Photoinduced molecular transformations. Part 149. Stereospecific photoadditions and photorearrangements of the oximes of some steroidal alpha;,beta;-unsaturated cyclic ketones and their deuterio derivatives

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1994 Photoinduced Molecular Transformations. Part 149.' Stereospecific Photoadditions and Photorearrangements of the Oximes of Some Steroidal a,P-Unsaturated Cyclic Ketones and Their Deuterio Derivatives Hiroshi Suginome," Koji Ohshima, Yoshihiko Ohue, Takashi Ohki and Hisanori Senboku Organic Synthesis Division, Faculty of Engineering, Hokkaido University, Sapporo 060, Japan The photolysis of several steroidal cyclic a,p-unsaturated ketone oximes as model substrates in methanol showed that these excited oximes react in either one of two ways, depending upon their structural features. Thus, while the excited oximes, such as those of 5a-cholest-4-en-6-one and the 5-en-4-one oxime, having their C=C bond at their ring junction, lead to the corresponding enamides (1 540%) arising from a photorearrangement, the excited oximes, having their C=C bond at their non-ring junction (such as the oximes of 5a-cholest-2-en-I -one and the 3-en-2-one), principally lead to photoisomerization to form transient trans geometrical isomers from which stereospecific additions of proton or methanol to their trans C=C bond take place.The irradiation of (€)-5a-cholest-2-en-I -one oxime in benzene-acetic acid (94: 6) gave 1 -aza- 4a-homo- 5a -c holest -3-en-2-one arising from a reg ioselective photorearra ngement, while irradiation of the oxime in methanol gave 3~-methoxy-5~-cholestan-1-one arising from photoaddition in low yield. Thus. organic acid accelerates the photorearrangement to the lactam in competition to the a-fission.In contrast to these photochemical transformations, ground-state Beckmann rearrangements of (E)-cholest-4-en-6-one oxime and (E)-cholest-5-en-4-one oxime, having their C=C bond at their ring junction, under the standard conditions gave the corresponding cyclic enamines. Treatment of (E)-5a-cholest-2-en-I -one oxime under the standard conditions of the Beckmann rearrangement, however, gave an unsaturated nitrile as well as the corresponding enamide. The regioselectivities of the formation of cyclic enamine and enamides in the photo- and nonphoto-rearrangements, as well as the structure-photoproduct correlation of the oximes, are discussed. Our previous study concerning photoreactions of the oximes of arising from a stereospecific syn addition of methanol to the a,P-unsaturated cyclic ketones using a number of steroidal photogenerated strained trans C=Cbond of the enone oximes oximes as a model substrate disclosed that two principal from their less hindered side (Scheme 2).3*5 An isoxazole 6 photoinduced reactions, a photorearrangement to the corres- (X = H) arising from a skeletal photorearrangement was the ponding lactams and cis-to-trans isomerization of the a,P- by-product in the photoreaction of the oxime 4 (Scheme 2).unsaturated double bond, take place competitively in protic Deuterium-labelling studies of these processes established solvents.2 Thus, while the photoreaction of (E)-and (2)-that the addition of methanol to the trans C=C bond of the cholest-4-en-3-one oximes 1 and 2 in methanol gave an enamine oximes and the photorearrangement to the isoxazole 6 are 3 as the exclusive lactam arising from a regiospecific photo- stereospecific; the hydroxy-group protons of methanol in the rearrangement (Scheme I), irradiation of 5a-cholest- 1-en-3-photolysis of Sa-oxime 4 is attached to the 2a-position (X in 6) one oxime 4 and its 50-isomer 9 in methanol did not give any of photoproduct 6, while a proton of methanol in the photo- unsaturated lactams that arise from the photo-Beckmann-type lysis of SP-oxime 9 is attached to the 2P-position (X in 10) of rearrangement, but gave, respectively, 1P-methoxy-5a-chol-adduc t 10.estan-3-one oxime 5 (X = H) and its la,5P-isomer 10 (X = H), Irradiation of 1-methyl-5a-cholest-I -en-3-one oxime 7and its SP-isomer 11 in methanol, on the other hand, gave almost exclusively 1-methylene-5a-cholestan-3-oneoxime 8 (X = H) and its SP-isomer 12 (X= H), respectively, arising from a photodeconjugation of the a,P-unsaturated enone oximes into the P,y-enone oxime~.~,~ Deuterium-labelling studies again i ___t established the stereospecific incorporation of the hydroxylic OH protons of methanol to products 8 and 12 in these photo- reactions; the hydroxylic proton of the methanol is attached to 1 2 the 2a-position of product 8 in the photolysis of the 5a-isomer, while the hydroxylic proton is incorporated into the 2P-position of product 12.li Of these behaviours of steroidal a$-unsaturated oximes towards light irradiation, it was especially notable that excited steroidal a$-unsaturated oximes such as cholest-4-en-3-one oxime l2 gave exclusively an enamine lactam 3 which is inaccessible by thermal Beckmann rearrangement.Thus, we felt that further elaboration of some fundamental behaviour of 3 excited steroidal oximes is worthwhile from the viewpoint of the synthesis of azasteroids to which many biologically active Scheme 1 Reagents and conditions: i, MeOH, hv molecules 3240 J. CHEM. SOC. PERKIN TRANS. I 1994 + HO' 5 6 4 R=H 7 R-Me 8 9 R=H 11 R=Me HOHN--wH 12 Scheme 2 Reagents and conditions: i, MeOH, hv We have thus examined the photoreactions of oximes 15,19, 20, 26, 32 and 34 of cholest-2-en-l-one, choIest-3-en-2-one, cholest-2-en4one, cholest-4-en-6-one and cholest-5-en-4-one and the deuteriated derivatives 17 and 27, in order to obtain additional information concerning the effects of altering the structure of the starting oximes.The principal structural features of these oxime substrates are that: (a) the carbon- carbon double bond of oximes 15, 19 20 and 26 is located at their non-ring junction in ring A, (b) oxime 15 has a tertiary carbon centre adjacent to the hydroxyimino group and (c) the carbon-carbon double bond of oximes 32 and 34 is located at their ring junction. R6!!Sult!5 Preparation of (E)-Sa-Cholest-2-en- 1 -one Oxime 15, (E)- and (Z)-5a-Cholest-3-en-2-oneOximes 19 and 20, (E)-Sa-Cholest-2-en-4-one Oxime 26 and their Deuterio Derivatives 17 and 27, (E)- Cholest-4-en-6-one Oxime 32, and (E)-Choiest-5-en-4-one Oxime 34.The title steroidal oximes 15, 19, 20,26,32 and 34 used as substrates in the present photoreactions were synthe- sized as outlined in Schemes 3-7.Oximation of 5a-cholest-2-en- 1 -one 13,'-'' prepared from 1 a,2a-epoxy-5a-cholestan-3-oneby a Wharton rea~tion,~ in a mixed solvent of ethanol and water gave 3a-hydroxyamino-5a-cholestan-1-one oxime 14 exclus-ively. A conjugate addition of hydroxylamine to the a$-unsaturated double bond of enone 13 apparently takes place in preference to an addition to the carbonyl group under these conditions. The oximation of the enone 13 in ethanol in the absence of water under reflux gave oxime 15 in poor yield.Finally, oximation of the enone in pyridine at room temperature gave oxime 15 in high yield as the exclusive product. The deuteriation of enone 13 with methanC2H 101and sodium in diethyl ether under reflux by the standard method gave 2,4,4- 'in \ 14 R-R ti 16 15 R=H 17 R=D Scheme 3 Reagents and conditions: i, NH20H-HCI-NaOAc~3H20-EtOH, reflux; ii, NH20H~HCI-NaOAc~3H20EtOH,room temp.; iii, NH,OH-HCI-pyridine, room temp.; iv, MeOD-Et,O-Na, reflux trideuterio-5a-cholest-2-en-1-one 16. The oximation of trideu- terio enone 16 with hydroxylamine hydrochloride in pyridine gave (E)-trideuterio enone oxime 17. Oximation of 5a-cholest-3-en-2-one 18 (prepared according to the method of Nakano and colleagues") by the standard method gave a 1 :1 mixture of the corresponding (E)-and (Z)-oximes 19 and 20 (Scheme 4).Attempted preparation of a trideuterio derivative of the enone 18 by the standard procedure was unsuccessful. Finally, 5a-cholest-2-en-4-one 24 was prepared from 4- methoxycholest-4-en-3-one21 according to the method of Pate1 and Reusch,I2 as outlined in Scheme 5. Thus, application of the J. CHEM. soc. PERKIN TRANS. 