Unusual reaction of aziridine dimer with acetylene dicarboxylates

摘要

Mendeleev Communications Electronic Version, Issue 2. 1997 (pp. 47–86) Unusual reaction of aziridine dimer with acetylene dicarboxylates Remir G. Kostyanovsky,*a Yurii I. El’natanov,a Ivan I. Chervin,a Mikhail Yu. Antipinb and Konstantin A. Lyssenkob a N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 117977 Moscow, Russian Federation. Fax: +7 095 938 2156 b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 117813 Moscow, Russian Federation.Fax: +7 095 135 5085 The 1-(2-aminoethyl)aziridine (aziridine dimer) 1 reacts with acetylene dicarboxylates to give 1,4-diaza- 5-oxobicyclo4.3.0nonanes (7-azaindolizines) 3 together with the usual enamine adducts 4; the product structures are confirmed spectroscopically and, in the 3 also by X-ray diffraction and by an independent synthesis from furan 5.Treatment of the aziridine dimer 11 and the terminally labelled dimer 1-15NH2 † with acetylene dicarboxylates 2a,b afforded the 7,8,9-tris(alkoxycarbonyl)-1,4-diaza-5-oxobicyclo4.3.0nonanes 3a–c, along with the usual adducts (E)- and (Z)-4a–c (Scheme 1). The structures of 3,4 were confirmed spectroscopically‡ (Figure 1).The structure of 3a was also confirmed by X-ray diffraction§ (Figure 2) and also by an independent synthesis of 3b from furan 53,‡ (Scheme 2). The formation of 3a,b which is also accompanied by ethylene elimination and 15N label randomization can be explained by the transformations † NMR spectra were recorded at 400 MHz (1H) and 100.61MHz (13C). The aziridine dimer 1-15N was prepared by the reduction of aziridinoacetamide-15NH2 (LiAlH4 in boiling THF, 12h), yield 12.3, bp 127 °C; 1H NMR (CDCl3): d 1.13 (m) and 1.72 (m) (2×2H, CH2 ring), 1.43 (br.s, 2H, HN), 2.26 (dt, 2H, a-CH2, 3JHH 5.8, 3JHN 2.1Hz) and 2.85 (dt, 2H, b-CH2, 2JHN 0.9Hz); 13CNMR (CDCl3): d 26.6 (dd, CH2 ring, 1J 163.7 and 173.4 Hz), 41.79 (ddt, b-CH2, 1J 133.2, 2J 2.8, 1JCN 4.2 Hz) and 64.36 (dt, a-CH2, 1J 133.2, 2JCN 1.4 Hz).The starting material aziridinoacetamide-15NH2 was prepared from ethyl aziridinoacetate2 by amidation with 15NH3 (90 of 15N) in MeOH–MeONa, 7days at 20°C; yield 89.4, mp 88 °C; 1HNMR (CDCl3): d 1.27 (m) and 1.84 (m) (2×2H, CH2 ring), 2.90 (s, CH2CO) and 6.72 (2H, HAHB 15N, ABX spectrum, Dn =200, 2JAB 4.3, 1JBX 89.5, 1JBX 90.3Hz); 13C {1H} NMR (CDCl3): d 27.4 (s, CH2 ring), 63.4 (d, CH2CO, 2JCN 5.6 Hz) and 173.0 (d, CO, 1JCN 15.3Hz).indicated in Scheme 3. The key stages of the proposed mechanism are confirmed by the known easy ethylene ‡ Spectroscopic data for 3a: obtained from 1 and 2a in Et2O at 20 °C, 1h; yield 19.1, mp188–189°C. Found: C, 50.41; H, 4.48; N, 9.12. Calc. for C13H14N2O7: C, 50.32; H, 4.55; N, 9.03. 