Terpenoids. Part VI. Preparation ofent-13,14α-2H2kaur-16-ene and some derivatives; bridgehead enolisation ofent-17-nor13,14α-2H2kauran-16-one

摘要

378 J.C.S. Perkin ITerpenaids. Part V1.l Preparation of ent-13,14a-2H2Kaur-16-ene andSome Derivatives ; Bridgehead Enolisation of ent-I 7-Norl3,1 4a-$Hn-kauran-16-0110By David H. Bowen, Christopher Cloke, and Jake MacMittan," The School of Chemistry, The University,Rearrangement of the phenylsulphonylhydrazone of ent-beyeran-16-one (ent-l3-methyl-l7-nor-8~,13c3-kauran-16-one) (1 7) with sodium methoxide in methan2Hol yielded ent-l 6-,Hbeyer-l 5-ene (1 l ) , ent-13,14ar-2H2)kaur-l 6-ene (5). ent-l3,1 4a-ZH2 kaur-15-ene (20). and three methoxy-substituted isomers ofwhich ent-I 6-meth0xy~H, kaurane was the main component. Bridgehead enolisation of ent-l7-norl3.14a-2H, kauran-16-one (6) was demonstrated by oxidation of the ketone, before and after heating with potassium t-butoxide, to the lactones (23) and (25).respectively, in which the absence or presence of the 13-hydrogen atomwas shown by the presence or otherwise of a one-proton multiplet at 7 5.22 in the n.m.r. spectra.The mass spectra of some of the *H,diterpenes, and the n.m.r. spectra of the enr-beyeran-15- and 16-ones(1 6) and (17) in the presence of the shift reagent Eu(dpm),. are discussed.Bristot BS8 1TSPRECEDENTS 2-4 for the formation or intermediacy ofbridgehead olefins encouraged us to examine 13-bridge-head enolisation of e.nt-17-norkauran-16-one (1) as a basisfor an auto-oxidative route to ent-13-hydroxykauranesDrequired for metabolic studies. Since the completion ofthis study numerous additional examples of the inter-mediacy of bridgehead olefins in normal-sized rings haveappeared.6 A particularly relevant example is thebridgehead enolisation in the bicyclo3.2.loctanonescopacamphor and longicamphor, reported by Turnbullet aL6 prior to our preliminary note.'Direct base-catalysed deuteriation of the nor-ketone(1) with potassium t-butoxide in t-butyl alcohol wasexamined first.Mass spectrometry of the recoveredketone showed the following distribution of label:6 2Ho, 34.5 2Hl, 58 eH2, 1.5 2H,. After treat-ment with 0.05~-sodium hydroxide, the 2H distributionwas 96.5 2Ho, 3.5 2Hl. ?'he low percentage of tri-deuteriated material precluded the unambiguous assign-ment of the third 2H atom to the bridgehead position,and the known 8 stereospecificity of 2H-1H exchange atthe 15-position in the nor-ketone (1) made interpretationof these results difficult.Moreover, deuteriation at C-12via the homoenolate anion9 could not be excluded.Accordingly, definitive evidence for bridgehead enolis-ation was sought by studying 2H-1H exchange in the13-2Hnor-ketone (2), derived from ent-13-2Hkaur-16-ene (3), the latter being rationally synthesised by re-arrangement of ent-beyeran-16-one phenylsulphonyl-hydrazone (13) in a deuteriated alcohol. The startingpoint was ent-kaur-16-ene (4), which was isolated lo fromCryj6tomeria japonica var. elegans. It was isomerised byiodine in boiling xylene to give a mixture containing 70ent-beyer-15-ene (lo), 15 ent-kaur-16-ene (4), and 15ent-kaur-15-ene (18) (cf. ref.ll), which was separated bypreparative layer chromatography (p.1.c.) with difficulty.Hydroboronation of ent-beyer-15-ene (10) l2 provided the1 PartV, J. MacMillan and E. R. H. Walker, J.C.S. Perkin I,2 W. Carruthers and M. J. Qureshi, Chem. Comm., 1969, 832.R. Keese and