A remarkable [2.2.2] propellane

Article abstract of DOI:10.1021/ja030077y

To explore the effects of fluorine substitution on the highly strained [2.2.2]propellane skeleton, a new representative of this ring system, perfluorotricyclo[2.2.2.0_1,4]octan-2-one ethylene ketal, was prepared by a rapid and quantitative [2+2] cycloaddition to the strained alkene perfluorobicyclo[2.2.0]hex-1(4)-ene. The propellane displays impressive thermal stability, and the vulnerable C-C bond joining the bridgeheads is very resistant to attack by electrophilic reagents. On the other hand, that electron-deficient bond is cleaved quickly at room temperature by a variety of nucleophiles and mild reducing agents. The behavior of this compound contrasts dramatically with that of the only known [2.2.2]propellane lacking fluorine substituents. Copyright

Full text of DOI:10.1021/ja030077y

Published on Web 04/18/2003
A Remarkable [2.2.2]Propellane
Yigang He,* Christopher P. Junk,1 John J. Cawley, and David M. Lemal*
Department of Chemistry, Dartmouth College, HanoVer, New Hampshire 03755
Received February 3, 2003; Revised Manuscript Received March 19, 2003; E-mail: david.m.lemal@dartmouth.edu
Scheme 1
Molecules possessing the highly strained [2.2.2]propellane ring
system are very rare.2 The first representative to be isolated,
carboxamido derivative 1, was synthesized in 1973;3 the highly
fluorinated derivative 2 appeared in 1996.4 We now report the
synthesis of a third [2.2.2]propellane, 3, the structure, properties,
and chemistry of which are striking.5
Scheme 2
The new propellane was synthesized from dibromide 44 as shown
in Scheme 1. Reductive debromination of 4 generated alkene 6,
which was efficiently trapped with N-benzylpyrrole to give adduct
5. retro-Diels-Alder reaction of 5 made possible the isolation of
the strained alkene, which underwent [2+2] cycloaddition with
acetal 76 rapidly and quantitatively at room temperature. Propellane
3 is a volatile crystalline solid, mp 48-50 °C.7 Its X-ray crystal
structure reveals that the C1-C4 bond is 1.573 Å in length (cf.
cyclobutane,8 1.548 Å).9 The propellane 1 ring opens to dimeth-
ylenecyclohexanes with a half-life of 28 min at 25 °C,3 but 3
displays extraordinary thermal stability for a [2.2.2]propellane. It
is unchanged after at least 10 h at 100 °C. The stabilization of
cyclobutane rings by fluorine substitution is presumably responsible,
at least in large measure, for this contrast.10
Despite its robustness, 3 is a very reactive molecule. Tetrabu-
tylammonium iodide in moist acetonitrile cleaved the C1-C4 bond
reductively, giving dihydro compound 8 immediately at room
temperature. In the same medium, tetrabutylammonium fluoride
yielded the HF adduct 9 and its regioisomer in the ratio 9:1. The
similar ratio, 3.7:1. The higher standard potential for chlorine/
chloride is apparently compensated for by lower nucleophilicity of
chloride relative to bromide ion. Assignment of regiochemistry to
the HX adducts was facilitated by the fact that the base peak in the
mass spectrum of compounds 8, 9, 13, and 14 has the elemental
composition of ion 15.
contrasting behavior reflects the great difference in reducing power
of the two halide ions (E° ) 0.536 V for iodide, 2.866 V for
fluoride).11 These transformations probably occur as shown in
Scheme 2, via radical anion 10 and bridgehead anion 11, respec-
tively. The favored site of fluoride ion attack (C1) is such that
anionic charge develops at the bridgehead with the greater num-
ber of â-fluorines (C4); radical ion 10 is assumed to have its
charge largely at that site12 and thus to give mainly 12 upon
protonation.13
Bromide ion (E° ) 1.066 V) displays intermediate behavior,
yielding both 8 and 13, the bromine analogue of 9, in the ratio
4.2:1. It is noteworthy that reduction is the dominant process even
with the chloride ion (E° ) 1.358 V), which gives 8 and 14 in a
Addition of methyl iodide across the C1-C4 bond occurs in the
presence of iodide ion. With a large excess of MeI and a 50:1 molar
9
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J. AM. CHEM. SOC. 2003, 125, 5590-5591
10.1021/ja030077y CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3
Strong electrophiles also cleave the C1-C2 bond, not the highly
electron-deficient central bond. Bromine, for example, reacts slowly
with 3 in the dark to give a 1:1 adduct, dibromoester 20. For
comparison, bromine cleaves the central bond of 1 instantaneously
at -70 °C.3
Clearly, the consequences of heavy fluorine substitution on the
nature and chemical behavior of a [2.2.2]propellane are profound.
Electron withdrawal by the fluorines stoutly protects the fragile
bond between bridgehead carbons from thermal cleavage and
electrophilic attack, but renders it highly vulnerable to reducing
agents and nucleophiles.
Acknowledgment. The authors are grateful to the National
Science Foundation for support of this work. We also thank Victor
