Ceric Ammonium Nitrate (CAN) Catalyzed Baeyer-Villiger Oxidation of Carbonyl Compounds, Specially 20-Oxosteroids

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

AcO 1a

75 318

o 91 352 354(M++2) 3. CI CI

80 334

4. HO

77 290

78 348

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

0 0 8a 0

78.8 390

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

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

(

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. Found: C, 78.73 ; H, sodium bicarbonate solution. The organic extract was 10.62%. evaporated under reduced pressure after drying over anhydrous sodium sulfate to get the desired oxidation 3~-Acetoxy-13a-hydroxy-13,17, 5a-androstan- product, which was further purified by preparative 17-oie acid lactone 6a. Compound 6 (500 mg) furnished ring-8-lactone 6a, yield 79% (410 mg); TLC (EtOAc-pet. ether). Since the reaction with all 25 {a}D -47° (c 2, CHCI3); mp 129-31 °C; IR (CHCI3): the substrates were carried out on a small scale with I minimum amount of CAN, the catalyst could not be 1735, 1400, 1250, 950 cm- ; ' H NMR (300M Hz, recycled and went into the aqueous phase during CDCI3): 0.80 (s,3H), 1.0 (s, 3H), 2.1 (s, 3H), 4.1 (q, work-up. 1=3 .5 Hz,2H), 4.3 (m, IH); MS ( mlz): 348 (M+). Anal. Calcd for C21H320 4: C, 72.41; H, 9.19. Found: 5a-Androstan-3~, 17~-diol diacetate 1a. Com pound 1 (500 mg) furnished 17-acetoxy compound C, 72.63; H, 9.30%. 25 3~-Chloro-13a-hydroxy-13,17, 5a-androstan- la, yield 80% (420 mg) ; {a}D -1.4° (c 2, CHCI3) [lit21 {a}o25- 1.5°; mp 124-28°C (Jit21 mp 128-29°C); 17-oie acid lactone 7a. Compound 7 (500 mg) fur IR (CHCI ): 1735, 1400, 1250, 950 cm-I; 'H NMR ni shed ring-8-lactone 7a, yield 82% (430 mg); 3 25 o {a}D -25° (c 2, CHCI ); mp 98-lOl C; IR (CHCl ): (300M Hz, CDCI3): 0.70 (s,3H), 1.1 (s, 3H), 2.0 (s, 3 I 3 6H,), 4.5 (m, 2H); MS (m/z): 376(M+). Anal. Calce! 1735, 1400, 1250, 950 cm- ; IH NMR (300MHz, for C23 H360 4: C, 73.40; H, 9.57. Found: C, 73.25 ; H, CDCI 3): 0.80 (s,3 H) , 1.0 (s, 3H), 4.1 (q, 1=3 .5 Hz, 9.29%. 2H), 4.3 (m, 1H ); MS (mlz): 324 (M+), 326(M++2 ). Anal. Calcd for C'9H290 2CI: C, 70.37; H, 8.95 . 5a-Androstane-17~-acetate 2a. Compound 2 (500 mg) furnished 17-acetoxy compound 2a, yield 74% Found: C, 70.14; H, 8.77%. 25 2 25 3~, 13a-Dihydroxy-13,17,5a-androstan-17 -oic acid (380 mg); {a}D + 4.0° (c 2, CHCI3) [li e (a}D + 5°); mp: 78-80°C (Ji e 2 mp 82°C); IR (CHCI ): 1732, lactone 8a. Compound 8 (500 mg) furnished ring-8- 3 25 1400, 1250, 950 cm-I; ' H NMR (300MHz, CDCI ): lactone 8a, yield 79% (430 mg); {a}D -40° (c 2, 3 25 0.70 (s,3H) , I.l (s, 3H), 2.1 (s, 3H), 4.5 (m, I H); MS CHCb) [ lit 24 {a}D -43°J; mp 164-68°C [ lit 24 mp I (mlz): 3 18 (M +). Anal. Calcd for C21H3402: C, 79.25; 169°J; IR (CHCJ )): 3200, 1735, 1400, 1250,950 crn- ; H, 10.69. Found: C, 79.53; H, 10.82%. IH NMR (300M Hz, CDCl3): 0.80 (s,3H), 1.0 (s, 3H), 5a-Androstan-3J3-chloro-17J3-acetate 3a. Com 3.8 (m, I H), 4.1 (q, 1=3.5 Hz, 2H); MS (mlz): pound 3 (500 mg) furnished 17-acetoxy compound 306(M+). Anal. Calcd for C19H300 3: C, 74.51; H, 9.80. Found: C, 74.38; H, 9.96%. 3a, yield 91 % (450 mg); mp 95-98°C; IR (CHCI3): I 1735 , 1400, 1252, 950 cm- ; 'H NMR (300 MHz, 3~,17~-Diacetoxy-5a, 6a-epoxy androstane 9a. CDCb): 0.70 (s,3H), 1.1 (s, 3H), 2.1 (s, 3H), 4.5 (m, Compound 9 (500 mg) furnished 17 -acetoxy com 2H); MS (mlz): 352 (M+);354 (M+ +2). Anal. Calcd pound 9a, yield 79% (400 mg); {a}D25 -1 8. 1° (c 2, for C21H33 0 2 CI: C, 71.59; H, 9.37. Found: C, 71.87; CHCI3); mp ISO-54°C; IR (CHCI3): 1730, 1400, 1250, I H, 9.55%. 950 cm- ; IH NMR (300MHz, CDCI3): 0.70 (s,3H), 12 80 INDIAN J. C HEM., SEC B, JUNE 2004

