The pyridylseleno group in organic synthesis. Part 5. Amidoseleniation of alkenes

摘要

J. CHEM. soc. PEKKIN TRANS. I 1988 2113 The Pyridytseleno Group in Organic Synthesis. Part 5.' Amidoseleniation of Alkenes Akio Toshimitsu," Gen Hayashi, Keiji Terao, and Sakae Uemura Institute for Chemical Research, Kyoto University, Uji, Kyoto 67 7 Japan The reaction of fbmethoxyalkyl 2-pyridyl selenides with acetonitrile in the presence of trifluoromethanesulphonic acid and water affords p-acetamidoalkyl 2-pyridyl selenides in good to excellent yields. This reaction has been used in the two-step amidoseleniation of electron-rich alkenes such as styrene and buta-I ,3-dienes, and of tri- or tetra-substituted alkenes, previously reported as being resistant to amidoselen iation. We have already reported a Ritter-type amide synthesis which affords P-amidoalkyl phenyl selenides by the reaction of alkenes with benzeneselenenyl chloride in acetonitrile in the presence of trifluoromethanesulphonic acid and ~ater.~.~ Subsequently, we reported the improved procedure which used P-hydroxyalkyl phenyl selenides as starting materials and which overcame some of the limitations of the previously reported procedure.In spite of this, the amidoseleniation of electron-rich alkenes such as butadienes and tri-or tetra-substituted alkenes was not successful. We attributed this failure to the very effective stabilization of the episelenonium ion intermediate? by the electron-donating substituents and argued that the use of the 2- pyridylseleno group instead of the previously used phenylseleno group should increase the reactivity of the episelenonium ion.When p-hydroxy-or P-methoxy-alkyl 2-pyridyl selenides were prepared from electron-rich alkenes and were treated with acetonitrile in the presence of trifluoromethanesulphonic acid (and water), 0-acetamidoalkyl 2-pyridyl selenides were produced in good to excellent yields. In addition to the expected 1,2-addition (amidoseleniation) products, 1,4-addition products were obtained from 3-methoxy-4-(2-pyridylseleno)but-l-ene derivatives. The allylic selenide structure in these 1,4- addition products were capable of undergoing further 2,3- sigmatropic rearrangements in order to introduce other nitrogen or oxygen functional groups. The results obtained here clearly show another example of the usefulness of the 2-pyridylseleno group in organic synthesis.Results and Discussion l-Phenyl-2-(2-pyridylseleno)ethanol (la) was prepared in moderate yield from styrene oxide, 2,2'-dipyridyl diselenide, and sodium borohydride by a reported pr~cedure.~ Reaction of (la) with acetonitrile (also the solvent) in the presence of trifluoro- methanesulphonic acid and water (2 equiv. each) at reflux temperature for 1 h afforded N-l -phenyl-2-(2-pyridylseleno)-ethyllacetamide (2) in 91 isolated yield (Scheme 1). How-ever, when the amount of the acid and water was reduced to 1 equiv., the yield of (2) was unsatisfactory (Table 1). These results suggest the protonation of both oxygen (in alcohol) and nitrogen (in pyridine) atoms to produce a highly electrophilic episelenonium ion intermediate as depicted in Scheme 1.We tried the use of methoxy substituted (lb) as the starting material instead of (la), as (lb) can be pre- pared quantitatively from styrene and pyridine-2-selenenyl bromide in methanol.' Although a longer reaction time was required, (2) was produced from (lb) in comparable yields to t It has been reported that an excessive stabilization of a carbonium ion can inhibit the alkylation of nit rile^.