Gabriel Beckmann sp 2 displacement Beckmann earrangement of ximes 2 S 4 2 ' ' ' Displacement on itrogen Atom of ximes Y u Y u S 2
n-bu 4 e 4 p 33% 10 mol% (n-bu) 4 e 4 5 mol% Ts 2 C 2 Cl 2, rt, 5 min e e 49% n-bu 4 e 4 Beckmann n-bu 4 e 4 Tf 4 Tf cat. CF 3 S 3 cat. 2 Cl cat. n-bu 4 e 4 1 2 C 3 2, azeotropic 1 2 Beckmann 20 mol% n-bu 4 e 4 20 mol% CF 3 S 3 20 mol% 2 Cl C 3 2, reflux 88% 7% Beckmann Beckmann Lewis acid
C- Zn, Ac 24% S 3 Si 3 (i-bu) 2 Al C 2 Cl 2 78 0 C 42% - -S TsCl, pyridine 84% C- Beckmann n-bu 4 e 4 n-bu 4 e 4 ClC 2 C 2 Cl MS 5A, reflux 100 mol% n-bu 4 e 4, 100 mol% CF 3 S 3 20 mol% n-bu 4 e 4, 100 mol% CF 3 S 3, 50 mol% chloranil 44% 15% 85% n-bu 4 e 4 Tf p X = C p X =,
X 51% 15% X X = C 76% X = 4% 76% X = 91% eaction conditions: 20 mol% n-bu 4 e 4, 100 mol% CF 3 S 3, 50 mol% chloranil, MS 5A, ClC 2 C 2 Cl, reflux, 1-2 h. -X X X X =, X = C X - 4-chloranil X Beckmann S 2 sp 2 sp 2 S 2 S 2 sp 3 E/ Z S 2 p 1 1 E ZE Z S 2
2 (t-bu)si S 2 S 2 CsF C reflux 1 E : Z = 2 : 1 46% 30% sp 2 S 2 Beckmann S 2 Beckmann 3 2 2 Beckmann reagents solvent reflux reagents 2 solvent 3 2 3 polyphosphoric acid m-xylene 4% 72% CF 3 S 3 ClC 2 C 2 Cl 50% 22% (n-bu) 4 e 4, CF 3 S 3 ClC 2 C 2 Cl 91% 0% Beckmann kcal/mol 2 2.067 Å 8.8 kcal/mol 1.788 Å 2.534 Å 2 2.017 Å 2.085 Å 8.0 kcal/mol 1.622 Å -36.6 kcal/mol -47.4 kcal/mol S 2 Beckmann Beckmann sp 2 S 2
sp 2 S 2 γ δ (E)- DBU Z eber 2 C 2 C E S 2 DBU C 2 Cl 2, 0 C 2 C 2 C S 2 2 C 2 C quant. ( from Z isomer: no reaction ) β 4 5 5 6 4 1) S 2 Cl, Et 3 2) C 6 F 5 CCl Cl CC 6 F 5 6 79% S 2 Cl Et 3 C 6 F 5 CCl S 2 Et 3 5 S 2 n-bu 4 e 4 S 2 u syn ' ' u anti u '
runs 1 2 run 3 run 4 run 5 run 5 run 1 2 (C 2 ) 2 (C 2 ) 2 (C 2 ) 2 anti anti syn conditions CF 3 S 3 (2.0), C 2 Cl 2, rt, <20 min 2 : 1 a CF 3 S 3 (2.0), C 2 Cl 2, rt, 12 h >99 : <1 3 CF 3 S 3 (2.0), CD 3 D (2.0), C 2 Cl 2, rt, 20 min 4 Ac C 2, toluene, 80 C, 6 h 5 CCF 3 CF 3 C 2, CDCl 3, rt, 28 h a) At equilibrium. anti : syn 2 : 1 a 3 : 1 a 3 : 1 a 7 (CF 3 C) 2 4-Chloranil 7 C 2 Cl 2 rt, 20 h [] from anti from syn 83% 81% CCF 3 5% 9% (CF 3 C) 2 4-Chloranil C 2 Cl 2, rt 86%
γ δ = C 2 C 2-1 2 C 3 C 2 C 2 (10) C 3 2, MS 4A 70 C, 24 h 'C 2 1 2 1 2 1 2 83% 72% (3 : 2) 88% Beckmann Grignard Grignard Grignard Ts MgBr (7 mol) TF, -78 C = 95% = n-bu - - Main product Ts Li 2 Cu 3 Et 2 20 C 45% Beckmannp 8 Grignard Grignard MgBr S 2 CF 3 CF 3 8 1) cat. CuC 2LiCl MPA - TF, 0 C, 0.5 h 2) aq. Cl, acetone 2 Cl 96%