1.1 (s, 3H), 2.1 (bs, 6H), 4.5 (m, 2H ), 3.8 (m, I H); MS of a Seni or Research Fe ll owship. The Quality Control (mlz): 390 (M+). Anal. Ca lcd for C23H34 0 .'i : C, 70.77; Center of our laboratory is th ankfull y ac kn ow ledged H, 8.72. Fo und: C, 70.51; H, 8.60%. for lR, NMR, mass and GLC experiments. £-Lactone of cholesterol lOa. Compound 10 (500 mg) furni shed the rin g A £-Iactone lOa, yield 82 % References 25 25 (4 30 mg); {a}D + 11.2° (c 2, CHCI3) I lit {a}1)25 + I Hcwc J R, Chen K. -L & Anathan S, Chelll CO II/II/III1 , 199.t, 1425. 12. 1°]; mp IS7-60°C JR (CHCI3) : 1735 , 1400, 1250, I 2 Rcddy M V R, Rcddy B & Vankcr Y D, Telrailedroll Leu. 36. ) : 9 ~ i O cm- ; IH NMR (300M Hz, CDCI3 0.80-1.1 1995,4861. (rn , ISH ), 2.6 (b, 4a BH), 2A (d, 1=3.5 Hz,4 a a H), 3 (a) Young L B & Trahanovsky W, J All/ Chell/ Soc, 91, 1969, 4. 1 (q, 1=3.5 Hz, 2H).; MS (mlz): 402 (M +). Ana l. 5060. Calcd fo r Cn H460 2: C, 80.60; H, 11.44. Found : C, (b) T rahanovsky W, Flash P J & Smith L M, .1 Alii Chell/ Soc. 80A3; H, 11 .24 %. 9 1, 1969,5068. 3-0xo-4-oxa-5a-cholestane 11a. Compound 11 4 Atcs A, Gautier A, Leroy B, Planchcr J M, Qucnsel Y & Marko E, Telrahedroll Leu, 44, 1999, 1299. (500 mg) furni shed the rin g A 8-lactone 11a, yield 25 26 25 5 Nair V, Nair L G, Balagopal '_. & Rajan R, Illdiall J Chell/, 79 % (380 mg); {a}D + 78° (c 2, CHCI 3) [ lit {a}D 26 38B, 1999, 1234. + 81.4°]; mp 11 3- 16°C (Iit mp 1 16-1 8°C) ; lR 6 (a) Trahanovsky W & Young L B, J Chell/ Soc. 1965, 5777. (CHCI 3) : 1735 , 1400, 1250, 950 cm-I ; IH NMR (b) Trahanovsky W & Young L B, J Org Chell/ , 3 1, 1966, (3 00MHz, CDCI 3): 0.80-1.1 (m,lSH), 4.1 (q, 1=3.5 2033. HZ,2 H); MS (mlz):388(M+). Anal. Calcd for 7 (a) Baciocchi E & Ruzziconi R, J Org Chem, 5 1, 1986, 1645. C26 H44 0 2: C, 80A l ; H, 11.34. Found: C, 80.24; H, (b) Baciocchi E, Giacco T D, Ro l C C & Sebasti ani G V, Tel 11 .39%. rahedroll Leu, 30, 1989, 3573. Phenyl benzoate 12a. Compound 12 (500 mg) 8 (a) Renz M & Meunier B, Eur J Org Chelll, 1999, 737. (b) Strukul G, All gew Chell/IIII Ell gl, 37, 1998, 11 98. fu rni shed ph enyl benzoate 12a, yield 55 % (GLC) 27 (c) Bolm C & Beckmann 0 , in COlllprehel/.\ive ASYllllllelric (300 mg); mp 63-69°C (I it mp 69-72 0C) ; IR Calalysis, cdited by E N Jacobsen, A Pfaltz an d H Yamamoto. (CHCI ,).: 1735 , 1400, 1250, 950 cm-I; IH NMR (Springer Berlin), 1999, p 803. (3 00M Hz, CDCI3): 6.8-7.2 (m,SH), 7.6-8.2 (m, SH ); (d) Jih R H & King K Y, Cu rr Sci, 8 1, 2001, 1043. MS (mlz): 198 (M+). Anal. Calcd for CI3H IO0 2: C, (e) Nair Y, Math ew J & Prabhakaran, J Ch elll Soc Rev, 26, 78.79; H, 5.05. Found: C, 78.96; H, 5.27 %. 1997, 127. 2-(2,2,6-Trimethylcyclohexyl) ethyl acetate 13a. 9 Khripach V A, Zhabi nsk ii Y N, Kotyatkina A I, Fando G P. Compound 13, (500 mg) furnished ethyl acetate de Zhiburtovich Y Y, Lyakhov A S, Govorova A A, Grocn M B, van der Louw J & de Groot, ColleC/, Czech Ch elll COIIIIIIIIII , rivative 13a, yield 66% (GLC) (350 mg); IR (CHCI 3): 66, 2001 ,1764. 1730, 1400, 1250, 950 cm-I; IH NMR (300 MH z, 10 Goswami P & Chowdhury P K, New J Chelll , 24, 2000, 955. CDCl 3): 0.7-1.1 (m,9 H), 2.1 (s, 3H), 4.97-5 .1 (q , II Chowdhury P K, Bordoloi M J, Bania N C , Goswami P K, 1=3.5 Hz, 2H); MS (mlz): 2 12 (M+) . Sarmah H P, Sharma R P, Baruah A P, Mathur R K & Ghosh 1-Methyl-4-isopropyl-£ -lactone 14a. Compound A C, US Palelll No :5,808 ,117 ; 1998: Ind Pm No: I 645/DEU94. 141 (500 mg) furni shed the E-Iactone 14a, yie ld 71 % 12 Borah P & Chowdhury P K, J Chelll Res (S), 1996, 502. 950 (GLC) (390 mg) ; IR (CHCl3) : 1736, 1400, 1250, 13 (a) Borah P, Ahmed M & Chowdhury P K. J Chelll Res (S), cm-'; 'H NMR (300MHz, CDCI 3): 0.80-1.1 (m,9H), 1998, 237. 3.7-4.1 (q, 1=3.5 Hz, 2H) ; MS (mlz): 170 (M+) . (b) Borah P, Ahmed M & Chowdhury P K, J Chelll Res Phenyl acetate 15a. Compound 15 (500 mg) fur (M),1998, 1173. nished the £-Iactone 15a, yield 71 % (390 mg); JR 14 Borah P & Chowdhury P K, Illdiall J Ch elll , 37B, 1998,408. (CHCI3): 1766, 1250,950 cm-'; 'H NMR (3 00MHz, IS (a) Sheldon R A & Kochi J K, Metal ailalysed oxidalioll 0/ Organic Compolillds (Academic Press, NY), 1981. CDCI 3): 6.2-7.3 (m,SH), 2.1 (s, 3H); MS (mlz): 136 (M+). (b) Hudlicky M , in Oxidations in Organic Chelllislry, ACS Monograph 186, (ACS, Washi ngton DC). 1990. (c) Krow G R, ill Organic Reactions, (Wiley, NY), 43, 1993, Acknowledgement 25 1. 16 Kaneda K, Ueno S & Imanaka T, J Chem Soc Ch em COIII/I1I1I1 , The authors thank Director of the Insti tute for pro 1997, 797. viding necessary facilities for thi s work. One of the 17 Djerassi C, in Steroid Reaclions: An oUIlille/or organic chelll authors (PG) thanks CSlR, New Delhi for the award ists, (Ho lden-Day Inc, San Francisco), 1963, 457. GOSWAMI et al.: CATALYZED BAEYER-YILLIGER OXIDATION OF 20-0XOSTEROroS 128 1

