摘要:
J. CHEM. SOC. PERKIN TRANS. I 1993 Radical-mediated Synthesis of the 5,11-Methanomorphanthridine Ring System: Formal Total Synthesis of Montanine-type Amary//idaceae Alkaloids, (+)-Montanine, (+)-Coccinine and (-t)-Pancracine Miyuki Ishizaki, Ken-ichi Kurihara, Eiko Tanazawa and Osamu Hoshino Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12, lchiga ya Funaga wara-machi, Shinjuku-ku, Tokyo 162,Japan Radical-mediated reaction of the phenyl sulfide 16 and the phenyl selenide 17 in boiling toluene or o-xylene containing Al BN gave, in moderate yields, the 5,11 -methanomorphanthridine ring system 4, which is a basic skeleton of montanine-type Arnaryllidaceae alkaloids, and formal total synthesis of the title alkaloids 1-3 by conversion of 5,11 -methanomorphanthridin-2-one 5, derived from N-(4-oxocyclo hex- 2-eny l) -4-phenyIth iotetra hydroisoqui no1 ine 21 using this methodology, into the 2,3-benzylidenedioxy-5,ll -methanomorphanthridine 31 is achieved.It has been widely known that free-radical reactions are useful methods in organic synthesis, since the discovery of the reaction of chemically generated radicals by D. H. R. Barton et al.' Although there are numerous reports2 on the synthesis of natural products by means of radical reactions, to our knowledge no derivatives of the title ring system 4 have been synthesized by this method. In continuation of our study3 on the synthesis of Amaryilidaceae alkaloids we have recently reported the formation of the title ring system 4 by reduc- tive cyclization of 1 1-hydroxymethyl-5-tosylmorphanthridine using sodium bis-(2-methoxyethoxy)aluminiumhydride, and a first total synthesis of (i-)-montanine 1,7 (-t)-coccinine 2,7 and (f)-pancracine 38 starting from the 1 l-hydroxymethyl-5- tosylmorphanthridine 6 using this method.Concurrently, Overman and Shim' have also succeeded in a total synthesis of ( k)-panmacine 3 via aza-Cope rearrangement-Mannich cyclization. Montanine 1 R = H, R'= OMe 4 X=H2 Coccinine 2 R = OMe, K=H 5 x=o Pancracine 3 R = H, R' = OH 6 In order to explore the biological activity of 5,ll-methanomorphanthridine derivatives, however, a more con- venient method for the synthesis of the ring system was a necessary requirement. As mentioned above, in the execution of this project radical reactions seemed to be suitable for bond formation between 11- and 1 la-positions in the ring system (ex.compounds 4 or 5), because the radical precursors could be readily prepared and the reaction might proceed in a favoured 5-exo-trigonal process." In this paper, we describe a convenient synthesis of the title ring system 4 by radical-mediated reaction of 4-[(methylthio)(thiocarbonyl)oxy]-(lo), 4-phenylthio-( 16) or 4-phenylseleno-(17) N-(cyclohex-2-enyl)-6,7-(methylenedioxy)-tetrahydroisoquinolines and formal total synthesis of (&)-montanine 1, (+)-coccinine 2, and (+)-pancracine 3 via 5,ll-methanomorphanthridine-2-one 5 starting from N-(4-oxocy- clohex-2-enyl)-4-(phenylthio)tetrahydroisoquinoline 21 by application of this methodology.Results and Discussion As radical precursors, N-(cyclohex-2-enyl)tetrahydroisoquino-lines having halogeno, (alkylthio) (thiocarbonyl)oxy, arylthio, or arylseleno groups l1 were considered. However, since attempts to displace hydroxy groups with halogeno groups were unsuccessful, the xanthate 10, phenyl sulfide 16 and phenyl selenide 17 were chosen as the precursors. Their preparation is as follows. 6,7-Methylenedioxy-4-trimethyl-siloxytetrahydroisoquinoline 8, obtained by trimethylsilylation of the tetrahydroisoquinolin-4-01 7,' reacted with 3-bromo- cyclohexenel3 under basic conditions to give, after acid treatment, the N-(cyclohex-2-enyl)tetrahydroisoquinolin-4-ol9 in 79% yield.Treatment of compound 9 in the usual way afforded, in 56% yield, xanthates 10 as a 1 :1 diastereoisomeric mixture, which was separated by column chromatography into its components 1Oa and lob, although their stereochemistry was uncertain (Scheme 1). As for the phenyl sulfide 16 and the phenyl selenide 17, the N-(trifluoroacetyl)tetrahydroisoquinolin-4-ol 11, prepared by trifluoroacetylation of compound 7, was treated with PhSH or PhSeH in the presence of ZnI2I4 in 1,2-dichloroethane at room temperature to give the corresponding phenyl sulfide 12 or phenyl selenide 13in 98 or 79% yield, respectively. Hydrolysis of compound 12 or compound 13with aq. K2C03 in methanol gave the corresponding tetrahydroisoquinoline 14 or 15in good yield, treatment of which with 3-bromocyclohexene in a similar manner to that described above afforded compound 16 (quantitative yield) or compound 17 (6873, each as an inseparable 1:1 mixture of diastereoisomers.At first, attempted cyclization under usual conditions [Bu,SnH, azoisobutylnitride (AJBN)] was performed using the diastereoisomeric mixture 10, because the same radical intermediate could be generated from each diastereoisomer. Surprisingly, reaction of diastereoisomeric mixtures 10 with Bu3SnH (1.2-2.0 mol equiv.) in the presence of AIBN (0.5 mol equiv.) in boiling benzene did not take place. In addition, a similar attempt in boiling toluene or o-xylene gave $11- methanomorphanthridine 45bin low yields, accompanied by the 1,2-dihydroisoquinoiine18,which could be formed by Chugaev reaction, and recovered substrate 10.However, the results were J. CHEM. SOC. PERKIN TRANS. 1 1993 OR 7 R=H 9 10 8 R=TMSJa 14 X=SPh 16 X=SPh 15 X=SePh 17 X = SePh Scheme 1 Reugenfs: (a) TMSCI, Et,N, CH,CI,; then water; (b) 3-bromocyclohexene, Et,N, CHCI,; (c) NaH, CS,, MeI, THF; (d) (CF,CO),O, K,CO,, CHCI,; then water (e) PhSH or PhSeH, ZnI,, CH,CICH,Cl; (f) K2C03, aq. MeOH Table 1 Radical reaction of xanthates 10 with Bu,SnH in the presence of Et,B ~ ~~~ Yield (%) Et,B Bu,SnH Time Recovery Entry' (mol equiv.) (mol. equiv.) (t/h) 4 19 20 oflo(%) 1 1.2 1.2 9 12.7 7.8 19.5 19.5 2 2.0 1.2 9 14.3 19.7 11.7 14.7 3 1.2 2.0 4 15.7 57.3 5.6 6.2 4 2.0 2.0 4 17.8 42.2 12.2 0 5' 2.0 2.0 4 18.1 45.4 13.8 0 6' 2.0 2.0 4 17.6 44.7 13.5 0 'See Experimental section for the general procedure.Isolated yield. 'One of the diastereoisomers was used. Table 2 Radical reaction of xanthates 10 with Bu,SnH in the presence of Et,B under various conditions ~ ~ ~ ~ ~~~ Yield (%) Concentration Time Recovery Entry' Solvent (mol drn-,) Wh) 4 19 20 oflo(%) benzene 0.04 9 4.0 40.6 0 10.0 benzene 0.01 11 9.3 37.2 10.0 6.9 toluene 0.08 4 7.1 62.9 0 0 toluene 0.04 4 13.5 44.9 13.9 5.7 toluene 0.02 4 17.8 42.2 12.2 0 toluene 0.01 9 18.5 33.9 9.0 1.7 toluene 0.01 5 11 20.1 5.3 27.6 22.2 o-xylene 0.04 4 6.2 0 15.4 19.3 'See Experimental section for general procedure. Isolated yield. 'A syringe pump was used. 10 X=OCS&le 18 A33.4 20 16 X=SPh 17 X=SePh 19 3,aihydro Scheme 2 Reagents: AIBN or Et,B, Bu,SnH not reproducible and the yield of cyclized product 4 was less at elevated temperature gave compound 4.The results are given than 17%. in Tables 1 and 2. As expected, diastereoisomers 1Oa and 10b It is known that trialkylboranes l5 are suitable mediators for gave similar results (Table 1, entries 5 and 6) to those obtained radical reaction, and Et,B l6 was recently used as a radical with diastereoisomeric mixtures 10 (entry 4), showing that the initiator. Therefore, a similar reaction in the presence of Et,B diastereoisomeric mixture could be used without separation. In instead of AIBN under various conditions was carried out. these cases, formation of 6,7-methylenedioxyisoquinoline20 l7 Whereas the reaction did not proceed at low temperature, that accompanied with the tetrahydroisoquinoline 19 and substrate J.CHEM. SOC. PERKIN TRANS. 