J. P. Chen, Angew. Chem. Internat. Edn., 1971,J. R. Wiseman and W. A. Pletcher, J. Amer. Chem. SOC.,K. W. Turnbull, S. J. Gould, and D. Arigoni, J.C.S. Chem.1972, 1274.10, ,262.1970, 92, 966.6 J. Mellor, Ann. Reports (B), 1972, 69, 408.Comna., 1972, 697.15- and 16-alcohols (14) and (15), which were oxidised tothe respective ketones (16) and (17). Since the hydro-carbons (10) and (18) and the alcohols (14) and (15) wereR' R2 R3 R' ( 10 ) R' = Me, R2 = H( 1 ) Me H H 0 ( 1 1 1 R* =Me, R2=D( 3 ) M e H D CH2( A ) Me H H CH2( 5 ) Me D D C b( 6 ) M e D D 0( 7 1 Me D H 0( 8 ) Me D D Me,OMe( 2 ) Me H D 0 t 12 I R' = C02Me, R~ =H( 9 ) Q M e H H CH,( 13 ) R'= Hz, R2=N-NH602Ph( 14) R'=H$- OH, R2 H2( I 5 1 R' = H,, R,= H.p - OH(18) R'=Me,R2=R3=H(19) R1=C02Me,#=@=H(20) R1=Me,F?=$ = D(16) R'= 0,R2=H2( 17) R'= H,,R~ =odifficult to separate it was more economical to convertent-kaur-16-ene (4) directly into the readily separableketones (16) and (17) and ent-kauran-lhne withoutD. H. Bowen and J. MacMillan, Tetrahedron Letters, 1972,8 R. Evans and J. R. Hanson, J.C.S. Perkin I , 1972, 2382.A. Nickon and J. L. Lambert, J. Amer. Chem. SOC., 1966,88,lo J. MacMillan and E. R.H. Walker, J.C.S. Perkin I, 1972,l1 A. Yoshikoshi, M. Kitadami. and Y. Kitahara, Tetrahedron,la P. R. Sobti and S. Dev, Tetrahedron Letters, 1966, 3939.4111.1906.981.1967, 28, 11761975 379intermediate separations. Like their enantiomers,13 theketones (16) and (17) were distinguished by the non-reactivity of the less polar and more hindered 15-0x0-group (16) to carbonyl reagents. They were also dis-tinguished by their n.m.r. spectra run in the presence ofthe shift reagent Eu(dpm),.The gradient of the least squares plot of the observedshift (So) against Eu(dpm), concentration (Lo) was ob-tained for the methyl and CH,CO protons in the 15- and16-ketones (16) and (17). In the 16-ketone one of the15-methylene protons was located by INDOR.ForSo 4 8, (shift for the substrate-reagent complex), thegradient of a plot of so against the ratio Lo : So (sub-strate concentration) is given by SoSc/(S, + l / K ) whereK is the equilibrium constant for the formation of thecomplex. Since measurements are usually made atsimilar concentrations (So ca. 0.1 mM), the shift gradientscan be usefully compared." If K is large, the gradientsimplifies to 8,. However, some recently determined l5values of K are not sufficiently large for 1/K to beneglected. We therefore elected to normalise thegradients relative to the smallest gradient, which wastaken as unity. The term So/(So + 1/K) cancels out forall proton gradients and the normalised gradients areindependent of the concentration So.Relative gradientscalculated from the McConnell equation by using reitera-tive computation, were compared with the observedrelative gradients for a series of parameters. The bestfits, shown in Table 1, are not intended to indicate theTABLE 1Relative shift gradients for ent-beyeran-15- and 18ones16-Ketone (16)Proton Obs. Ca1c.a16-HA 8.4 6.716-HB 8.3 6.72O-H, 6-1 6-119-Hs 1.2 1.417-H3 1.1 1.618-Ha 1.0 1.016-Ketone (17)67-0 40.060-0 48.06.6 9.91-0 1.03-1 1.648.0 44.0Obs. Calc.iA@ Eu-O-C 140"; Eu-0 2 A; ring A in boat conformation.b Eu-0-C 180"; Eu-0 2.7 A; ring A in chair conformation.best conformations but to illustrate that sufficient agree-ment was obtained to assign the methyl signals for bothketones. In the spectra of the uncomplexed ketones the17-proton signals were at