Cook Me and Call Me the Molecular Dice! Key Words

Home , Cubane

P. E. EATON, T. COLE (THE UNIVERSITY OF CHICAGO, USA) Category Cubane Synthesis of J. Am. Chem. Soc. 1964, 86, 3157–3158. Materials and Unnatural Products Cook Me and Call Me the Molecular Dice! Key words

cubanes O O hydrocarbons O 1. NBS, CCl4 O O Br 1. ethylene glycol, PTSA, PhH Br 2. Br2, CH2Cl2–pentane strained structures 3. diethylamine, Et2O Br 2. HCl (aq)

Br Br 1 O O 2 3 40% yield 85% yield

hν, MeOH

1. SOCl O 2 O O 2. t-BuO2H, pyridine, Et2O O 3. cumene, 152 °C O O KOH (aq) O Br Br Br HO C 2 Br 6 5 4 52% yield 95% yield 95% yield

H2SO4 (aq)

O 1. SOCl2 2. t-BuO2H, pyridine, Et2O KOH (aq) COOH 3. diisopropylbenzene, 150 °C Br

7 8 9 90% yield 55% yield 30% yield

Significance: Cubane (9) is a highly strained hy- Comment: The classic synthesis of cubane starts drocarbon in which eight carbon atoms are ar- from 2-cyclopentenone and consists of fifteen dis- ranged at the corners of a cube, adopting unusually crete steps with an overall yield of about 5%. There 90° bonding angles. Before it was first synthesized are three key synthetic elements: (a) the highly in 1964 by Eaton and Cole, researchers believed endo-selective Diels–Alder reaction of 2-bromo- that such cubic carbon-based molecule would be cyclopentadienone (1) generated in situ, producing too unstable to exist. Initially, cubane was consid- the endo-dimer 2 (J. Am. Chem. Soc.1964, 86, 962); ered just a laboratory curiosity of interest only to (b) the [2+2] photocyclization of 3, obtaining 4; and academics, however, over time this remarkable hy- (c) the double Favorskii ring contraction of the cage This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. drocarbon and derivatives have found applications diones 4 and 7, producing 5 and 8, respectively. in controlled energy storage, the explosives indus- Nowadays, the chemistry of cubane is well devel- try, pharmaceuticals, and polymer science. oped and it can be easily obtained on a multi-gram scale (see Review below).

Review: K. F. Biegasiewicz, J. R. Griffiths, G. P. Savage, J. Tsanaktsidis, R. Priefer Chem. Rev. 2015, 115, 6719–6745.

SYNFACTS Contributors: Timothy M. Swager, Alberto Concellón Synfacts 04062019, 15(06), 0613 Published online: 20.05.20191861-19581861-194X