Alkene-allenecyclopropane radical cyclisations promoted by tris-(trimethylsilyl)silane

Article abstract of DOI:10.1016/j.tetlet.2009.03.024

Treatment of the butenyl-substituted allenecyclopropanes 5 and 12 with tris-(trimethylsilyl)silane (TTMSS)-AIBN results in facile radical cyclisations into the cyclopropane-carbon centres of the allene moieties, followed by cyclopropane ring-opening and a

Full text of DOI:10.1016/j.tetlet.2009.03.024

Tetrahedron Letters 50 (2009) 3527–3529
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Alkene-allenecyclopropane radical cyclisations promoted
by tris-(trimethylsilyl)silane
*
Nigel R. Jones, Gerald Pattenden
School of Chemistry, The University of Nottingham, Nottingham, England, NG7 2RD, United Kingdom
a r t i c l e i n f o
a b s t r a c t
Article history:
Treatment of the butenyl-substituted allenecyclopropanes 5 and 12 with tris-(trimethylsilyl)silane
(TTMSS)–AIBN results in facile radical cyclisations into the cyclopropane-carbon centres of the allene
moieties, followed by cyclopropane ring-opening and allene isomerisation, leading to the bicyclic 1,3-
dienes 10 and 13, respectively. By contrast, treatment of the pentenyl-substituted allenecyclopropane
15a and the iodoethane 18 with TTMSS–AIBN, led to the alkylsilane 16, and the enyne 21, respectively.
Desilylation of 10 and 13 gave the corresponding bicyclic hydrocarbons.
Received 23 January 2009
Revised 24 February 2009
Accepted 5 March 2009
Available online 11 March 2009
Keywords:
Crown Copyright Ó 2009 Published by Elsevier Ltd. All rights reserved.
Allenecyclopropane
Tris-(trimethylsilyl)silane (TTMSS)
Radical cyclisations
Allenes and methylenecyclopropanes are widely used in a range
of useful synthetic processes, including electrophilic and nucleo-
philic additions, metallation reactions, cycloaddition and cyclo-
metallation reactions, and free radical additions.1,2 By contrast,
synthetic applications of allenecyclopropanes, which incorporate
both allene and methylenecyclopropane functionalities, are rela-
tively sparse.3 Early studies by Crandall et al.,4 and later by others,5
have shown that favoured cyclisation reactions involving car-
bon-centred radicals and allenes take place preferentially at the
sp-carbon centre of the allene. In similar, related studies with
methylenecyclopropanes, Kilburn et al.6 established that the
favoured radical cyclisations take place by initial addition of the
carbon radical into the cyclopropane carbon centre of the methyl-
enecyclopropane. In earlier work,7 we showed that the C10-allene-
cyclopropane 1, derived from isoprene, reacted with thiophenol,3,8
in a free-radical chain-addition process, to give exclusively the thi-
oether 2. The thioether 2 was then transformed into the natural
product karahanaenone 3 by Cope rearrangement followed by
hydrolysis of the resulting vinyl sulfide (Scheme 1). To our knowl-
edge, no investigations of cyclisation reactions involving carbon-
centred radicals and allenecyclopropanes have been reported. In
this Letter we describe the formation of functionalised carbocycles
resulting from intramolecular radical-mediated cyclisations
involving allenecyclopropanes and alkenes promoted by tris-(tri-
methylsilyl)silane in the presence of AIBN.
SPh
O
PhSH
i, Δ
•
C6H6, 25 °C
ii, HgCl2
CH3CN-H2O
1
2
3
Scheme 1. Synthesis of karahanaenone 3 from the allenecyclopropane 1.
thesise the substituted allenecyclopropane 5, containing a terminal
alkene group, from which the radical centre would be generated by
hydrosilylation using tris-(trimethylsilyl)silane (TTMSS)–AIBN.9
Thus, under phase–transfer conditions,10 a solution of the known
diene 411 in benzene, was treated with 3-chloro-3-methylbut-1-
yne12 in the presence of aqueous KOH and debenzo-18-crown-6
at room temperature. Work-up followed by chromatography then
gave the allenecyclopropane 5 in 46% yield.13 When a solution of
the allenecyclopropane 5 in dry toluene containing AIBN at 90 °C
was treated with TTMSS for 2 h, the bicyclic allene 9 was produced
as a 3:2 mixture of diastereoisomers in 73% yield. Interestingly,
when the reaction mixture was left for longer periods of time at
90 °C, the isomeric 1,3-diene 10 was isolated instead, in similar
yield (Scheme 2).
The bicyclic allene 9 is produced from 5 by anti-Markovnikov
addition of (Me3Si)3SiÅ to the terminal alkene bond in 5, leading
to the secondary radical centre 6, which then undergoes an intra-
molecular cyclisation into the allenecyclopropane group leading
to the strained tricyclic vinyl radical species 7. Fragmentation of
the radical species 7, accompanied by cleavage of the cyclopropane
ring, regenerates the allene unit and leads to the tertiary radical
centre 8. The radical centre 8 is then quenched by HÅ from its
In order to explore the scope for cyclisations involving carbon-
centred radicals and allenecyclopropanes, we first decided to syn-
* Corresponding author.
E-mail address: GP@nottingham.ac.uk (G. Pattenden).
0040-4039/$ - see front matter Crown Copyright Ó 2009 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.03.024