higher field for the 16-ketone,indicating that ring D in this ketone is twisted to place the17-protons in the shielding zone of the 16-carbonyl group.This twisting would relieve steric interaction between the20- and the 15-protons.A close analogy for the rearrangement of the phenyl-sulphonylhydrazone (13) to ent-kaur-16-ene (4) is pro-vided by Coates and Bertram,16 who obtained methyl ent-kaur-16-en-18-oate (9) and the epimeric 15-ene togetherwith methyl ent-beyer-15-en-18-oate (12) and methyl ent-13,16-cycloatisan-18-oate (22) by decomposition of thesodium salt of the $-tolylsulphonylhydrazone (21).We** Y. Kitahara and A. Yoshikoshi, Tetrahedron Letters, 1964,14 J.K. M. Saunders and D. H. Williams, J. Amer. Chem. SOC.,A1771.1971, 95, 641.examined the decomposition of the phenylsulphonyl-hydrazone (13) under a variety of conditions, analysingthe products by g.1.c. and g.1.c.-mass spectrometry0 5 0 5 0 5 10t I minG.1.c. of products from decomposition of the phenylsulphonyl-hydrazone (13) with sodium methoxide in: (a) 3,6-dioxaoctan-1-01 at 190"; (b) 3,6-dio-xaoctan-l-ol at 90"; and (c) methanol.Products : 1, ent-beyer-16-ene; 2, ent-kaur-16-ene ; 3, ent-kaur-16-ene; 4 and 6, unknown isomers of 6; and 6, ent-16-methoxykaurane(Figure). With sodium methoxide in 3,6-dioxaoctan-l-,HI01 at 190" for 1 h the main product (35) was non-deuteriated ent-beyer-l5-ene (lo), obtained in conjunc-tion with e~tt-~Hkaur-15- and 16-enes (each 4)Figure (a) containing ca. 20 2H.At 90" for 2 h with@ -NH*S02C6H,Me flMe' H ' C02Me H C02Me( 21 1 ( 2 2 )( 23 ) R'= R2= D( 2 4 ) R ~ = R ~ = H(25) R ' = D , R ~ = Hanother preparation of the same solvent the total yield ofhydrocarbons was 75 Figure (b) of which 17 wasent-kaur-16-ene containing 50 ,HI. However, at bothl5 I. Armitage, G. Dunsmore, L. D. Hall, and A. G. Marshall,Canad. J . Chem., 1972, 50, 2119.l6 R. M. Coates and E. F. Bertram, J . Org. Chem., 1971, 86,3722380 J.C.S. Perkin Itetroxide-sodium periodate gave the r2HAnor-ketone (6)without change in the 2H content (Table 2) either beforeor after treatment with dilute sodium hydroxide, showingthe absence of 15- and 17-2H in ent-2H2kaur-16-ene.Oxidation of the nor-ketone (6) to the lactone (23) alsooccurred without change in the 2H content (Table 2).The n.m.r. spectrum of the lactone (23) showed that the13-H multiplet occurring at 5 5.22 in the spectrum of theundeuteriated lactone (24) was absent.The formation of e~tt-l6-~Hbeyer-15-ene (1 l), a t -13,14a-2Hkaur-16-ene (5), and ent-13,14a-2H,Jkaur-15-ene (20) from the rearrangement of the hydrazone (13)with sodium methoxide in methan2Hol may be ex-plained by the intermediary of the 15-ene (26).Stereo-specific 15-deuteriation of this enamine followed byacid-catalysed decomposition l7 would provide the ion(27). The latter ion can either give ent-16-2Hbeyerene(11) by stereospecific loss of the W2H or undergo re-arrangement to the ion (28) and hence the ent-13,14a-2H2kaurene~ (5) and (20).Capture of the ion (28) bymethanol would explain the formation of ent-16-methoxy-C2Hkaurane (8). However similar capture of the ion(27) by methanol does not account for the formation ofeither of the two isomers of ent-meth~xy~H, kaurane.Both showed different mass spectral fragmentationsfrom those of the two products obtained by treatment ofent-beyer-15-ene (10) with methanol and sulphuric acid,and their structures are unknown.Bridgehead enolisation in