Chemistry 206 Advanced Organic Chemistry Handout-35B The Synthetic Applications of Carbonyl Ylides avid m. barnes Evans group seminars, March 16, 1993 Monday Matthew d. shair December 16. 2002
Chemistry 206 Advanced Organic Chemistry Handout–35B The Synthetic Applications of Carbonyl Ylides Matthew D. Shair Monday , December 16, 2002 David M. Barnes Evans Group Seminars, March 16, 1993
The Synthetic Applications of Carbonyl Ylides Stabilized(Isolable) Carbonyl Ylides °Push-Pu" Stabilization David M. Barnes Evans Group Seminars, March 16, 1993 Arduengo, A.J., Ill; Janulis, E P, Jr. J. Am. Chem. Soc. 1983 iIsomunchnons Hamaguchi, M; Ibata, T. Tetrahedron Lett. 1974, 4475-4476. Isomunchnons cycloadd to dipolarophiles mEws·Ydes A: Hornbuckle S F. Chem. Rev. C6H4NO2 M. P Acc. Chem. Res. 1986. 19. 348. M.P.chem.Rev.1986,86,919939. PhH. reflux Hamaguchi, M; Ibata, T. Chem. Lett. 1975, 499-502. 35B-01 Ylides12/17991207PM
- + : The Synthetic Applications of Carbonyl Ylides David M. Barnes Evans Group Seminars, March 16, 1993 Reviews - Ylides Padwa, A.; Hornbuckle, S. F. Chem. Rev. 1991, 91, 263-309. Padwa, A.; Krumpe, K. E. Tetrahedron. 1992, 48, 5385-5483. Padwa, A. Acc. Chem. Res. 1991, 24, 22-28. Carbenes Doyle, M. P. Acc. Chem. Res. 1986, 19, 348-356. Doyle, M. P. Chem. Rev. 1986, 86, 919-939. "Push-Pull" Stabilization Stabilized (Isolable) Carbonyl Ylides Cu(acac)2 - + - + PhH, 80 °C Hamaguchi, M.; Ibata, T. Tetrahedron Lett. 1974, 4475-4476. X = H, Br, OMe - + Hamaguchi, M.; Ibata, T. Chem. Lett. 1975, 499-502. hν + - Arduengo, A. J., III; Janulis, E. P., Jr. J. Am. Chem. Soc. 1983, 105, 5929-5930 "Isomünchnons" Isomünchnons cycloadd to dipolarophiles PhH, reflux quantitative 87% R1 R2 O R1 O R2 A B A B R1 O R2 N N2 O O X O2N CH3 N O O CH3 O2N X N O O CH3 O2N X N O O CH3 N O2N CH3O2C CO2CH3 N O O CH3 Ph C6H4NO2 O O CH3 Ph C6H4NO2 CO2CH3 CO2CH3 NPh O O NPh O O H3C N N CH3 O CH3 CH3 CF3 F3C CF3 F3C N2 CF3 F3C CF3 F3C O NMe2 Me2N 35B-01 Ylides 12/17/99 12:07 PM
Equivalence of Oxirane Ring-Opening Intermediate to Generation of Carbonyl Ylides via the Ring-opening Carbene-Carbonyl Lone Pair Interaction Intermediates of epoxides isooctane A H3CO2C HcHO k2 125°C,15min HoC cOaCH Ratios CO2CH3 n 40(9,175) 125℃c,10da HcHO 40(10.5.230 - c(co,CH3 C(CO2 CH3)2 bach, W: Brokatzky, J; Fritz, H. Angew. Chem. Int. Ed. Engl. 1980, 19, 47-48. atzky, J: Eberbach, W. Tetrahedron Letf. 1980, 21, 4909-4912 Ratio k2 lk2 3 Photochemical ring-openings gave a complex mixture of products was due in part to a scrambling of the ylide Huisgen, R; de March, P J. J. Am. Chem. Soc. 1982, 104, 4952, 4953. See Brokatzky-Geiger, J. Eberbach, W. Heterocycles. 1983, 20, 1519-1524 Tetrahedron Lett. 1 35B-02Ydes3/16/933:23PM
Photochemical ring-openings gave a complex mixture of products in overall low yields. This was due in part to a scrambling of the ylide substituents. See Brokatzky-Geiger, J.; Eberbach, W. Heterocycles. 1983, 20, 1519-1524. Tetrahedron Lett. 1984, 25, 1137-1140. Eberbach, W.; Brokatzky, J.; Fritz, H. Angew. Chem. Int. Ed. Engl. 1980, 19, 47-48. Brokatzky, J.; Eberbach, W. Tetrahedron Lett. 1980, 21, 4909-4912. 