1 1993 A 4 10 X=OCS&le 16 X=SPh 17 X= SePh L - B H not observed Scheme 3 Table 3 Radical reaction of the phenyl sulfide 16 and the phenyl selenide 17 with Bu,SnH in the presence of AIBN Yield (%) Time Entry a Substrate Solvent (m 4 19 20 1 16 benzene 16.5 67.6 d 2 16 toluene 22.1 53.2 d 3' 16 toluene 45.5 26.7 7.6 4 16 0-x ylene 46.2 44.0 trace 5' 16 0-x ylene 39.1 19.4 12.4 6 17 benzene 9.4 64.2 d 7 17 toluene 14.8 55.3 d 8' 17 toluene 42.6 18.1 17.1 9 17 0-xylene 16.4 41.6 d See Experimental section for general procedure.Isolated yield. A syringe pump was used. Not isolated. Table 4 Radical reaction of the phenyl sulfide 21 with Bu,SnH in the presence of AIBN under various conditions Yield (%) Concentration Time Entry" Solvent (mol drn-,) (Vh) 5 23 1c.d toluene 0.01 3 51.3 e 2d toluene 0.01 2 46.3 e 3 toluene 0.01 4 74.4 9.1 4d 0-xylene 0.0 1 2 53.5 21.2 5 o-x ylene 0.01 4 80.1 8.9 6 0-xylene 0.02 4 75.3 12.4 7 u-x ylene 0.04 4 72.2 17.3 8 o-x ylene 0.08 4 61.5 20.0 9 o-xylene 0.01 0.5 79.8 8.2 1of o-xylene 0.01 8 68.2 trace " See Experimental section for general procedure. * Isolated yield. ' 12.9% of substrate 21 was recovered. A syringe pump was not used. Not isolated. 12.2% of substrate 21 was recovered.10 was observed (Scheme 2). Although a 0.014.02 mol dm-3 concentration in toluene was found to be favourable (Table 2, entries 5-7), the yield of cyclized product 4 could not be improved. The structure of product 4 was identical in all respects with that of an authentic sample5* as shown by comparison of both its 'H NMR and its IR spectrum. Since xanthate 10 was found to be an unsuitable radical precursor even in the reaction at elevated temperature because of its low reactivity, the similar reaction of the phenyl sulfide 16 or the phenyl selenide 17 was examined. In contrast to xanthate 10, reaction of substrate 16 or 17 under the usual conditions (Bu,SnH, AIBN)* readily proceeded to give compound 4 in improved yields, although formation of the tetrahydroiso- quinoline 19 could not be reduced.The results are summarized in Table 3. Interestingly, the higher the reaction temperature the higher the yield of product 4 (entries 1,2 and 4). These findings suggested that the transition state in the radical cyclization of substrates 16 and 17 would require a high activation energy. The reaction in boiling o-xylene afforded compound 4 in 46.2% yield (entry 4).A dilution method using a syringe pump seemed to be effective both in giving compound 4 and in retarding formation of unwanted product 19 (entries 3, 5 and 8). Furthermore, the phenyl sulfide 16 was found to be a radical precursor superior to the phenyl selenide 17, since the latter was slightly unstable. It is noteworthy that the radical reaction proceeded at elevated temperature" to give compound 4 in acceptable yields.Stereoselective formation of one isomer 4 from a dia-stereoisomeric mixture could be interpreted by assuming steric repulsion between the tetrahydroisoquinoline ring and the cyclohexenyl group in benzylic radical A or B in the transition state of the radical cyclization, in which benzylic radical A is preferable to the radical B as depicted in Scheme 3. Therefore, the 5,ll-methanomorphanthridine4 was prepared in moderate yields by radical-mediated cyclization of the phenyl sulfide 16 and the phenyl selenide 17. This methodology appeared to be readily applicable to the preparation of the 5,11-methanomorphanthridin-2-one 5, which could be converted into 2,3-benzylidenedioxy-5,11-methanomorphanthridine 31, previously synthesized as a key compound for the total synthesis6 of (+)-montanine 1, (-t)-coccinine 2, and (& )-pancracine 3.As a radical precursor for this route, the N-(4-oxocyclohex-2- enyl)-4-(phenylthio)tetrahydroisoquinoline 21 was prepared by heating a mixture of compound 14, 4-bromocyclohex-2-enone and Et3N in acetonitrile-tetrachloromethanecontain-ing Et,NI. In this case, an inseparable 1:l mixture of diastereoisomers 21 and a regioisomer 22 were obtained in 55.8 and 11.7% yield, respectively. * Use of Ph,SnH-AIBN in place of Bu,SnH-AIBN in boiling toluene (0.01 mol drn-,) gave unsatisfactory results (4 6.1% and 19: 81.2%).J. CHEM. SOC. PERKIN TRANS. 1 1993 SPh SPh 1 I 0 21 2214 1. 23 5 24 Scheme 4 Reagents: (a) 4-Brornocyclohex-Zenone,Et,N, Et,NI, MeCN, CCl,; (b) Bu,SnH, AIBN; (c) MsCl, Et,N, CHCl,; then H,, 2% PdCl,, charcoal, MeOH; then DBU, PhMe Contrary to our expectations, reaction of sulfide 21 with Bu,SnH (2.0 mol equiv.) in boiling toluene (0.01 mol drn-,) containing AIBN (0.2 mol equiv.) did not occur. After several attempts, the reaction was found to require 4.0 mol equiv. of Bu,SnH and 0.4 mol equiv. of AIBN, with which the dilution method using o-xylene as solvent was likewise effective. The results are shown in Table 4. Interestingly, in these cases the tetrahydroisoquinoline 23, which could be formed by conjugated reduction2' of the a$-unsaturated carbonyl group, was obtained (Scheme 4).Although prolonged reaction times did not afford compound 23, the reaction was incomplete (entry 10). The analogous reaction of compound 21 in higher concentration using o-xylene, however, decreased the yield of compound 5 and increased formation of uncyclized product 23 (entries 6-8). The findings that the yield of compound 5 in the present reaction was better than that of compound 4 can be attributed to the enhanced reactivity of radical precursor 21 bearing an electron- deficient olefin 2' such as an a$-unsaturated carbonyl moiety. The structure of product 5 was confirmed by comparison of the spectral data ('H NMR, IR) with those of an authentic sample derived from U6in 3 steps (overall 63.5% yield) (see Experimental section).With 5,1l-methanomorphanthridin-2-one5 in hand, we turned our attention to 2,3-benzylidenedioxy-5,11-methano-morphanthridine 31 derived from compound 5, completing a formal total synthesis of the title alkaloids 1-3.To this end, conversion of ketone 5 into intermediate 28 uia mesate 26 or 27 was carried out. Reduction (NaBH,)* of ketone 5 gave an inseparable diastereoisomeric mixture of alcohols 25 in quantitative yield. Unexpectedly, dehydroxylation (POC1,- pyridine) or Chugaev reaction (uia xanthate) of substrate 25 failed. However, the alcohol 25 was converted in the usual manner to a mesyl derivative, which was readily separated into its constituents 26 and 27 in 47 and 49% yield, respectively (Scheme 5).Their stereochemistry was confirmed by conversion of compound 246 into the mesate 26 in 4 steps22 (see Experimental section). Based on an inspection of Dreiding models, dehydromesyl- ation of compound 26under basic conditions was anticipated to * Reduction of compound 5 with diisobutylaluminium hydride or BH,*THF gave a -1 :1 diastereoisomeric mixture of alcohols 25 in moderate yield. produce more predominantly the desired olefin 28 compared with 