^ OR NHCOMe I ICFJS03~-~2~ Ph CH CH, Se P y * PhCHCH2SePyMeCN (1) a; R=H b; R = Me r PhCH-CH2 'A' py= QL 4 Scheme 1. those from (la). Typical results are summarized in Table 1; cf: the yields of the phenylseleno analogue of (2) N-(l-phenyl-2-phenylselenoethy1)acetamideJ (36-4574) using the initially reported 2*3 and subsequently improved 4*8 procedures. This difference indicates that the 2-pyridylseleno group is superior to the phenylseleno group for the introduction of the acetamide group to a carbon framework bearing electron- donating substituents.The direct reaction of pyridine-2-selenenyl bromide with styrene in acetonitrile for the preparation of (2) was unsuccessful owing to the formation of an addition product between pyridine-2-selenenyl bromide and acetonitrile.1 OMe NHCOMe I IPhC H CH Me CF3SO3H-HZO PhCHCHMe MeCN II SePy SePy (31 a;erythro (4) b; threo Scheme 2. 1Several attempted reactions of (I) with alkenes resulted in failure. Me 'C=N ~r' 'SePy (I) Spectral data of (I) are as follows; m.p.164.5-165 "C (decornp.) (Found: C, 30.75; H, 2.5; N, 10.35. C,H,BrN,Se requires C, 30.25; H, 2.55; N, 10.1);v,,,,(KBr disc) 3 100, 3 020, 1 626, 1 599, 1 448, 1 370, 776,721, and 711 cm-'; 6,(100 MHz; D,O) 3.25 (3 H, s),7.67 (1 H,dt, J 1.5 and 6 Hz), 8.01 (1 H, dt, J 1.5 and 7 Hz), 8.38 (1 H, br d, Jca. 8 Hz), and 8.85 (1 H, br d, J ca. 7 Hz). 21 14 Table 1. Reaction conditions for conversion of (1) into (2)" Starting material CF,SO,H (mmol) H,O (mmol) Temp. ("C) Time (h) Yield (2) ()b (14 (la) (la) (14 (1b) (1b) 2 1 2 2 2 3 2 1 10 2 2 3 Reflux Reflux Reflux 25 Reflux Reflux 1 1 44 100 8 10 91 29 46 86 83 87 " Carried out using (1) (1 mmol) in acetonitrile (3 ml). Isolated yield by column chromatography.Table 2. Yield and stereochemistry of the conversion of (3) into (4)" Yield Starting CF3S0,H H,O Temp. Time (ratio) material (mmol) (mmol) ("C) (h) Product(s) (34 3 3 25 24 (4a) 69 (3b) 3 3 25 24 (4b) 33 (3b) 3 3 Reflux 3 (4a) + (4b) 77 (78:22) (3b) 10 10 25 36 (4b) 74 " Carried out using (3) (1 mmol) in acetonitrile (3 ml). Isolated by column chromatography. We prepared erythro-and threo-1 -methoxy- 1-phenyl-2-(2- pyridylse1eno)propane (3a)and (3b)* and tried the substitution of the methoxy group by the acetamide group. While (4a) was obtained in a good yield by the reaction of (3a) (erythro isomer) with acetonitrile in the presence of 3 equiv. of the acid and water at 25 "C, the yield of (4b) from (3b) (threo isomer) was not satisfactory under the same conditions.When this reaction was carried out at reflux temperature, (3b) afforded a mixture of stereoisomers (4a) and (4b). By the addition of 10 equiv. of the acid and water at room temperature, (4b) was produced selectively from (3b) in good yield (Scheme 2, Table 2). The two-step amidoseleniation of alkenes described thus far was applied to tri- and tetra-substituted alkenes. Markovnikov- type oxyseleniation products (5a)and (5b)were regioselectively PySe R3 R'R NHCOMeHR4 (6) a; R' = H, R2 = R3 = R4 = Me; 48 h, 60 b R', R3 = -(CHz)4-, R2 = H, R4 = Me; 1 h, 44 c; R' = R2 = R3 = R4 = Me; 48 h, 54 Scheme 3. Reagents: i, PySeBr-MeOH;' ii, CF,SO,H-water (3 equiv.) MeCN, 25 "C * Compound (3a) was prepared selectively from (E)-B-methylstyrene by oxyseleniation using pyridine-2-selenenyl bromide in methanol.Compound (3b) was isolated by column chromatography from a mixture of (3b) and (3a) which was obtained from a mixture of (2)-and (E)-p-methy 1st yrene. J. CHEM. SOC. PERKIN TRANS. I 1988 converted into the corresponding amidoseleniation products (6a)and (6b)in 44-60 yield (Scheme 3). Regioisomers of (6a) and (6b) were not detected by t.1.c. and n.m.r. spectroscopy. 