Baran Group Meeting Platonic Hydrocarbons 02/15/06 Background Ryan Shenvi

The knowledge at which geometry aims is knowledge of the eternal, and Platonic hydrocarbons are the corresponding carbogens, where each vertex is a carbon, not of aught perishing and transient . . . My noble friend, geometry will each edge a bond, and each face a ring. draw the soul towards truth, and create the spirit of philosophy, and raise up that which is now unhappily allowed to fall down. . . Nothing should be more sternly laid down than that the inhabitants of your fair city by all means learn geometry. –Plato (ca. 427-347 BC) “The Republic,” ca. 370 BC

en arch hn o logoz kai o logoz hn proz ton qeon kai qeon hn o logoz In the beginning was the word (logos) and the word was with God and the word was God. • Not all platonic solids translate to platonic hydrocarbons; limited by carbon valence, bonding angles, and strain. Octahedrane and icosahedrane have not been prepared, –St. John, (ca. 10 AD-100 AD) nor has unsubstituted tetrahedrane. “The Gospel of John,” ca. 96 AD • However, numerous inorganic molecules adopt these geometries:

What are the 'platonic hydrocarbons'? Platonic Solids: • Regular solids, regular polyhedra: convex polyhedra whose faces are equivalent, convex regular polygons. • Discovered 'first' by the neolithic Scots, ca. 1300-1400 BC.

C B H 2 10 12 3– carboranes [Zr6Cl18] • Tetrahedrane and cubane have been called "super s-aromatic and super s-antiaromatic, respectively: Cyclopropane exhibits strong s-aromaticity as evidenced by its 1. large diamgnetic sus- ceptibility and anisotropy, 2. upfield shifts of attached protons, 3. shielding of protons • Described mathematically by Theaetetus (417 BC-369 BC), who proved the existance above its ring and 4. a stabilization of 11.3 kcal/mol (compare 33.2 kcal/mol for benzene). of 5 and only 5 regular solids; included in Euclid's Elements, Book X. Cyclobutane exhibits strong s-antiaromaticity: 1. similarity to cyclopropane's strain (27.5 vs. 26.5 kcal/mol), 2. abnormally low diamagnetic susceptibility, 3. deshielded 1H and Polyhedron Faces Edges Vertices Symmetry Group 13C shifts. Tetrahedron 4 6 4 Td Hexahedron 6 12 8 O h geometric duals Octahedron 8 12 6 Oh Dodecahedron 12 30 20 Ih geometric duals Icosahedron 20 30 12 Ih

• Included in Plato's Timaeus as part of his 'theory of everything,' which assigned the regular geometry of the solids to each of the elements: earth, water, air, fire, and ether (an element of order or logic added to the original elements described by Emedocles of Agrigentum, 495-435 BC). • In 1852, Schläfli proved the existance of exactly six regular polyhedra in four dim- Planar cyclopropane, cyclobutane, tetrahedrane, and cubane dissected nucleus-independent ensions and three in all higher dimensions (some may be familiar with the hypercube, chemical shift grids. Red and green points denote positive and negative NICS values, respectively or tesseract, of A Wrinkle in Time fame). Baran Group Meeting Platonic Hydrocarbons 02/15/06 Dodecahedrane Ryan Shenvi

DODECAHEDRANE O Considerations: CO2Me CO2Me • tandem bond-forming events Late-stage reactions must O a) NaOH, MeOH O require proper alignment all be able to take place from KOH (aq.), MeOH; I b) H2SO4, Na2Cr2O7 O • severe entropic disadvantage the exo-face. O I2, NaHCO3 c) Zn/Cu, MeOH in dimerization events I O (94%) (78%) • new bonds must form on the

endo face CO2Me CO2Me Ph Ph S heat, high pressure, (77%) irradiation, transition O metals . . . MeO C O 2 CO2Me O CO2Me

H2, Pd/C, EtOAc a) H2O2, MeOH O (100%) O O b) P4O10, MsOH (83%) CO2Me CO2Me CO2Me

