Synthesis of tetrakis(cyclopropylmethyl)methane, a new symmetric product has been described using the radical mediated gem-diallylation of cyclopropylmethyl xanthate as a key step and its single crystal X-ray analysis established its C2-symmetry

Baquer, Syed M.

Gonnade, Rajesh G.

Gurjar, Mukund K.

Ramana, C. V.

English

Publications of the IAS Fellows

An expedient synthesis of tetrakis(cyclopropylmethyl)methane
C. V. Ramana,* Syed M. Baquer, Rajesh G. Gonnade and Mukund K. Gurjar*
National Chemical Laboratory, Pune-411 008, India. E-mail: chepuri@dalton.ncl.res.in;
gurjar@dalton.ncl.res.in; Fax: +91-20-5893614
Received (in Cambridge, UK) 13th November 2001, Accepted 8th February 2002
First published as an Advance Article on the web 22nd February 2002
Synthesis of tetrakis(cyclopropylmethyl)methane, a new
symmetric product has been described using the radical
mediated gem-diallylation of cyclopropylmethyl xanthate as
a key step and its single crystal X-ray analysis established its
C2-symmetry.
The art of organic synthesis encompasses an enormous range of
activities, in which synthesis of the designed symmetric
molecules is an aesthetically pleasing endeavour.1 The elegant
synthesis of tetracyclopropylmethane 1 by de Meijere and co-
workers2 that has remained elusive until now (although the
corresponding hexacyclopropylethane 2 was made about three
decades back)3 illustrates the difficulties in attaining the
designed symmetric molecules.4 The inherent steric crowding
in 1 affects its conformation in the solid state resulting in an
unexpected S4 symmetry (Fig. 1).2 In this context, it will be
interesting to see what one can expect when such a steric
crowding is relaxed to a certain extent as in 3, the homologue of
1, and how the solid state structure of 3 will be influenced by the
diminished steric crowding around the central quaternary
carbon and by the directional preferences of the cyclopropyl
group. This communication describes the synthesis of tetra-
kis(cyclopropylmethyl)methane (3) and its solid state structure.
The planned synthesis of 3 consists of an exquisite application
of our gem-diallylation approach5 for the synthesis of the diallyl
derivative 9, and subsequent twofold cyclopropanation of 9.
The synthesis commenced from the dicyclopropyl acetone (4)
which was made according to the known procedure.6 The
Wadsworth-Emmons-Horner olefination of 4 by treating with
diethylethoxycarbonylmethyl phosphonate resulted in the a,b-
unsaturated ester 5 (Scheme 1). The ester 5 was subsequently
reduced to the allyl alcohol 6, by treating with DIBAL-H at 278
°C. 1H, 13C-NMR and MS studies substantiated the assigned
structure of 6. Cyclopropanation of the allyl alcohol 6 was
carried out by using Furukawa’s modification7 for Simmons-
Smith cyclopropanation (Et2Zn and CH2I2 in ether at 220 °C
for 12 h) to obtain the cyclopropanated alcohol 7. In the 1H-
NMR spectrum of 7,10a the hydrogens of three cyclopropane
rings appeared separately and in the high field region. In the
13C-NMR spectrum, one of the methylene carbons bearing the
cyclopropyl (cyclopropyl = Cp) group shielded strongly (ca. 6