2,3- Dimethylbut-2-ene was also converted to (6c)in 54 yield. Amidoseleniation of 1,3-dienes was also realized by this methodology. The initial step, oxyseleniation of buta- 1,3-diene and 2,3-dimethylbuta- 1,3-diene7 afforded 172-addition products (7a) and (7b) in good to quantitative yields. Reaction of (7a) with acetonitrile in the presence of the acid and water (3 equiv.) at reflux for 1h produced a mixture of (8a) and (9a)in a yield of 78 (67 :33).The coupling constants in the n.m.r. signals of the vinylic protons confirmed that (9a)was present only as the trans isomer. As the ratio (8a):(9a) was largely unaffected by increased reaction time (24 h: 63:37), we supposed the allylic cation shown in Scheme 4 to be the intermediate in this reaction. R F! bsol;ii RI I Pysev (8) R NHCOMe+ F! a;R = H b; R = Me R Scheme 4. Reagents: i, PySeBr-MeOH, 25 "C; ii, CF,SO,H-water (3 equiv.)-MeCN When the dimethyl substituted selenide (7b) was used as the starting material, the reaction proceeded at 25 "C to afford only the rearranged product (9b).In contrast with (9a), (9b) consisted of trans-and cis-isomers, the ratio being ca. 1. These isomer distributions seem to reflect the thermodynamic stability. The L J two-step amidoseleniation reactions using the 2-pyridylseleno group should complement the previously reported phenylseleno as the latter were not suitable for the preparation of phenylseleno analogues of (6), (8), and (9). It has been reported that 2,3-sigmatropic rearrangements of allylic selenoxides or N-substituted selenoimides proceed spontaneously to afford, ultimately, allylic alcohols 6a4 or N-substituted allylic amines.6e The allylic selenide (9) was subjected to these reactions in order to introduce other oxygen or nitrogen functional groups. Reaction of (9)with hydrogen peroxide under reported conditions afforded the amino alcohol derivatives (10a) and (lob)in good to excellent yields (Scheme 5).Thus, selective introduction of nitrogen and oxygen func- tional groups into 1-and 2-positions of 1,3-dienes was realized J. CHEM. SOC. PERKIN TRANS. I 1988 2115 R OH (10) a;R = H , 60 b; R = Me, 85(9) bsol; Rbsol; ;; , kNHCOMe R NHC02CHzPh (11) a; R = H , 70 b; R = Me, 75 Scheme 5. Reugents: i, (9)(1 mmol)-H,0,(3 mmolkpyridine (3 mmo1)-CH,Cl,(5 ml); at 0 OC, 0.5 h; 25 OC, 1 h; ii, (9) (1 mmo1)-NH,CO,-CH,Ph (3 mmo1)-Et,N (6 mmo1)-NCS (3 mmolkMeOH(I.2 ml); at 0 OC, 0.5 h; 25 OC, 1 h by the use of the amidoseleniation reaction.Similar oxidation of (9) using N-chlorosuccinimide in the presence of benzyl carbamate produced the 1,2-diamine derivatives (lla)and (llb) via the rearrangement of allylic selenoimide intermediates. It should be noted that two amino groups in (11) were protected by different groups, potentially allowing the differentiation of the amino groups. It may be concluded that allyl 2-pyridyl selenides are at least as efficient as phenyl allyl selenides in undergoing 2,3-sigmatropic rearrangement reactions. Another procedure which utilizes the amidoseleniation reaction in organic synthesis is the oxidative and reductive removal of 2-pyridylseleno groups to produce unsaturated and saturated amides. We selected (2)as the substrate for selenoxide elimination.The elimination of methine hydrogen is required for the formation of N-(cr-styry1)acetamide (12)from (2), and this seems to be more difficult than the selenoxide elimination * to afford N-( P-styry1)acetamide reported in the literat~re.