1 1994 H 10 H H 19 20 Scheme 4 Reagents and conditions: i, NH2OH~HCI-NaOAc~3H,O-EtOH, room temp. H Ts" OMe 21 OMe 22 OMe 24 R=H 2325 R=D R$@ HOHN 26 R=H 27 R=D Scheme 5 Reagents and conditions: i, TsNHNH,-EtOH, reflux; ii, MeLi-Et,O, reflux; iii, SiO,H+; iv, NaOMe-MeOD, reflux; v, NH,OH-HCI-NaOAc~3H,O-E~OH,room temp.Shapiro reaction to 4-methoxycholest-4-en-3-one21 I3 gave 4- methoxycholesta-2,4-diene 23 via a tosylhydrazone 22.Spon-taneous acidic hydrolysis of the diene 23 over silica gel during preparative TLC (PLC) separation gave enone 24.l4 Oximation of enone 24 by the standard method gave the corresponding (E)-oxime 26. The deuteriation of enone 24 with methan[*H]ol and sodium in diethyl ether under reflux by the standard method gave 1, 1,3,5-tetradeuterio-5~t-cholest-2-en-4-one25. Oximation of deuterio enone 25gave the corresponding oxime 27. The preparation oftwo oximes, 32and 34,of cholest-4-en-6- one 31 and cholest-5-en-4-one 33has already been recorded in the literature.l5 The preparation of one of the parent enones, cholest-4-en-6-one 31, first prepared by Reich et a1.,16 has subsequently been reported by four groups of workers." The latest method is that by Ahmad et al., reported in 1985.'7d They reported that this enone 31 can be prepared in excellent yields 3241 by reaction of 3P-chloro-, 3P-hydroxy-, or 3P-acetoxy-S,6a- epoxy-5a-cholestane (28, 29 or 30),with phenyl isocyanate in dimethylformamide (DMF) in the presence of LiCl as a catalyst (Scheme 6)."' We, however, failed to obtain this enone in our X -OH,OAc.OT CI Q4-I29 X=OH 30 X=OAC 1'" "oH 32 Scheme 6 Reagents and conditions: i, MgBr,~3Et20-Et,0-benzene, reflux; ii, PhNCS-LiCl-DMF, reflux; iii, NH,OH=HCl-pyridine, room temp. several repetitions of their work. The reason for this failure has not yet been clarified.We found that this enone was most conveniently prepared by treatment of 5,6-epoxy-5~-cholestan- 3p-01 29 with MgBr, according to a procedure reported by Turner. '' Cholest-5-en-4-one 33 in the present experiment was prepared according to a method reported by Shoppee and colleagues 17' from cholest-4-ene in 5 steps. Oximation of these enones, 31 and 33, by the standard method gave the corresponding oximes, 32and 34l5 (Schemes 6 and 7). The 'H NMR spectrum of cholest-4-en-6-one oxime 32 0 N 33 HO' 34 Scheme 7 Reagents and conditions: i, NH,OH.HCl-pyridine, room temp. exhibited two doublet signals, at 6 3.30 (J 14.7 and 4.4 Hz), and at 6 5.86 (J3.3 and 4.0 Hz), assignable to the 7-HB and 4-H.The downfield shift of the signal due to the 7-HB, attributable to the deshielding by the hydroxy group of the oxime, indicated the (E) configuration of the oxime 32.The 'H NMR spectrum of cholest-5-en-4-one oxime 34 similarly exhibited two double doublet signals, at 6 3.30 (J 12.7 and 2.6 Hz) and at 6 5.87 (J 5.4 and 2.4 Hz), assignable to the 3-HP and 6-H. The downfield shift of the signal due to the 3-HP by deshielding due to the hydroxy group of the oxime indicated that the hydroxyimino group had an (E)configuration, as was expected. Electronic Spectra of Enone Oximes 15,19,20, 26, 32 and 34.19-Electronic spectra of (E)-5~-cholest-2-en-l-one oxime 15 and (E)-Sa-cholest-2-en-4-one oxime 26 in methanol exhibited an absorption maximum at 229-232 nm (E 9000-9500 dm3 mol-' cm-') assignable to their 7c ---+7c * transition while those of (E)-and (2)-5a-cholest-3-en-2-one oximes 19 and 20 in methanol exhibited the absorption maximum at 236 nm with a much higher intensity (E 18 700).Similarly, the electronic spectra of the two oximes 32 and 34 in methanol exhibited an absorption maximum at 224 nm (E 6700) and 234 nm (E 7800), respectively, assignable to their x __+ x * transitions. l9 Photoreactions of (E)-Cholest-2-en-1-one Oxime 15 and its Trideuterio Derivative 17 (Scheme 8).-The photoreaction of oxime 15 in methanol (3.8 x lop3mol dm-3) was carried out with a low-pressure mercury arc generated by a Rayonet RPR photochemical chamber reactor, as described in previous papers.2p5A solution of oxime 15 in methanol placed in a quartz vessel was irradiated under nitrogen for 10 h at room temperature to give the parent enone 13 (6.2%) as well as another product 35 (4.5%) by PLC (Scheme 8).E i15or17 -13or16 + H'-35 R=H 36 R=D Scheme 8 Reagents and conditions: i, MeOH, hv, room temp. The molecular formula of product 35 was established to be C28H4802by high-resolution mass spectrometry (HRMS). The IR spectrum showed the presence of a 6-membered cyclic ketone. This product was shown to be 3P-methoxy-5~chol-estan-I-one on the basis of the 'H NMR spectrum which exhibited a singlet due to the methoxy group at 6 3.33, a signal at 6 2.60 (ddd, J 1.7, 5.6 and 11.2), assignable to 2-Ha, and signals for 2-HP and 3-Ha. The configuration of the methoxy group was further confirmed to be p on the basis of the results of the following photoreaction of oxime 17 labelled with deuterium.The photoreaction of 5a-[2,4,4-2H3]cholest-2-en-l-one oxime 17 in methanol under the above mentioned conditions gave a mixture of products from which the parent enone 16 and its methanol adduct 36 were isolated in 7.6 and 2.8% yield, respectively. The 'H NMR spectrum of the trideuterio adduct 36 exhibited a doublet at 6 2.58 (1 H, J 5.3 Hz), a singlet at 6 3.33 (3 H) and a doublet at 6 3.35 (1 H, J 5.3 Hz). These chemical shifts and coupling constants indicated that the signals are assignable to the equatorial 2-Ha, the equatorial 3P-methoxy group and the axial 3-Hu,respectively. The photoreaction of oxime 15 in benzene containing glacial acetic acid (94 :6) for 3 h under the conditions mentioned above, however, gave different results (Scheme 9): the photolysis i15 -13 + 37 + 38 + H 39 Scheme 9 Reagents and conditions: i, benzene-AcOH, hv,room temp.resulted in a 78% conversion of the oxime and gave a product mixture which comprised at least four products, apart from the recovered oxime 15 (PLC). The second mobile fraction was the parent enone 13 (13.3%) and the fourth mobile fraction was a new compound, which was chracterized as 1-aza-4a-homo-5a-cholest-3-en-2-one 39 (13%) by combustion analysis, mass spectrometry and spectral analysis. Extraction of the most mobile product 37 and the third mobile product 38 from the TLC plates with a solvent gave the parent enone 13 (1 3.3%) and the starting oxime 15 (1 7.9%).These products are thus unstable J. CHEM. SOC. PERKIN TRANS. I 1994 and are converted into the parent enone and the oxime 15 during extraction from the TLC plates. No evidence concerning the structures of these products Is available, although products 37 and 38 might be an imine and a (Z)-oxime, respectively. Beckmann Rearrangement of (E)-Cholest-2-en-1-one Oxime 15 (Scheme 10)-It is known that only cyclic enamides can be obtained by Beckmann rearrangement of a mixture of (E)-and (Z)-cholest-4-en-3-one oximes, where E/Z isomerization takes place prior to C -N migration. Beckmann rearrangement of (E)-cholest-2-en-l -one oxime 15 should thus give an enamide.Treatment of the oxime with thionyl dichloride in 1,4-dioxane, in fact, gave the expected lactam 39 in 16% yield. The nitrile 40 i 15 -39 + NGC 40 Scheme 10 Reagents and Conditions: i, S0CI2-l,4-dioxane, room temp. (40%) arising from a Beckmann fission was an accompanying product. The 'H NMR spectrum indicated that the (Z) stereochemistry of the original carbon-carbon double bond of the oxime was retained in the nitrile. Photoreaction of (E)-and (Z)-Cholest-3-en-2-one Oximes 19 and 20.