27because of the former having the sterically less hindered proton at the 4-position as compared with the latter. With this in mind, reaction of mesyl ester 26 with Bu'OK in dimethyl sulfoxide (DMSO) at room temperature was performed to give, after purification, intermediates 28 and 29 in 42 and 40% yield respectively, whereas that with 1,8-diazabicyclo[5.4.O]undec-7-ene (DBU) in boiling toluene gave compounds 28 and 29 in 13 and 39% yield.Structures of compounds 28 and 29 were deduced on the basis of their 'H NMR spectra, showing that 1-and 4-protons (6 1.56-2.60) for the former 28 resonate at lower field than the 3- and 4-protons (6 1.36-2.20) for the latter 29. This assumption was supported by the conversion of the alkene 28 into compound 31 as described below. On the other hand, unfortunately, similar reaction of the 2a-mesate 27furnished, in 89% yield, the undesired regioisomer 29as the sole product. The reason why only compound 29was formed is unknown. Since reaction of the mesyl esters 26 and 27 resulted in predominant formation of the undesired olefin 29, syn elimination of sulfides 32 and 33 was explored.Reaction of alcohols 25 with diphenyl disulfide and Bu,P in refluxing 1,2- dimethoxyethane (DME) 23 afforded 2a- and 2P-phenyl sulfides (32and 33)in 46.4 and 49.5% yield, respectively. Stereochemistry of the a-product 32 was confirmed by comparison of its 'H NMR spectrum with that of the 2a-sulfide derived from the 2p-alcohol 25a in a similar manner. Conversion of sulfides 32 and 33 into olefin 28 or 29 was carried out as follows. Oxidation of the alcohol 32 with NaIO, in methanol afforded, in 95.2% yield, a 1.3: 1diastereoisomeric mixture of sulfoxides, which was heated in toluene to give olefins 28 and 29 in 48.7 and 40.8% yield.Similar reaction of sulfide 33 gave a 1.2: 1 diastereo- isomeric mixture of sulfoxides, heating of which in toluene produced olefins 28 and 29in 41.6 and 51.3% yield, respectively. Although the reaction took place as expected, the desired olefin 28could not be obtained preferentially. This result might be due to the diastereoisomeric mixture of sulfoxides. $ In order to improve the yield of olefin 28,an alternative route was examined. Although conversion of p-tosylhydrazone 30 into olefin 28 was attempted under various basic condi- tions 24 [BuLi, Bu'Li, Bu'Li or lithium diisopropylamide (LDA)], the reaction did not occur. However, treatment of $ syn Elimination of 8,9-methylenedioxy-2-phenylseleno-5,1l-methano-morphanthridines was also unfruitful.J. CHEM. SOC. PERKIN TRANS. 1 1993 -b or c 26 R = OMS,R'= H 32 R=H,R'=SPh 27 R=H,W=OMs 33 R=SPh,R'=H d ]ore 30 28 29 34 31 (i)-montanine 1 (*)-cotxinine 2 (*)-pancracine 3 Scheme 5 Reagenrs and conditions: (a) NaBH,, MeOH; (b) MsCl, Et,N, CHCI,; (c)(PhS),, Bu,P, DME (d) Bu'OK, DMSO; (e) NaIO,; aq. MeOH; then PhMe, heat; (f) TsNHNH,, MeOH; (g) OsO, (cat.), NMNO; then PhCH(OMe),, p-TsOH*H,O, CHCI,; (h) DDQ, 1P-dioxane compound 30with Bu'OK in DMSO at 100 "C gave olefins 28 and 29 in 34 and 277; yield, respectively, although stereo- selectivity in the reaction was again poor. Finally, since olefin 28 was obtained in moderate yields, vicinal dihydroxylation of compound 28 by oxidation with OsO, in the presence of N-methylmorpholine N-oxide '' (NMNO), followed by benzylidenation in the usual manner afforded compound 31 in 75% overall yield, 'H NMR and IR spectra of which were identical with those of an authentic sample.6 In conclusion, the present radical reaction, which readily proceeded at elevated temperature, was found to be the third method for synthesis of the 5,ll-methanomorphanthridinering system, and a formal total synthesis* of montanine-type Amaryllidaceae alkaloids 1-3 was accomplished through sulfide 21 by application of this methodology (see Scheme 5).Experimental M.p.s were measured on Biichi or Yanagimoto (hot plate) melting-point apparatus and are uncorrected. IR spectra were performed with a Hitachi 260-10 spectrometer and 'H NMR spectra were taken with a JEOL JMX-FX 100 (100 MHz) spectrometer using tetramethylsilane as internal standard.J-* Oxidation of compound 5 with 2,3-dichloro-5,6-dicyano-p-benzo-quinone (DDQ) 26 in boiling dioxane gave a known enone 34 (m.p. 49-50 "C;76%) (see Experimental section), which is converted already into ( +)-pancracine 3, although compound 34 was not identified directly with an authentic ample.^ Values are given in Hz. Mass spectra were measured on a Hitachi M-80 or a JEOL JMS D-300 spectrometer. Preparative TLC (PLC) was run on Merck 5744 or Merck 7730 plates (Kieselgel). 6,7-Methylenedioxy-4- trimethylsiloxy- 1,2,3,4-?etrahydro- isoquinoline %-To a stirred solution of the tetrahydro-isoquinolin-4-017" (1.0027 g, 5.2 mmol) and Et,N (1.31 g, 12.9 mmol) in tetrahydrofuran (THF) (50cm3) was added dropwise at room temperature chlorotrimethylsilane (TMSCl) (1.5 cm3, 11.7 mmol).After 0.5 h, the mixture was filtered through Celite 545. The filtrate was evaporated under reduced pressure to give an oily residue, which was stirred at room temperature in a mixture of dichloromethane (20 cm3) and water (10cm3) for 0.5 h. The organic phase was separated, dried (Na'SO,), and evaporated under reduced pressure to give the title compound 8 (1.374 g, 99.4%) as an oil; G,(CDCl,) 6.70 and 6.44 (each 1 H, s, 2 x ArH) 5.88 (2 H, s, OCH,O), 4.52 (1 H, t, J4,4-H), 3.86 (2 H, s, 1-H2),3.04 (2 H, d, J4,3-H2), 2.20 (1 H, s, NH) and 0.20 (9 H, s, 3 x Me); v,,,(CHCl,)/cm-' 1480; m/z 265 (M+) (Found M+, 265.1128.Calc. for C,,H,,NO,Si: M, 265.1 133). N-(Cyclohex-2-enyl)-6,7-methylenedioxy-1,2,3,4-tetrahydro-isoquinolin-4-01 9.-To an ice-cold, stirred solution of TMS ether 8 (3.0806 g, 11.6 mmol) and Et,N (1.41 g, 13.9 mmol) in chloroform (100 cm3) was added dropwise a solution of 3-bromocyclohexene (2.05 g, 12.7 mmol) in chloroform (10 cm3). The mixture was stirred at room temperature for 15 h and the solvent was removed under reduced pressure to give a residue, which was dissolved in 3 mol dm-, HCl. The aqueous phase was washed with diethyl ether and was then made alkaline with 3 mol dm-, NaOH. The aqueous phase was extracted with chloroform. The extract was washed with brine, dried (K,CO,), and evaporated under reduced pressure to give an oily residue.Chromatography of the oil on alumina [(1 :1) ethyl acetate-hexane and then ethyl acetate only] afforded the alcohol 9 (2.511 g, 79.4%) as an oil: d,(CDCl,) 6.80 and 6.46 (each 1H, s, 2 x ArH), 5.88 (2 H, s, OCH,O), 5.50-5.98 (2 H, m, CH=CH), 4.324.50 (1 H, m, 4-H), 3.67 and 3.62 (each 1 H, s, 1-H,), 3.24-3.48 (1 H, m, NCH), 2.52-3.12 (4 H, m, 3-H, and CH,CH=) and 1.40-2.12 (4 H, m, CH,CH,); vmax(CHCl,)/m-' 3200-3625; m/z 273 (M+) (Found: M+ 273.1362. Calc. for C16H19N03:M, 273.1364). S-Methyl 0-[N( Cyclohex-2-enyi)-6,7-methylenedioxy-1,2,3,-4-tetrahydroisoquinolin-4-y1]Dithiocarbonate 10.