~ When rn-chloroperbenzoic acid or hydrogen peroxide was used as the oxidizing reagent, the yield of (12)was unsatisfactory. However, the use of ozone as the oxidizing reagent and the addition of triethylamine in the elimination step,' produced (12)in an acceptable yield (76). The characteristic feature of this amidoseleniation reaction was utilized in the preparation of the tertiary allylic amide (13)as shown in Scheme 6. Selenoxide (12) (6a) H2deg;2 , THF amp;NHCOMe (13) Scheme 6.elimination from (6a)proceeded smoothly using a convenient oxidation reagent (H,O,) to give (13) in a yield of 91. Reductive removal of the 2-pyridylseleno group from (14)and (16)t was carried out using triphenyltin hydride 3*11 or nickel * The 4-nitrophenylseleno group was used as the leaving group presumably because the rate was expected to be enhanced by the electron-withdrawing nitro substituent. i or ii -MeCHCH2Me i 100I ii 55 '1.HI;MKpyMe NHCOMeMeCONH H (16) (15) BuCHCH, SePy i or ii i 85 '1.-BuCHMeI I ii 62 "10 NHCOMe NHCOMe (16) (17) Scheme 7. Reagents: i, Ph,SnH (4 equiv.ktoluene, reflux, 4 h; ii, NiCl,*6H2O (2 equiv.)-NaBH, (6 equiv.)-THF-MeOH(4: I), 0 "C, I5 min boride l2 as the reducing agent.As shown in Scheme 7, N-(butan-2-y1)- and N-(hexan-2-yl)acetamide, (15)and (17),were obtained in good to quantitative yields. These yields were similar to or better than those obtained from phenylseleno analogues of (14)and (16).3 Experimental 1.r. spectra were recorded with a JASCO IR-810 spectro- photometer. 'H N.m.r. spectra were obtained with JEOLCO JNM-FX-100 (100 MHz) and JEOLCO-GX-400 (400 MHz) instruments for solutions in CDC1, with Me,Si as the internal standard. M.p.s were determined with a Shimadzu MM-2 micro melting-point determination apparatus and are uncorrected. G.1.c. analyses were carried out with a Shimadzu 4CMPF apparatus with PEG-6000 (25)-Shimalite (1 m) column. 2,2'-Dipyridyl diselenide and pyridine-2-selenenyl bromide were prepared by the reported methods.'Ob p-Hydroxy- and 0-met hoxy-alkyl2-pyridyl selenides were prepared using modified reported procedures.1,7 Spectral and combustion analytical data of as yet unreported compounds are as follows. l-Phenyl-2-(2-pyridylsefeno)ethanof(la). Colourless liquid (Found: C, 55.85; H, 4.75; N, 5.05. C,,H,,NOSe requires C, 56.1; H, 4.7; N, 5.05); v,,,,(liquid film) 3 350, 1 570, 1447, 1 410,752, and 697 cm-'; 6,(100 MHz) 3.33 (1 H, dd, J 13.9 and 6.8Hz),3.55(1 H,dd,J13.9and3.9Hz),5.16(1 H,dd7J6.8and 3.9Hz),5.78(1 H,brs),6.8-7.6(8H,m),and8.2--8.5(1 H,m). 1-(2-Pyridylseleno)hexan-2-o1.Yellow liquid (Found: C, 5 1.2; H, 6.75; N, 5.65. C, lH17NOSe requires C, 51.15; H, 6.65; N, 5.4); v,,,,(liquid film) 3 370, 2 955, 2 930, 2 860, 1 572, 1 450, 1 412,753, and 697 cm-'; 6,(100 MHz) 0.5-1.9 (9 H, m), 3.35 (1 H, dd, J 13.7 and 3.4 Hz), 3.18 (1 H, dd, J 13.7 and 6.4 Hz), 3.7- 4.3 (1 H, m), 5.G6.0 (1 H, m), 6.8-7.2 (1 H, m), 7.2-7.6 (2 H, m), and 8.0-8.5 (1 H, m).erythro-1-Methoxy- 1-phenylpropan-2-yl 2-pyridyl selenide (3a). White plates, m.p. 145-146 "C from hexane-ethyl acetate (1 : l) (Found: C, 58.9; H, 5.6; N, 4.6. C, ,H17NOSe requires C, 58.85; H, 5.6; N, 4.55); v,,,.