-(a) In methanol (Scheme 1 1).The photoreaction of the (E)-and (2)-oximes 19 and 20 in methanol under the same conditions as in the photolysis of oxime 15 for 4 h gave the parent enone 18 (4%),5a-cholestan-2-one 41 (3%) and two new products, 42 (14.3%)and 43 (9.5%).The mass, IR and 'H NMR spectral results of these products indicated that products 42 and 43 were ( 2)-and (E)-4cr-methoxy-5a-cholestan-2-oneoximes, respectively, arising from the addition of methanol to the double bond. Details concerning the analysis of the structures are given in the Experimental section. (b) In rnethanC2H]ol. In order to establish the stereochemistry of the addition of methanol to the enone oxime 19, photo-reaction of the oxime in methanC2H]ol was carried out. Irradiation of the oxime 19 in methanC2H]ol under the above mentioned conditions thus resulted in only a 43% conversion of the oxime, and gave much better yields of 5a-cholest-3-en-2-one 18 (2479, (2)-3~-deuterio-4a-methoxy-5a-cholestan-2-one oxime 44(37%) and its (E)-isomer 45 (13%).Incorporation of the deuterium and methoxy groups into the 3P and 4a positions of oximes 44 and 45 was established by 'H NMR spectroscopy; signals due to the 4P-protons of deuterio oximes 44 and 45 appeared as triplets (J 10.4)at 6 3.02 and 3.05, respectively, while the corresponding signals of oximes 42 and 43 appeared as a double triplet at 6 3.02 (J 5.3 and 10.4)and at 3.05 (J 5.0 and 10.2), respectively. Photoreaction of (E)-Cholest-2-en-4-one Oxime 26 in Meth-anol.-Photoreaction of oxime 26 in methanol under the same conditions as mentioned above for 8 h gave the parent enone 24 (10.7%) and two products, 46 and 47, in 4.5 and 5.4% yield, respectively (Scheme 12).HRMS indicated the molecular formulae of these products to be C28H4802and C28H49N02, respectively. Spectroscopic analyses of these products then established that products 46 and 47 were 2a-methoxy-5a-cholestan-4-one and (E)-2a-methoxy-5a-cholestan-4-one oxime, respectively. Details concerning the analysis of the structures are given in the Experimental section. Photoreaction of (E)-1,1,3,5-Tetradeuterio-5a-cholest-2-en-4-one Oxime 27 in Methanol.-The stereochemistry of the J. CHEM. SOC. PERKIN TRANS. I 1994 19 and 20 i or liI 18 + OMe OMe 41 42 R=H 43 R=H i only 44 R=D 45 R=D Scheme 11 Reagents and conditions: i, MeOH, hv;ii, MeOD, hv 26 or 27Ii Me0 '' \ 24or25 + H 0 HOrN 46 R=H 47 R=H 48 R=D 49 R=D Scheme 12 Reagents and conditions: i, MeOH; hv addition of methanol to the enone oxime 26 was then established by the photolysis of oxime 27 labelled with deuterium.Thus, the irradiation of labelled oxime 27 in methanol under the above mentioned conditions gave the parent deuterio enone 25 (1 2.6%), 1,1,3~,5-tetradeuteri0-2a-methoxy-5~-cholestan-4-one48 (5.0%), and (E)-1,1,3a$tetra-deuterio-2~-methoxy-5a-cholestan-4-oneoxime 49 (5.4%). The stereochemistry of the incorporation of methanol into the 2a and 3p positions of oxime 27 was established by 'H NMR spectroscopy; signals due to the 2P-position of deuterio oxime 49 appeared at 6 3.36 (d, J 5.3), while the corresponding signal of unlabelled oxime 47 appeared at 6 3.36 as a multiplet.Photoreaction of the Oximes 32 and 34 (Schemes 13and 14)-iii OT iv32 -H '0 II ior ii 52 50 51 Scheme 13 Reagents and conditions: i, MeOH, hv;ii, benzene-AcOH (94:6), hv;iii, SOC1,-dioxane, room temp.; iv, POC1,-pyridine, room temp. Irradiation of (E)-cholest-4-en-6-one oxime 32 in methanol (3.1 x 1 0-3 mol dm-3) for 4 h resulted in a 96% conversion of the oxime and gave cholest-4-en-6-one 31 (33%) and two other products, 50 (1 5%) and 51 (15%). Product 50 was identified as 34 " -54Ii 0 53 55 Scheme 14 Reagents and conditions: i, MeOH, hv; ii, SOCI,-I,4-dioxane, room temp. (Z)-cholest-4-en-6-one oxime on the basis of H NMR, IR and mass spectral evidence. The molecular formula, C,,H,,NO, of product 50, established by combustion analysis and mass spectrometry, indicated that the product was an isomer of the starting oxime 32.Its IR spectrum showed a band at 3340 cm-' assignable to the hydroxyimino group. Its 'H NMR spectrum exhibited a broad doublet signal at 6 2.41 (J 9.9 Hz) and a double doublet signal at 6 5.96 (J 2.7 and 4.9 Hz) assignable to the 7-HB and 4-H. A comparison of the chemical shifts of these signals with those of the corresponding signals of the (E)-oxime 32 mentioned above indicated an upfield shift of the 7-HP signal (Ad +0.89 ppm) and a downfield shift (A6-0.10 ppm) of the 4-H signal. These results clearly indicated that product 50 was (Z)-cholest-4-en-6-one oxime. The molecular formula of product 51 was also established to be C,,H,,NO by HRMS.The IR, 'H NMR, mass and UV spectra of product 51 indicated that it was 7-aza-7a-homo- cholest-4-en-6-one. Its IR spectrum exhibited the presence of a lactam group. Apart from the signals due to 18-H3 and 19-H3, the 'H NMR spectrum exhibited four signals (each 1 H) at 6 2.86 (ddd, J 14.3, 3.7 and 10.3 Hz), 3.03 (ddd, J 14.3, 7.2 and 2.0 Hz), 5.92 (dd, J3.7 and 7.2 Hz) and 6.02 (t, J3.7 Hz) assignable to the 7a-Ha, 7a-HD, 7-H and 4-H. Its UV spectrum in methanol exhibited an intense absorption maximum at 206 nm (E 16 000) attributable to an enone chromophore. The photolysis of oxime 32 in benzene containing glacial acetic acid (94: 6) under the above mentioned conditions for 3 h converted 77% of the oxime and gave lactam 51 in better yield (39%) with the parent enone 31 (15%) and (2)-oxime 50 (27%).Irradiation of (E)-cholest-5-en-4-one oxime 34 in methanol (3.8 x mol dm-3) under conditions similar to those of oxime 32 for 10 h converted 93% of the oxime to give the parent enone 33 (17.0%) and three other products: 53 (1 1.6%), 54 (9.8%) and 55 (29.5%). An unstable product 53 was identified as (Z)-cholest-5-en-4-one oxime based on ‘H NMR and IR spectral analyses. HRMS indicated its molecular formula to be C,,H,,NO. Its IR spectrum showed a band attributable to the hydroxyimino group. Its ‘H NMR spectrum exhibited a double doublet signal at 6 5.98 (J2.2 and 5.9 Hz) and a broad doublet at 6 2.43 (J 13) assignable to 6-H and 3-HB. Each signal appeared 0.1 1 ppm downfield and 0.87 ppm upfield from the signals due to the 6-H and 3-H6 of (E)-oxime 34, respectively.These results were in agreement with the structure of product 53 being the (2)-isomer of oxime 34. HRMS confirmed that products 54 and 55 were also isomers of oxime 34. Their IR, ‘H NMR, mass, and UV spectra indicated that these products were 4a-aza-4a-homocholest-5-en-4-one and 4-aza-4a-homocholest-5-en-4a-one,respectively, which could readily be distinguished by means of their IR and ‘H NMR spectra; the ‘H NMR spectrum of product 54 exhibited a broad doublet (1 H) at 6 5.54 and a broad singlet (1 H) at 6 6.89 assignable to the olefinic 6-H and NH while that of product 55 exhibited a multiplet (2 H) at 6 3.19, a double doublet (1 H) at 6 5.96 and a broad singlet (1 H) at 6 6.45 assignable to the C-3 methylene protons attached to the NH, the olefinic 6-H and NH, respectively.The absence of a signal due to the methylene protons attached to an NH in the spectrum of compound 54 and the presence of such a signal in the spectrum of compound 55 clearly indicated the assigned structures for products 54 and 55. These assignments were further supported by their electronic spectra. As expected, the intensity of the absorption maximum of enamine 54 was about a half of that of enamide 55 as in enamine 52 (see below). Beckmann Rearrangement of the Oximes 32 and 34.