Grignard Grignard Grignard 9 -MgBr (in Et 2 ) F 3 C Ts CF 3 CF 3 CF 3 9 toluene rt, 30 min Ar Ar 1) 3 2) CCl, Et 3 Ts = p-c 3 -C 6 4 -S 2, Ar = 3,5-(CF 3 ) 2 C 6 3 -C = Et 87% = 96% 10Grignard Grignard 10 11 11 -MgBr (in Et 2 ) S 2 Cl or C 2 Cl 2 10 0 C 11 1) 3 2) Cl - 3 Cl - = C 2 C 2 90% = p-tol 97% m a E Z 2 2 a 1,4-dioxane 50 C, 20 h from E-isomer from Z-isomer 44% 36% 36% 41%
S 2 p S 2 a ClC 2 C 2 Cl, MS 5A E Z Z m a 2 2 a 1,4-dioxane, 50 C ) 2 27% 24% a a 2 2 2 2 a 1,4-dioxane a (a) n electron transfer 2 2 a 2 2 m a
a DDQ ab 3 Ca 2 2 1) a 1,4-dioxane 50 C 2) 4-chloranil Ac 60% t-bu 2 C n-bu 2 2 a ab 3 C 1,4-dioxane rt t-bu 2 C n-bu t-bu 2 C 93% n-bu Forrester Zard γ,δ C 2 C 2 K 2 S 2 8 2 reflux Se (n-bu) 3 Sn cat. AIB cyclohexane reflux γ,δ
2 2 a, radical acceptor 1,4-dioxane 50 C, 6-10 h 2 Y 2 radical acceptor 91% (Y = ) CCl 4 (S) 2 (Se) 2 75% (Y = Cl) 70% (Y= S) 69% (Y = Se) S 2 γ,δ 12 13 14 13 14 Ac (C 2 ) 2 12 additive, Ac 1,4-cyclohexadiene 1,4-dioxane reflux (C 2 ) 2 13 = Ac 14 = additive (5 mol%) time/h 13 14 none hydroquinone 14 15 24 6 12% 29% 32% 53% Ac cat. hydroquinone 1,4-cyclohexadiene Ac C 3 Ac 15 Ac C 2 γ,δ α β
γ,δ Ac 1 2 cat. 1,5-naphthalenediol 1,4-cyclohexadiene Ac 1,4-dioxane, reflux 1 2 1 2 Yield 1 2 (C 2 ) 2 C 69% (C 2 ) 2 C2Et 72% (C 2 ) 3 C * * -Pivaloyl oxime was employed. Yield 75% 61% Ac cat. hydroquinone 1,4-cyclohexadiene Ac 1,4-dioxane, reflux 1 = C 2 C 2 = C 3 67% 67% γ,δ β α (C 2 ) 2 C cat. CuBr S 2 LiBr (C 2 ) 2 1,4-dioxane 80 C C Cu II Br (C 2 ) 2 86% Br Ac CC 6 F 5 1) cat. Cu powder (C 2 C 2 2 ) 2 ClC 2 C 2 Cl, 80 C 2) 4-chloranil, C 2 Cl 2, rt Ac 75% 8 Pd(P 3 ) 4 17
16 S 2 Pd Ms Pd(P 3 ) 4 Ar Ar CF 3 CF TF 3 8 rt, 20 min 16 2 3 Ar Ar Ar Ar Ar = 4-(CF 3 )C 6 4 17 94% 16 Pombeiro Tillact CM trans-[e I Cl( 2 )(dppe) 2 ] Tl[BF 4 ]-Tl[S 4 ] TF [e III ()(dppe) 2 ][BF 4 ] 179 eck eck (E) γ,δ 18 DMF Pd(P 3 ) 4 20 21 Z Beckmann CC 6 F 5 CC 6 F 5 Pd cat Pd(P 3 ) 4 Et 3 DMF 18 80 C, 1 h 19 C 2 C 3 3 SiCl C 2 Cl 20 rt, 0.5 h 21 from E 85% from Z 82% exo CC 6 F 5 cat. Pd(P 3 ) 4 additive Et 3 DMF, 80 C additive none n-bu 4 Cl 48% 77%
Pd(0) eck 35 36 CC 6F 5 cat. Pd(P 3 ) 4 Et 3, MS 4A DMF, 110 C 0.5 h. 82% CC 6 F 5 1) cat. Pd(dba) 2, (t-bu) 3 P Et 3, MS 4A, DMF 80 C, 0.5 h 2) Mn 2, C 2 Cl 2 reflux, 2 h 78% CC 6 F 5 cat. Pd(P 3 ) 4 Et 3 DMF 80 C, 0.5 h 86% eck α Beckmann β β C cat. Pd 2 (dba) 3 CCl 3 ()-()-BIAP K 2 C 3, TF reflux C Pd C C Pd C C 4% 84% Beckmann