NaBH , (81%) 4 MeOH first non-meso (C10H10) + (C10H10) (C15) + (C5) (C16) + (C4) intermediate O Woodward et al, Eaton et al, Paquette et al, O OPh MeO C Cl JACS, 1964, 3162. JACS, 1972, 1014. JACS, 1978, 1600. H 2 CO2Me FAILED FAILED FAILED HCl, MeOH Li/ NH3, BOMCl H Cl (62%) O O (48%) SUCCESS! Paquette, L. A.; Ternansky, R. J.; Balogh, D. W. JACS, 1982, 104, 4502 CO2Me a) hn O b) TsOH c) HN=NH

9 OHOH OPh OPh Ni 50 °C CHO CO2Me H H H H (i-Bu) AlH CO2Me + CO2Me a) hn 2 , THF I2 b) Li/ NH3 °C + –80 c) H3O Na MeO2C MeO2C

PCC H H H H H H O CHO CO2Me H H + + CO2Me CO2Me CO2Me H a) KOH, EtOH Pd/ C CO2Me CO2Me H CO Me CO Me b) hn 250 °C (15-20%) 1 : 1 2 2 c) TsOH d)HN=NH Baran Group Meeting Platonic Hydrocarbons 02/15/06 Dodecahedrane Ryan Shenvi Prinzbach et al. Angew. Chem. Int. Ed. Engl. 1994, 2239. TETRAHEDRANE O O • Numerous attmpts towards its synthesis . . . NLiTs S O O Cl Cl S Cl Cl Cl Cl H Cl A Cl H Cl O Cl Cl Cl Cl Cl Cl Cl Cl [–SO2] H • Cl Cl Cl Cl Cl Cl O N D Cl H N O O Cl Cl Cl O H Cl Cl Cl TsLiN isodrin O O H2 transfer D " . . . leaving as the only consolation the knowledge of how not to make tetrahedrane." -Henning Hopf Cl • High-energy diradical-like intermediate can rapidly convert to its lower energy lumomer. Cl a) A, D Cl • High-energy diradical-like intermediate can rapidly convert to its lower energy lumomer. b) Li, t-BuOH Li, t-BuOH H nearly equal energies Cl H HOMO-LUMO crossing Cl Cl of activation c) Pd/C, 250 °C (95%) Cl through diradical bicyclo- (35%) Cl butane Cl Cl (30%) hn 'bonding' interaction ~126 between 'radicals, O O and s-conjugation O O O O Cu2O, bipy., H2O E ~22 PhH, D ~32(kcal/ mol) a) B2H6•THF, quinoline, 150 °C 'anti-bonding' interaction (73%) between 'radicals and b) NaOH, H2O2 c) CrO , Me CO through space interaction 3 2 with central bond ~94 O O N2 Schematic representation of the MERP (minimum energy reaction path) for conversion of MeO2C CO2Me hn a) HCO2Me, NaH tetrahedrane to cyclobutadiene. N2 O O MeOH b) TsN3, Et3N (95%) (83%) • However, tetrahedrane (Estr= 126-140 kcal/mol) can be stabilized by 'corset effect.' a) OH– (76%) b) Pb(OAc)4, I2 any movement away tetrahdral geometry increases tert-butyl CCl4, hn steric interactions, imparting kinetic stability c) Na-K, THF; t-BuOH t-Bu

t-Bu t-Bu Pt/Re/Al2O3/H2 E t-Bu

H 250 °C H H decomposition 'black box' (3 - 8%) products H H ° 64.4 – 42.2 kcal/mol 22.2 D f Rxn Coordinate (Estr) (115.0) (–46.1) (68.9) • Originally proposed and utilized by G. Maier et al in the first synthesis of a tetrahedrane Pagodane: 14 pots 24% overeall (90%/step) Maier, G. et al Angew. Chem. Int. Ed. Engl., 1978, 520. Baran Group Meeting Platonic Hydrocarbons 02/15/06 Platonic Hydrocarbons Ryan Shenvi