-In our previous paper2 we reported that, regardless of the con-figuration of its hydroxyimino group, only a cyclic enamine 3 can be obtained in a Beckmann rearrangement of cholest-4-en- 3-one oxime 1, where E/Z isomerization takes place prior to C+N migration.It would thus be interesting to confirm the products of the Beckmann rearrangement of oximes 32 and 34, both of which adapt the configuration of their hydroxyimino groups so as to satisfy the conditions for formation of the enamine. Treatment of oxime 32 with either thionyl dichloride in 1,4-dioxane or phosphoryl trichloride in pyridine gave a single lactam 52 in 46 or 56% yield. The structure was found to be 6-aza-7a-homocholest-4-en-6-one,an enamine, by spectral analysis (see Experimental section). Similar treatment of oxime 34 with thionyl dichloride in 1,4- dioxane again gave a single product (60%) which was identical with the enamine 54 obtained from the photoreaction.Examination of the products obtained by Beckmann rearrange- ment of the oximes 32 and 34 by TLC showed that neither of the cyclic enamides, 51 and 55, the products in the photo- reaction, were formed. Discussion The foregoing results concerning the photoreactions of oximes 15, 19, 20 and 26 of cholest-2-en-1 -one, cholest-3-en-2-one and cholest-2-en-4-one in methanol have shown that no unsaturated lactam arising from a Photo-Beckmann-type rearrangement was formed, and that the principal products 35, 42,43,46 and 47 are those arising from the addition of methanol to the a,P-unsaturated double bond of the oximes.These results are nearly parallel to those obtained in the photoreaction of the oxime 4 of cholest-1 -en-3-one previously reported by ~ 3.~9 The foregoing studies also disclosed the contrasted be-haviours of oximes 32 and 34 of cholest-4-en-6-one and cholest- 5-en-4-one in the photoreactions in methanol; the excited J. CHEM. soc. PERKIN TRANS. 1 1994 oximes result in the formation of cyclic enamides 51 and 55 arising from photorearrangements in up to 39% yield and the excited oxime of cholest-5-en-4-one 33 also gives a cyclic enamine 54 as a by-product. These results are nearly parallel to those obtained in the photoreaction of oximes of cholest-4-en-3- one and -5-en-7-one previously reported by us,’ although the regioselectivity in the formation of the lactams is the reverse of the previous examples.2 The results reported in this and previous papers ’-’have thus indicated that the excited oximes of fused a$-unsaturated cyclic ketones react in either of two directions, depending upon their structural features: while the excited enone oximes, such as those of cholest-4-en-3-one and -5-en-7-one7* having their C==C bond at their ring junction, result in the formation of the corresponding lactams arising from their photorearrangement, those generated from the enone oximes having their C=C bond at their non-ring junction (such as oximes of cholest-1 -en-3- -2-en-1-one, -2-en-4-one and -3-en-2-one) lead to an isomerization of the C=C bond to a twisted trans double bond, from which the products arose by a stereospecific syn addition of methanol.The present study also disclosed that while photolysis of the oximes of cholest-4-en-3-one and -5-en-7-one in methanol gave only cyclic enamines,2 the photoreaction of oximes 32 and 34 of cholest-4-en-6-one and -5-en-4-one gave selectively cyclic enamides, 51 and 55, although an enamine 54 was formed as the by-product in the case of the photolysis of oxime 34.Thus, the regioselectivity in the formation of the lactams in the photo- rearrangement of oximes 32 and 34 was the reverse of the examples which we previously found.’ The specific formation of cyclic enamide has also been reported in the photorearrange- ment of 17P-hydroxyandrosta- 1,5-dien-3-0ne oxime.2o The present work has also shown that while excited cholest- 2-en-I -one oxime in methanol resulted in no rearrangement to lactam, the addition of acetic acid accelerated the formation of cyclic enamide 39 in accord with a previous report.2 The factor which controlled these regioselectivities is still obscure. The different regioselectivity, however, may originate from a stereoelectronic effect; the relative geometry between a lone pair on the nitrogen and the migrating C-C bond in the oxaziridine intermediate generated from these oximes may be such that it favours migration of the C-C bond to give amides. The simultaneous formation of both enamine and cyclic enamides, 54 and 55, may indicate the involvement of two isomeric oxaziridine intermediates.A deuterium-labelling study concerning the photoadditions of oximes 15, 19, 20 and 26 established that the addition of methanol takes place in a stereospecific manner, as in the case of our previous observations concerning the photoaddition of methanol in the oximes of cholest-1 -en-3-0nes.~*~ The pathways for the formation of the methanol adducts (such as 35,42,43,46 and 47) from the excited a,p-enone oximes (15,19,20 and 26) should be parallel to those for the formation of methanol adducts 5 and 10 from oximes 4 and 9 (Scheme 2). Thus, irradiation of deuteriated oximes 17 and 27 (in methanol) as well as oximes 19 and 20 (in methanC2H]01) generates twisted ground-state intermediates 17t, 19t, 20t and 27t in which the C==€bonds are twisted by more than 90°, uia either singlet or, more likely, triplet excited oximes (Fig.1). A nucleophilic syn addition of either methanol or methanC2H]ol to the reactive trans double bonds of the intermediates from the front side of each molecule gives the observed adducts 36,44,45,48 and 49, in agreement with the results of the deuterium-labelling studies. The attack of methanol or methanC2H]ol to the double bond of intermediates 17t, 19t, 20t and 27t from the rear side is blocked ~ by the fused ring. In the photolysis of oxime 17, only the methanol adduct of the parent enone 16 was obtained in low yield. This product most probably arose from a secondary J. CHEM. soc. PERKIN TRANS. 1 1994 D 8 8 s MeOH (rear-side attack) MeOH (front-side attack) 17t H MeOD (front-side attack) 19t and 201 Me IH (front-side attack) 27 t Fig.1 Ground-state intermediates in the addition of methanol to oximes 17,19,20 and 27 photochemical decomposition of the initially formed methanol adduct. The energy of the excited oximes, having their double bond at their ring junction, principally dissipates so as to isomerize their C=C bond in preference to rearranging to the lactams. Energy dissipation through this 2-E isomerization is, however, prohibited in the excited oximes having their C=C bond at the ring junction, resulting instead in a rearrangement to the lac tarn^.'*^^*'^ The formation of a cyclic enamide in the photorearrangement of 17P-hydroxyandrosta-l,5-dien-3-one oxime, reported by Bonet and colleagues,20 might seem to be an exception.In this case, however, a new strain introduced by the presence of the C=C bond at the C(5) position of the oxime may make the photochemical geometrical isomerization of the C=C bond at the C( 1) position less easy than in the case of cholest-l- en-3-one ~xime.