ent-17-nor13,14a-2H2-kauran-16-one (6) was demonstrated by heating withpotassium t-butoxide in t-butyl alcohol. The nor-ketone used in this experiment was obtained from a re-arrangement of the phenylsulphonylhydrazone (13) withthe following label distribution: 4 2H,, 51 2Hl, and45 2H2 (Table 2).After treatment with base, the nor-ketone (7) had clearly exchanged one 2H atom (Table 2).This exchange was shown to be at the 13-position byoxidation to the lactone (25), the n.m.r. spectrum ofwhich showed the one-proton multiplet at 7 5-22 for the13-hydrogen atom.Evans and Hanson have shown that the M+ - 43 ionsin the mass spectrum of ent-kaur-16-ene (4) and ent-17-norkauran-16-one (1) are formed by loss of ring D. Theysuggested that this fragmentation also involves thetransfer of the 9-hydrogen atom together with thetransfer of one of the 14-hydrogen atoms in the case of thehydrocarbon (4) or, in the case of the ketone (1) with thetransfer of an unspecified hydrogen atom.Comparison(Table 3) of the ZH content of the M+ and M+ - 43 ionsfor the .2H2 derivatives indicates partial loss of the ent-14a-2H in both the ent-kaur-16-ene and the nor-ketone,and also some loss of the 13-2H in the ent-kaur-16-ene.The data also show that the M+ - 43 ion in ent-13,14a-2HJkauran-lEi-one does not involve loss of the deuterium ;on the other hand the M+ - 58 ion in the fragmentationof this compound appears to involve the stereospecificloss of one 2H atom, probably that at position 14.17 J. W. Powell and M. C. Whiting, Tetrahedron, 1969, 7, 306.18 J. M. Coxon, M. P. Hartshorn, D. M. Kirk, andM. A. Wilson,Tetrahedron, 1969, 25, 3017.temperatures the yield of ent-kaur-16-ene varied from0 to 20; the 2H incorporations were also low andvariable owing to difficulty in the preparation of thedeuteriated solvent.As expected17J* the use of lessacidic alcohols such as propan-2-01 and t-butyl alcoholyielded almost entirely ent-beyer-15-ene (lo), presumablyvia the carbene. With sodium methoxide in methan-2Hol Figure (c) nearly equal amounts of the hydro-carbons were obtained together with three isomericmethoxy-compounds of which ent-l6-metho~y~Hkaurane (8) was the major product. The 2H content ofthese products is shown in Table 2; the incorporation ofTABLE 2gH Content (yo) a of en 13, 14a-2H,kaur-16-eneand related compoundsCompound 2H, 2Hl 2H26 38 576 37 6619 79 26 38 676 36 596 36 694 61 4643 62 642 61 7(6)(20)(11)( 6)(6)(23)(6)( 7)(26)'Average of 10 mass spectral scans; corrected for 1.c Secondtwo deuterium atoms in the ent-kauranes was unexpectedand is discussed later.The positions of the 2H atoms inthe products were determined from the following data.The hydrocarbon mixture Figure (c), separated fromthe methoxy-compounds by p.l.c., was further fraction-ated on silica gel-silver nitrate layers to give ent-2HJ-kaur-16-ene and a 2 : 1 mixture of ent-2H,beyer-15-eneand ent-ZHJ kaur-15-ene. The latter mixture washydroboronated, then oxidised to give a mixture ofketones which was analysed by g.1.c.