(KBr disc) 2 925, 1 570, 1 553,l 447,l 412,755,708, and 508 cm-'; 6,(100 MHz) 1.41 (3 H,d, J6.8Hz),3.34(3H,s),4.42(1H7dq,J3.4and6.8Hz),4.64 (1 H, d, J 3.4 Hz), 6.8-7.6 (8 H, m), and 8.3-8.5 (1 H, m). threo- 1 -Methoxy- 1 -phenylpropan-2-yl2-pyridvfselenide (3b).t Compound (14) was prepared from (Z)-but-2-ene PZO methoxy-seleniation as described in the text the second step was carried out at reflux for 24 h; in contrast to the case of (4b), the rhreo isomer was found to be the sole product under these reaction conditions. However, (16) was not obtained from 2-methoxyhexyl 2-pyridyl selenide even under the more forcing conditions. When 1-(2-pyridylseleno)hexan-2-01 was used as the starting material (16) was produced in 57 yield (reflux, 3 h). This seems to reflect the leaving ability of methoxy and hydroxy groups in a substrate which bears a poor electron-donating substituent. 2116 Colourless liquid (Found: C, 58.7; H, 5.6; N, 4.6. C,,H,,NOSe requires C, 58.85; H, 5.6; N, 4.55); v,,,~(liquid film) 2 130, 1 572,1448,1410,752, and 700 cm-'; 6,(400 MHz) 1.47 (3 H, d, J7.3 Hz), 3.28 (3 H, s), 4.22 (1 H, dq, J5.9 and 7.3 Hz), 4.37 (1 H, d, J5.9 Hz), 6.99 (1 H, ddd, J7.3,4.9, and 1.5 Hz), 7.25-7.4 (7 H, m), and 8.40 (1 H, ddd, J 4.9, 2.0, and 1.0 Hz).3-Methoxy-3-methylbutan-2-yl2-pyridyl selenide (5a). Pale yellow liquid (Found: C, 51.3; H, 6.55; N, 5.2. C,,H,,NOSe requires C, 51.15; H, 6.65; N, 5.4); v,,,.(liquid film) 2 975, 1 575, 1 450, 1 412, 1 108, 1 082, 753, and 700 cm-'; 6,(100 MHz) 1.32 (6 H, s), 1.58 (3 H, d, J6.8 Hz), 3.25 (3 H, s), 4.22 (1 H, q, J6.8 Hz), 6.8-7.1 (1 H, m), 7.2-7.5 (2 H, m), and 8.2-8.5 (1 H, m). 3-Methoxy-4-(2-pyridylseleno)but-1-ene (7a). Pale yellow liquid (Found: C, 49.55; H, 5.3; N, 5.9.C,,H,,NOSe requires C, 49.6; H, 5.4; N, 5.8); v,,,.(liquid film) 2 940,l 575, 1 415, 1 110, 757, and 702 cm-'; 6,( 100 MHz) 3.33 (3 H, s), 3.39 (2 H, d, J 5.9 Hz), 3.95 (1 H, dt, J7.3 and 5.9 Hz), 5.24 (1 H, dd, J9.8 and 2.0 Hz), 5.30 (1 H, dd, J 17.6 and 2.0 Hz), 5.79 (1 H, ddd, J 17.6,9.8, and7.3Hz),6.9-7.1(1 H,m),7.1-7.6(2H,m),and8.3-8.5(1 H, m).2,3-Dimethyl-3-methoxy-4-(2-pyridylseleno)but-1 -ene (7b). Pale yellow liquid (Found: C, 53.35; H, 6.3; N, 5.25. C,,H,,NOSe requires C, 53.35; H, 6.35; N, 5.2); v,,,,(liquid film) 2 980,2 940,l 572,1449,l 410,753, and 697 cm-'; 6,(100 MHz) 1.42(3H,s), 1.76(3H,s),3.12(3H,s),3.57(2H,s),5.03(2 H, br s), 6.8-7.1 (1 H,m), 7.1-73 (2 H,m),and 8.2-8.5 (1 H, m).All other organic materials were commercial products and were purified before use by distillation.Inorganic materials were all commercial products and were used without further purification. Preparation of N- 1-Phenyl-2-(2-pyridylseleno)ethylacet-amide (2)from (la).-General procedure. To a solution of (la) (0.28 g, 1 mmol) in acetonitrile (3 ml) was added a 1:1 (molar ratio) mixture of trifluoromethanesulphonic acid and water (0.34 g, 2 mmol) and the resulting mixture was heated at reflux temperature for 1 h. The solution was poured into saturated aqueous sodium hydrogen carbonate (50 ml) and was extracted with dichloromethane (20 ml x 5). The extract was washed with brine, dried, and evaporated under reduced pressure to leave a pale yellow oil. Column chromatography of this on silica gel with hexane+thyl acetate (1 :1) as the eluant yielded (2) (0.29 g, 0.91 mmol, 91); white needles, m.p.1261 27 "C from hexane-ethyl acetate (1 :l) (Found: C, 56.5; H, 5.05; N, 8.75. C,,H,,N,OSe requires C, 56.45; H, 5.05; N, 8.75); v,,,.