~ While the ground-state Beckmann rearrangement of oxime 15gave a mixture of lactam 39by rearrangement and nitrile 40 by Beckmann fission, the photoreaction gave no nitrile arising from x-fission, in spite of the fact that it had a tertiary carbon centre adjacent to the hydroxyimino group. The present results again indicated that, in contrast to the ground-state reaction, x-fission rarely takes place in the photoreaction, as we had previously found.' A survey of the past literature concerning the Beckmann rearrangement of a,P-unsaturated ketone oximes indicates that there are a number of examples "in which alkyl groups are apt to migrate more readily to the nitrogen centre if syn-anti isomerization of the geometry of the hydroxyimino group takes place faster than C --+ N migration under the experimental conditions, although the vinyl group seems to migrate more readily to electron-deficient centres.', However, a normal migration of a vinyl group has been observed in oximes, in which the geometry of the hydroxyimino group for vinyl migration is preserved under the experimental conditions, and the overlap of the p-orbitals of the vinyl group and the emptying orbital generated on the nitrogen atom by the loss of the leaving group is not hindered.24 The foregoing results showed that Beckmann rearrange- ments 25 of(E)-chokst+enb-one oxime 32and (E)-cholest-5- en-4-one oxhe 34gave enamines 52 and 54, as expected from the geometry of the hy&oxyhku group.The results are in contrast with those oftbeEkohnmn rearrangement of cholest- 2-en-I-one oxime 15 and chokM-en-3-one oxime 1.2*22"6 Whatever is the cause of the regkelectivity of the photo- rearrangements of oximes 32 and 34, the formation of the enamide lactams (such as SI and 55), which are not accessible by Beckmann rearrangements, at room temperature should demonstrate the usefulness of photoreactions for the prepar- ation of azasteroids.Experimental M.p.s were determined using a Yanaco micro m.p. apparatus and are uncorrected. The IR spectra were determined for Nujol mulls (unless stated otherwise) with either a Hitachi 285 grating infrared spectrophotometer or a JASCO IR 810 infrared spectrophotometer. The 'H NMR spectra of compounds 13-22, 24-27, 35, 36 and 42-49 were determined using a JEOL JNM-JX 270 FT high-resolution spectrometer operating at 270 MHz (aH)(solvent CDCl,: SiMe, as internal reference). The 'H NMR spectra of compounds 31, 32, 39,40 and 9-55 were determined with either a Hitachi R90 H high-resolution spectrometer operating at 90 MHz, a JEOL JNM-FX 200 FT NMR spectrometer operating at 200 MHz, or a JEOL JNM- GX 270 FT NMR spectrometer operating at 270 MHz (solvent CDCI,; SiMe, as internal reference).The J-values are given in Hz. UV Spectra were measured with a JASCO U best-30 instrument. The mass spectra of the enones and oximes were determined either with a JEOL JMS-HXl 10 or a JMS-DX303 spectrometer (70 eV). The mass spectra of compounds 28-34 and 52-55 were determined with either a JEOL model JMS-300 mass spectrometer, a JEOL model JMA-2000 mass data analysis system, or a JEOL JMS-01 SG-2 mass spectrometer. Elemental analyses were performed at the Faculty of Pharmaceutical Sciences of this University. PLC was carried out on a Merck Kieselgel 60 PF254. Column chromatography was carried out using Merck Kieselgel 60. The photoreaction was carried out with a low-pressure Hg arc generated by Rayonet RPR photochemical reactor.Choiest-2-en-1-one 13.''-This enone 13 was prepared from 5a-cholestan-3-one in 4 steps; its trimethylsilyl enol ether was treated with 2,3-dichloro-5,6-dicyano-p-benzoquinone(DDQ) according to a procedure reported by Fleming and Paterson9 to give cholest-l-en-3-one [SH(270 MHz) 0.67 (3 H, s, 18-H3), 1.05 (3 H, s, 19-H3), 5.78 (1 H, dt, J2.0 and 10.2,2-H) and 6.64 (1 H, dt, J 3.4 and 10.2, 3-H)]. Its conversion into la,2a- epoxy-5a-cholestan-3-one,followed by the Wharton reaction according to the procedure of Djerassi et a/.,' gave cholest-2- en-l-one 13." 2,4,4-Trideuterio-5a-choiest-2-en-1-one 16.--Toa solution of 5a-cholest-2-en-l-one 13 (100 mg, 0.26 mmol) in diethyl ether (1.O cm3) and MeOD (3.5 cm3) was added sodium (12 mg, 0.52 mmol).The solution was heated under reflux for 2 days. After evaporation of the solvent, the residue was dissolved in diethyl ether. The solution was neutralized with 5% hydrochloric acid, washed successively with water and brine, and dried over anhydrous Na2S04. Removal of the solvent gave a crude trideuterio derivative 16(100 mg). This product was subjected to PLC [(5 :1) hexane-ethyl acetate] to give trideuterio enone 16 (67 mg). This was recrystallized from acetone-methanol to give pure enone 16(63 mg, 62.7%), m.p. 66.5-67.5 "C; 6,(270 MHz) 0.67 (3 H, s, 18-H3), 1.05 (3 H, s, 19-H,) and 6.64 (1 H, s, 3-H). (E)-3a-Hydroxyamino-5a-cholestan-1-one Oxime 14.-Enone 13 (50 mg, 0.13 mmol), hydroxylamine hydrochloride (37 mg, 0.53 mmol), and sodium acetate trihydrate (71 mg, 0.52 mmol) were dissolved in ethanol (1.7 cm3) containing water (0.1 cm3). The solution was heated under reflux for 3 h and was then poured into water-ice to give crystals, which were collected by filtration.The crystals were dissolved in diethyl ether. The ethereal solution was washed with brine and dried over anhydrous MgSO,. The product (58 mg) was crude (E)-3a- hydroxyamino-5a-cholestan-1-one oxime 14 (58 mg), m.p. 179.5- 181.0 "C (from CHCl,); vmax/cm-' 3320 (NHOH), 1333, 1032, 941,924 and 915; 6,(270 MHz) 0.67 (3 H, s, 18-H3), 1.07 (3 H, s, J. CHEM. SOC. PERKIN TRANS. 1 1994 Turner,"" m.p.105-106 "C (from MeOH) (lit.,I7" 107- 108 "C); 6,(90 MHz) 0.70 (3 H, s, 18-H3), 0.96 (3 H, s, 19-H,) and 6.38 (1 H, t, J3.7, 4.H). (E)-Cholest-4-en-6-one Oxime 32.-A solution of cholest-4- en-6-one 31 (1 04 mg) and hydroxylamine hydrochloride (1 23 mg) in pyridine (4.4 cm3) was stirred for 20.5 h at room temperature. After the addition of water to the solution, crystals were collected by filtration. The solution was extracted with diethyl ether. The crystals were dissolved in diethyl ether. The combined ethereal solution was worked up in the usual manner. The crude oxime was recrystallized from methanol to give oxime 32 (83 mg, 7773, m.p. 154162°C (lit.,, 163-165°C); v,,,/cm-' 3246 (OH), 1298, 953, 920 and 803; 6, 0.67 (3 H, s, 18-H3),0.93(3H,s, 19-H3), 3.30(1 H,dd, Jl4.7and4.4,7-HD) and5.86(1 H,dd, J3.3and4.0,4-H);m/z399(M+,4.9%),384 (13.6), 382 (6,1), 368 (6.8), 356 (18.7) and 111 (100); ,l,,,(MeOH)/nm19-H3),2.03(1H,dd,J3.5and13.4,2-HD),3.49(1H,brs,3-HB) and 3.51 (1 H, d, J 19.1, NH); m/z 432 (M+, 3.473430 (29.4), 414 (28.1), 413 (31.2), 400 (46.1), 399 (97.3), 397 (82.3), 383 (29.4), 382 (37.8), 121 (53.3) and 43 (100) (Found: C, 73.3; H, I 1.2; N, 6.3.C,,H4,N20,-1/2 H,O requires C, 73.42; H, 11.40; N, 6.34%). (E)-Cholest-2-en-1-one Oxime 15.-(a) In pyridine. Enone 13 (497 mg, 1.29 mmol), hydroxylamine hydrochloride (61 5 mg, 8.86 mmol) and pyridine (22 em3) were stirred together for 24 h. To the solution was added more hydroxylamine hydrochloride (367 mg, 5.28 mmol); the solution was then stirred for 17 h.Water was added to the solution; the crystals, collected by filtration, were dissolved in diethyl ether. The ethereal solution was worked up in the usual manner to give a crude crystalline product (510 mg). This product was subjected to PLC (benzene) to give two fractions. The less mobile fraction (142 mg) was the starting enone and the more mobile fraction (340 mg, 92.2% based on the converted enone) was the oxime 15, m.p. 153.0-1 54.0 "C (from Me,CO); v,,,/cm-' 3290 (OH), 952 and 938; 6,(270 MHz) 0.69 (3 H, s, lS-H,), 0.99 (3 H, s, 19-H,), 6.10 (1 H, ddd, J 10.3,4.5 and 2.5, 3-H) and 6.63 (1 H, d, J 10.2, 2-H);m/z399(M+, 23.1%), 384(44.1), 382(100)and 149(58.0); i,,,(MeOH)/nm 228 (F 9080) (Found: C, 81 .O; H, 11.4; N, 3.6.C,,H,,NO requires C, 81.14: H, 11.35; N, 3.51%). (b) In ethanol. Enone 13 (50 mg, 0.13 mmol), hydroxyl- amine hydrochloride (51 mg, 0.73 mml) and sodium acetate trihydrate (58 mg, 0.43 mmol) were dissolved in ethanol (3 cm3). The solution was heated under reflux for 3 h and was then poured into water-ice. The crystals collected by filtration were dissolved in diethyl ether. The ethereal solution was first washed successively with water and brine, and dried over anhydrous Na,S04. The product was subjected to PLC to give (E)-cholest- 2-en-1-one oxime 15 (7 mg, 13.5%). (E)-2,4,4,-Trideuterio-5a-cholest-2-en-1-one Oxime 17.-A solution of 2,4,4-trideuterio enone 16 (60 mg, 0.15 mmol) and hydroxylamine hydrochloride (57 mg, 0.82 mmol) in pyridine (4 cm3) was stirred for 12 h at room temperature.The solution was then poured into water. The crystals collected by filtration were dissolved in diethyl ether. The solution was then neutralized with 5% hydrochloric acid, washed successively with water and brine, and dried over anhydrous Na,SO,. Removal of the solvent gave crude oxime 17. This oxime was subjected to PLC [(5: 1) benzene-diethyl ether] to give trideuterio enone oxime 17 (41 mg, 68.1%), m.p. 153.0-154.0 "C; 6,(270 MHz) 0.69 (3 H, s, 18-H3), 0.99 (3 H, s, 19-H,) and 6.09 (1 H, s, 3-H). Cholest-4-en-6-one 31.''