1HNMR (2H8toluene): d 2.73 (m, 2H, 3-CH2), 3.62 (m, 2H, 2-CH2), 3.54 (s), 3,62 (s) and 3.71 (s) (3×3H, MeO), and 7.30 (br.s, 1H, HN); 13C NMR (2H6DMSO): d 38.52 (t, 3-CH2N, 1J 141.0 Hz), 43.65 (2-CH2, 1J 146.4 Hz), 51.56 (q), 52.05 (q) and 52.36 (q) (3MeO, 1J 147.7Hz), 118.3 (s), 119.2 (s) (7- and 8-C), 122.64 (s, 9-C) and 125.58 (dt, 6-C, 3JCNCH 2.7, 3JCCNH 5.6Hz), 156.81 (q, 5-C, 2J = 3J = 4.2 Hz), 159.32 (q), 162.88 (q) and 163.29 (q) (CO2Me, 3J 4.2Hz); MS (EI, 70 eV, 240 °C): m/z (): 310 (34.3) M+, 280 (15), 279 (100), 59 (13.2).For 3b: obtained from 1 and 2b in Et2O at 20 °C, 18 h, yield 31, or quantitatively from 6 in 2H8toluene in a sealed tube at 140 °C, 1h; mp140–141°C. Found: C, 54.62; H, 5.68; N, 8.10. Calc.for C16H20O7N2: C, 54.54; H, 5.72; N 7.95. 1H NMR (2H8toluene): d 1.08 (t), 1.13 (t) and 1.21 (t) (3×3H, Me, 3J 7Hz), 2.47 (br. m, 2H, 3- CH2), 3.53 (br.m, 2H, 2-CH2), 4.07 (q), 4.19 (q) and 4.33 (q) (3×2H, 3CH2O) and 7.41 (br. s, 1H, HN); 13C NMR (CD3OD): d 14.32 (q, 2Me, 1J 126.2 Hz), 14.38 (Me, 1J 127.4Hz), 40.43 (tt, 3-CH2, 1J 142.9, 2J 2.8 Hz), 45.14 (tt, 2-CH2, 1J 147.0, 2J 2.8 Hz), 62.64 (tq, 2CH2O, 1J 148.4, 2J 4.2 Hz), 62.9 (tq, CH2O, 1J 148.2, 2J 4.2 Hz), 120.79 (s), 122.65 (s) and 124.6 (s) (9-, 7-, 8-C), 127.02 (m, 6-C, 3J 2.8 Hz), 159.96 (t, 5-C, 2J 4.2 Hz), 160.73 (m), 165.11 (m) and 165.15 (m) (CO2Et, 3J 4.2 Hz).For 3c: yield 12.1, mp 143–144 °C (PriOH); 1H NMR (2H8toluene): 1.09 (t), 1.14 (t) and 1.23 (t) (3×3H, 3Me, 3J 7.0Hz), 2.45 (br.m, 2H, 3-CH2, 2JHN 1.8 Hz), 3.5 (br.m, 2H, 2-CH2, 3JHN 2.1Hz), 4.08 (q), 4.20 (q) and 4.33 (q) (3×2H, 3CH2O) and 6.65 (d, 1H, HN, 1JHN 91.6Hz); 13C NMR (CD3OD): 14.31 (q, 2Me, 1J 126.2Hz), 14.42 (Me, 1J 127.4Hz), 40.43 (ttd, 3-CH2, 1J 142.9, 2JCH 2.8, 1JCN 8.4Hz), 45.14 (ttd, 2-CH2N, 1J 147.0, 2JCH 2.8, 1JCN 7.7Hz), 62.61 (tq), 62.62 (tq) and 62.9 (tq) (3CH2O, 1J 148.2Hz), 120.8 (dd, 7-C, 2J = 3JCN =2.9Hz), 122.63 (d, 8-C, 2JCN 4.2 Hz), 124.58 (d, 9-C, 1JCN 14.6Hz), 126.96 (d, 6-C, 1JCN 4.5Hz), 159.93 (d, 5-C, 1JCN 16.7Hz), 160.73 (m), 165.08 (m) and 165.14 (m) (CO2Et, 3J 4.2 Hz).For 4a: (Z : E, 3:1), yield 36.3. For (Z)-4a: 1H NMR (CDCl3): d 1.12 (m) and 1.75 (m) (4H, 2CH2 ring), 2.34 (t, 2H, a-CH2, 3J 6.0Hz), 3.53 (td, b-CH2, 3JHCNH 6.0 Hz), 3.65 (s) and 3.81 (s) (2×3H, 2MeO), 5.07 (s, 1H, HC= ), 8.31 (br.s, 1H, HN).For (E)-4a: 1H NMR (CDCl3): d 1.15 (m) and 1.74 (m) (4H, 2CH2 ring), 2.41 (t, 2H, a-CH2, 3J 6.0Hz), 3.13 (td, 2H, b-CH2, 3JHCNH 6.0 Hz), 3.62 (s) and 3.86 (s) (2×3H, 2MeO), 4.64 (s, 1H, HC= ) and 5.3 (br. s, 1H, HN). For 4b, 4c: (Z : E, 1.2 : 1), yields 27. (Z)-4b: 1H NMR (CDCl3): d 1.12 (m) and 1.74 (m) (4H, 2CH2 ring), 1.24 (t) and 1.34 (t) (2×3H, 2Me, 3J 7.0 Hz), 2.34 (t, 2H, a-CH2, 3J 6.1 Hz), 3.53 (td, b-CH2, 3JHCNH 6.1Hz), 4.07 (q) and 4.25 (q) (2×2H, 2CH2O), 5.05 (s, 1H, HC= ), 8.30 (br.s, 1H, HN).