3528
N. R. Jones, G. Pattenden / Tetrahedron Letters 50 (2009) 3527–3529
•
H
H
H
H
•
TTMSS, AIBN
•
•
Si(TMS)3
Δ
Toluene,
Si(TMS)3
•
•
Si(TMS)3
7
4
5
6
8
•
H•
AIBN
H
H
H
H
H
TBA F
THF
Si(TMS)3
Si(TMS)3
Δ
Toluene,
quench
H
9
10
11
Scheme 2. Synthesis, and mechanism of formation, of the bicyclic 1,3-diene 10.
concave face producing the cis ring-fused system 9. The major dia-
stereoisomer of 9 could be cleanly separated by chromatography.14
When either a mixture of the diastereoisomers of the allene 9, or
the separated diastereoisomer, was heated in toluene in the pres-
ence of a catalytic amount of AIBN, the same 1,3-diene 10 was pro-
duced,13 interestingly as a 1:1 mixture of rotamers, in 80% yield.
The 1,3-diene 10 was not obtained when the allene 9 was heated
alone in toluene. Presumably, the conversion is initiated by
HÅ-abstraction by AIBN from an allylic centre in 9, propagated by
an intermediate vinylic radical, and completed by a thermal 1,5-
H shift process. Molecular models show that the rotation about
the isobutenyl group in 10 is severely restricted by the proximate,
sterically demanding, –Si(SiMe3)3 group, which accounts for the
formation of the two rotamers of the substituted 1,3-diene. As ex-
pected, when the mixture of rotamers of 10 was desilylated, using
TBAF at 9 °C, a single isomer of the corresponding hydrocarbon 11
was obtained, in 71% yield.
ring, using the same synthetic steps that had been used to prepare
5. Subsequent treatment of 12 with TTMSS–AIBN in toluene at
90 °C for 24 h, led to a 3:2 mixture of rotamers of the anticipated
bicyclic 1,3-diene 13 in 62% yield.14 Desilylation of 13, using
TBAF then gave the corresponding hydrocarbon 14 in 60% yield
(Scheme 3).
To explore the scope of the interesting radical cyclisations
5?10 and 12?14, we next synthesised the allenecyclopropane
homologues 15 of 12 containing one more, that is, 15a and one
less, that is, 15b, methylene groups in their terminal alkene side
chains. To our surprise when the allenecyclopropane 15a was trea-
ted with TTMSS–AIBN under the usual conditions the only product
isolated, in 80% yield, was the alkylsilane 16 resulting from hydro-
silylation of the terminal alkene unit in 15a. None of the 1,3-diene
product 17 resulting from the anticipated 7-exo radical cyclisation
was produced, even as a minor product. Equally surprising was the
observation that when the homologue 15b, containing one carbon
less than 12 in its side chain, was treated with TTMSS–AIBN, not
even the product of hydrosilylation was obtained. Instead, only
We next synthesised the analogous allenecyclopropane 12,
associated with a cyclohexane rather than with a cyclopentane
H
H
H
H
TTMSS, AIBN
•
TBAF
Si(TMS)3
, Δ
THF
Toluene
H
12
13
14
Scheme 3. Conversion of the allenecyclopropane 12 into the 1,3-diene 14 via 13.
H
H
•
•
Si(TMS)3
n
Si(TMS)3
15
16
17
a, n = 3
b, n = 1
H
H
H
H•
TTMSS, AIBN
, Δ
•
•
•
Toluene
•
I
H
•
18
20
21
19
Scheme 4. Conversion of the allenecyclopropane 15a into the alkylsilane 16 and the iodide 18 into enyne 21. Reaction of 15b led to recovery of starting material.