-This unsaturated ketone l6 was prepared in 36% yield by treatment of 5,6a-epoxy-5a-cholestan-3P-01 29 with MgBr, according to a procedure reported by 224 (E 6700).Photoreaction of (E)-Cholest-2-en-l -one Oxime 15.-(a) In methanol. A solution of the oxime 15 (75 mg, 0.19 mmol) in methanol (50 cm3) was flushed with nitrogen and was then irradiated for 10 h. The solvent was removed by a rotary evaporator. The product was then subjected to PLC with (7:1) hexane-ethyl acetate to afford three products. The most mobile product (5.5 mg, 6.2%) was the parent ketone 13. The next mobile fraction (4.3 mg) could not be characterized. The least mobile fraction was 3 P-methoxy-5a-cholestan- 1 -one 35 (2.8 mg, 4.5%); v,,,/crn-' (neat) 1709 (M);6,(270 MHz) 0.65 (3 H, s, 19-H3), 1.14(3H,s, 18-H3),2.60(1 H,ddd, J1.7,5.6and 11.2,2- H"), 2.69 (1 H, dd, JO and 11.2, 2-HB), 3.33 (3 H, s, OMe) and 3.35(1 H,m, 3-Ha);m/z416(M', 30.3%), 384[(M -MeOH)', 20.3],369[(M -MeOH -Me)', 11.7],230(12.7), 154(23.8), 93 (30.6), 81 (33.6), 69 (27.7), 57 (47.3) and 43 (100) (Found: M', 416.3667 C2,H4,02 requires M, 416.3642).(b) In benzene-glacial acetic acid (94: 6). A solution of the oxime 15 (50 mg) in benzene-glacial acetic acid (43 cm3) was flushed with nitrogen and was then irradiated for 3 h. The product mixture was then subjected to PLC with benzene to give five fractions (A to E in order of their mobility). The second mobile fraction (B; 1 1 mg) was the recovered oxime. '' The third mobile fraction (C; 5 mg, 13.3% based on the converted oxime) was cholest-2-en-1-one 13. Fraction E (24 mg) was again purified by PLC with (1 : 1) benzene-diethyl ether to give l-aza- 4a-hom0-5u-cholest-3-en-2-one39 (5 mg, 13% based on the converted oxime), m.p. 144.5-145.5 "C (from MeOH); vmax/ cm ' 3250 and 3200 (NH), 1677, 1626 (COC=C), 1227 and 815;6,(270 MHz) 0.69 (3 H, s, 19-H), 1.1 1 (3 H, s, 18-H3), 5.89 (1 H,d, J12.54,3-H),6.08(1 H, brs,NH)and6.19(1 H,ddd, J 3.3, 5.0 and 12.5, 4-H); m/z (JEOL JMS-DX300) 399 (M', 7.2%), 384 [(M -Me)', 13.81, 136 (65.7), 122 (IOO), 107 (23.0), 93 (33.9), 81 (12.9) and 67 (13.0) (Found: C, 80.2; H, 11.6; N, 3.6.C2,H,,NO~1/4H,0 requires C, 80.24; H, 11.35; N, 3.47%). Extraction of fraction A with ethyl acetate gave more cholest-2-en-1-one 13(5 mg, 13.3% based on converted oxime); extraction of fraction D gave more of the starting oxime 15 (7 mg).Photoreaction of 2,4,4,- Trideuterio Enone Oxime 17 in Meth- anol.-A solution of oxime 17 (41 mg, 0.10 mmol) in methanol (27 em3) was flushed with nitrogen and was then irradiated as in the case of oxime 15 to give the parent enone 16 (3 mg, 7.6%) and 2~,4,4-trideuterio-3~-methoxy-5~-cholestan-1-one 36 (1.2 mg, 2.8%), 6,(270 MHz) 0.65 (3 H, s, 18-H3), 1.14 (3 H, s, 19-H,), 2.58 (1 H, d, J 5.3, 2-Ha), 3.33 (3 H, s, 3P-OMe) and 3.35 (1 H, d, J 5.3, 3-Ha). Beckmann Rearrangement of (E)-Cholest-2-en-I -one Oxime 15.-To a solution of the oxime 15 (50 mg, 0.13 mmol) in 1,4- J. CHEM. SOC. PERKIN TRANS. 1 1994 dioxane (2 cm3) under nitrogen was added thionyl dichloride (0.03 cm3) dropwise. The solution was stirred for 40 min at room temperature.After the addition of water, the solution was extracted with diethyl ether. The extract was washed suc-cessively with aq. 5% Na,CO,, water, and brine, and was then dried over anhydrous Na,SO,. Evaporation of the solvent gave a product mixture (40 mg), which was subjected to PLC (benzene) to give three fractions. The most mobile fraction (19 mg, 40%) was an unsaturated nitrile 40, m.p. 10C110 "C (from MeOH); v,,,/cm-' 2217 (C=N), 1645 and 1623; 6,(270 MHz) 0.68 (3 H, s, 18-H3), 2.48 (1 H, m, one of MCH,), 2.71 (1 H, m, one of C=CCH,), 4.61 (1 H, s, 19-H), 4.74 (1 H, s, 19-H), 5.36(1 H,d, Jll.O,C=CHC=N)and6.54(1 H,ddd, J11.0,6.6 and 8.1, CH,CH=CH); m/z 381 (M', 24%), 366 (28.6), 315 (26.9), 268 (58.4), 226 (90.2) and 57 (100) (Found: C 84.8; H, 11.5; N, 3.7.C,,H,,N requires C, 84.97; H, 11.36; N, 3.67%). The next mobile fraction (5 mg) was the recovered oxime 15. The most polar fraction (13 mg, 16%) was the lactam 39, which was identical with the lactam obtained from the photoreaction. 5a-Cholest-3-en-2-one 18.-Enone 18 was prepared accord- ing to a method from the literature." M.p. 106.5-107.5 "C (from hexane) (lit.,9 112-1 13 "C); vmax/cm-' 1671 (CO-M); 6,(270MHz)0.66(3H,s, 18-H3),0.87(3H,s, 19-H3),2.07(1 H, d, J 16.6, 1-H"), 2.31 (1 H, ddd, J3.1, 5.3 and 13.2, 5-H"), 2.55 (1 H. d, J 15.84, 1-He), 5.96 (1 H, dd, J 3.3 and 9.9, 3-H) and 6.57 (1 H, dd, J2.0 and 10.2, 4-H). (E)- and (Z)-S~t-Cholest-3-en-2-one Oximes 19 and 20.-A solution of 5a-cholest-3-en-2-one 18 (100 mg, 0.26 mmol), hydroxylamine hydrochloride (102 mg, 1.47 mmol) and sodium acetate trihydrate (130 mg, 0.96 mmol) in ethanol (5 cm3) was stirred for 24 h at room temperature.Removal of the solvent gave crystals, which were dissolved in diethyl ether-water. The organic layer was washed successively with water and brine, and was dried over anhydrous Na,SO,. Removal of the solvent gave a product, which was subjected to PLC [(5 : 1) benzene- ethyl acetate] to give two oxime isomers, 19 and 20. The more mobile oxime (37.8 mg, 36.4%) was (Z)-oxime 19, m.p. 171.0- 172.5 "C (from acetone); vmax/cm-' 3324 (OH), 1639 and 1630 (C=C-C=N); dH(270 MHz) 0.66 (3 H, S, 18-H,), 0.78 (3 H, S, 19-H3),2.47(1 H,d, J14.5, 1-HP),5.90(1 H,dd, J1.8and 10.1, 3-H) and 6.76 (1 H, dd, J3.0 and 9.9,4-H); m/z 399 (M', 8.873, 383 (loo), 368 [(M -Me)', 38.01, 314 (19.2), 120 (68.2), 106 (75.2), 7 1 (82. I), 55 (88.3) and 43 (98.9); A,,,(MeOH)/nm 236 (t: 18 700) (Found: C, 81.0; H, 11.5; N, 3.5.C2,H,,N0 requires C. 81.14; H, 11.35; N, 3.51%). The less mobile product 20 was (E)-Sa-cholest-3-en-2-one oxime (40.7 mg), m.p. 225-228 "C (from Me,CO); v,,x/cm-l 3320 (OH), 1638 and 1619 (CS-EN); 6,(270 MHz) 0.66 (3 H, s, 18-H3), 0.78 (3 H, s, 19-H), 3.19 (1 H, d, J 16.8, 1-HP), 5.78 (1 H, dd, J 1.7 and 9.9, 3-H) and 6.07 (1 H, dd, J2.6 and 9.6, 4-H); mi2 399 (M', 54.0%), 382 [(M -OH)', 1001, 366 (6.5), 287 (23.6), 121 (18.6), 107 (22.9), 95 (37.9), 81 (35.1), 69 (37.3, 57 (49.7) and 43 (55.7) (Found: C, 80.85; H, 11.25; N, 3.6%).Photolysis of (E)- and (Z)-Sa-Cholest-3-en-2-0neOximes 19 and 20.-(a) In methanol. Solutions of the oximes (75 mg, 0.19 mmol) in methanol (50 cm3) were flushed with nitrogen and irradiated for 4 h to give four fractions (A, B, C and D in order of their mobility on PLC). The most mobile fraction (A; 2 mg, 3%) was identical with 5a-cholestan-2-one 41. The second mobile fraction (3 mg, 4%) was the parent 5a-cholest-3-en-2-one 18.The third mobile fraction (12 mg, 14%) was (Z)-4a-methoxy- 5a-chofestan-2-one oxime 42 (1 1.6 mg, 14.3%), m.p. 159.5- 162.0 "C (from Me,CO-MeOH); v,,,/cm-' 3214 (OH), 1665 (C=N) and 1092; 6,(270 MHz) 0.64 (3 H, s, 18-H,), 0.72 (3 H, s, 19-H,), 2.35 (1 H, dd, J 1.0 and 13.2, l-HB), 3.02 (1 H, dt, J5.3 3247 and 10.4, 4-He) 3.38 (3 H, s, 4-OMe) and 3.89 (1 H, ddd, J 1.0, 5.3 and 13.7, 3-He); m/z 431 (M', 17.8%), 399 [(M -OMe)', 44.81, 382 [(M -OMe -OH)', 29.31, 273 (15.0), 219 (14.4), 107 (22.6), 95 (38.4), 81 (38.5), 71 (44.7), 55 (74.5) and 43 (100) (Found: M', 431.3743.C,,H,,NO, requires M, 43 1.375 1). The most polar fraction (7.7 mg, 9.5%) was (E)-LCa-rnethoxy- 5a-cholestan-2-one oxime 43 (7.7 mg, 9.573, v,,,/cm-' 321 6 (OH), 1702, 1658 (C=C-C=N) and 1094; 6,(270 MHz) 0.65 (3 H, s, 1 8-H,), 0.73 (3 H, s, 19-H,), 2.88 (1 H, ddd, J 1.3,5.0 and 13.9, 3-He), 3.05 (1 H, dt, J 5.0 and 10.2, 4-HO) 3.35 (3 H, s, 4-OMe) and 3.40 (1 H, dd, J 1.3 and 13.2, 1-He); mjz 431 (M', loo%), 416 [(M -Me)', 12.21, 399 [(M -OMe)', 89.91, 382 [(M -OMe -OH)', 531, 273 (24.7), 115 (26.4), 95 (42.8), 81 (43.1), 71 (50.1), 55 (76.9) and 43 (85.5) (Found: M+, 431.3757).