(Z)-4c: 1H NMR (CDCl3): d 1.12 (m) and 1.74 (m) (4H, 2CH2 ring), 1.24 (t) and 1.33 (t) (2×3H, 2Me, 3J 7.0 Hz), 2.34 (dt, 2H, a-CH2, 3JHH 6.1, 3JHN 2.8 Hz), 3.53 (tdd, 2H, b-CH2, 2JHCN ca. 1, 3JHCNH 6.1Hz), 4.08 (q) and 4.24 (q)(2×2H, 2CH2O), 5.04 (d, 1H, HC=, 3JHN 4.0 Hz) and 8.26 (dt, 1H, HN, 1JHN 90.4 Hz). (E)-4b: 1H NMR (CDCl3): d 1.16 (m) and 1.74 (m) (4H, 2CH2 ring), 1.23 (t) and 1.33 (t) (2×3H, 2Me, 3J 7.0Hz), 2.41 (t, 2H, a-CH2, 3J 6.0 Hz), 3.13 (td, b-CH2, 3JHCNH 6.0 Hz), 4.10 (q) and 4.30 (q) (2×2H, 2CH2O), 4.64 (s, 1H, HC= ) and 5.09 (br.s,1H, HN). (E)-4c: 1H NMR (CDCl3): d 1.15 (m) and 1.74 (m) (4H, 2CH2 ring), 1.23 (t) and 1.35 (t) (2×3H, 2Me, 3J 7.0Hz), N NH2 + E C C E N NH E E E O + + N NH E E E O * + * N NH E E H N NH E H E * * * 1 2 3 4 5 6 7 8 9 1 2a,b 3a–c (E)-4a–c (Z)-4a–c a E = CO2R, *N = 14N, R = Me b E=CO2R, *N = 14N, R = Et c E = CO2R, *N = 15N, R=Et Scheme 1 D O E E E E H2N NH2 NH N HB HC HF E E E E HE HO HA HD + 3b E=CO2Et Scheme 2 1 2 3 4 5 6 7 5 6Mendeleev Communications Electronic Version, Issue 2. 1997 (pp. 47–86) elimination from aziridinium ylides4 the first intermediate zwitterion in Scheme 3 can be represented as a mesomeric form of carbenaziridinium ylide (CAI) and by the isolation of the intermediate 6 before the lactamization in 3b (Scheme 2). This work was accomplished with financial support from 2.41 (br.m, 2H, a-CH2, 3.12 (tdd, b-CH2, 2JHCNH 6.1 Hz), 4.10 (q) and 4.29 (q) (2×2H, 2CH2O), 4.62 (d, 1H, HC=, 3JHN 1.5 Hz), 5.37 (dt, 1H, HN, 1JHN 93Hz). Furan 5, under the action of ethylene-1,2-diamine in toluene (14 days, 20°C) gave intermediate 6. The latter was isolated by gradient chromatography (silica gel, heptane–ethyl acetate, 0® 60), yield 24, colourless oil.Found: C, 52.10; H, 6.69; N, 6.82. Calc. for C18H28N2O9: C, 51.92; H, 6.78; N, 6.76. 1H NMR (CDCl3): d 1.11 (t), 1.13 (t) and 1.20 (t) (3×3H, 3Me, 3J 7.0 Hz), 2.29 (dt, 1H, HA, 2JAB –10.4, 3JAC 10.4, 3JAD 5.8Hz), 2.83 (dt, 1H, HB, 3JBC 5.8, 3JBD 10.4 Hz) and 3.02 (ddd, 1H, HC, 2JCD –11.6Hz), 3.08 (ddd, 1H, HD), 3.43 (d, 1H, HF, 3J 12.5Hz), 4.32 (1H, HE), 4.03 (m), 4.11 (m) and 4.13 (m) (3×2H, 3CH2); 13C NMR (CDCl3): d 13.62 (q), 13.71 (q) and 13.81 (q) (3Me, 1J 127.9Hz), 45.36 (dd, 7-C, 1J 138.1 and 143.9Hz), 48.22 (dd, 6-C, 1J 138.1 and 143.9 Hz), 52.14 (dd, 3-C, 1J 133.7, 2J 4.4 Hz), 54.48 (dd, 4-C, 1J 138.1, 2J 5.8Hz), 89.81 (m) and 89.87 (m) (2-C and 4-C, 2J, 3J 4.4Hz), 168.14 (m) and 169.54 (m) (CO, 2J 7.3, 3J 4.4 Hz), 171.36 (m) and 172.1 (m) (C=O, 3J 4.4 Hz).