Cubane (Hexahedrane) Eaton, P. E. et al. JACS 1964, 962. t-Bu O O t-Bu t-Bu H Eaton, P. E. et al. JACS 1964, 3157. t-Bu t-Bu O hn O hn 1. NBS O + O O – t-Bu t-Bu 2. Br2/ Br hn, MeOH, HCl t-Bu 3. Et N O Br H O 3 O O (40%) t-Bu + Br O Br t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu 50% KOH (aq.) (30%) t-BuLi, DME Br2, CCl4; –10 °C to rt 6N KOH, 2d O t-Bu t-Bu t-Bu Br t-Bu H 1. SOCl 2d (80%) diisopropylbenzene 2 CO2H (22%) O2t-Bu O O O 100 °C t-BuO 2. t-BuO2H, 2 HO2C DHf = 144-159 kcal/mol Py. 13 (prepared by Fluorochem C NMR: d = 32.26, 28.33, 10.20 (calculated) O in CA, and EniChem mp = 135 °C 1H NMR: d = 4 Synthesis in Milan on a t-Bu multi-kilogram scale) t-Bu t-Bu 130 °C, t-Bu t-Bu cyclosilane hn (254 nm), R. Pettit and co-workers JACS 1966, 1328. O Br t-Bu t-Bu 8:3 t-hexane/ hn (300 nm), Br O O t-Bu t-Bu t-Bu t-Bu Br hn, PhH pentane rt + CAN O (Rigisolve) t-Bu (90%) –196 °C Fe(CO)3 Br O O Br Br (35%) O 12% hn

O t-Bu t-Bu t-Bu O Mg(TMP) , O • hn 2 CO2Me THF N(i-Pr)2 N(i-Pr)2 t-Bu – –78 °C; CO NC t-Bu aromatic 6p e MeO2C NC 2 t-Bu CO H cyclobutadiene (85%) 2 a) CH Cl , (COCl) ; TMS 2Li 2 2 2 (99%) TMS TMS TMS TMS THF, NH3, –78 °C Li, THF, rt 2– Eaton et al. JACS, 1993, 10202 b) CHCl3, DMF, TMEDA + CpCo(CO)2 (77%) SOCl2, –10 °C TMS Co TMS TMS TMS TMS O O O NC a) CH2Cl2, (COCl)2; HO2C BrMgTMP, THF, Me SO , R THF, NH , –78 °C –78 °C; 2 4 N(i-Pr) 3 N(i-Pr) N(i-Pr) C D , rt BrCH CH Br, 2 2 2 6 6 2 2 (85%) CO OR R = Me, H (2.85 ppm) THF NC b) SOCl2, D NC 2 NC CN (90%) CN (90%) CN C6D6, TMS TMS rt (77%) a) BrMgTMP, THF, Li TMS TMS –78 °C; CO2 TMS TMS (100%) b) KOH (aq), EtOH, D MeLi, THF, rt hn (254 nm), DMDO, Me CO; 2 AcO OAc O SOCl2; Barton's pentane, HO2C AcO OAc TMS TMS (67%) TMS TMS LAH, THF, D; NaNHPT, DMAP; HO2C –100 °C TMS TMS N(i-Pr)2 N(i-Pr) AcO (50%) Ac O, AcO 2 t-BuSH, h , TMS TMS HO C 2 n OAc 2 (89%) OAc PhH (72%) Sekiguchi, A. et al. JACS, 2003, 12684. CO2H Baran Group Meeting Platonic Hydrocarbons 02/15/06 Cubane Ryan Shenvi

SOCl , MeCN; AcO OAc 10% NaOH (aq.) CO2H 2 NO2 KMnO CH Cl , TMSN ; 4 HO2C 2 2 3 O2N AcO (85%) CHCl , ; DMDO, HO2C 3 D O2N OAc CO H 2 Me2CO, H2O NO2 (30%) 4 equiv. NHMDS, THF/MeTHF –78 °C; (74%) N2O4, –130 °C, i-pentane; + H , Et2O

NO NO NO O2N 2 O2N 2 O2N 2 O LHMDS, CH Cl O2N NO2 3 O2N NO 2 2 O2N H

NO2 (45-55%) NO2 NO2 O2N O2N –78 °C O2N NO NO NO O2N 2 O2N 2 O2N 2

DHf = 81-144 kcal/mol

density ~ 1,9-2.2 g/cm O2N NO2 Me O2N 'leads to calculated detonation velocities NO2 N N N O N NO NO and pressures much higher than 2 2 N 2 N N N that of TNT, 15-30% greater than HMX O N NO N 2 2 and perhaps even better than CL-20, O2N N the most powerful nonnuclear explosive N known.' NO2 NO2 NO2 TNT HMX CL-20