1. rganonitrogen Chemistry, P. D. Bailey, and K. M Morgan, xford Chemistry Primers 38, xford Science, 1996. 2. E. Erdik, and M. Ay, Chem. ev., 89, 1947 (1989); C. Greck and J. P. Genet, Synlett, 1997, 741; P. Dembech, and G. Seconi, A. icci, Chem. Eur. J., 6, 1281 (2000); Modern Amination thod, ed. by A. icci, Wiley-VC, Weinheim (2000). 3. K. arasaka,. Kusama, and Y. ayashi, Chem. Lett., 1991, 1413; Tetrahedron, 48, 2059 (1992). 4. syn anti syn anti 5. K. arasaka,. Kusama, Y. Yamashita, and. Sato, Chem. Lett., 1993, 489;. Kusama, Y. Yamashita, and K. arasaka, Bull. Chem. Soc. Jpn., 68, 373 (1995). 6. S. Goszczynski, and A. I. Kucherenka, Zh. rg. Khim., 8, 2586 (1972); Chem. Abstr., 78, 84230w (1973). 7.. Griot, and T. Wagner-Jauregg, elv. Chim. Acta, 41, 867 (1958),. Griot, and T. Wagner-Jauregg, elv. Chim. Acta, 42, 121 (1959); D. Schinzer, and Y. Bo, Angew. Chem. Int. Ed. Engl., 30, 687 (1991). 8. M. amana,. oda, and J. Uchida, Yakugaku Zasshi, 90, 991 (1970); D... Barton, W. B. Motherwell, E. S. Simon, and S. Z. Zard, J. Chem. Soc., Chem. Commun., 1984, 337; Y. Ishida, S. Sasatani, K. Maruoka, and. Yamamoto, Tetrahedron Lett., 24, 3255 (1983). 9.. Kusama, Y. Yamashita, and K. arasaka, Chem. Lett., 1995, 5. 10.. Kusama, K. Uchiyama, and K. arasaka, Chem. Lett., 1995, 715;. Kusama, Y. Yamashita, K. Uchiyama, and K. arasaka, Bull. Chem. Soc. Jpn., 70, 965 (1997). 11. S. Mori, K. Uchiyama, Y. ayashi, K. arasaka, and E. akamura, Chem. Lett., 1998, 111. 12. M. Yoshida, K. Uchiyama, and K. arasaka, eterocycles, 52, 681 (2000). 13. K. Tanaka, Y. Mori, and K. arasaka, Chem. Lett., 2004, 26. 14. M. Kitamura, M. Yoshida, T. Kikuchi, and K. arasaka, Synthesis, 2003, 2415. 15.. A. agopian, M. J. Therien, and J.. Murdoch, J. Am. Chem. Soc., 106, 5753 (1984). 16. E.-U. Würthwein and. Weigmann, Angew. Chem. Int. Ed. Engl., 26, 923 (1987); W. M. David and S. M. Kerwin, J. Am. Chem. Soc., 119, 1464 (1997). 17. G. Alvernhe, and A. Laurent, Tetrahedron Lett., 1972, 1007; E. Erdik, and M. Ay, Synth. eact. Inorg. t.-org. Chem., 19, 663 (1989); E.-U. Würthwein and. Weigmann, Angew. Chem., Int. Ed. Engl., 26, 923 (1987); E. Erdik, and T. Daskapan, Synth. Commun., 29, 3989 (1999); E. Erdik, and T. Daskapan, J. Chem. Soc., Perkin Trans. 