-To a stirred suspension of NaH (97 mg, 2.4 mmol) in THF (1 cm3) was added dropwise a solution of the alcohol 9 (550 mg, 2 mmol) in CS2 (2.5 cm3) under argon.The mixture was refluxed for 0.5 h before being cooled to room temperature, Me1 (0.18 cm3, 2.9 mmol) was added, and the mixture was refluxed for 10 min. After the reaction was quenched with water, the product was taken up in chloroform. The extract was washed with brine, dried (K2C03), and evaporated under reduced pressure to give an oily residue. Chromatography of this oil on silica gel [( 1:5) hexane<hloroform and then chloroform only] yielded a mixture of diastereoisomers 10 (407 mg, 55.7%) as an oil; d,(CDCl,) 6.76 and 6.44 (each 1 H, s, 2 x ArH), 5.88 (2 H, s, OCH,O), 5.50-5.96 (2 H, m, CHSH), 4.97 (1 H, t, J 3, 4-H), 3.72 and 3.69 (each 1 H, s, 1-H,), 3.40 (1 H, br s, w+ 14.3, NCH), 2.78-3.18 (2 H, m, 3-H,), 2.44 (3 H, s, SMe) and 1.36- 2.12 (6 H, m, SHCH2CH2CH,); vm,,(CHCl3)/cm-' 1625 and 1480; m/z 363 (M+) (Found: M+, 363.0947.Calc. for Cl8H2,NO3S,: M, 363.0961). A mixture of diastereoisomers 10 was separated by chromatography on silica gel with the same eluent to give components 10a and lob, each as an oil, although stereo- chemistry was not characterized. Compound 10a: d,(CDCl,) 6.76 and 6.44 (each 1 H, s, 2 x ArH), 5.88 (2 H, s, OCH,O), 5.50-5.96 (2 H, m, CHCH), 4.97 (1 H, t, J3, 4-H), 3.72 (2 H, s, 1-H,), 3.40 (1 H, br s, w-) 14.3, NCH), 3.10 and 2.89 (each 1 H, dd, J3 and 13,3-H,), 2.44 (3 H, s, SMe) and 1.36-2.11 (6 H, m, =CHCH,CH,CH,); v,,,(CHCl,)/cm-' 1625 and 1480; m/z363 (M') (Found: M+, 363.0955.Calc. for C,,H,,NO,S,: M, 363.0961). Compound lob: d,(CDCl,) 6.76 and 6.44 (each 1 H, s, 2 x ArH), 5.88 (2 H, s, OCH,O), 5.52-5.96 (2 H, m, CH=CH), 4.97 (1 H, t, J3, J. CHEM. SOC. PERKIN TRANS. 1 1993 v,,,(CHCl,)/cm-' 3200-3625 and 1680; m/z289 (M+) (Found: C, 49.9; H, 3.6; N, 4.9. Calc. for C12H,,F,N04: C, 49.84; H, 3.49; N, 4.84%). N-(Cyclohex-2-enyZ)-6,7-methylenedioxy-4-phenylthio-1,2,3,4-tetrahydroisoquinoline 16 and N-(Cyclohex-2-enyl)-6,7-methyl-enedioxy-4-phenylseleno-1,2,3,4-tetrahydroisoquinoline-l7.-Compound 16.A mixture of the trifluoroacetamide 11 (2.0233 g, 7.0 mmol), anhydrous ZnI, l4 (1.1758 g, 3.68 mmol), and PhSH (0.86 cm3, 8.38 mol) in 1,2-dichloroethane (50 cm3) was stirred at room temperature for 1 h.After addition of 3 mol dm-, NaOH, the organic phase was separated and the aqueous phase was extracted with chloroform. The combined extracts were washed with brine, dried (Na,SO,), and removed under reduced pressure to give 6,7-methylenedioxy-4-phenylthio-N-trifluoroacetyl-l,2,3,4-tetrahydroisoquinoline12 (2.606 g, 97.7%) as a 1 :1 mixture of diastereoisomers, m.p. 123-123.5 "C (from ethyl acetate-hexane); d,(CDCl,) 7.42-7.64 (1 H, m, ArH), 7.16-7.42 (4 H, m, 4 x ArH), 6.92 and 6.88 (each 0.5 H, s, ArH), 6.56 and 6.52 (each 0.5 H, s, ArH), 5.94 (2 H, s, OCH,O) 4.80 and 4.36 (each 0.5 H, d, J 16, 1-H), 4.59 (1 H, s, 1-H), 4.22- 4.52 (1 H, m, 4-H), 3.90 (1 H, d, J4,3-H) and 3.35-3.64 (1 H, m, 3-H); vm,,(CHC13)/cm-' 1675; m/z381 (M+) (Found: C, 56.6; H, 3.9; N, 3.5.Calc. for C,,H,,F,NO,S: C, 56.69; H, 3.70; N, 3.67%). A mixture of sulfide 13 (1.9046 g, 5.0 mmol) and 5% aq. K,C03 (20 cm3) in methanol (50 cm3) was refluxed for 0.5 h. After removal of methanol under reduced pressure, the mixture was extracted with chloroform. The extract was washed with brine, dried (K2C03), and evaporated under reduced pressure to give 6,7-methylenedioxy-4-phenylthio-1,2,3,4-tetrahydroiso-quinoline 14 (1.4211 g, 99.779, m.p. 67 "C (from diethyl ether-hexane); d,(CDCl,) 7.12-7.52 (5 H, m, Ph), 6.84 and 6.47 (each 1 H, s, 2 x ArH), 5.88 (2 H, s, OCH,O),4.24 (1 H, t, J3,4- H), 3.88 (2 H, s, l-H2), 3.10 and 3.20 (each 1 H, dd, J 3 and 13.2, 3-H,) and 2.17 (1 H, s, NH); v,,,(CHCl,)/cm-' 3280; m/z285 (M+) (Found: M+, 285.0825.Calc. for C,,H,,NO,S: M, 285.0822). To a stirred solution of secondary amine 14 (854.5 mg, 3.0 mmol), Et,N (793.9 mg, 7.85 mmol) and 4-(dimethylamino)- pyridine (DMAP) (221.5 mg, 1.97 mmol) in chloroform (30 cm3) was added at room temperature a solution of 3-bromocyclohexene (840.1 mg, 5.22 mmol) in chloroform (1 cm3). After 26 h, the mixture was washed successively with saturated aq. NaHCO, and brine, dried (K2C03), and evaporated under reduced pressure to give an oily residue. Chromatography of this oil on silica gel (chloroform) afforded a mixture of diastereoisomers 16 (1.0918 g, 99.8%) as an oil: 4-H),3.69(2H,s, l-H2),3.36(1H,brs,w+14.3,NCH),3.04(2H,d,(CDCl,) d, J 3, 3-H,), 2.44 (3 H, s, SMe) and 1.40-2.12 (6 H, m, =CHCH,CH,CH,); v,,,(CHCl,)/cm-' 1625 and 1480; m/z(M +) (Found: M +,363.0945).6,7-Methylenedioxy-N-triJuoroacetyl-1,2,3,4-tetrahydroiso-quinolin-4-oi 11.-To a stirred suspension of amino alcohol 7 (7.66 g, 30.7 mmol) and K,CO, (18.93 g, 137 mmol) in chloroform (300 cm3) was added dropwise at room temperature trifluoroacetic anhydride (15 cm', 106 mmol). After 0.5 h, water (150 cm3) was added and the mixture was stirred for an additional 2 h. The organic phase was then separated and the aqueous phase was re-extracted with chloroform. The combined extracts were washed successively with 1 mol dm-, HCl and brine, dried (Na,SO,), and removed under reduced pressure to give a solid. Chromatography of this solid on silica gel [( 1:10) hexane<hloroform] afforded the amide 11 (9.04 g, 78.8%), m.p.99-100 "C (from chloroform-hexane); G,(CDCl,) 6.86 (1 H, s, ArH), 6.54 and 6.57 (each 0.5 H, s, ArH), 5.94 (2 H, s, OCH,O), 4.03-5.00 (3 H, m, 1-H, and 4-H) and 3.484.03 (2 H, m, 3-H,); 7.36-7.55 (2 H, m, 2 x ArH), 7.12-7.35 (3 H, m, 3 x ArH), 6.80 and 6.89 (each 0.5 H, s, 5-H), 6.45 (1 H, s, 8-H), 5.86 (2 H, s, OCH,O), 5.52-5.92 (2 H, m, CHSH), 4.24-4.44 (1 H, m, 4-H), 3.72 (2 H, br s, 1-H,), 3.40 (1 H, br s, w+ 18.9, NCH), 2.70-3.14 (2 H, m, 3-H,) and 1.36-2.08 (6 H, m, =CHCH,CH,CH,); v,,,(CHCl,)/cm-' 1480; m/z 365 (M '); (Found: M+, 365.1436. Calc. for C2,H,,N02S: M, 365.1447). Further separation of diastereoisomers was not attempted. Compound 17.A mixture of trifluoroacetamide 11 (289.2 mg, 1.0 mmol), anhydrous ZnI, (164.7 mg, 0.5 mmol), and PhSeH (130 x lo-, cm', 1.2 mmol) in 1,2-dichloroethane (5 cm3) was stirred at room temperature for 0.5 h. Similar work- up as described for sulfide 12 gave an oily residue. Chromatography of this oil on silica gel [(1 :1) chloroform- hexane and then chloroform only] produced 6,7-methylene- dioxy-4-phenylseleno-N-trifluoroacetyl-1,2,3,4-tetrahydroiso-quinoline 13 (336.1 mg, 78.5%), m.p. 130-130.5 "C (from chloroform-hexane); G,(CDC1,) 7.58-7.74 (1 H, m, ArH), 7.20- 7.52 (4 H, m, 4 x ArH), 6.84 and 6.80 (each 0.5 H, s, ArH), 6.50 and 6.49 (each 0.5 H, s, ArH), 5.94 (2 H, s, OCH,O), 4.80 and J. CHEM. SOC. PERKIN TRANS. 