(b) In rneth~n[~H]of.A mixture of oximes 19 and 20 (57.5 mg, 0.14 mmol) in methanC2H]ol (33 cm3) was subjected to photolysis to give five fractions in order of their mobility on a TLC plate. The most mobile fraction (5.8 mg, 24.2% based on the converted oxime) was the parent enone 18. The second fraction (1 5.2 mg) was recovered (Z)-Sa-cholest-3-en-2-0ne oxime 19. The third fraction (17.4 mg) was its (E)-isomer 20. The fourth fraction (9.9 mg, 36.8% based on the converted oximes) was (2)-3 ~-deuterio-4~-methoxy-5a-cholestan-2-oneox-ime 44, m.p. 174.0-175.5 "C (from Me,CO); v,,,/cm-l 3262 (OH) and 1669; 6,(270 MHz) 0.65 (3 H, s, 18-H3), 0.72 (3 H, s, 19-H,), 2.35 (1 H, d, J 13.5, l-He), 3.02 (1 H, t, J 10.4, 4-He) and 3.38 (s, 3 H, 4a-OMe); m/z432 (M', 1.1%), 415 [(M -OH)', 1.71, 400 [(M -MeOH)', 13.81, 383 (27.9).229 (12.6), 157 (22.6), 121 (60.4), 107 (49.9), 95 (54.4), 69 (59.4), 55 (82.7) and 43 (100) (Found: M', 432.3801. C,,H,,DNO, requires M, 432.3847). The most polar fraction (3.6 mg, 13.4% based on the converted oxime) was the isomeric (E)-3a-deuterio-4a-meth-oxy-5a-cholestan-2-one oxime 45, m.p. 148.5-1 50.0 "C (from acetone-methanol); v,,,/cm-' 3240 (OH), 1720 and 1657; 6,(270 MHz) 0.65 (3 H, S, 18-H,), 0.73 (3 H, S, 19-H,), 3.05 (1 H, t, J 10.4, 4-HB), 3.35 (3 H, s, 4-OMe) and 3.40 (1 H, d, J 13.2, 1-HB); m/z432 (M', 79.8%), 417 [(M -Me)', 15.5],400 [(M -Me -OH)', 100],383(70.6), 274(13.1), 121 (16.5), 107(19.3), 95 (25.0), 81 (26.1), 69 (25.3), 57 (36.5) and 43 (52.7) (Found: M', 432.3819). 4-Methoxycholest-4-en-3-one21 .-This enone was prepared in 58.7% yield from cholest-4-en-3-one according to the published method.l3 M.p. 13 1.&132.5 "C (from MeOH-Me,- CO) (lit.,' ' 133-1 35 "C); vmax/cm- ' 1605 and 1675 (CS-C=O), 1100 and 1080; 6,(270 MHz) 0.70 (3 H, s, 18-H,), 1.18 (3 H, s, 19-H,), 3.04 (1 H, ddd, J2.7,4.1 and 14.9, 6-He) and 3.59 (3 H, s, OMe). 4-Methoxycholest-4-en-3-one Tosylhydrazone 22.-A solu-tion of enone 21 (452 mg, 1.1 mmol) and tosylhydrazine (235 mg, 1.2 mmol) in absolute ethanol (4 cm3) under nitrogen was heated under reflux for 5 h.Removal of the solvent gave crys- tals, which were dissolved in water-diethyl ether. The ethereal layer was washed successively with water and brine, and was dried over anhydrous Na,SO,. Evaporation of the solvent gave tosylhydrazone 22 (687 mg, 98.2%), m.p. 151.0-152.5 "C (from Me,CO); v,,,/cm-' 3218 (NH), 1600 (C=N) and 1188; 6,(270 MHz)0.67(3H,s,18-H,),l.00(3H,s,19-H,),2.40(3H,s,Me) 2.97(1 H, ddd, J2.3,4.6and 13.7,6-He), 3.52(3 H,s,OMe), 7.29 (2 H, d, J 8.2, ArH) and 7.88 (2 H, d, J8.2, ArH); rn/z (by JEOL JMS DX300) 398 [(M -TsNHN)', 9.8%], 383 [(M -TsNHN -Me)',4.5],247(7.7), 185(24.9), 135(47.7),91 (loo), 65 (44.3) and 44 [Found: (M -C7H,02N,S)', 398.3560. C2,Ha60 requires m/z 398.35371. 3248 J.CHEM. SOC. PERKIN TRANS. 1 1994 5a-ChoZest-2-en-4-one 24.l4-To a solution of crude tosylhy-drazone 22 (622 mg, 1.1 mmol) in dv diethyl ether (50 an3) was added methyllithium (1.5 mol dm-3 ethereal solution) (4.3 cm3, 6.6 mmol) dropwise. The solution was then heated under reflux for 18 h. To this solution was added aq.ammonium chloride and the solution was stirred. The ethereal layer was washed successively with water ad brine, and was dried over anhydrous Na2S0,. Evaporation ofithe solvent gave de 4-methoxycholesta-2,4ene 23 (488mg). This dime was sub-jected to PLC [(5: 1) hexane-ethyl acetate] to give directly 5a-cholest-2en-4-one 24 (123 mg, 30.4% from enone211, m.p. 84.5-85.0 "C (from Me,CO) (lit.,*4b 89 "C; lit.,'& no description of m.p.); v-/cm-' 1679 and 1621 (--GO); &(270 MHz) 0.66 (3 H, S, 18-H3),0.85 (3 H, S, 19-H,), 2.41 (1 H,dd, J5.9and 18.8,5-Hq),5.98(1 H, brdd, J3.0and 10.2,3- H)and6.79(1 H,ddd,J2.3,5.9and10.2,2-H).(E)-Sa-Cholest-2-en40ne Oxime %.-A solution of cholest- 2-en-4-one 24 (100 mg, 0.26 mmol), hydroxylamine hydro- chloride (102 mg, 1.47 mmol) and sodium acetate trihydrate (130 mg, 0.96 mmol) in ethanol (5 cm3)was stirred for 18 h at room temperature. Removal of the solvent gave a residue, which was dissolved in a mixture of diethyl ether and water. The organic layer was washed successively with water and brine, and was then dried over anhydrous Na2S04. Removal of the solvent gave crude oxime 26 (1 13 mg), which was recrystallized from acetone to give pure oxime (102 mg, 98.5%), m.p.203.0- 2050°C; vmax/cm-' 3272 (OH), 1685 and 1642 (C==C-C=N); &(270MH~)0.66(3H,~,18-H3),0.78(3H,s, 19-H3),6.15(1 H, ddd, J2.3,5.6and 10.2,2-H)and6.77(1 H,dd, J2.6and 10.2,3- H); m/z 399 (M', 74.1%), 382 [(M -OH)', 41.41, 368 (loo), 120(51.9), 106(60.6), 95 (40.7), 81 (42.7), 55(61.2)and43 (82.9); h,,,(MeOH)/nm 232 (E 9500) (Found: C, 81.05; H, 11.4; N, 3.4. C2,H4,N0 requires C, 81.14; H, 11.35; N, 3.51%). 1,1,3,5-Tetradeuteri0-5a-cholest-2-en-4-one25.-To a solu-tion of 5a-cholest-2-en-4-one 24 (150 mg, 0.39 mmol) in dry diethyl ether (1.5 ~rn~)-methan[~H]ol (4.5 cm3) was added sodium metal (18 mg, 0.78 mmol). The solution was heated under reflux for 2 days. The residue obtained by removal of the solvent was dissolved in diethyl ether and neutralized with 5% hydrochloric acid.The solution was washed with brine and dried over anhydrous Na2S0,. Removal of the solvent gave crude deuterio ketone 25 (148 mg). Recrystallization from acetone gave pure deuterio ketone 25 (118 mg, 77.779, m.p. 85.0-86.0 "C; vmax/cm-l 1650 and 1675 (CS-CO); 6,(270 MHz) 0.66 (3 H, s, I 8-H3),0.85 (3 H, s, 19-H3) and 6.78 (1 H, s, 2-H); m/z 388 (M', 11.2%), 373 [(M -Me)', 14.2],233 (loo), 135(57.5), 123(61.3), 113 (73.1),99(71.9), 55(72.2)and43(74.1) (Found: M +,388.3636. C2,H,,D,0 requires M, 388.3633). (E)-1,I ,3,5-Tetradeuterio-5~t-cholest-2-en-4-oneOxime 27.- The deuterio ketone 25 (1 18 mg, 0.30 mmol), hydroxylamine hydrochloride (1 15 mg, 1.65 mmol), and sodium acetate trihydrate (143 mg, 1.05 mmol) in ethanol were stirred for 18 h at room temperature.The reaction mixture was worked up as described for the preparation of oxime 26 to give deuterio oxime 27 (120 mg, 98.1%), m.p. 202.5-205.5"C (from Me2CO); v,,,/cm-' 3328 (OH), 1667 and 1620 (CS-C=N); 6,(270 MHz) 0.66 (3 H, s, 18-H,), 0.78 (3 H, s, 19-H3) and 6.14 (I H, s, 2-H); m/z 403 (M+ , 9.3%), 386 [(M -OH)', 24.51, 372 (47.1), 248 (194,232 (20.2), 162 (40.3), 123 (57.9, 109 (86.0), 55 (84.6) and 43 (100) (Found: M', 403.3763. C2,H4,D,N0 requires M, 403.3 742). Photoreaction of (E)-~u-Cholest-2-en-4-one Oxime 26.-A solution of oxime 26 (75 mg, 0.19 mmol) in methanol (50 cm3) was flushed with nitrogen, and was then irradiated under nitrogen for 8 h.The product mixture was subjected to PLC [(7: 1) hexane-ethyl acetate] to give three products. The most mobile product (7.8 mg, 10.7%) was the parent enone 24.The second mobile product (3.6 mg, 4.5%) was 2a-methoxy-5a- cholestan4orpe 46,m.p. 95.0-96.5 "C (from MeOH-Me2CO); v,,,/c~-' 1711 (GQ);6,(270 MHz) 0.66 (3 H, S, 18-H3), 0.71 (3 H,s,19-H3),2.84(1 H,ddd,J1.8,5.3and 12.9,3-Ha),3.35(3H, s, 2-OMe) and 3.57 (1 H, tt, J 5.3 and 10.9, 2-He); m/z 416 (M+, 88-TA),401 [(M-Me)+, 21.91, 384 (38.7), 343 (87.3), 230 (59.4), 95 (70.3),81 (77.9), 55 (92.6) and 43 (100) (Found: M+, 416.3672. Ct,-,H4802requires M, 416.3656). The most polar fraction (4.2 mg, 5.4%) was (E)-~~-I~z&ox~-5a-chhtun40ne oxh 47, m.p.184.5-186.5 "C (from Me2-CO-MeOH); v,-/cm-' 3274 (OH), 1709,1670 and 1097;&(270 MHz) 0.65 (3 H, S, i8-H3), 0.74 (3 H, S, 19-H3), 2.20 (1 H, dd, J 4.3 and 12.5,3-H"), 3.36 (1 H, m, 2-Hg), 3.38 (3 H, s, 2-OMe)and 3.86 (1 H, dd, J5.3 and 12.5, 3-HB); m/z 431 (M+,28.0%), 414 [(M -OH)+,6,6],399[(M -OH -Me)', lOOj,382(44.3), 368 (47.5), 121 (29.21, 106 (31.8), 95 (32.4), 81 (35.0), 55 (50.8) and 43 (77.7) (Found: M', 43 1.3761. C28H4,N02 requires M, 43 1.3751). Photoreaction of (E)-Tetradeuterio-5a-cholest-2-en-4-oneOx-ime 27.