1, 1999, 3139. 18.. Tsutsui, Y. ayashi, and K. arasaka, Chem. Lett., 1997, 317. 19.. Tsutsui, T. Ichikawa, and K. arasaka, Bull. Chem. Soc. Jpn., 72, 1869 (1999). 20. M. Kitamura, S. Chiba, and K. arasaka, Bull. Chem. Soc. Jpn., 76, 1063 (2003). 21. M. Kitamura, T. Suga, S. Chiba, and K. arasaka,rg. Lett., 6, 4619 (2004). 22. K. Uchiyama, Y. ayashi, and K. arasaka, Synlett, 1997, 445. 23. K. Uchiyama, A. no, Y. ayashi, and K. arasaka, Bull. Chem. Soc. Jpn., 71, 2945 (1998). 24. A. no, K. Uchiyama, Y. ayashi, and K. arasaka, Chem. Lett., 1998, 437. 25. A.. Forrester, M. Gill, J. S. Sadd, and.. Thomson, J. Chem. Soc., Perkin Trans. 1, 1979, 612; A.. Forrester, M. Gill, J. S. Sadd, and.. Thomson, J. Chem. Soc., Chem. Commun., 1975, 291. 26. J. Boivin, E. Fouquet, and S. Z. Zard, Tetrahedron, 50, 1745, 1769 (1994); S. Z. Zard, Synlett, 1996, 1148. 27. K. Uchiyama, Y. ayashi, and K. arasaka, Chem. Lett., 1998, 1261; K. Uchiyama, Y. ayashi, and K. arasaka, Tetrahedron, 55, 8915 (1999). 28. M. Yoshida, M. Kitamura, and K. arasaka, Chem. Lett., 2002, 144; M. Yoshida, M. Kitamura, and K. arasaka, Bull. Chem. Soc. Jpn., 76, 2003 (2003). 29. Y. Koganemaru, M. Kitamura, and K. arasaka, Chem. Lett., 2002, 784. 30.. Tsutsui, and K. arasaka, Chem. Lett., 1999, 45;. Tsutsui, M. Kitamura, and K. arasaka, Bull. Chem. Soc. Jpn., 75, 1451 (2002). 31. C. M. P. Ferreira, M. F. C. Guedes da Silva, V. Yu. Kukushkin, J. J.. Fraüsto da Silva, and A. J. L. Pombeiro, J. Chem. Soc., Dalton Trans., 1998, 325; V. Yu. Kukushkin, and J. J.. Pombeiro, Coord. Chem. ev., 181, 147 (1999).
32. A. Tillack, P. Arndt, A. Spannenberg,. Kempe, and U. osenthal, Z. Anorg. Allg. Chem., 624, 737 (1998). 33. M. Kitamura, and K. arasaka, Chem. ec., 2, 268 (2002). 34.. Tsutsui, and K. arasaka, Chem. Lett., 2001, 526. 35. M. Kitamura, S. Zaman, and K. arasaka, Synlett, 2001, 974; S. Zaman, M. Kitamura, and K. arasaka, Bull. Chem. Soc. Jpn., 76, 1055 (2003). 36. M. Kitamura, S. Chiba,. Saku, and K. arasaka, Chem. Lett., 2002, 606; S. Chiba, M. Kitamura,. Saku, and K. arasaka, Bull. Chem. Soc. Jpn., 77, 785 (2004). 37. T. ishimura, and S. Uemura, J. Am. Chem. Soc., 122, 12049 (2000); T. ishimura, Y. ishiguchi, Y. Maeda, and S. Uemura, J. rg. Chem., 69, 5342 (2004). (eceived ovember, 2004) (Mitsuru Kitamura) (Koichi arasaka) rck Schucardt-Lectureship IAP Lectureship