-mass spectrometry.The 2H atom was retained in the ketone (16) but notin the 16-ketone (17), showing that the ent-beyer-15-enecontained a 16-2H atom.Moreover the n.m.r. spectrumof the mixture of ent-16-2Hbeyer-15-ene (11) and ent-2H2kaur-15-ene did not show the higher field proton(7 4.60) of the AB-vinylic proton signal of ent-beyer-15-ene (lo), and the lower field proton ( T 4.33, J 6 Hz) of (10)was present in the case of (1 1) as a broad singlet ( T 4.32).Thus the higher field vinylic doublet in the spectrum of(10) is due to the 16-proton. Comparison of the n.m.r.spectrum of eat-kaur-15-ene (18) with that of ent-2HfJ-kaur-15-ene admixed with ent-16-2H,beyer-15-ene (1 1)showed the following significant differences. The multi-plet at T 7-63, assigned to the lproton, was absent fromthe spectrum of the 2H2 compound.Also the doublet(7 7.82, J 11 Hz) which was assigned to the ent-14a-proton in ent-kaur-15-ene (18) since there was no furthercoupling to the 13-proton (0 ca. 90") occurred in thespectrum of the 2H2 compound as a broad singlet. Fromthese facts ent-13, 14a-2HJkaur-15-ene (20) was identifiedas one of the products.The presence of a 13-2H atom in the ent-2H2kaur-16-ene was established as follows. Oxidation with osmium8 After treatment with aqueous sodium hydroxide.preparation1975TABLE 32H Content a of some fragment ions fromend-13, 14a-2H2kaur-16-ene and related compoundsCompound Ion 2H, 3H, 2H,M+ 6 36 57M+ - 16 4 39 57M+ - 43 25 60 25M+ 3 37 59M+ - 15 3 42 661M+ - 43 9 53 35A f t 43 62 5M+ - 15 46 61 3M+ - 43 62 32 6ent-Kauran-16-one M+ 10 37 63M+ - 15 17 36 48M+ - 43 17 34 49M+ - 58 10 83 7t 5 )(6)( 7)Data from a single mass spectral scan of each compoundSignificant ions at mle 246, 245, and 244 occur in thespectrum of both the ent-beyeran-one (16) and the16-2H derivative with the same relative abundance, andclearly represent the loss of ring D with the transfer ofnone, one, and two hydrogen atoms.corrected for lac.EXPERIMENTALFor general experimental details see Part II.l0 G.1.c.-mass spectrometry was carried out as described in ref.19.For g.1.c. and g.1.c.-mass spectrometry a 2 SE-33 columnwas routinely used isothermally a t 181".Calculation of ReZative Shift Gradients.-For a distantproton (Hd), the measured distance Hd * * - 0 (a), the relativeshift gradient (= l), and trial values for the Eu - - Hddistance ( r ) and Eu .* - 0 distance (b) were used to calculateK from the expression (i). The s and a values for theK3(r2 + b2 - - 4b2r2(i) 4b2r6 Shift (s) =remaining protons were considered in turn. For the valuesr between a lower limit and rising by increments to a higherlimit the values s were calculated. If the observed valuesfor s lay between two successive calculated values for s, oneof the calculated s values was printed out together with theappropriate value Y . Thus a set of r values were obtainedwhich best fitted the observed data for the trial values of band Y for the proton Hd. If an observed value of s lay on aturning point it might be missed ; to avoid this the relevantturning points were printed out by using the expression (ii).Y (at turning point)= bz + 3a2 f 2(a4 - a2b2 + b4)*1" (ii)Direct Deuteriation of ent-17-Norkauran-16-one (1) .-Thenor-ketone (45 mg) , t-butyl2Halcohol (1 g) , and potassiumt-butoxide (1 g) were heated a t 140" for 6 days in a sealedtube. After addition of deuterium oxide (0.9 ml) theproduct was recovered in ethyl acetate and purified by p.1.c.on silica gel with light petroleum-acetone (4 : 1).Extrac-tion of the band a t RF 0-5-0-7 gave the 2Hnor-ketone ( l ) ,which crystallised from methanol in needles (40 mg), m.p.117-1 18O, with isotope distribution 6 2H,, 34.5 ZH,,58 2H2, 1.5 2H3; m/e 277 (7.5y0), 276 (36), 275 (20), 274(3), 262 (9), 261 (49), 260 (25), 231 (17), 123 (93), and 43 (100).ent-Beyer-15-ene (ent-l3-MethyZ-l7-nor-8P, 13P-kaur-15-me) (lO).