18 Bruckner K K, Hampe ll , B & John sen U, Chell/ Ber, 94, 1961, 25 Ruyle W Y, Erickson A E, Lovell A & Chamberl in E M, J 1225. Org Chelll , 25, 1960, 1260. 19 Andre (Sr), Phillamy A F Mac, Nelson H B, Shabiaca J A & 26 Hill R A, Kirk D N, Makin H L J & Murphy G M, /Jictiol/ary Scholz A C, J Alii Chelll Soc, 74, 1952, 5506. oISteroids, (Chapman & Hall , London), 1991. 20 Mehta G & Pandey P N, J Ort{ Ch elll , 41 , 1976,953. 27 Knox L H, Yilloti R, Kinci FA & Ringold H J, J Org Ch elll , 2 1 Hatt ori Z, J Phann Soc Japal/, 60, 1940, 125. 26, 1961,501. 22 Hunt K. W & Grieco P A, Org Lell, 2, 2000, 171 7. 28 Burchardt Y & Reichstcin T, Hel ll Chilli Acta, 25, 1942. 23 Ho T-L, SYllthesis, 1973, 347. 1434. 24 (a) Dictiol/ ary of Orgallic CO lllpolIl/ds, Yol.l , (Eyre & Spot 29 Petit G R & Kasturi T R, J Org Chelll, 26, 1961 ,4557. tiswoode Publis hers Ltd, London), 1965, 73. 30 Aldrich Cataloglle 2000-2001, p 1298.