(KBr disc) 3 290, 1 652, 1 557,753, and 707 cm-'; amp;,(lo0 MHz) 1.89 (3 H, s), 3.38 (1 H, dd, J 13.4 and 4.4 Hz), 3.53 (1 H, dd, J 13.4 and 8.8 Hz), 5.19 (1 H, ddd, J 10.7,8.8, and 4.4 Hz), 7.0-7.5 (8 H, m), and 8.2-8.5 (2 H, m). Spectral and combustion analytical data of other amidoalkyl 2-pyridyl selenides are as follows. ery thro-N- 1-Phenyl-2-( 2-pyridylseleno)propyl acetamide (4a). White semisolid (Found: C, 57.45; H, 5.55; N, 8.4. C,,H18N,0Se requires C, 57.65; H, 5.45; N, 8.4); v,,,,(KBr disc) 3 300, 1 647, 1 570, 1 548,757, and 702 cm-'; 6,( 100 MHz) 1.46 (3 H, d, J 7.3 Hz), 2.00 (3 H, s), 4.20 (1 H, dq, J 3.4 and 7.3 Hz), 5.20 (1 H, dd, J 6.4 and 3.4 Hz), 7.1 1 (1 H, ddd, J 6.4, 4.9, and 2.4 Hz), 7.2-7.6 (7 H, m), and 8.1-8.6 (2 H, m).threo-N- 1-Phenyl-2-(2-pyridylseleno)prop~~lacetamide (4b). Yellow liquid (Found: C, 57.8; H, 5.55; N, 8.15. C16H18N20Serequires C, 57.65; H, 5.45; H, 8.4); v,,,~(liquid.film) 3 280, 1 650, 1 572, 1 555, 1 450, 1 412, 755, 730, and 700 cm-'; amp;,(lo0 MHz) 1.40 (3 H, d, J7.3 Hz), 1.84 (3 H, s), 3.97 (1 H, dq, J9.3 and 7.3 Hz), 4.97 (1 H, dd, J9.3 and 7.3 Hz), 7.15 (1 H, ddd, J8.7, 5.2, and 2.6 Hz), 8.2-8.6 (7 H, m), 8.3-8.6 (1 H, m), and 8.7-9.1 (1 H, br d, J ca.7 Hz). J. CHEM. SOC. PERKlN TRANS. I 1988 N-2-Methyl-3-(2-pyridylsele~o)butan-2-ylacetamide(6a). White needles, m.p. 82.5-83.5 "C (from hexane) (Found: C, 50.35; H, 6.15; N, 9.75. C, ,H ,N,OSe requires C, 50.55; H, 6.35; N, 9.8); v,,,,(KBr disc) 3 294, 1 646, 1 577, 1 558,749, and 699 cm-'; amp;,(lo0 MHz) 1.56 (6 H, s), 1.57 (3 H, d, J7.3 Hz), 1.85 (3 H, s), 3.81 (1 H, q, J7.3 Hz), 7.10 (1 H, ddd, J 5.9, 4.9, and 2.9 Hz), 7.3-7.5 (2 H, m), 8.27 (1 H, br s), and 8.42 (1 H, ddd, J4.9, 2.0, and 1.0 Hz). N- 1-Methyl-2-( 2-pyridylseleno)cyclohexylacetamide (6b). Pale yellow liquid (Found: C, 53.85; H, 6.85; N, 8.75. C,4H,,N,0Se requires C, 54.0; H, 6.5; N, 9.0); v,,,,(liquid film) 2 938, 1 769, 1 580, 760, 735, and 700 cm-'; 6,(1o0 MHz) 1.0-2.0 (6 H, m), 1.58 (3 H, s), 1.86 (3 H, s), 2.0-2.4 (1 H, m), 2.8-3.2 (1 H, m), 3.70 (1 H, dd, J 12.9 and 4.2 Hz), 7.0-7.2 (1 H, m), 7.3-7.6 (2 H, m), 8.3-8.5 (1 H, m), and 8.62 (1 H, br s).N-2,3- Dimethyl-3-( 2-pyridylseleno)hutan-2-ylacetamide(6c).Yellow needles, m.p.44-45 "C (from hexane) (Found: C, 52.1; H, 6.9; N, 9.3. C,,H,,N,OSe requires C, 52.15; H, 6.75; N, 9.35); v,,,,(KBr disc) 1 662,l 562, and 757 cm-'; 6,( 100 MHz) 1.57 (12 H, s), 2.04 (3 H, s), 7.CL7.3 (1 H, m), 7.4-7.6 (2 H, m), 8.3-8.5 (1 H, m), and 9.4 (1 H, br s). N- 1-(2-Pyridylseleno)but-3-en-2-ylacetamide(8a). White needles, m.p. 49-49.5 "C (from hexane) (Found: C, 48.85; H, 5.2; N, 10.45. C H ,,N,OSe requires C, 49.1; H, 5.25; N, 10.4); v,,,,(KBr disc) 3 276, 3 070, 3 052, 1 654, 1 575, 1 558, 1 415, 757, and 702 cm-'; 6,( 100 MHz) 1.90 (3 H, s), 3.33 (2 H, d, J 6.4 Hz), 4.69 (I H, dtq, J 5.4, 1.5 and 6.4 Hz), 5.15 (1 H, dt, J 9.8 and 1.5 Hz), 5.28 (1 H, dt, J 17.1 and 1.5 Hz), 5.88 (1 H, ddd, J 17.1, 9.8, and 5.4 Hz), 6.9-7.6 (3 H, m), 7.22 (1 H, br s), and 8.3-8.5 (1 H, m- (2E)-N-4-(2-PyridyIseleno)but-2-en~~lacetamide (9a).Colourless liquid (Found: C, 48.6; H, 5.1; N, 10.25.C,,H,,-N,OSe requires C, 49.1; H, 5.25; N, 10.4); v,,,,(liquid film) 3 284,l 657,l 650,l 573,1 553,l 413,757, and 700cm-'; 6,(400 MHz) 1 97 (3 H, s), 3.81-3.83 (4 H, m), 5.54 (1 H, br s), 5.64 (1 H, dt, J 15.1 and 6.4 Hz), 5.85 (1 H, dtt, J 15.1, 7.6, and 1.5 Hz), 7.05(lH,ddd,J7.3,4.9,andl.OHz),7.31 (lH,dt,J8.3andl.O Hz), 7.46 (1 H, ddd, J8.3, 7.3, and 2.0 Hz), and 8.46 (1 H, ddd, J 4.9, 2.0, and 1.0 Hz).N -2,3- Dimethyl-4-( 2 -pj*ridylseleno) but-2-eny lacetamide (9b). Mixture of two isomers, ca. 54:46; yellow liquid (Found: C, 52.2; H, 6.0; N, 9.4. C1,H18N,OSe requires C, 52.55; H, 6.1; N, 9.473; v,,,,(liquid film) 3 290, 1 652, 1 575, 1 558, 1 453, 1 415, 757, and 702 cm-'; 6,(400 MHz) (major isomer) 1.70 (3 H, q, J 1.0 Hz), 1.79 (3 H, q, J 