-ent-Kaur-l6-ene (4) (500 mg), xylene (300 ml),and iodine (ca.200 mg) were boiled for 20 11. The mixturewas washed with aqueous sodium thiosulphate (3 x 60 nil)and water (3 x 50 ml), then dried and evaporated underreduced pressure to give a yellow oil. This product, shownby g.1.c. to contain 70 of eutt-beyer-15-ene (lo), 16 of ent-kaur-15-ene (18), and 15 of ent-kaur-16-ene (a), was frac-tionated by p.1.c. on silica gel-lOyo silver nitrate withbenzene-light petroleum (3 : 2). Rechromatography of thematerial recovered from the lower portion of the elongatedzone was repeated under the same conditions until ent-beyer-15-ene (10) (200 mg), m.p.ca. 30°, was obtained freefrom ent-kaur-15-ene (18) as judged by g.1.c. (Found: IMf,272.250. Calc. for C20H32: M , 272.250) ; T 9-26, 9.20, 9-17,and 9.02 (each 3H, s), 4.60 and 4.32 (d, J 6 Hz, 15- andent-Beyeran- 15- mzd 16-02s ( 14) and ( 15) .-ent-Beyer- 15-ene (200 mg) in tetrahydrofuran (50 ml) was treated with anexcess of sodium borohydride and boron trifluoride-ethercomplex. After 16 h a t room temperature, 3~-sodiumhydroxide (1 ml) and hydrogen peroxide (5 mi; 30 v/v)were added and stirring was continued for 0.5 h. Recoveryin ethyl acetate from the residue obtained by evaporationgave a gum which was separated by p.1.c. on silica gel H Fwith light petroleum-acetate (9 : 1) to give: (a) the morepolar ent-beyemn- 16-oZ (15), crystallising from ethyl acetatein needles, m.p.98-101" (Found: M+, 290.261. C,H,,Orequires M , 290.261); T 9-20, 9.15, 9.11, and 9.07 (each 3H, s)and 6-30 (lH, d, J 6 Hz); and (b) the less polar 15-alcohol(14), T 9.18, 9.14, 9.05, and 9.02 (each 3H, s) and 5.72 (4H, d,J 6 Hz), characterised by oxidation to the 15-one (16)(see later).ent-Beyeran-16-0ne (1 7) .-The 16-alcohol (15) (70 mg) wasoxidised with an excess of Jones reagent a t 0" for 15 min.The usual work-up gave the 16-ketone (17), crystallisingfrom light petroleum in needles (70 mg), m.p. 103-104"(lit.13 m.p. for enantiomer, 102-103") (Found: C, 83-7; H,11.0; M+, 288.245. C,,H,,O requires C, 83.5; H,11.1; M , 288.245); vmK (CHCI,) 1735 cm-l; T 9.19(18-H3), 9.14 (19- and 20-H3), 9-04 (17-H3), 8.34 (15-HB,J 18 Hz), and 7.31 (15-HA, J 3 and 18 Hz); m/e 288 (62y0),273 (68), 246 (12), 245 (38), 244 (24), and 123 (100).ent-Beyerafi-15-om (16) .-The 15-alcohol(l4) was oxidisedas in the previous experiment to the 15-ketone (16), crystal-lising from methanol in needles, m.p.88-89' (lit.13 m.p. forenantiomer, 88-89°) (Found: C, 83.5; H, 11.4. C,,H,,Orequires C , 83.3; H, 11.1); T 9.22 (20-H,), 9-18 (18-H8),9.16 (19-H3), 8.96 (17-H3), 8.14 (16-HB, J 19 Hz), and 7-86(16-H~, J 3 and 19 Hz); m/e 288 (52), 273 (31), 246 (16),245 (20), 244 (23), and 123 (100).Routine Preparation of ent-Beyerart- 15- and 1 ones froment-Kaur- 16-ene.--The following typical procedure wasroutinely used. The reaction product (910 mg) from ent-kaur-16-ene (1.3 g) and iodine (1.0 g) in xylene (500 ml) wasfreed from unchanged ent-kaur-16-ene by p.1.c.on silica gel-10 silver nitrate (0.4 mm) with light petroleum-benzene(4 : 1). The lower band gave a mixture of ent-beyer-15-eneand ent-kaur-15-ene (536 mg; 2 : 1 by g.l.c.), which wasdirectly hydroboronated in tetrahydrofuran (40 ml) withsodium borohydride (520 mg) and boron trifluoride-ethercomplex (5 ml). The resultant mixture (764 mg) of alcoholswas oxidised in acetone (50 ml) with Jones reagent (2 ml)to