1 1993 4.51 (each 0.5 H, d, J 16, 1-H), 4.50 (1 H, s, 1-H), 4.36468 (1 H, m, 3-H), 3.99 (1 H, t, J 5, 4-H) and 3.32-3.64 (1 H, m, 3-H); v,,,(CHCl,)/cm-' 1680; m/z 428 (M') (Found: C, 50.4; H, 3.5; N, 3.0.Calc. for C,,H,,F,NO,Se: C, 50.48; H, 3.30; N, 3.27%). A mixture of selenide 13 (852.2 mg, 2.0 mmol) and 5% aq. K2C03 (10 cm3) in methanol (25 cm3) was refluxed for 15 min. Similar work-up as described for sulfide 14 gave 6,7- meth ylenediox y-4-phenylseleno-1,2,3,4-tetrahydroisoquinoline 15 (649.5 mg, 97.8%), m.p. 69.5 "C (from diethyl ether-hexane); d,(CDCI,) 7.44-7.68 (2 H, m, 2 x ArH), 7.12-7.38 (3 H, m 3 x ArH), 6.80 and 6.41 (each 1 H, s, 2 x ArH), 5.87 (2 H, s, OCHZO), 4.46 (1 H, t, J 2,4-H), 3.90 (2 H, S, 1-HZ) 3.16 (2 H, d, J 2, 3-H,) and 2.04 (1 H, br s w+ 15.7, NH); v,,,(CHCl,)/cm-' 3300; m/z 333 (M') (Found: M+ 333.0245.Calc. for C16H1 ,NO,Se: M, 333.0266). To a stirred solution of secondary amine 15 (649.5 mg, 1.96 mmol), Et,N(509.0 mg, 5.03 mmol) and DMAP (145.6 mg, 1.99 mmol) in chloroform (30 cm3) was added at room temperature a solution of 3-bromocyclohexene (606.4 mg, 3.77 mmol) in chloroform (1 cm'). After 26 h, similar work-up as described for sulfide 16 produced an oily residue. Chromatography of this oil on silica gel (chloroform) gave a mixture of diastereoisomers 17 (555.7 mg, 68.9%) as an oil; G,(CDCl,) 7.44-7.66 (2 H, m, 2 x ArH), 7.12-7.34 (3 H, m, 3 x ArH), 6.72 and 6.60 (each 0.5 H, S, 5-H), 6.43 (1 H, S, 8-H), 5.85 (2 H, S, OCHZO), 5.56-5.94 (2 H, m, CH=CH), 4.364.52 (1 H, m, 4-H), 3.76 and 3.72 (each 1 H, s, 1-H,), 3.40 (1 H, br s, w+ 18.9, NCH), 2.76-3.26 (2 H, m, 3-H2) and 1.362.08 (6 H, m, =CHCH,CH,CH,); v,,,(CHC1,)/cm~' 1480 m/z 413 (M') (Found: M+, 413.0894.Calc. for C2,H2,NO,Se: M, 413.0893). Further separation of dia-stereoisomers was not attempted. General Procedure for Radical Reaction of Substrate 10,16 or 17 (Tables 1 and 2).--(a) In the presence of Et,B. A mixture of radical precursor 10 (0.28 mmol), Et3B (1.2-2.0 mol equiv.; 1 rnol dm-, in hexane) and Bu,SnH (1.2-2.0 mol equiv.) in an appropriate solvent was refluxed under argon. The solvent was then evaporated off under reduced pressure to leave a residue, which was dissolved in diethyl ether. The organic phase was re- extracted with 3 mol dm-, HCl and the aq.phase was washed with diethyl ether and made to alkaline with 3 mof dm-3 NaOH. The product was taken up in chloroform. The organic extract was washed with brine, dried (K2C03), and evaporated under reduced pressure to produce an oily residue, which was purified by PLC on silica gel plates with (1 :30) and (1 :10) methanol-chloroform as developing solvent to afford products 4,19 and 20. 8,9-Methylenedioxy-5,ll-methanomorphanthridine4: 6,-(CDCI,) 6.46 (1 H, S, 7-H), 6.41 (1 H, S, 10-H), 5.84 (2 H, S, OCH20),4.32and3.69(each 1H,d,J17.1,6-H2),3.12(1H,dd, J2.8 and 12, 12-H), 2.86 (1 H, d, J 12, 12-H), 2.84-3.12 (1 H, m, 4a-H), 2.38 (1 H, d, J2.8, 11-H), 2.06-2.38 (1 H, m, lla-H) and 1.061.88 (8 H, m, 1-, 2-, 3- and 4-H,); V,,,,(CHCI,)/C~-~ 3040, 1500,1480 and 1340; m/z 257 (M+) 'H NMR and IR spectra of compound 4 were identical with those of an authentic sample.5b N-(Cyclohex-2-enyl)-6,7-methylenedioxy-1,2,3,4-tetrahydro-isoquinoline 19 was an oil; 6,(CDCl,) 6.52 and 6.47 (each 1 H, s, 2 x ArH), 5.81 (2 H, s, OCH20), 5.56-5.98 (2 H, m, CH=CH), 3.68 (2 H, s, 1-H2), 3.40 (1 H, br s, w.)12.9, NCH), 2.78 (4 H, s, 3-and 4-H,) and 1.40-2.12 (6 H, m, =CHCH,CH,CH,); v,,,(CHCl,)/cm-' 1480 m/z 257 (M+)(Found M+,257.1413.Cak. for C16H19N02: hf,257.1414). 6,7-Methylenedioxyisoquinoline20 m.p. 1 19-120 "C (from chloroform-hexane) (lit." 119-120 "C); G,(CDCI,) 8.96 (1 H, s, 1-H), 8.34 and 7.45 (each 1 H, d, J6, 3- and 4-H), 7.16 and 7.04 (each 1 H, s, 8-and 5-H) and 6.08 (2 H, s, OCH20); v~,,(CHC~,)/C~-~ (Found: C, 69.1; H, 3.8; 1600; m/z 173 (M+)N, 8.1.Calc. for C,,H,NO,: C, 69.36; H,4.07; N, 8.09%). (b) Without a syringepump in thepresence of AIBN. A mixture of radical precursor 16 or 17 (0.28 mmol), AIBN (0.2 mol equiv.) and Bu,SnH (2.0 mol equiv.) in an appropriate solvent was refluxed under argon. Similar work-up as described above afforded compounds 4, 19 and 20. The results are shown in Table 3. (c) With a syringe pump in the presence of A IBN.-A solution of AIBN (0.2 mol equiv.) and Bu3SnH (2 rnol equiv.) in an appropriate solvent was added dropwise to a solution of radical precursor 16 or 17 (0.28 mmol) in the same solvent using a syringe pump over a period of 1 h except for entries 3, 5 and 8 (Table 3) (over a period of 7 h).After the addition was complete, the mixture was refluxed for an additional 1 h. Similar work-up as described above afforded compounds 4, 19 and 20. The results are shown in Table 3. 6,7-~ethylenedioxy-N-(4-oxocyclohex-2-enyl)-4-phenylthio-1,2,3,4-tetrahydroisoquinoline* 21 and 6,7-Methylenedioxy-N-( 3-oxocyclohex-1 -enyl)-4-phenylthio- 1,2,3,4-tetrahydroiso- quinoline* 22.-To a stirred suspension of compound 14 (2.85 14 g, 10.0 mmol), Et,N (3.56 g, 35.2 mmol) and Et,NI (7.715 g, 30.0 mmol) in acetonitrile (60cm3)was added dropwise at room temperature a solution of 4-bromocyclohex-2-enone (30 mmol), freshly prepared from cyclohex-2-enone (2.89 g, 30 mmol), N-bromosuccinimide (5.34 g, 30 mmol) and benzoyl peroxide (37.4 mg, 0.15 mmol) in tetrachloromethane (40 cm3) according to the reported method." After the mixture had been refluxed for 3 h, 3 mol dm-, NaOH was added to the ice-cooled mixture.The organic phase was separated and the aqueous phase was extracted with chloroform. The combined organic extracts were washed with brine, dried (K,CO,), and evaporated under reduced pressure to give an oily residue. Chromatography of this oil on silica gel [(1:3) ethyl acetate-hexane] produced compounds 21 (2.1 144 g, 55.8%) and 22 (0.4430 g, 11.7%), each as an oil. For compound 21: GH(CDCl3) 7.16-7.52 (5 H, m, Ph), 6.99 (1 H, dt, J 2 and 10, NCHCHSHCO), 6.88 and 6.79 (each 0.5 H, s, ArH), 6.46 (1 H, s, 8-H), 6.00 (1 H, dt, J 2.8 and 10, NCHCHSHCO), 5.88 (2 H, S, OCHZO), 4.37 (1 H, t, J4,4-H), 3.79 and 3.74 (each 1 H, s, l-H2), 3.54-3.88 (1 H, m, NCH), 2.84-3.02 (2 H, m, 3-H2) and 1.68-2.60 (4 H, m, COCH,CH,); vmax(CHC1,)/cm-' 1680; m/z 379 (M+)(Found: M +,379.1240.Calc. for C,,H,,NO,S: M, 379.1240). For compound 22 6,(CDCl3) 7.12-7.52 (5 H, m, Ph), 7.04 and 6.46 (each 1 H, s, 5-and 8-H), 5.99 (1 H, t, J4.4, COCHS), 5.89 (2 H, s, OCH,O), 4.46 (1 H, dd, J4.8 and 6.8,4-H), 3.92 (2 H, s, 1-H,), 3.52 (1 H, dd, J4.8 and 12.4,3-H), 3.24 (1 H, dd, J6.8 and 12.4,3-H), 2.20- 2.58 (4 H, m, COCH, and =CHCH,) and 1.76-2.08 (2 H, m, CH2CH2CH2); v,,,(CHCl,)/cm-' 1675; m/z 379 (M +)(Found:M+379.1235). General Procedure for Radical Reaction of Enone 21 (Table 4).+a) Without a syringe pump (entries 1, 2 and 4).A stirred solution of the phenyl sulfide 21 (0.20 mmol), AIBN (0.08 mmol) and Bu,SnH (0.8 mmol) in toluene or o-xylene was refluxed under argon. The solvent was then evaporated off under reduced pressure to leave a residue, which was dissolved in diethyl ether. The organic phase was re-extracted with 3 mol dm-, HCl. The aqueous phase was washed with diethyl ether and made alkaline with 3 mol dm-, NaOH. The product was taken up in chloroform. The organic extract was washed with brine, dried (K2C03), and evaporated under reduced pressure to give an oily residue. PLC with (1 :20) methanokhloroform as a developing solvent afforded compounds 5 and 23. The spectra of cyclised product 5 was identical with those of an authentic sample derived from compound 24 as described below. * 4-(21) and 3-(6,7-methylenedioxy-4-phenylthio-1,2,3,4-tetrahydro-quinolin-2-yl)cyclohex-2-enone(22). Compound 23: oil; GH(CDC1,) 6.53 and 6.46 (each 1 H, s,2 x ArH),5.84(2 H,s,OCH,O),3.68(2 H,s, l-H,),2.68-2.93 (1 H, m, NCH), 2.80 (4 H, s, 3- and 4-H,), 2.28-2.58 (4 H, m, CH,COCH,) and 1.80-2.24 [4 H, m, NCH(CH,CH,),CO]; +v,,,(CHCl,)/crn-' 1705; m/z 273 (M +) (Found: M 273.1368.Cak. for c16H 1,NO,: M, 273.1366). (b) With a syringe pump. (i) Entries 3, 5-10. To a 0.01 mol dm-3 solution of enone 21 (0.21 mmol) in toluene or o-xylene was added a mixture of Bu,SnH (0.84 mmol) in the same sol- vent containing AIBN (0.084 mmol) over a period of 3 h and the whole was refluxed for 1 h.Similar work-up as described above gave compounds 5 and 23. (ii) Preparative scale. To a solution of compound 21 (3.58 g, 9.4 mmol) in o-xylene (370 cm3) was added dropwise under reflux a solution of Bu,SnH (10.9 g, 37.5 mmol) and AIBN (0.6170 g, 3.76 mmol) in o-xylene (100 cm3) over a period of 1 h. After the addition was complete, the mixture was refluxed for an additional 1 h. Similar work-up as described above afforded compound 5 (1.9630 g, 76.7%), m.p. 126-1 27 "C, and compound 23 (0.2424 g, 9.4%), spectral data of which were identical with those of authentic samples obtained in method (a) above. 