G. Young, Jr., and the X-ray Crystallographic Laboratory in the
Department of Chemistry, University of Minnesota for the X-ray
crystal structure.
ratio of 3 to iodide ion, adduct 16 and its regioisomer 17 are formed
in the ratio 2.5:1.14 With equimolar amounts of 3 and iodide ion,
Supporting Information Available: Experimental procedures and
characterization data, including, for 3, X-ray crystallographic data plus
ORTEP (PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
References
(1) Walter H. Stockmayer Fellow, 1998-2000.
(2) Wiberg, K. B. Chem. ReV. 1989, 89, 975. The strain energy of the parent
[2.2.2]propellane was calculated to be 97 kcal/mol.
(3) Eaton, P. E.; Temme, G. H. J. Am. Chem. Soc. 1973, 95, 7508.
(4) Zhang, Y.; Smith, J. R.; Lemal, D. M. J. Am. Chem. Soc. 1996, 118,
9454.
the product ratio becomes 15:1. The initially formed radical anion
10 reacts twice with methyl iodide, methylating in one step (SN2)
and abstracting an iodide atom in the other to give predominantly
the expected regioisomer 16 (Scheme 3). Both iodide ion and methyl
radical are generated in those steps, with the result that an ionic
chain process giving predominantly 16 and a radical chain sequence
yielding 17 ensue. The result with equimolar iodide shows that the
ionic chain process is highly regioselective; the outcome with a
trace of iodide indicates that 3 is attacked by iodide ion about 2.5
times faster than by methyl radical.
Inclusion of a small amount of acetic acid in the reaction of 3
with methyl iodide and catalytic iodide ion provided strong evidence
for the above interpretation. Now only regioisomer 17 was formed,
along with a lesser amount of HI adduct. Acetic acid eliminated
the ionic chain pathway by protonating 10, thereby forestalling the
regeneration of iodide ion. It follows that the radical chain pathway
is cleanly regioselective; because methyl is a donor radical, it attacks
as nucleophiles do, at C1.
All of the reactions of propellane 3 described above occur rapidly
at room temperature. In methanol, 3 undergoes slow solvolysis,
forming a 1:1 adduct. In further contrast with the above transforma-
tions, the C1-C4 bond remains intact, as the product is ortho ester
18. The C1-C2 bond apparently suffers heterolysis in this good
ionizing solvent with the help of π-donation by the oxygens,
stabilization of developing negative charge by four â-fluorines, and
release of ring strain. That bond is the longest (1.590 Å) of the 10
cyclobutane bonds in 3, perhaps by virtue of negative hypercon-
jugation.15 Analogously, the slow solvolysis of propellane 3 in
aqueous acetonitrile yields hydroxyester 19, presumably via an ortho
acid.
(5) This molecule was chosen as a model for perfluoro[2.2.2]propellane, which
has not yet submitted to synthesis. Oxygen plays a duel role as substituent,
greatly facilitating propellane formation by virtue of its π donor ability,
then mimicking fluorine in the product with its electron-withdrawing power
as the second most electronegative element.
(6) This new ketene acetal was prepared by treatment of 2-trifluoromethyl-
1,3-dioxolane with butyllithium.
(7) 19F NMR (CDCl3) δ -104.1(s, 2F); -106.5, -107.3 (AB q, J ) 228 Hz,
4F); -106.7, -107.6 (AB q, J ) 223 Hz, 4F); 1H NMR (CDCl3) δ 4.25
(m, 2H), 4.21 (m, 2H); 13C NMR (CDCl3, 125.7 Hz, 19F decoupled) δ
119.6 (s), 115.5 (s), 115.0 (s), 111.0 (s), 66.9 (t, J ) 154 Hz), 53.2 (s),
51.5 (s); HRMS (CI) calcd. for C10H5O2F10 (M + H+) 347.0130; found
347.0127.
(8) Almenningen, A.; Bastiansen, O.; Skancke, P. N. Acta Chem. Scand. 1961,
15, 711. See also: Stein, A.; Lehmann, C. W.; Luger, P. J. Am. Chem.
Soc. 1992, 114, 7684.
(9) Despite its high degree of p character, ab initio calculations predict the
central bond of the parent hydrocarbon to be only 1.51 Å long: Zhao,
C.-Y.; Zhang, Y.; You, X.-Z. J. Phys. Chem. A 1997, 101, 5174-5182.
Wiberg, K. B.; Bader, R. F. W.; Lau, C. D. H. J. Am. Chem. Soc. 1987,
109, 985.
(10) Liebman, J. F.; Dolbier, W. R., Jr.; Greenberg, A. J. Phys. Chem. 1986,
90, 394.
(11) Handbook of Chemistry and Physics; Lide, D. R., Ed.; 83rd ed.; CRC
Press: Boca Raton, FL, 2002-2003; pp 8-22, 8-23.
(12) The two bridgeheads should be coupled primarily by through-bond
interaction: Stohrer, W. D.; Hoffmann, R. J. Am. Chem. Soc. 1972, 94,
779.
(13) The possibility that one of the hydrogens in 8 was introduced by hydrogen
atom abstraction instead of protonation was ruled out by the finding that
in the presence of D2O both bridgeheads become deuterated.
(14) The methyl group was located by NMR as follows. NOEs resulting from
selective irradiation of the 19F resonances permitted assignment of the
13C signals for C1 and C4. In the 19F broadband decoupled 13C spectrum,
it was the signal for C4 that was split into a quartet by the methyl protons.
(15) Kirby, A. J. The Anomeric Effect and Related Stereoelectronic Effects at
Oxygen; Springer: New York, 1983.
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