1.0 Hz), 1.94 (3 H, s), 3.93 (2 H, s), 3.95 (2 H, d, 5.4 Hz), 6.25 (1 H, br s), 7.02-7.06 (1 H, m), 7.32-7.34 (1 H, m), 7.42-7.45 (1 H, m), and 8.42-8.45 (1 H, m); 6, (minor isomer) 1.74 (3 H, q, J 1.5 Hz), 1.85 (3 H, q, J 1.5 Hz), 1.98 (3 H, s),3.86(2H,d,J5.4Hz),4.01 (2H,s),6.10(1 H,brs),7.02-7.06 (I H, m), 7.32-7.34 (1 H, m), 7.42-7.45 (1 H, m), and 8.42-8.45 (1 H, m).t hreo-N-3-( 2-Pj~id~~Iseleno)butun-2-y1acetamide(14). Pale yellow liquid (Found: C, 48.65; H, 6.1; N, 10.15. C,,H,,N,OSe requires C, 48.7; H, 5.95; N, 10.350);v,,,.(liquid film) 3 270, 2 970,l 647,l 570,l 553,1 447,1 410,763, and 697 cm-'; 6,(100 MHz) 1.28 (3 H,d, J6.4 Hz), 1.54 (3 H, d, J7.3 Hz), 1.91 (3 H, s), 3.74(1 H,dq,J6.8and7.3Hz),4.13(1 H,ddq,J7.3,6.8,and6.4 Hz),7.0-7.2(1 H,m),7.4-7.55(2H,m),7.7-8.1(1H,m),and 8.35-8.5 (1 H, m). N- 1-(2-P~ridyIseleno)he.uan-2-~l~cetami(16). Colour-less liquid (Found: C, 52.05; H, 6.65; N, 9.4. C,,H,,N,OSe requires C, 52.15; H, 6.75; N, 9.35); v,,,,(liquid film) 3 280, 2 964, 2937, 1 650, 1 573, 1 559, 1453, 1415, 757, and 701 cm-'; 6,(100 MHz) 0.8-1.0 (3 H, m), 1.2-1.8 (6 H, m), 1.83 (3 H, s), 3.32 (2 H, d, J 5.9 Hz), 4.08 (1 H, br sextet, J ca.6.5 Hz), 7.k7.15 (2 H, m), 7.4-7.5 (2 H, m), and 8.35-8.45 (1 H, m). J. CHEM. soc-PERKIN TRANS. I 1988 Conversion of'(9a) into 1-Acetamidobut-3-en-2-u1(10a).-To a solution of (9a)(0.27 g, 1 mmol) and pyridine (0.16 g, 2 mmol) in dichloromethane (5 ml) was added 30 aqueous hydrogen peroxide (0.34 g, 3 mmol) dropwise under ice-bath cooling. After having been stirred at 0 OC for 0.5 h and then at 25 *C for 1 h, the mixture was added to 1M aqueous sodium thiosulphate (25 ml). The phases were separated and the aqueous layer was extracted with dichloromethane (25 ml x 35).The dried extract was evaporated under reduced pressure to leave a yellow oil. Column chromatography of this on silica gel with hexane- acetone (2:5) as the eluant yielded (10a) (0.077 g, 0.6 mmol, 60)(Found: M', 129.0772. C6H 1 'NO, requires M, 129.0790); v,,,.(liquid film) 3 305,l 650, and 1 558 cm-'; 6,(100 MHz) 1.99 (3 H, s), 3.15 (1 H, ddd, J 13.7,7.3, and 5.4 Hz), 3.48 (1 H, ddd, J 13.7,6.4,and 3.9 Hz), 4.14.3 (1 H, m), 4.34.7 (1 H, br s), 5.16 (1 H, ddd, J 10.3,2.0,and 1.5Hz), 5.31 (1 H, ddd, J 17.1,2.0,and 1.5 Hz), 5.86 (1 H, ddd, J 17.1, 10.3, and 5.4 Hz), and 6.7-7.2 (1 H, br s). 1-Acetctmido-2,3-dimethylbut-3-en-2-o1(lob). This was ob-tained similarly as a pale yellow liquid (Found: C, 60.85; H, 9.6; N, 8.7. CBH 15N02requires C, 61.1; H, 9.6; N, 8.9); v,,,~(liquid film) 3 350, 2 985, 1 660, 1550, 1 377, 1 146, and 905 cm-'; 6,( 100 MHz) 1.30 (3 H, s), 1.77 (3 H, br s), 1.99 (3 H, s), 3.37 (2 H, d, J 5.9 Hz), 3.49 (1 H, br s), 4.90 (1 H, quintet, J 1.4 Hz), 5.06-5.14 (I H, m), and 6.1-6.5 (1 H, br s).Conversion of (9a) into N-(2-Benzyloxycarbonylaminobut-3-eny1)acetumide (I la). A solution of (9a) (0.27 g, 1 mmol), benzyl carbamate (0.45 g, 3 mmol), and triethylamine (0.61 g, 6 mmol) in methanol (1 ml) was cooled to 0 "C and N-chlorosuccinimide (0.40 g, 3 mmol) was added in several portions. The resulting mixture was stirred at 0 "C for 0.25 h, and then at 25 "C for 1 h. The solution was poured into water (25 ml) and extracted with dichloromethane (25 ml x 40).The extract was dried and evaporated under reduced pressure to leave a yellow oil. Column chromatography of this on silica gel with hexane- acetone (2: 5) as the eluant yielded (lla)(0.21 g, 0.7 mmol, 70); white semi-solid (Found: M+,262.1267. C,,H 8N203requires M, 262.13 1 7); v,,,,(KBr disc) 3 300, 1 682, 1 652, 1 537,752, and 693 cm-'; 6,( 100 MHz) 1.88 (3 H, s), 3.33 (2 H, br t, Jca. 6.1 Hz), 4.27 (1 H, br quintet, J ca. 6.6 Hz), 5.07 (2 H, s), 5.09 (1 H, dt, J 10.3and 1.5Hz),5.13(1H,dt,J17.landlSHz),5.74(1H,ddd, J17.1,10.3,and5.4Hz),6.00(1H,d,J7.8Hz),6.86(1H,brt,J 5.9 Hz), and 7.30 (5 H, s). 