8,9-Methylenedioxy-5,11-methanomorphanthridin-2-one5 from 2p-Benzyloxy-8,9-methylenedioxy-5,11-methanomorphan-thridin-3P-o124.-To an ice-cold, stirred solution of the alcohol 24 (1.5646 g, 4.13 mmol) and Et,N (0.84 g, 8.3 mmol) in dichloromethane (20 cm3) was added dropwise methanesul- fonyl chloride (0.61 g, 8.0 mmol).After 15 min, the reaction was quenched with 3 mol dm-, NaOH and the aqueous phase was extracted with chloroform. The organic extract was washed with brine, dried (K2C03), and evaporated under reduced pressure to leave an oily residue. Chromatography of this oil on silica gel [( 1:20) methanol~hloroform] afforded 2p-benzyloxy- 8,9-met hylenedioxy-3 ~-methylsulfonyloxy-5,11-met hanomor- phanthridine (1.6428 g, 87.0%), m.p. 164-164.5 "C (from ethyl acetate-hexane); G,(CDCl,) 7.29 (5 H, s, Ph), 6.42 and 6.48 (each 1 H, s, 7- and 10-H), 5.86 (2 H, s, OCH,O), 4.85 (1 H, dt, J 3.6 and 10,3-H), 4.60 (2 H, s, PhCH,),4.22 and 3.72 (each 1 H, d, J 16, 6-H2), 3.92 (1 H, q, J 3.6, 2-H), 3.20-3.48 (1 H, m, 4a-H), 3.11(1H,dd,J2and10.9,12-H),2.99(3H,s,Me),2.90(1H,d, J 10.9, 12-H), 2.59 (1 H, d, J 2, 11-H), 1.76-2.68 (4 H, m) and 1.2k1.64 (1 H, m) v,,,(CHCl,)/cm-' 1480; m/z 457 (M+) (Found: C, 62.8; H, 6.0; N, 2.7.Calc. for C,,H,,NO,S: C, 63.01; H, 5.95; N, 3.06%). A suspension of the mesyl ester obtained above (456.6 mg, 1.0 mmol), charcoal (600 mg) and 2% aq. PdCl, (5 cm3) in methanol (16 cm3) was stirred under hydrogen at room temperature for 14 h. The mixture was then filtered and the filtrate was made alkaline with 3 mol dme3 NaOH. The mixture was extracted with chloroform.The organic extract was washed with brine, dried (K2C03), and evaporated under reduced pressure to give an oily residue, which was refluxed with 1,8- diazabicyclo[5.4.0]undec-7-ene (BDU) (151.7 mg, 1 mmol) in toluene (20 cm3) for 3 h. After removal of the solvent under reduced pressure, chromatography of the residue on silica gel [( 1:20) methanol-chloroform] afforded compound 5 (196.7 mg, 72.6%), m.p. 125 "c (from ethyl acetate-hexane); hH(CDC13) 6.47 and 6.44(each 1 H,s,2 x ArH),5.86(2 H,s,OCH,O),4.39 and3.79(each1H,d,J17.1,6-H2),3.32(1H,dd,J2and12,12-H), 3.22-3.48 (1 H, m,4a-H), 3.12 (1 H, d, J 12,12-H), 2.68 (1 H, d, J2, 11-H) and 1.68-2.60 (7 H, m) v,,,(CHCl,)/cm-' 1705; m/z 271 (M+ ) (Found: C, 70.6; H, 6.3; N, 5.0.Calc. for C16Hl,N03: C, 70.83; H, 6.32; N, 5.16%). 8,9-Methylenedioxy-2P-and -2a-methylsulfonyloxy-5,1l-me-thanomorphanthridine 26 and 27.-A solution of ketone 5 (200 mg, 0.738 mmol) and NaBH, (27.8 mg, 0.735 mmol) in methanol (5 cm3) was stirred at 0 "C for 10 min. The reaction J. CHEM.SOC. PERKIN TRANS. 1 1993 was quenched with water and the mixture was extracted with chloroform. The organic extract was washed with brine, dried (K2C03), and evaporated under reduced pressure to give 5,ll- methanomorphanthridin-2-01 25 (201 mg, 99.8%) as a mixture of diastereoisomers, m.p. 181-183 "C (from ethyl acetate-hexane); GH(CDC13) 6.46 and 6.42 (each 1 H, s, 2 x ArH), 5.84 (2 H, s, OCH,O), 4.004.21 (1 H, m, 2-H), 4.32, 4.27, 3.75 and 3.71 (each 0.5 H, d, J 17.1,6-H,), 2.80-3.29 (3 H, m, 4a-H and 12- H,), 2.50-2.68 (1 H, m, 11-H) and 1.00-2.40 (7 H, m, 1-, 3- and 4- H, and lla-H); V,~~(CHCI~)/C~-~ 3200-3650 m/z 273 (M') (Found: M +,273.1360. Calc.for C 6H ,NO3: M, 273.1366). To an ice-cold, stirred solution of the alcohols 25 (201 mg, 0.738 mmol) and Et,N (239.4 mg, 2.37 mmol) in chloroform (5 cm3) was added dropwise methanesulfonyl chloride (1 78.2 mg, 1.56 mmol). After 15 min, similar work-up as described above left an oily residue. Chromatography of this residue on silica gel [( 1:3) methanol-ethyl acetate and then (1:20) methanol~hloroform] afforded mesates 26 (120.4 mg, 46.6%) and 27 (125.4 mg, 48.5%). For compound 26: m.p. 46-48 "C; GH(CDC1,) 6.44 and 6.41 (each 1 H, s, 2 x ArH), 5.85 (2 H, s, OCH,O), 4.78 (1 H, br s, w320,2-H), 4.28 and 3.72 (each 1 H, d, J 17.1,6-H,), 3.18 (1 H, dd, J2 and 12, 12-H), 3.00 (3 H, s, Me), 2.72-3.06 (2 H, m, 4a- and 12-H), 2.63 (1 H, d, J2, 11-H) and 1.36-2.40 (7 H, m, 1-, 3- and 4-H2 and 1la-H); v,,,(CHCl,)/cm-' 1480; m/z 351 (M+) (Found: M+ 351.1146.Calc. for C,,H,,NO,S: M, 351.1139). For compound 27: m.p. 50-51 "C; GH(CDC1,) 6.48 and 6.43 (each 1 H, s, 2 x ArH), 5.85 (2 H, s, OCH,O), 5.07 (1 H, br s, w3 20,2-H), 4.31 and 3.76 (each 1 H, d, J 17.1, 6-H2), 2.96 (3 H, s, Me), 2.84-3.36 (3 H, m, 4a- and 12- H,),2.56(1H,d,J2,1l-H)andl.l(r-2.32(7H,m,1-,3-and4-H, and 1 la-H); v,,,(CHCl,)/cm-' 1470; m/z 351 (M+) (Found: M+, 351.1 129). Alternative Synthesis of Mesate 26.-A solution of 2p-benzyloxy-8,9-methylenedioxy-3~-methylsulfonyloxy-5,11-methanomorphanthridine (59.0 mg, 0.129 mmol) and NaBH, (39.0 mg, 1.03 mmol) in DMS02' (1.5 cm3) was heated at 150 "C for 0.5 h.After addition of water, the mixture was extracted with diethyl ether. The extract was dried (K,CO,), and evaporated under reduced pressure to give an oily residue. PLC of this oil with (1 :20) methanokhloroform as developing solvent afforded 2~-benzyloxy-8,9-methylenedioxy-5,11-meth-anomorphanthridine (20.3 mg, 43.3%) as an oil, G,(CDCl,) 7.26 (5 H, s, Ph), 6.47 and 6.43 (each 1 H, s, 2 x ArH), 5.84 (2 H, s, OCH20), 4.44 (2 H, s, PhCH,), 4.34 and 3.78 (each 1 H, d, J 17.1,6-H,),3.6(r3.92(1H,m,2-H),3.18(1H,dd,J2and12,12-H),2.94(1 H,d,J12-H),2.84-3.34(1H,m,4a-H),2.59(1H,d,J 2,1l-H),2.44-2.76(1 H,m,lla-H),1.72-2.27(3H,m)and1.04-1.66 (3 H, m); v,,,(CHCl,)/cm-' 1485; m/z 363 (M+) (Found: M+, 363.1833.Calc. for CZ3H,,NO,: M,363.1833). A suspension of the benzyl ether obtained above (18.3 mg, 0.05 mmol), charcoal (30 mg) and 2% aq. PdCl, (0.5 cm3) in methanol (2 cm3) was stirred under hydrogen at room temperature for 8 h. The mixture was then filtered and the filtrate was made alkaline with saturated aq. Na,CO,. The mixture was extracted with chloroform. The organic extract was washed with brine, dried (K2C03), and evaporated under reduced pressure to give 8,9-methylenedioxy-5,11 -methano- morphanthridin-2P-01 25a (13.1 mg, 95.2%) as crystals, m.p. 194-196 "C; GH(CDC13) 6.46 and 6.42 (each 1 H, s, 2 x ArH), 5.84 (2 H, s, OCH20),4.28 and 3.72 (each 1 H,d, J 16, 6-H2), 4.00-4.26 (1 H, m, 2-H), 3.08 (1 H, dd, J3 and 12, 12-H), 2.90 (1 H, d, J 12, 12-H), 2.90-3.26 (1 H, m, 4a-H) 2.53 (1 H, d, J 3, 11-H), 2.41-2.61 (1 H, m, lla-H) and 1.00-2.28 (6 H, m) v,,,(CHCl,)/cm-' 3050-3600 and 1475; m/z 273 (M +)(Found: M+ 273.1366.Calc. for C16H19N03: kf,273.1366). To an ice-cold, stirred solution of the alcohol 25a (8.0 mg, 0.029 mmol) and Et,N (8.2 mg, 0.081 mmol) in chloroform (1 J. CHEM. SOC. PERKIN TRANS. 