ppm) compared to the other similar methylene carbon. This can
be attributed to the g-effect8 resulting from the through space
interaction between the hydrogens of cis-oriented cyclopropyl-
methylene Cp–CH2, and of the H2C–OH. The alcohol was
converted to its xanthate derivative 8 by treatment with CS2 and
MeI in presence of NaH. The crucial reaction, i.e., transforma-
tion of 8 to the diallyl compound 9 was achieved by treating it
with allyltributylstannane, catalytic AIBN in refluxing benzene
in an overall yield of 43%.5 The 1H- and 13C-NMR spectra of
the diallyl compound 9 were as expected and only half of the
signals were seen.10b Following the similar protocol of de
Meijere and co-workers that has been used in the synthesis of
1,2 cyclopropanation of the diallyl compound 9 was succesfully
achieved by treating 9 with an excess ethereal solution of
diazomethane in the presence of catalytic Pd(OAc)2,9 and the
tetracyclopropyl derivative 3 was obtained in good yield.
As shown in Fig. 2, in the solid state compound 311 adopts a
C2-symmetric conformation showing diminished symmetry
when compared to 1, because of the flexibility around the
central carbon. In the crystal lattice, four molecules of 3 were
found having a dimeric structure and its 3-dimensional structure
consists of an antiparallel orientation between two adjacent
repeating dimeric units.
In conclusion, an expedient synthesis of the symmetric
product ‘tetrakis(cyclopropylmethyl)methane’ has been de-
scribed for the first time using a radical based diallylation
reaction as the key step. A similar approach for the synthesis of
Fig. 1
Scheme 1 Reagents and conditions: (a) (EtO)2P(O)CH2CO2Et, NaH, THF,
rt, 12 h, 62%; (b) DIBAL-H, THF, 278 °C, 6 h, 72%; (c) Et2Zn, CH2I2,
diethyl ether, 220 °C, 24 h, 90%; (d) CS2, MeI, NaH, THF, rt, 1 h; (e)
allylSnBu3, AIBN, benzene, reflux, 12 h, 42% from 7; (f) Pd(OAc)2,
CH2N2, ether, rt, 1 h, 92%.
Fig. 2 ORTEP representation (a) of 3 and (b) of 3 in C2-symmetric
orientation.
Th is journa l i s © The Roya l Soc ie ty of Chemist ry 2002614 CHEM. COMMUN. , 2002, 614–615
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Cp-subsituted (aromatic) tetrakis(cyclopropylmethyl)methane
derivatives and the dependence of their solid state structure on
substituent is under the way.
SMB is grateful to CSIR, New Delhi for the award of a
research fellowship.
Notes and references
1 P. E. Eaton, Synthesis of Non-Natural Products: Challenge and Reward,
(Tetrahedron Symposia-in-Print no. 26), Pergamon Press, Oxford,
1986; M. M. Haley and W. B. Wan in Advances in Strained and
Interesting Organic Molecules, ed. B. Halton, Jai Press Inc, Stamford,
2000, 8, p. 1; T.-L. Ho, Symmetry: A Basis for Synthetic Design, Wiley,
New York, 1995.
2 S. I. Kozhushkov, R. R. Kostikov, A. P. Molchanov, R. Boese, J.-B.
Buchholz, P. R. Schreiner, C. Rinderspacher, I. Ghiviriga and A. de
Meijere, Angew. Chem., 2001, 113, 179; Angew. Chem., Int. Ed., 2001,
40, 180.
3 For the synthesis of 2 see: J. C. Martin and J. W. Timberlake, J. Am.
Chem. Soc., 1970, 92, 978; For crystal structure of 2 see  W. Bernlohr,
H.-D. Beckhaus, K. Peters, H. G. von Schnering and C. Ruchardt, Chem.