21 17 Oxidative or reductive removal of the pyridylseleno group from (2), (6a), (14), and (16) was carried out using reported procedure^.^^'^-'^ N-(a-Styry1)acetamide (12) was isolated by column chrom- atography, m.p.89.5-90 "C (from hexane) (lit.,13 92 "C). N-(1,l -dimethylprop-2-enyl)acetamide(13) was also isolated by column chromatography on silica gel using hexane-thy1 acetate (1 :5) as the eluant; colourless liquid (Found: M+, 127.1033. C,H13N0 requires M, 127.0997); v,,,,(liquid film) 3 300, 3 090, 2 980, 2 930, 1 657, and 1 552 cm-'; 6,(100 MHz) 1.42 (6 H, s), 1.93 (3 H, s), 5.03 (1 H, dd, J 10.6 and 0.8 Hz), 5.09 (1 H,dd7J17.4and0.8Hz),5.35(1H,brs),and6.02(1 H,dd,J 17.4 and 10.6 Hz). Authentic samples of (15) and (17) were prepared by the acetylation of the corresponding amines. References 1 Part 4: A. Toshimitsu, H. Owada, K. Terao, S. Uemura, and M. Okano, J.Chem. Sue., Perkin Trans. I, 1985, 373. 2 A. Toshimitsu, T. Aoai, S. Uemura, and M. Okano, J. Chem. Sue., Chem. Commun., 1980, 1041. 3 A. Toshimitsu, T. Aoai, H. Owada, S. Uemura, and M. Okano, J. Org. Cheni., 1981, 46, 4727. 4 A. Toshimitsu, G. Hayashi, K. Terao, and S. Uemura. J. Chem. Soc., Perkin Trans. I, 1986, 343. 5 S. Top and G. Jaouen, J. Org. Chem., 1981,46, 78. 6 (a)K. B. Sharpless and R. F. Lauer, J. Am. Cheni. Soc., 1972,94,7 154; (b) W. G. Salmond, M. A. Barta, A. M. Cain, and M. C. Sobata, Tetrahedron Lett., 1977, 1683; (c) D. L. J. Clive, G. Chittattu, N. J. Curtis, and S. M. Menchen, J. Chem. Sue., Chem. Cummun., 1978, 770; (d)H. J. Reich, 'Oxidation in Organic Chemistry, Part C,' ed. W. Trahanovsky, Academic Press, New York, 1978, pp.102-107; (e) R. G. Shea, J. N. Fitzner, J. E. Fankhauser, A. Spaltenstein, P. A. Carpino, R. M. Peevey, D. V. Pratt, B. J. Tenge, and P. B. Hopkins, J. Org. Chem., 1986, 51, 5243. 7 K. B. Sharpless and R. F. Lauer, J. Am. Chem. SOL.,1973, 95, 2697. 8 A. Toshimitsu and S. Uemura, unpublished results. 9 U. Schmidt, A. Lieberknecht, H. Bokens, and H. Griesser, J. Org. Chem., 1983, 48, 2680. 10 (a)H. J. Reich, J. M. Renga, and I. L. Reich, J. Am. C'hem.Suc., 1975, 97,5434; (b)A. Toshimitsu, H. Owada, K. Terao, S. Uemura, and M. Okano, J. Org. Chem., 1984, 49, 3796. 11 D. L. J. Clive, G. J. Chittattu, V. Farina, W. A. Kiel, S. M. Menchen, C. G. Russell, A. Singh, C. K. Wong, and N. J. Curtis. J. Am. Chem. Soc., 1980, 102, 4438. 12 T. G. Back, J. Chem. Soc., Chem. Commun., 1984, 1417; D. H. R. Barton, M. R. Britten-Kelly, and D. Ferreira, J. Chern. Suc., Perkin Trans. I, 1978, 1090; D. H. R. Barton, X. Lusinchi. and P. Milliet,N-(2-Brn~~~l~~.~~~carbo~~ylumino-2,3-dimeth~~lbut-3-enyl)-ucetumidc. ( 1 I b). This was obtained similarly as a yellow liquid Tetrahedron Leii., 1982, 23,4949. (Found: M', 290.1616. C16H,2N203 requires M, 290.1630); 13 H. B. Kagan, N. Langlois, and T. P. Dang, J. Organomet. Chem., v,,,,(liquid film) 3 340, 1 710, 1 645, 1 530,l 445,l 375,740, and 1975, 90,353. 697 cm-'; 6,( 100 MHz) 1.40 (3 H, s), 1.75 (3 H, s), 1.94 (3 H, s), 3.31 (1 H, dd, J 13.7 and 6.4 Hz), 3.55 (1 H, dd, J 13.7 and 5.9 Hz), 4.90 (1 H, br s), 4.95 (1 H, br s), 5.03 (2 H, s), 6.00 (1 H, s), 6.7--6.95 ( 1 H, br s), and 7.31 (5 H, s). Received 28th September 1987; Paper 711724