 66 212 13a d 0 0 14 . 72 170 14ad 15 . 3 ~CH3 [::)-Jl CH 66 t(d 16. ~ 16ae (<I) Yields refer to the isolated products which were fully ch<lracterised by spectral analysis. (b) Yield c<llculated on the basis of GLC. (c) No re<lction W<lS observed and substrate was recovered gU<lntitatively. The following points are to be noted: drich Chemical Co. and were used without further (i) only catalytic amount of CAN is necessary in purification. m-CPBA used was purchased from the reaction (CAN:Substrate:: 0.10: 1.5 mmole). Merck-Schuchardt, Germany and its purity was 55 %. Oi) oxidation is complete within 4-6 hr at room Freshly distilled dichloromethane was used. The pro­ temperature. gress' of the reactions were monitored by TLC using (iii) the yield of product is high, specially in the ster­ silica gel (E Merck) and the plates were activated at oids. 100°C before use. IR spectra (in cm-!) were recorded (iv) the method is also applicable to the regioselec­ on a Perkin-Elmer model 2000 series FT IR spec­ tive transformation of acyclic ketones to esters. trometer in CHCI3; 'H NMR spectra on a Bruker DPX (300 MHz) spectrometer with TMS as internal Experimental Section standard (chemical shifts in 0, ppm); and mass Melting points were determined with an electro­ spectrometric analysis was performed by positive thermal melting point apparatus and are uncorrected. mode electro spray ionization with Bruker Esquire All the chemicals used were of reagent grade of AI- 3000 LC-MS instrument. Specific rotations (a\) were recorded on a Perkin-Elmer Polarimeter 343 GOSW AM! et al.: CATALYZED BAEYER-V!LLIGER OXIDA nON OF 20-0XOSTEROTDS 1279 corded on a Perkin-Elmer Polarimeter 343 instru­ 5a-Androstan-3-~ol-17~-acetate 4a. Compound ment. Elemental analysis was carried out in Varian 4 (500 mg) furni shed 17 -acetoxy compound 4a, yield 25 CHN Analyzer. 80% (400 mg); {a}D -O.9° (c 2, CHCI3); mp 143- Cerie ammonium nitrate (CAN) induced selec­ 46°C (Jit23 mp 148°C); IR (CHCb) : 3300, 1730, l tive Baeyer-Villiger oxidation of carbonyl com­ 1400, 1250, 950 cm· ; 'H NMR (300 MHz, CDCI3): pounds with m-CPBA: General method. To the so­ 0.70 (s, 3H), 1.1 (s, 3H), 2.0 (s, 3H), 4.5 (m, 1H) , 4.1 lution of a substrate (1.5 mmoles) in 10 mL of di ­ (m,lH); MS (mlz): 334 (M+). Anal. Calcd for chloromethane was added CAN (0.10 mmole) and m­ C21H340 3: C, 75.45; H, 10.18. Found : C, 75.76; H, CPBA (Merck-Schuchardt, Germany, 55% pure) (2.0 10.22%. mmoles). The reaction mixture was kept at room tem­ 13a-Hydroxy-13,17, 5a-androstan-17-oie acid perature for 4-6 hr. The reaction mixture was worked lactone Sa. Compound 5 (500 mg) furnished ring-8- up by pouring into cold water (150 mL) and was ex­ lactone Sa, yield 77% (400 mg); mp 109-1 1°C; IR tracted with petroleum ether (60-80°C). The organic I (CHCI3): 1735, 1400, 1250, 950 cm- ; 'H NMR extract was first treated with aqueous solution of po­ (300MHz, CDCI3): 0.80 (s, 3H), 1.0 (s, 3H), 4.1 (q, tassium iodide and the liberated iodine was neutral­ 1=3 .5 Hz,2H); MS (mlz): 290 (M+) . Anal. Calcd for ized with sodium thiosulfate and finally washed with C19H300 2: C, 78.62; H, 10.34.