Ber., 1984, 117, 1013.
4 For recent reviews on multiple cyclopropyl systems see:  A. de Meijere
and S. I. Kozhushkov, Chem. Rev., 2000, 100, 93; R. Faust, Angew.
Chem., 2001, 113, 2312; Angew. Chem., Int. Ed., 2001, 40, 2251.
5 M. K. Gurjar, S. V. Ravindhranath and S. Karmakar, Chem. Commun.,
2001, 241.
6 R. C. Kerber and C.-M. Hsu, J. Am. Chem. Soc., 1973, 95, 3239.
7 J. Furukawa, N. Kawabata and J. Nishimura, Tetrahedron, 1968, 24, 53;
N. Kawabata, T. Nakagawa, T. Nakao and S. Yamashita, J. Org. Chem.,
1977, 42, 3031.
8 K. Seidman and G. E. Maciel, J. Am. Chem. Soc., 1977, 99, 659.
9 R. Paulissen, A. J. Hubert and P. Teyssie, Tetrahedron Lett., 1972,
1465; J. Kottwitz and H. Vorbruggen, Synthesis, 1975, 636.
10 (a) Spectral Data of Compound 7: 1H-NMR (300 MHz, CDCl3):
0.04–0.07 (m, 4 H); 0.19 (t, J = 5.2 Hz, 1 H); 0.38–0.51 (m, 4 H); 0.60
(dd, J = 8.8, 4.9 Hz, 1 H); 0.67–0.80 (m, 2 H); 1.03 (ddt, J = 8.7, 6.9,
5.4 Hz, 1 H); 1.15–1.30 (m, 2 H); 1.45–1.63 (m, 2 H); 3.56 (dd, J = 11.
2, 8.3 Hz, 1 H); 3.68 (dd, J = 11.2, 6.9 Hz, 2 H). 13C-NMR (75 MHz,
CDCl3): 4.1, 4.5, 4.7, 4.8 (4 t, 4 C); 8.3, 8.9 (2 d, 2 C); 16.1 (t, 1 C); 25.6
(d, 1 C); 36.3, 42.2 (2 t, 2 C); 63.5 (t, 1 C). (b) Spectral Data of
Compound 9: 1H-NMR (300 MHz, CDCl3): 0.01–0.06 (m, 4 H);
0.40–0.49 (m, 4 H); 0.58–0.74 (m, 2 H); 1.27 (d, J = 6.3 Hz, 4 H); 2.8
(d, J = 7.3 Hz, 4 H); 5.00–5.08 (m, 4 H); 5.74–5.94 (ddt, J = 16.5, 9.2,
7.5 Hz, 2 H). 13C-NMR (75 MHz, CDCl3): 5.1 (t, 4 C); 5.9 (d, 2 C); 41.0
(s, 1 C); 41.8 (t, 4 C); 117.0 (t, 2 C); 135.4 (d, 2 C). (c) Spectral Data
of Compound 3: 1H-NMR (500 MHz, CDCl3): 0.01–0.06 (m, 8 H);
0.39–0.44 (m, 8 H); 0.64 (br.septet, J = 6.4, 4 H); 1.42 (d, J = 6.3 Hz,
8 H). 13C-NMR (125 MHz, CDCl3): 5.26 (t, 8 C); 6.18 (d, 4 C); 29.76
(s, 1 C); 42.69 (t, 4 C). Elemental analysis Calc. for C17H28 (Mol. Wt.:
232.39) C, 87.86; H, 12.14; found C, 87.62; H, 12.27%.
11 Single crystals of 3 were recrystallised from hexane and data were
collected on a Bruker SMART APEX CCD diffractometer. Crystal
data: C17H28, M = 232.39, crystal dimensions 0.07 3 0.23 3 0.77 mm,
monoclinic, space group P21/n, a = 8.8129(7) , b = 10.3361(8) , c =
16.6850(13) Å, b = 100.858(1)°, V = 1493(2) Å3, Z = 4, Dc = 1.034
g cm23, m (Mo-Ka) = 0.057 mm21, T = 293(2) K, 7607 reflections
measured, 2620 unique [I > 2s(I)], R value 0.0615, wR2 = 0.1451 (all
data R = 0.0785, wR2 = 0.1551). All the data were corrected for
Lorentzian, polarisation and absorption effects. SHELX-9712 was used
for structure solution and full matrix least squares refinement on F2.
Hydrogen atoms were included in the refinement as per the riding
model. CCDC 174509. See http://www.rsc.org/suppdata/cc/b1/
b110246j/ for crystallographic files in .cif format.
12 G. M. Sheldrick, SHELX-97 program for crystal structure solution and
refinement, University of Gottingen, Germany, 1997.
615CHEM. COMMUN. , 2002, 614–615


An expedient synthesis of tetrakis (cyclopropylmethyl) methane

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An expedient synthesis of tetrakis (cyclopropylmethyl) methane

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