1 1993 cm3) was added methanesulfonyl chloride (6.0mg, 0.052mmol). After the mixture had been stirred at room temperature for 0.5 h, work-up in the usual manner afforded the required mesate 26 (7.2mg, 70.0%), the spectra ('H NMR, IR) of which were identical with those of the mesate obtained from mixed diastereoisomers 25 (see above).8,9-Methylenedioxy-2ac- and -2P-phenylythio-5,ll-methano-morphanthridine 32 and 33.-A solution of alcohols 25 (136.5 mg, 0.5 mmol), diphenyl disulfide (1.094g, 5 mmol) and Bu3P (1.3 cm3, 5 mmol) in DME (8 an3)was refluxed for 4 h. The reaction was quenched with 3 mol dm-, NaOH and the mixture was extracted with chloroform. The organic extract was washed with brine, dried (K2C03), and evaporated under reduced pressure to give an oily residue. Chromatography of this residue on silica gel [( 1 :30) methanol-chloroform] afforded a-sulfide 32 (84.6mg, 46.4%) and P-sulfide 33 (90.4mg, 49.5%). For compound 32: oil; G,(CDCl,) 7.12-7.44(5 H, m, 5 x ArH), 6.41and 6.44(each 1 H, s, 2 x ArH), 5.84 (2 H, s, OCH,O), 4.27 and 3.69(each 1 H, d J 16.4,6-Hz), 2.76-3.40 (2 H, m, 2-and 4a-H),3.12(1H,dd,J3and12,12-H),2.89(1H,d,J12-H),2.56(1H,d, J 3, 11-H)and 1.162.44 (7 H, m, 1-, 3-and 4-H2 and lla-H); m/z 365 (M') (Found: M', 365.1445. Calc.for CZ2Hz3NO2S:M, 365.1448). For compound 33: m.p. 119.5-120.5"C; G,(CDCl,) 7.12-7.40(5 H, m, 5 x ArH), 6.46and 6.42 (each 1 H, s, 2 x ArH), 5.85 (2 H, s, OCH,O), 4.28 and 3.72 (each 1 H, d, J 16,6-H,), 3.48-3.80 (1 H, m, 2-H), 3.08(1 H, dd, J 3 and 11, 12-H), 2.90 (1 H, d, J 11,12-H), 2.88-3.22 (1 H, m, 4a-H),2.48(1 H, d, J3,ll-H)and 1.00-2.32 (7 H, m, 1-,3-and 4-H2 and 1 la-H);m/z 365 (M') (Found: M', 365.1449). Synthesis of Surfide 32 from 2P-Alcohol25a.-A solution of 2P-alcohol 25a (15.0 mg, 0.055mmol), diphenyl disulfide (12.1 mg, 0.55 mmol) and Bu,P (0.14cm3, 0.55 mmol) in DME (1 cm3) was refluxed for 4 h.Similar work-up as described above gave sulfide 32 (29.3 mg, 93.6%), the 'H NMR spectrum of which was identical with that of the authentic sample obtained above. 2,3-and 1,2-Didehydr0-8,9-methylenedioxy-5,11-methano-morphanthridine 28 and 29.-(a) From P-Mesate 26. (i) With Bu'OK. A mixture of mesate 26 (35.5 mg, 0.1 mmol) and Bu'OK (24.8mg, 0.22mmol) in DMSO (0.5cm3) was stirred at room temperature for 10 h. The reaction was quenched with water. After extraction with diethyl ether, the extract was washed with brine, dried (K,CO,),and evaporated under reduced pressure to give an oily residue.PLC with (1:15) methanol-chloroform as developing solvent yielded A',,-product 28 (10.9mg, 42.3%) and A',2-product 29 (10.2 mg, 39.5%), each as an oil. For compound 28: G,(CDC1,) 6.48and 6.44(each 1 H,s, 2 x ArH), 5.86 (2 H, s, OCH,O),5.64-6.01 (2H, m, CHXH),4.33and 3.74(each 1 H, d, J 17.1,6-HZ), 3.24 (1 H, dd, J 3 and 12, 12-H), 2.94 (1 H, d, J 12, 12-H), 2.90-3.26 yield compounds 28 (1.7mg, 13.3%) and 29 (5.0mg, 39.1%), each as an oil. (b) From a-mesate 27. A mixture of mesate 27 (88.1mg, 0.25 mmol) and Bu'OK (61.6mg, 0.55 mmol) in DMSO (3 cm3) was stirred at room temperature for 4 h. Similar work-up as described above gave A'i'-product 29 (56.7 mg, 88.6%), the spectra ('H NMR, IR) of which were identical with those of the authentic sample obtained in method (a) above.(c) From a-suljde 32.To a solution of the sulfide 32 (45.0mg, 0.123 mmol) in methanol (1 cm3) was added an aqueous solution of sodium periodate (30.9mg, 0.144mmol in 0.2cm3). After 7h, 3 mol dm-, NaOH and chloroform were added to the mixture. After the organic phase had been separated, the aqueous phase was extracted with chloroform. The combined organic phases were washed with brine, dried (K2C03), and evaporated under reduced pressure to give an oily residue. Chromatography of this residue on silica gel [( 1 :10)methanol-chloroform] afforded sulfoxides (44.7 mg, 95.2%) as 1.3:l mixture of oily diastereoisomers (estimated by the height of peaks due to the methylenedioxy group in the 'H NMR spectrum), G,(CDCl,) 7.28-7.72 (5 H, m, 5 x ArH), 6.52, 6.51, 6.40and 6.39 (2 H,each s, 2 x ArH), 5.86and 5.84 (2 H,each s, OCH20), 4.27and 3.69 (each 1 H, d, J 16.4, 6-H2), 2.763.40 (2H, m, 2-and 4a-H), 3.12(1 H, dd, J 3 and 12,12-H), 2.89 (1 H, d,J12,12-H),2.56(1H,d,J3,1l-H)and1.162.44(7H,m,1-,3-and 4-H, and lla-H); m/z 381 (M') (Found: M+ 381.1397.Calc. for C22H2,N03S: M, 381.1397). A solution of these sulfoxides (43.9mg, 0.12mmol) in toluene (1 cm3) was refluxed for 1.5h. The solvent was evaporated off under reduced pressure to give an oily residue, which was purified on PLC with (1 :15) methanol-chloroform as de-veloping solvent to yield A2*3-compound 28 (14.3 mg, 48.7%) and A'*'-compound 29 (12.0mg, 40.8%), each as an oil.The 'H NMR spectra of products 28 and 29 were identical with those of authentic samples obtained above. (d) From P-sulJide 33. To a solution of the sulfide 33 (30.0mg, 0.082 mmol) in methanol (1 cm3) was added an aqueous solution of sodium periodate (20.2mg, 0.094in 0.2cm3). Similar work-up as described above gave the sulfoxide of compound 33 (29.3mg, 93.6%) as a 1.2:l mixture of oily diastereoisomers (estimated by the height of peaks due to the methylenedioxy group in the 'HNMR spectrum); G,(CDCl,) 7.367.68(5 H, m, 5 x ArH), 6.42and 6.40(2H, each s, 2 x ArH), 5.84and 5.83 (2 H, each s, OCH,O), 4.26and 3.67(each 1 H,d, J 17, 6-H2), 2.52-3.20 (2 H, m, 2-and 4a-H), 3.07(1 H, dd, J2 and 12,12-H), 2.88(1 H, d, J 12,12-H), 2.60 (1 H, d, J2,ll-H)and 1.12-2.44 (7 H, m, 1-, 3-and 4-H,and Ila-H); m/z 381 (M+)(Found: M', 381.1389.Calc. for C22H,3N03S: M, 381.1397).A solution of the sulfoxides of compound 33 (24.8mg, 0.065 mmol) in toluene (1 cm3) was refluxed for 5 h. The solvent was evaporated off under reduced pressure to give an oily residue, which was purified by PLC with (1 :15) methanol-chloroform and 4-H,and lla-H); v,,,(CHCl,)/cm-' 1480;m/z 255 (M+) (Found: M+, 255.1255.Calc. for C,,H,,NO,: M, 255.1257). For compound 29: G,(CDC13) 6.52 and 6.44 (each 1 H, s, 2 x ArH), 5.86(2 H,s,0CH20),5.76-6.04and 5.52-5.74(each 1 H, m, CH=CH),4.23and 3.74(each 1 H, d, J 17.1,6-H2),3.00-3.22(1 H,m, 4a-H), 2.96(1 H,dd, J2and 10,12-H), 2.89 (1 H,d, J 10,12-H),2.69(1 H,d, J2,Il-H)and 1.36-2.20(5 H,m, 3-and 4-H, and lla-H); v,,,(CHCl,)/cm-' 1475; m/z 255 (M+) (Found: M 255.1256).