--Deuterio oxime 27 (50 mg, 0.12 mmol), as a solution in methanol (33 cm3), was subjected to photolysis under con- ditions similar to those for oxime 26,to give three products. The most mobile compound (9.1 mg, 12.6%) was the parent deuterio enone 25 (9.1 mg, 12.6%).The second most mobile compound (3.9 mg, 5.0%) was 1,1,3a,5-tetradeuteri0-2a-methoxy-5a-chol-estan-Cone 48, m.p. 95.0-96.5 "C (from MeOH-Me2CO); vmax/cm-' 171 1 (GO)and 1082; dH(27O MHz) 0.65 (3 H, s, 18-H3), 0.70 (3 H, S, 19-H3), 2.81 (I H, d, J5.3, 3-HB), 3.35 (3 H, S, 2-OMe) and 3.55 (1 H, d, J5.3, 2-Hs); m/z 420 (M', loo%), 405 [(M -Me', 15.6],387(36.4),343(83.3),316(37.4),234(27.1), 95 (27.0), 81 (29.0), 55 (37.7) and 43 (63.4) (Found: M', 420.3886. C28H,4D,02 requires M, 420.3894). The most polar product (4.4 mg, 5.4%) was (E)- 1,1,3a,5-tetradeuteri0-2a-meth-oxy-5a-cholestan-4-one oxime 49, m.p. 185.5-1 87.5 "C (from MeOH-Me2CO); v,,,/cm-' 3340 (OH), 1737, 1686 and 1261; BH (270 MHz) 0.65 (3 H, s, I8-H3), 0.74 (3 H, s, 19-H,), 3.36 (1 H, d, J5.3, 2-Ha), 3.38 (3 H, s, 2-OMe) and 3.83 (1 H, d, J5.3,3- Ha); m/z 435 (M', 17.8%), 418 [(M -OH)+, 6.6],403 [(M -OH -Me)', 1001, 385 (36.8), 371 (35.0), 109 (28.9), 95 (29.7), 69 (33.4), 55 (43.7) and 43 (56.5) (Found: M', 435.4009.C2 H, ,D4N02requires M, 435.4003). Photoreaction of (E)-Cholest-4-en-6-one Oxime 32.-(a) In methanol. A solution of oxime 32 (49 mg, 0.12 mmol) in methanol (40 cm3) in a quartz tube was irradiated for 4 h. The products which were subjected to PLC [(2 : 1) benzene-diethyl ether] gave four fractions (A, B, C and D in order of their mobility on a TLC plate). The most mobile fraction (A; 15 mg, 33% based on the converted oxime) was the parent enone 31.Fraction B (7 mg, 15%) was (Z)-oxime 50, m.p. 152-158 "C (from MeOH); v,,,/cm-' 3340 (OH), 976 and 928; 6,,(90 MHz) 0.66(3 H, S, 18-H,), 0.95(3 H, S, 19-H3), 2.41 (1 H,d, J9.9, 7-HB) and 5.96 (1 H, dd, J 2.7 and 4.9,4-H); m/z 399 (M', 3.9%), 384 (13.2), 368(4.3),356(16.8)and 111 (100)(Found:M+,399.3490. C2,H,,N0 requires M, 399.3500). Fraction C (2 mg) was the starting oxime 32. Fraction D (17 mg) was again subjected to PLC [(l : I) ethyl acetate-diethyl ether] to give the amorphous lactam 51 (7 mg, IS%), vmax/cm-' 3420 (NH) and 1639 (CONH); ~5~0.69 (3 H, s, 18-H3), 1.08 (3 H, s, 19-H3), 2.86 (1 H, ddd, J 14.3, 3.7 and 10.3, 7a-Ha), 3.03 (1 H, ddd,J14.3,7.2and2.0,7a-HD),5.92(lH,dd,J3.7and7.2,NH) and 6.02 (1 H, t, J 3.7, 4-H); m/z 400 [(M + l)', 31.8%], 399 (M', loo), 384 [(M -Me)', 12.41, 371 (11.7), 151 (39.3) and 123 (46.9); A,,,(MeOH)/nrn 206 (E 16 000) (Found: M+, 399.3490).J. CHEM. soc. PERKIN TRANS. I 1994 (b) In benzene-glacial acetic acid (94:6). A solution of the oxime 32 (53 mg, 0.13 mmol) in the mixed solvent (42.6 cm3) was flushed with nitrogen and was then irradiated. The product was subjected to PLC [(2: 1) benzenediethyl ether] to give four fractions (A, B, C and D in order of their mobility on PLC). Fraction A was again subjected to PLC [(l : 1) benzene- dichloromethane] to give the parent ketone 31 (6 mg, 15% based on the converted oxime). Fraction B was (2)-oxime 50 (1 1 mg, 27%). Fraction C was the starting (E)-oxime 32 (1 2 mg).Fraction D was again subjected to PLC [(l :1) ethyl acetate- diethyl ether] to give lactam 51 (16 mg, 39%). Beckmann Rearrangement of (E)-Cholest&n-6-one Oxime 32.--(a) With thionyl dichloride. To a solution ofoxime 32 (52 mg, 0.13 mmol) in 1,4-dioxane (2 em3) was added thionyl dichloride (0.03 cm3). The solution was stirred for 50 min at room temperature. Water was added to this solution. The reaction mixture was extracted with diethyl ether. The extract was washed successively with aq. 5% Na,CO, and water, and was then dried over anhydrous MgSO,. Removal ofthe solvent gave a product (31 mg), which was subjected to PLC [(2: 1) benzene-diethyl ether] to give cyclic enamine 52 (24 mg,46%)as a gum, v,,,/cm-' 3390 (NH), 1659 (CONH) and 1651; BH 0.68 (3 H, s, l8-H,), 0.96 (3 H, s, 19-H,), 5.54 (1 H, t, J3.6,4-H) and 7.14 (1 H, br s, NH); m/z 400 [(M + 1)', 32.0%], 399 (M', 100), 371 (16.9), 328 (14.8), 151 (15.5) and 123 (27.5); Am,-(MeOH)/nm 21 1 (E 6200) (Found: M', 399.3523.C2,H,,N0 requires M, 399.3500). (b) With POCl,. To a solution of the oxime 32 (50 mg, 0.13 mmol) in pyridine ( -0.1 an3)was added a mixture of POCl, (0.32 cm3) in pyridine (0.7 cm3) at 0 "C. The solution was stirred for 4 h at room temperature and was then acidified by addition of conc. hydrochloric acid (0.14 cm'). To the solution was added water-ice; the reaction mixture was extracted with diethyl ether. The extract was worked up in the usual manner. The product was subjected to PLC to give two fractions.The more mobile fraction (22 mg) could not be characterized. The less mobile fraction (28 mg, 56%) was lactam 52 described above. (E)-Cholest-5-en-4-one Oxime 34.-This a,P-unsaturated ket- one oxime3 was prepared by the standard method. M.p. 172- 174 "C (from Me,CO) (lit.,3 168.170 "C); 6,(270 MHz) 0.68 (3 H, S, 18-H3), 0.94 (3 H, s, 19-H3), 3.30(1 H, dd, J 12.7 and 2.6, 3-HD) and 5.87 (1 H, dd, J 5.4 and 2.4, 6-H); m/z 399 (M', 63.0%), 382 [(M -OH)', 31.21, 356 (100) and 331 (26.4); A,,,(MeOH)/nm 234 (E 7800). Photo-Beckmann Rearrangement of (E)-Cholest-5-en-4-one Oxime 34.-A solution of the oxime 34 (120 mg) in methanol (80 cm3) was irradiated for 10 h under nitrogen. The product was subjected to PLC [silica gel; (7 : 1) dichloromethanediethyl ether] to give five fractions [A (19 mg), B (8 mg), C (13 mg), D (1 1 mg), and E (33 mg) in order of their mobility on a TLC plate].Fraction A (1 7.0%) was the parent ketone 33. Fraction B was the starting oxime 34. Fraction C (1 1.6%) was unstable, amorphous (Z)-cholest-5-en-4-one oxime 53, S,(270 MHz) 0.69 (3 H, s, 18-H,), 0.95 (3 H, s, 19-H3) and 5.98 (1 H, dd, J2.2 and 5.9) (Found: M', 399.3492. C,7H,,N0 requires M, 399.3500); Fraction D (9.8%) was 4a-aza-4a-homocholest-5-en-4-one54, m.p. 169-1 71 "C (from Me,CO); v,,,/cm-' 3 156 (NH) and 1688 and 1676 (lactam C=O); 6,(270 MHz) 0.68 (3 H, s, 18-H3), 1.01 (3 H, s, 19-H,), 5.54 (1 H, br d, 6-H) and 6.89 (1 H, br s, NH); mi= 399 (M', loo%), 384 [(M -Me)+, 20.31, 342 (14.1), 108 (27.0), 96 (18.5), 55 (25.1) and 43 (29.7); A,,,(MeOH)/nm 221 (E 6500) (Found: M +,339.3498).Fraction E (29.5%) was 4-aza-4a-homocholest-5-en-4a-one55, m.p. 178-180 "C (from Me,CO); vmax/cm-' 3192 (NH) and 1657 and 1639 (lactam GO);6,(270 MHz) 0.68 (3 H, s, 18-H3), 1.04 (3 H, s, 19-H3), 3.19 (2 H, m, 3-H2), 5.96 (1 H, dd, J2.2 and 5.5, 6-H) and 6.45 (1 H, br s, NH); 1,,,(MeOH)/nm 217 (E 14 000) (Found: M', 339.3495). Beckmann Rearrangement of (E)-Cholest-5-en-4-one Oxime 34.-To a solution of the E-oxime (50 mg) in 1,4-dioxane (2 cm3) was added thionyl dichloride (0.1 an3);the solution was then stirred for 5 min at room temperature. The reaction mixture was worked up as in the previous case. The crude product was subjected to PLC [silica gel; (4: 1) dichloro-methane-diethyl ether] to give the enamine 54 (30 mg, 60%) obtained by the photorearrangement described above.References 1 Part 148, H. Suginome, Y. Nakayama, H. Harada, H. Hachiro and K. Orito, J. Chem. SOC.,Chem. Commun., 1994,451. 2 H. Suginome, M. Kaji and S. Yamada, J. Chem. SOC.,Perkin Trans I, 1988,321 and the papers cited therein. 3 H. Suginome, M. Kaji,T. Ohtsuka, S. Yamada, T. Ohki, H. Senboku and A. Furusaki, J. Chem. Soc., Perkin Trans. I, 1992,427. 4 H. Suginome, T. Ohki, A. Nagaoka and H. Senboku, J. Chem. Soc., Perkin Trans. I, 1992, 1849. 5 H. Suginome, A. Nagaoka and H. Senboku, J. Chem. SOC.,Perkin Trans. I, 1992,3103. 6 For reviews, see P. Morand and J. Lyall, Chem.Rev., 1968, 68, 85; H. 0. Huisman and W. N. Speckamp in Steroids, International Review of Science, Organic Chemistry, ed. W. F. 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