give a product which was separated by p.1.c. on silica gelH F (0.3 mm) by multiple elution with light petroleum-acetone (99 : 1). From the lower band ent-beyeran-16-one19 J.R. Bearder, J. MacMillan, and B. 0. Phinney, Phyto-chemzstry, 1973, 12, 2655.16-H) J.C.S. Perkin I(200 nig) was obtained by extraction with ethyl acetate thencrystallisation from methanoL From the upper bandrecovery in ethyl acetate gave a crystalline solid (232 mg)which was separated into ent-beyeran-15-one (1 13 mg) andent-kauran-l5-one (18 mg) by preparative g.1.c. (2 SE 30;12 ft X # in; 230 ---c. 250° a t 2" min-1).ent-Beyeran- 16-one Phenylsulphonylhydvazone ( 13) .-The16-ketone (17) (65 mg) in methanol (5 ml) was boiled for 6 hwith phenylsulphonylhydrazine (120 mg). The productwas purified by p.1.c. on silica gel HI? (0.4 mm) with lightpetroleum-acetone (3 : 1) to give the sulphouzylhydrazone (13)as needles (80 mg), m.p.199201O (decomp.) (Found: C,70.1: H, 8.7. C2,H,,N20,S requires C, 70.5; H, 8.6);v , ~ ~ (CHCl,) 1710, 1370, and 1170 cm-l. Under the sameconditions ent-beyeran- 1 !?-one (16) was unchanged.Aearrangemmt of ent-Beyeran- 16-one Phenylsulfihonyl-hydrazone (13) .-(a) I n 3,6-dZoxao~tan-l-~Hjol at 190". Thehydrazone ( 5 mg), sodium methoxide (5 mg), and 3,6-dioxaoctan- 1-2Hol (0.5 ml ; prepared by distillation froma mixture of the sodio-derivative and deuterium oxide) wereheated at 190" for 1 h. Water was added to the mixture,which was then extracted with ethyl acetate. Recoveryfrom the extract gave a gum shown to contain efit-kanr-16-ene (41, ent-kaur- 15-ene (1 8), and ent-beyer- 1 ene ( 10) in theratio 1 : 1 10 by g.1.c. Figure (a) and by g.1.c.-massspectrometry.Fractionation of this mixture by p.1.c. onsilica gel-25 silver nitrate with benzene-light petroleum(3 : 2) and recovery from the band at Rp 0-7 gave ent-kaur-16-ene (4); m/e 274 (4), 273 (17.5), 272(35.5),and43(100);78.5 2H0, and 21.5 2Hl. Recovery from the band a t RF0.2 gave a mixture of ent-beyer-15-e (10) and enb-kaur-15-ene (18).The hydrazone (5mg), sodium methoxide (5 mg), and a new preparation ofdeuteriated dioxaoctanol(0-5 ml) were heated a t 90" for 2 h.Work-up as in (a) gave e.lzt-kaur-16-ene (4) (50 2Ho, 50BH1) admixed with ent-beyer-15-ene (10) and ent-kaur-15-ene(18) Figure (b).(c) I n propan-Z-oZ. The hydrazone (0.5 mg), sodiummethoxide (0.5 mg), and propan-241 (0.4 ml) were heated at95" €or 12 h in a sealed tube.Addition of water and extrac-tion with ethyl acetate gave a product which containedmainly ent-beyer-15-ene (10) (g.1.c. at 185").Replacing the propan-2-01 in theprevious experiment by t-butyl alcohol gave a similar result.The hydrazone (60 mg), sodiummethoxide (80 mg), and methan2Hol (2 ml) were heated a t95" for 16 h in a sealed tube. Work-up as in (a) gave a gum(50 mg) with a composition shown in Figure (c) (by g.1.c.).P.1.c. of this gum on silica gel with light petroleum-acetone(9 : 1) gave a hydrocarbon fraction (10 mg; RF 0.7) and afraction (25 mg; RF 0.5-0.6) shown by g.1.c. (2 SE-33;185") and g.1.c.-mass spectrometry (2 OV-1; 188") tocontain three isomeric compounds (M+ 396) of which themain component (80) was identified as ent- 16-methoxy-kaurane (8) (4 *Ho, 41 2H,, 55 2H2) by comparison(n.m.r.and mass spectra) with an authentic specimen. Thetwo other methoxy-containing isomers had a similar 2Hcontent, they showed similar fragmentation pathways withbase peaks a t m/e 245.The hydrocarbon fraction was further fractionated onsilica gel-lO silver nitrate layers, developed with benzene-zo L. H. Briggs, R. C. Carnbie, B. R. Davis, P. s. Rutledge, andJ. K. Wilmhurst, J. Chem. SOC., 1963, 1346.