+ (iij With DBU.A mixture of mesyl derivative 26 (17.6mg, 0.05mmol) and DBU (14.9 mg, 0.098 mmol) in toluene (2 cm3) was refluxed for 3 h. After evaporation of the solvent under reduced pressure, the oily residue was purified by PLC with (1 : 10) methanol-chloroform as developing solvent to as developing solvent to yield compounds 28 (6.9mg, 41.6%) (1 H,m,4a-H),2.67(1H,d,J3,ll-H)and1.562.60(5H,m,l-and 29 (8.5mg, 51.3%), each as an oil. (e) From p-tosylhydrazone 30.A solution of ketone 5 (54.4mg, 0.2 mmol) and p-tosylhydrazine (100.6 mg, 0.6 mmol) in methanol (2 cm3) was refluxed for 1 h. Evaporation of the solvent, followed by chromatography on silica gel [( 1 :50) and then (1 :10)methanol-chloroform], produced p-tosylhydrazone 30 (80.2 mg, 91.0%), m.p.158-160 "C (from ethyl acetate- hexane): S,(CDCl,) 7.80and 7.28(each 2 H,d, J 8,C,H,Me), 6.40(2 H,s, 2 x ArH), 5.85 (2 H, s, OCH,O), 4.29and 3.70 (each 1 H,d, J 17.1,6-H2), 3.09(1 H,dd, J2 and 12, 12-H), 2.92 (1 H,d, J 12, 12-H), 2.88-3.28 (1 H, m, 4a-H), 2.62 (1 H,d, J 2, 11-H),2.41 (3 H, s, Me) and 1.46-2.54 (7 H, m): v,,,(CHC13)/cm-' 1480 m/z 439 (M+) (Found: M+,439.1363. Calc. for C2,H2,N,0,S: M, 439.1363). A solution of hydrazone 30 (65.7 mg, 0.15 mmol) and Bu'OK (52.5 mg, 0.468 mmol) in DMSO (2 cm3) was heated at 100°C for 2 h. After the reaction had been quenched with water, the mixture was extracted with diethyl ether.The organic extract was washed with brine, dried (K,CO,), and evaporated under reduced pressure to give an oily residue. PLC with (1 :20) methanol-chloroform as developing solvent afforded com-pounds 28 (13.1 mg, 34.3%) and 29 (10.4 mg, 27.3%), which were identified by comparison of their respective spectral data ('H NMR, IR) with those of authentic samples obtained above. 2,3-Benzylidenedio.xy-S79-rnethylenedioxy-5,11 -methanomor- phanthridine 31.-A mixture of olefin 28 (25.4 mg, 0.1 mmol), OsO, (15 x lo-, cm', 0.003 mmol; 0.02 mol dm-, in 174-dioxane) NMNO 25 (1 2.6 mg, 0.1 1 mmol), 1,4-dioxane (1.6 cm3) and water (0.4 cm3) was stirred at room temperature for 1 h. Then 10% aq. Na,S,O, and 3 mol dmP3 NaOH were added to the mixture, which was then extracted with chloroform.The organic extract was washed with brine, dried (K2C03), and evaporated under reduced pressure to give a solid, which was treated with benzaldehyde dimethyl acetal(20.8 mg, 0.14 mmol) in the presence of p-TsOH monohydrate (19.7 mg, 0.10 mmol) in chloroform (2 cm3) at room temperature for 1 h. After dilution with chloroform, the organic phase was washed successively with saturated aq. NaHCO, and brine, dried (K,CO,), and evaporated under reduced pressure to give an oily residue, which was purified by PLC with (1 :15) methanol- chloroform as developing solvent to afford compound 31 (28.1 mg, 74.8%). 'H NMR and IR spectra were identical with those of an authentic sample.6 1,11a-Didehydro-8,9-methylenedioxy-5,11-methanomorphan-thridin-2-one 34.-A mixture of ketone 5 (100 mg, 0.37 mmol) and DDQ (250.1 mg, 1.10 mmol) in 1,4-dioxane (8 cm3) was refluxed for 0.5 h.The mixture was diluted with chloroform. The organic phase was washed successively with saturated aq. NaHCO, and brine, dried (K2C03) and evaporated under reduced pressure to leave an oily residue. PLC of the oil with (1:15) methanol-chloroform as developing solvent afforded enone 34 (75.0 mg, 75.6%); m.p. 49-50 "C; G,(CDCl,) 6.53 and 6.47 (each 1 H, s, 2 x ArH), 5.89 and 5.86 (each 1 H, d, J 2, OCH,O), 5.72-5.94 (1 H, m, 1-H), 4.40 and 3.84 (each 1 H, d, J 17, 6-H2), 3.36-3.68 (1 H, m, 4a-H), 3.43 (1 H, br s, 11-H), 4.16 (2 H, br s, at'+ 3.4, 12-H2) and 1.60-2.56 (4 H, m, 3- and 4-H,); v,,,(CHCl,)/cm-' 1660 m/z 269 (M +) (Found M +,269.1049.Calc. for C 6H, ,NO,: M, 269.1050). Acknowledgements We are indebted to Miss N. Sawabe, Mrs. F. Hasegawa and Mr. H. Igarashi, of this faculty, for their 'H NMR and mass spectral measurements and elementary analysis. References 1 D. H. R. Barton and S. W. McCombi, J. Chem. Soc., Perkin Trans. 1, 1975, 1574; D. H. R. Barton and W. B. Motherwell, in Organic Synthesis Today and Tomorrow, ed. B. M. Trost and C. R. Hutchison, Pergamon Press, 1981, pp. 1-1 7; Pure Appl. Chem., 198 1,53, 15. 2 For a recent review of radical cyclization, see (a)G. P. Jasperse, D. P. Curran and T. L. Feving, Chem. Rev., 1991, 91, 1237; (6) D.D. J. CHEM. SOC. PERKIN TRANS. 1 1993 Tanner, in Advances in Free Radical Chemistry, JAI Press Inc., 1990, vol. 1; (c) B. Giese, Angew. Chem., Int. Ed, Engl., 1989, 28, 969; (d) D. P. Curran, Synthesis, 1988, 417, 489; (e) M. Ramaiah, Tetrahedron, 1987, 43, 3541; (f)W. P. Neumann, Synthesis, 1987, 665; B. Giese (g) in Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds, Pergamon Press, Oxford, 1986; (h) Angew. Chem., Int. Ed. Engl., 1985,24,553;(i) Tetrahedron, 1985,41,3887;(j) D. J. Hart, Science, 1984,223,883. 3 0. Hoshino, M. Ishizaki, K. Kamei, M. Taguchi, T. Nagao, K. Iwaoka, B. Umezawa and Y. Iitaka, Chem. Lett., 1991, 1365; 0. Hoshino, M. Ishizaki, S. Sawaki, M. Yuasa and B. Umezawa, Chem. Pharm. Bull., 1988,36,3373;0.Hoshino, S.Sawaki, N. Shimamura, A. Onodera and B. Umezawa, Chem. Pharm. Bull., 1987, 35, 2734; B. Umezawa, 0. Hoshino, S. Sawaki, H. Sashida, K. Mori, Y. Hamada, K. Kotera and Y. Iitaka, Tetrahedron, 1984, 40, 1983; B. Umezawa, 0. Hoshino, S. Sawaki, H. Sashida and K. Mori, Heterocycles, 1979, 12, 1475; 0.Hoshino, S. Sawaki, N. Shimamura, A. Onodera and B. Umezawa, Heterocycles, 1978, 10, 51; B. Umezawa, 0.Hoshino, S. Sawaki, S. Sat0 and N. Numao, J. Org. Chem., 1977, 42, 4272; H. Hara, 0. Hoshino and B. Umezawa, Tetrahedron Lett., 1972,5031. 4 For a recent review of the chemistry of Amaryllidaceae alkaloids, see S. F. Martin, in The Alkaloids, ed. A. R. Brossi, Academic Press, New York, 1987, vol. 30, ch. 3, and references cited therein.5 (a)0.Hoshino, M. Ishizaki, K. Saito and K. Yumoto, J. Chem. Soc., Chem. Commun., 1990,420; (b) 0.Hoshino and M. Ishizaki, Chem. Lett., 1990, 1817. 6 M. Ishizaki, 0.Hoshino and Y. Iitaka, Tetrahedron Lett., 1991,32, 7079; J. Org. Chem., in the press. 7 Y. Inubushi, H. M. Fales, E. W. Warnhoff and W. C. Wildman, J. Org. Chem., 1960,25,2153. 8 F. Sandberg and K.-H. Michel, Lloydia, 1963,26, 78. 9 L. Overman and J. Shim, J. Org. Chem., 1991,56,5005. 10 J. E. Baldwin, J. Chem. Soc., Chem. Commun., 1976,734. 11 A. L. Beckwith and P. E. Pigou, Aust. J. Chew., 1986,39, 77; K. U. Ingold, J. Lusztyk and J. C. Scaiano, J. Am. Chem. Soc., 1984,106,343. 12 J. M. Bobbitt and J. M. Sih, J. Org. Chem., 1968,33,856. 13 M. C. Fond and W. A. Waters, J. Chem. SOC.,1952,2240. 14 Y. Guindon, R. Frenette, R. Fortin and J. Rokach, J. Org. Chem., 1983,48,1357. 15 cJ H. C. Brown and M. M. Midland, Angew. Chem., Int. Ed. Engl., 1972, 11,692. 16 K. Nozaki, K. Ohshima and K. Utimoto, Bull. Chem. SOC.Jpn., 1990, 63,2578; J. Am. Chem. Soc., 1987,109,2547. 17 A. J. Birch, A. H. Jackson and P. v. R. Shannon, J.Chem. Soc., Perkin Trans. 1, 1974,2185. 18 For temperature effect in radical cyclization, see: D. P. Curran and J. Tamine, J. Org. Chem., 1991,56,2763. 19 T. Toru, S. Kurozumi, T. Tanaka, S. Miura, M. Kobayashi and S. Ishimoto, Synthesis, 1974, 857. 20 For the conjugated reduction of %,&unsaturated carbonyl compounds with Bu,SnH/AIBN, see E. J. Enholm and K. S. Kinter, J. Am. Chem. Soc., 1991,113,7784;H. Laurent, P. Esperling and G. Baude, Liebigs Ann. Chem., 1983, 1996; M. Pereyre and J. Valade, Tetrahedron Lett., 1969,489. 21 Ref. 2g, p. 16. 22 P. Kocienski and S. D. Street, Synth. Commun., 1984, 14, 1087. 23 D. G. Cleary, Synth. Commun., 1989,19,737. 24 cJ: A. R. Chamberlin and S. H. Bloom, Org. React., 1990, 39, I; M. F. Lipton and R.H. Shapiro, J. Org. Chem., 1978,43,1049;R. H. Shapiro, Org. React., 1976,23,405. 25 V.Von Rheenen, R. C. Kelly and D. Y. Cha, Tetrahedron Lett., 1976, 1973. 26 cJ: A. B. Turner and H. J. Ringold, J. Chem. Soc C, 1967, 1728; H. J. Ringold and A. B. Turner, Chem. Ind., 1962,211. Paper 2/03837D Received 20th July 1992 Accepted 10th September 1992
ISSN:1472-7781
DOI:10.1039/P19930000101
出版商:RSC
年代:1993
数据来源: RSC