§ Crystal data for 3a: C13H14N2O7 (from PriOH): monoclinic, space group P21/n, at 293K: a =10.222(12), b =7.903(8), c = 18.07(2) Å, b = 102.88°, V =1423(3)Å3, Z =4, dcalc =1.448gcm–3, m = 1.19 cm–1, F(000)=648. Intensities of 2760 reflections were measured with a Siemens P3/PC diffractometer at 293 K (MoKa radiation, graphite monochromator, q/2q-scan method, 2q 2s(I) were used in the further calculations.The structure was solved by direct method and refined by the least-squares against F in an anisotropic-isotropic (H-atoms) approximation to R =0.065, vR = 0.062, GOF=1.69. All calculations were performed using the program package SHELXTL PLUS (ver. 5). Full lists of bond lengths, bond angles, atomic coordinates and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC). See Notice to Authors, Mendeleev Commun., 1997, issue 1.Any request to the CCDC for this material should quote the full literature citation and the reference number 1135/13. NH N H E E E E * HN NH E E E E * HN N H E E E E * N E E E E NH2 * N E E E E NH2 * –C2H4 –EtOH + – * N E E E E NH2 * N E E E E NH2 * N E E E E NH2 – + – + 3c 1-15N + 2× 2b *N = 15N Scheme 3 CAI Figure 1 (a) 1H NMR spectrum of the 4-NH proton of 3c and (b) 13C {1H} NMR spectrum of the 2-C and 3-C carbon atoms of 3c. 2-C15N 2-C14N 3-C15N 3-C14N 45.14 40.43 H15N H14N 6.8 d d (a) (b) Figure 2 Crystal structure of 3a. Selected bond lengths (Å) and angles (°): N1–C1 1.383(6), C1–C2 1.385(6), C2–C3 1.401(6), C3–C4 1.402(6), C4–N1 1.373(6), C4–C5 1.477(6), C5–N2 1.347(6), N2–C6 1.459(7), C6–C7 1.509(7), C7–N1 1.476(5); C1N1C4 109.7(3), N1C1C2 106.7(4), C1C2C3 109.2(4), C2C3C4 106.5(4), C3C4N1 107.9(4), C4N1C7 122.5(4), N1C4C5 120.2(4), C4C5N2 114.6(4), C5N2C6 122.6(4), N2C6C7 111.6(4), C6C7N1 107.7(4), C1N1C7 127.8(4), C3C4C5 131.3(4). C(11) C(9) O(3) C(8) O(2) O(5) O(4) C(10) C(2) C(1) N(1) C(7) C(3) C(4) C(6) C(5) N(2) O(1) O(6) C(12) O(7) C(13)Mendeleev Communications Electronic Version, Issue 2. 1997 (pp. 47–86) INTAS and the Russian Foundation for Basic Research (grants nos. 94-2839 and 94-03-08730, respectively). References 1 R. G. Kostyanovsky, V. P. Leshchinskaya, R. K. Alekperov, G. K. Kadorkina, L. L. Shustova, Yu. I. El’natanov, G. L. Gromova, A. E. Aliev and I. I. Chervin, Izv. Akad. Nauk SSSR, Ser. Khim., 1988, 2566 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1988, 37, 2315) and references cited therein. 2 H. Bestian, Ann., 1950, 566, 210. 3 I. J. Cantlon, W. Cocker and T. B. H. McMurry, Tetrahedron, 1961, 15, 46. 4 Y. Hata and M. Watanabe, Tetrahedron Lett., 1972, 3827, 4659. Received: Moscow, 14th October 1996 Cambridge, 20th November 1996; Com. 6/07096E