(b) I n 3,6-dioxaoctan-l-f2Hjol at 90".(d) I n t-htyl alcohol.(e) I n methan2HoZ.light petroleum. The upper band (RF ca. 0.6) gave ent-13,14~t-~H,kaur-l6-ene (5) (3 mg). The lower band (RFca. 0.2) gave a mixture (3 mg) shown by g.l.c., g.1.c.-massspectrometry, and n.m.r.to contain 33 of ent-l3,14at-2HJkaur-15-ene (20) and 67 of e~t-l6-~Hbeyer-l5-ene(11). Hydroboronation of this mixture (2.3 mg) with anexcess of sodium borohydride and boron trifluoride-ethercomplex followed by Jones oxidation gave a product shownby g.1.c.-mass spectrometry to contain equal amounts ofent-beyeran- 15-one (19 2H0, 81 yo SH,), ent-beyeran- 16-one(1OOyo 2Ho), and ent-kauran-15-one (10 2H0, 36 2Hl,53 2H2).ent-17-Nm~13,14~t-~H~kauran-l6-one (6).-ent-Kaur-16-ene (2 mg; 38 2H2) was stirred a t 20" for 16 h in tetra-hydrofuran (0.5 ml) and water (0.5 ml) with osmium tetra-oxide (2 mg) and sodium periodate (50 mg). Recovery inethyl acetate gave the nor-ketone (6), m.p.116-117"(lit.,20 117"); 39 2H1, 57 2H2; m/e 277 (12y0), 276 (65),275 (41), 262 (12), 261 (65), 260 (44), 234 (4), 233 (14), 232(16), and 123 (100). The undeuteriated ketone showed m/e274 (loo), 259 (86), 231 (23), and 123 (88).After refluxing in methanol (5 ml) and 0-1N-sodiumhydroxide (5 ml), the CeHJnor-ketone (2 mg) was recoveredquantitatively and with unchanged 2H content.Bayer- VilZiger Oxidation of ent- 17-Norkauran- 16-0ne.-(a) The undeuteriated nor-ketone (15 mg) in chloroform (2ml) containing toluene-p-sulphonic acid ( 1 mg) with per-benzoic acid was oxidised as described by Hanson 21 to givethe lactone (24) (15 mg), m.p. 146-147" (lit.,21 147-148') ;7 9.18, 9.14, 8.94 (each 3H, s), 7.80 (15-H2), and 5.22 (m,13-H); m/e 290 (23), 285 (ll), 234 (171, 231 ( l l ) , 123 (36),and 41 (100).(b) The nor-ketone (2 mg; 39 2H1, 57 2H,) in di-chloromethane (10 ml) was oxidised with trifluoroaceticanhydride and 90 hydrogen peroxide (0.17 ml) as describedby Briggs et al.22 Separation of the product by p.1.c. on silicagel with light petroleum-acetone (9 : 1) to give unchangednor-ketone (20; RF 0.4) and the lactone (23) (80; RF0.2), with unchanged 2H content (g.1.c.-mass spectrometry)and showing no signal below 7 7.76 in an accumulated ( x 20)n.m.r. spectrum.(c) The nor-ketone (2 mg; 43 2Ho, 52 2H1, 5 2H,)was oxidised and purified as in (b) to give the lactone (25)with unchanged 2H content (g.1.c.-mass spectrometry) andshowing a one-proton multiplet a t 7 5.22 (13-H) in anaccumulated ( x 40) n.m.r. spectrum.Treatment of ent-17-Nor 13,14~-~H~kauran-l one hBase.--The nor-ketone (3 mg; 51 2H1, 45 eH,) washeated a t 100" for 48 h in a sealed tube with t-butyl alcohol(3 ml) and potassium t-butoxide (100 mg). After additionof water, the nor-ketone was recovered in ethyl acetate andpurified by p.1.c. as described earlier. G.1.c.-mass spectro-metry showed the isotope distribution: 43 2H,, 52 2H,,5 2H2.The S.R.C. is thanked for research studentships (toD. H. B. and C. C.) and for a research grant towards thepurchase of a G.E.C.-A.E.I. MS30 instrument with inte-grated gas chromatography.4/1808 Received, 2nd September, 19743PL J. R. Hanson, J. Chem. Soc., 1963, 5061.29 L. H. Briggs, R. C. Cambie, and P. S. Rutledge, J. CLm-SOC., 1963, 6374