H O O O O H Br Br t-BuO3C The Platonic Solids Total SynOthesis of Convex Polyhedral Hydrocarbons Br Ph Ph COOH Ph Ph Br O Ph Ph HOOC Ph Ph Nat Sherden & Kevin Allan Monday, July 18, 2005 8 pm 147 Noyes O MeO C O 2 HO I I I OH I O O CO2Me The Five Elements - Platonic Solids Tetrahedron Hexahedron (Cube) Octahedron Fire Earth Air 4 + 4 - 6 = 2 8 + 6 - 12 = 2 6 + 8 - 12 = 2 Dodecahedron Icosahedron Heavenly Matter Water 20 + 12 - 30 = 2 12 + 20 - 30 = 2 • Polyhedron: a closed surface made up of polygonal regions. • Regular polyhedron: a polyhedron whose faces are congruent regular polygonal regions, and each vertex is the intersection of the same number of edges. • There are exactly FIVE that can be made: the Platonic solids, first emphasized by Plato. • Plato believed that each of the polyhedra represented an element, the combination of which resulted in the creation of all matter. • Each polyhedron obeys Euler’s Formula: # vertices + # faces - # edges = 2 http://www.3quarks.com/GIF-Animations/PlatonicSolids/ 1 The Platonic Solids as Hydrocarbons Reported: R R R R Substituted Tetrahedrane Cubane Dodecahedrane Maier (1978) Eaton (1964) Paquette (1983) Not Yet Reported (Chemically Unlikely): -- Chemical formula: C6 -- Carbon bonding orbitals are 60° away from each other. -- 8-sided octahedranes have been reported, though none with Oh symmetry. Impossible Hydrocarbon: Octahedrane -- 5 coordinate vertices make the use of carbon impossible. Icosahedrane In the Beginning there was Cubane. Ph • The first molecule containing the cubane carbon skeleton was reported in 1961 by Ph Ph Ph H. H. Freedman et al. in their "serendipitous" syntheses of octaphenyl cubane.1,2 (not discussed) Ph Ph Ph Ph COOH • Philip E. Eaton and Thomas W. Cole, Jr. finish the first "Tactical" synthesis of the cubane skeleton in 1964 with the synthesis of cubane-1,4-dicarboxylic acid.3 (not discussed) HOOC • Following a route elaborated from their cubane diacid synthesis, Eaton and Cole, publish the first synthesis of cubane later the same year (1964).4 - This synthesis was later streamlined by N.B. Chapman who combined a number of steps from the original Eaton and Cole synthesis creating the process used today to commercially manufacture cubane. • A shorter cubane synthesis was reported by James C. Barborak, L. Watts, and R. Pettit in 1966. At four steps from commercial materials it is still the shortest synthesis of cubane known to date.5 1) Freedman, H. H. J. Am. Chem. Soc., 1961, 83, 2195 - 2196. 2) Freedman, H. H.; Persen, D. R. J. AM. Chem. Soc., 1962, 84, 2837 - 2838. 3) Eaton, P. E.; Cole, T. W. J. Am. Chem. Soc., 1964, 86, 962 - 964. 4) Eaton, P.E.; Cole, T.W. J. Am. Chem. Soc., 1964, 86, 3157 - 3158. 5) Barborak, J. C.; Watts, L.; Pettit, R. J Am. Chem. Soc., 1966, 88, 1328 - 1329 2 Cubane Retrosyntheses O Br Br O O Br O Eaton Synthesis O is es O th Br yn it S Br ett d P an ak or rb Ba O O O O O Br Br Br Fe + Br Br OC OC CO Br O Original Synthesis by Eaton and Cole NBS Br 0 - 10 °C Br Br -20 °C "Radical-initiated" Br2 Et2NH Br Et O Br CCl4 Pentane/DCM 2 O O O O Diels-Alder stereochemical considerations Br Br Spontaneous O favorable O secondary Diels-Alder orbital overlap Br Br O O O Br exo endo Diels-Alder regiochemical considerations - Br Br ! O O O Only observed isomer and ! - diastereomer Br minimization of like dipoles 40 % overall yield Br Br across three steps O O ! - ! - Eaton, P. E.; Cole, T. W. J. Am. Chem. Soc., 1964, 86, 962 - 964. 3 Original Synthesis by Eaton and Cole O + Br 1) (CH2OH)2 / H O O O O 2) HCl / H O Br 2 O hv O (85% over two steps) (95%) O O Br Br Br O Br Br Br O 10% KOH(aq) (95%) O O O 1) SOCl O O 2 O cumene 152 °C 2) t-BuO2H Br (55%) Br (95% over two steps) Br t-BuO3C HOOC 75% H2SO4 (aq) (30%) O 1) SOCl2 25% KOH COOH CO3t-Bu (aq) 2) t-BuO2H 100 °C Br (55%) (95% over two steps) diisopropylbenzene (30%) Eaton, P.E.; Cole, T.W. J. Am. Chem. Soc., 1964, 86, 3157 - 3158. Barborak, Watts, Pettit synthesis O Ce(IV) Br Br (CAN) O O Br Fe + Br favorable O O OC OC CO secondary Br Br orbital O overlap exo endo spontaneous 2 + 2 cycloaddition (80%) O O O O O O hv Br Br Br Br (90%) Br Br KOH(aq) (90%) 1) SOCl HOOC 2 2) t-BuO2H COOH 3) !H Barborak, J. C.; Watts, L.; Pettit, R. J Am. Chem. Soc., 1966, 88, 1328 - 1329 4 Dodecahedrane C20H20 stabilomer Ih symmetry -- 12 pentagonal faces -- 30 edges -- 20 vertices First synthesis reported by Paquette and co-workers in 1983 -- 23 steps from sodium cyclopentadienide -- followed synthesis of 1,16-dimethyldodecahedrane in 1982 by same -- most intermediates contain C2 rotational axis or mirror plane, thus simplifying characterization For a review of dodecahedrane and related spherical molecules: Paquette, L. A. Chem. Rev. 1989, 89, 1051-1065. Paquette, L. A.; Wyvratt, M. J.; J. Am. Chem. Soc. 1974, 96, 4673. Paquette, L. A.; Wyvratt, M. J.; Schallner, O.; Schneider, D. F.; Begley, W. J.; Blankenship, R. M. J. Am. Chem. Soc. 1976, 98, 6744-6745. Paquette, L. A.; Wyvratt, M. J.; Schallner, O.; Muthard, J. L.; Begley, W. J.; Blankenship, R. M.; Balogh, D. J. Org. Chem. 1979, 44, 3616-3630. Paquette, L. A.; Balogh, D. J. Am. Chem. Soc. 1982, 104, 774-783. Paquette, L. A.; Ternansky, R. J.; Balogh, D. W. J. Am. Chem. Soc. 1982, 104, 4502-4503. Paquette, L. A. Proc. Natl. Acad. Sci. USA. 1982, 79, 4495-4500. Paquette, L. A.; Ternansky, R. J.; Balogh, D. W., Kentgen, G. J. Am. Chem. Soc. 1983, 105, 5446-5450. Retrosynthetic Analysis CO2R R CO2R X X Dodecahedrane CO2R O CO R CO2R 2 Na H O H CO2R CO2R 5 Formation of the Tetracyclic Core via 'Domino Diels-Alder' H I2 Na THF, -78 °C H MeO2C CO2Me R R R R CO2Me CO2Me CO2Me CO2Me A B CO2Me 40% combined yield over 2 steps, 1:1.4 A:B CO2Me Paquette, L. A.; Wyvratt, M. J.; J. Am. Chem. Soc. 1974, 96, 4673. Functionalization of Olefins O CO Me 2 CO2MO e AcOHg HO OH Hg(OAc)2 AcOHg HgOAc HgOAc O CO2Me CO Me O 2 CO Me O 2 O O CO2Me 1) BH 2 O 2) NaOH, H2O2, CrO3, H2SO4 acetone CO2Me CO2Me C : 50% s C2: 29% O O 1) KOH, H2O/MeOH I 2) I2, KI, NaHCO3 H O, dark 2 I 94% over 2 steps O O Paquette, L. A. et al. J. Org. Chem. 1979. 44, 3616-3630. van Tamelen, E. E.; Shamma, M. J. Am. Chem. Soc. 1954, 76, 2315-2317. 6 Diketone Formation O MeO C O 2 HO I I NaOMe -- SM is strained, so mild conditions at room temp I MeOH OH I open the lactones. -- rigidity of product and steric congestion within O cupped skeleton prevents epoxide formation. CO Me O 2 CO Me CO Me 2 O 2 O I CrO3, H2SO4 Zn-Cu acetone O I MeOH O 92% over 2 steps 78% CO2Me CO2Me Paquette, L. A. et al. J. Org. Chem. 1979. 44, 3616-3630. Paquette, L. A. et al. J. Am. Chem. Soc. 1976, 98, 6744-6745. Spirocyclobutanone Condensation CO2Me MeO2C O O SPh SPh2 2 O DMSO O CO2Me CO2Me MeO C MeO C O 2 O 2 HBF4 O O CO2Me CO2Me MeO2C O 77% yield O No monocondensation product observed CO2Me Paquette, L. A. et al. J. Org. Chem. 1979. 44, 3616-3630. 7 Cyclopentenone Annulation HO OH MeO2C O MeO C 2 O H2O2 O MeOH/H2O quantitative O Baeyer-Villiger Oxidation CO2Me CO2Me O MeO C MeO C 2 O 2 HO O OH 8% P2O5 O O O CH3SO3H 83% CO2Me CO2Me O CO2Me Friedel-Crafts acylation O CO2Me Paquette, L. A. et al. J. Org. Chem. 1979. 44, 3616-3630. Expanding the Cage O O CO2Me CO2Me H , 10% Pd/C O 2 EtOAc O quantitative 1) NaBH4 2) HCl work-up CO2Me NaBH4 CO2Me 86% MeOH O O O O p-TsOH, PhH, reflux O HO 81% over 2 steps O CO2Me Cl CO2Me HCl MeOH Cl 62% olefin elimination products CO2Me Paquette, L. A. et al. J. Org. Chem. 1979. 44, 3616-3630. 8 Norrish Photocyclization CO2Me CO Me Cl PhOH2C CO2Me 2 1) Li, NH3 Cl THF, -78 °C O HO 2) PhOCH2Cl 48% 22% CO2Me h! 90% PhOH2C CO2Me PhOH2C CO2Me PhOH2C CO2Me TsOH HN=NH PhH, reflux MeOH 85% over 2 steps HO Norrish Radical Cleavage of Aldehydes and Ketones HO Norrish Type I: O O h! R1 R2 R1 R2 Norrish Type II: H H O h! O HO OH Paquette, L. A. et al. J. Am. Chem. Soc. 1983, 105, 5446-5450. Norrish, R. G. W.; Bamford, C. H. Nature 1936, 138, 1016. Norrish, R. G. W.; Bamford, C. H. Nature 1937, 140, 195. Blocking Group Removal O PhOH2C CO2Me PhOH2C 1) DIBAL 2) PCC 92% over 2 steps OH OH CH2OPh CH2OH 1) Li, NH3 h! EtOH Norrish Type II 2) 3 M HCl 36% 99% over 2 steps O O O PCC KOH CH2Cl2 EtOH 77% retro-Claisen condensation 48% Paquette, L.