91 34 11 66 100 89 100 100 9 75 30 97 57 73 75 isooctane 40 (9, 175) 30 (9, 175) 72 (5, 170) 58 (7, 215) 55 (8, 240) 40 (10.5, 230) Ratios H CO2Me R 1 2 1 3 5 10 n conversion (hours, °C) yield A B C C A B Generation of Carbonyl Ylides Via the Ring-Opening of Epoxides + - - + - + (CH3O2C)2C-N2 + C6H5-CHO Oxirane 3.3 3.0 Ratio k2 / k2 Huisgen, R.; de March, P. J. J. Am. Chem. Soc. 1982, 104, 4952, 4953. PhCHO PhCHO Equivalence of Oxirane Ring-Opening Intermediate to Carbene-Carbonyl Lone Pair Interaction Intermediates + - 125 °C, 15 min. 125 °C, 10 days Starting material k2' k2 C6H5 O CO2CH3 H CO2CH3 O C(CO2CH3)2 C6H5 H C(CO2CH3)2 H O H CO2CH3 H3CO2C H C6H5 CH3O2C CO2CH3 CH3O OCH3 N2 O O O C(CO2CH3)2 H O H C6H5 C6H5 O ( )n Ph CN O O ( )n O Ph CN O ( )n O Ph CN O Ph H R O Ph H R R CN CN O Ph R H CN O O ( )n Ph CN R R R H H H H H 35B-02 Ylides 3/16/93 3:23 PM
Cycloadditions with Oxidopyrylium Ylides Photochemical Ring-Openings of Epoxides to Generate Ylides AEB Br2, MeOH 1)H3O° 150°ccH3CN,16h 12+2] cat HOAC/CH3CN Feldman, KS: Tetrahedron Lett. 1983, 24, 5585-5586. Sammes, P. G: Street, L.J. J. Chem. Soc., Chem. Commun. 1982. 1056- 35B-03 Ylides3/179311:16AM
[2+2] • • hν PhH, pyrex Photochemical Ring-Openings of Epoxides to Generate Ylides PhH, pyrex hν 65% 34% 35% Feldman, K. S.; Tetrahedron Lett. 1983, 24, 5585-5586. Cycloadditions with Oxidopyrylium Ylides + - Br2, MeOH -45 °C 1) H3O+ 2) Ac2O / pyr 80% from furfuraldehyde 150 °C, CH3CN, 16h 61% DBN, CH2Cl2, RT 75% Me2CuLi (n = 1) pyrolysis cat. HOAc / CH3CN 150 °C, 16h 52% Sammes, P. G.; Street, L. J. J. Chem. Soc., Chem. Commun. 1982, 1056-1057 n = 1 O O CH3 O O O O O O CH3 O O O O O O O O O O A B A B O ( )n OH O OH R MeO OMe O O ( )n AcO O O ( )n AcO ( )n O H O O O AcO O H O Me O O O O OH O O 35B-03 Ylides 3/17/93 11:16 AM
Intermolecular Trapping of Oxidopyrylium Ylides Applications of FMO Theory for the Rationalization of Product Regio- and stereochemistries Orbital Theory of Dipolar-Dipolarophile Cycloadditions Carbonyl Ylides have very small HOMO-LUMO gaps 30-135°C Hendrickson, J. B; Farina, J.A. J. Org. Chem. 1980, 45, 3359-3361. herefore, either raising the dipolarophile HOMo (electron-donating substituents)or lowering the LUMO (electron-withdrawing)will accelerate LUMO EtN RT R= Ph 5 Endo product as a result of secondary orbital overlap Sammes, P. G: Street, L J. J. Chem. Soc., Perkin Trans. I. 1983, 1261-1265 35B-04 Ylides3/16/934:40PM
- - + Intermolecular Trapping of Oxidopyrylium Ylides: Applications of FMO Theory for the Rationalization of Product Regio- and Stereochemistries Endo product as a result of secondary orbital overlap , Et3N, RT R = Ph, OEt Sammes, P. G.; Street, L. J. J. Chem. Soc., Perkin Trans. I. 1983, 1261-1265. 130-135 °C 69% 4:1 exo:endo Generally low yields with electron-poor olefins. Hendrickson, J. B.; Farina, J. A. J. Org. Chem. 1980, 45, 3359-3361. R = OEt; 56% R = Ph; 65% LUMO HOMO HOMO LUMO Orbital Theory of Dipolar-Dipolarophile Cycloadditions Carbonyl Ylides have very small HOMO-LUMO gaps Energy ylide dipolarophile Therefore, either raising the dipolarophile HOMO (electron-donating substituents) or lowering the LUMO (electron-withdrawing) will accelerate the reaction. O O O O R AcO R O O O O O O O H O O O O H O EtO 35B-04 Ylides 3/16/93 4:40 PM