N. R. Jones, G. Pattenden / Tetrahedron Letters 50 (2009) 3527–3529
3529
6. Destabel, C.; Kilburn, J. D. J. Chem. Soc., Chem. Commun. 1992, 596; Destabel, C.;
Kilburn, J. D.; Knight, J. Tetrahedron Lett. 1993, 34, 3151; Santagostino, M.;
Kilburn, J. D. Tetrahedron Lett. 1994, 35, 8863; Destabel, C.; Kilburn, J. D.; Knight,
J. Tetrahedron Lett. 1994, 50, 11267; Destabel, C.; Kilburn, J. D.; Knight, J.
Tetrahedron Lett. 1994, 50, 11289; Pike, K. G.; Destabel, C.; Anson, M.; Kilburn, J.
D. Tetrahedron Lett. 1998, 39, 5877.
7. Cairns, P. M.; Crombie, L.; Pattenden, G. Tetrahedron Lett. 1982, 23, 1405.
8. Miles, M. F.; Pasto, D. J. J. Org. Chem. 1976, 41, 2068.
9. Chatgilialoglu, C.; Giese, B.; Kopping, B. J. Org. Chem. 1992, 57, 3994.
10. Eguchi, S.; Nagata, F.; Ohno, M.; Sasaki, T. J. Org. Chem. 1976, 41, 2408.
11. Lawson, E. N.; Nishiyama, T.; Woodhall, J. F.; Kitching, W. J. Org. Chem. 1989, 54,
2183.
starting material was recovered, even after prolonged reaction
times. Realistically, we were not expecting to see any product
resulting from a 4-exo radical cyclisation in 15b, but we were hop-
ing to observe other products resulting from competitive ring clo-
sure reactions within the allenecyclopropane ring in the starting
material. We felt that one of the reasons for the failure of 15b to
react with TTMSS–AIBN could be associated with the steric
demands of the bulky Si(SiMe3)3 group in the silane. In order to
interrogate this system further, we decided to generate a carbon-
centred radical from the corresponding iodide 18 and study its
chemistry. The iodide 18 was easily available from iodination of
the corresponding alcohol produced from 2-(1-cyclohexenyl)etha-
nol and 3-chloro-3-methyl-butyne, as described earlier. Interest-
ingly, treatment of the iodide 18 with TTMSS–AIBN in toluene at
90 °C for 2 h resulted in the formation of the enyne 21 in 43%
yield.13 We suggest that the enyne 21 is produced from 18 by
way of a rarely encountered 1,4-hydrogen abstraction process15
from the radical intermediate 19, leading to the cyclopropylmethyl
radical centre 20 which then undergoes fragmentation to 21
(Scheme 4).
12. Hennion, G. F.; Nelson, K. W. J. Am. Chem. Soc. 1957, 79, 2142.
13. All new compounds showed satisfactory spectroscopic and mass spectrometric
data. Selected data: For the allenecyclopropane 5: IR (film/cmÀ1
) mmax 2999,
2905, 2850, 2010, 1641; 1H NMR (CDCl3, 250 MHz) d (ppm): 5.90 (1H, ddt,
J = 17.1, 10.3, 5.2 Hz, CH2@CHCH2), 5.00 (1H, dd, J = 17.1, 2.0 Hz, CH2@CHCH2),
4.95 (1H, dd, J = 10.3, 2.0 Hz, CH2@CHCH2), 2.05–2.27 (2H, m, CH2@CHCH2),
1.75 (6H, s, C(CH3)2), 1.27–2.02 (9H, m, 4CH2 + cyclopropyl CH); 13C NMR
(CDCl3, 67.8 MHz) d (ppm): 187.3 (s), 138.8 (d), 114.0 (t), 96.3 (s), 86.1 (s), 36.5
(s), 33.5 (t), 33.2 (t), 31.9 (t), 30.4 (d), 29.3 (t), 22.1 (t), 21.4 (q), 21.2 (q); HRMS
m/z 188.1582 [M+], C14H20 requires 188.1565. Allene 9: IR (film/cmÀ1
2950, 2854, 2050, 1970; 13C NMR (CDCl3, 67.8 MHz)
) mmax
(ppm): (major
d
diastereoisomer) 196.8 (s), 110.5 (s), 98.9 (s), 44.0 (d), 41.5 (d), 41.4 (d), 32.5
(t), 30.5 (t), 27.3 (t), 27.1 (t), 22.4 (t), 21.5 (q), 21.3 (q), 12.7 (t), 2.1 (q); (minor
diastereoisomer) 197.5 (s), 109.0 (s), 95.8 (s), 44.7 (d), 40.3 (d), 35.8 (d), 35.1
(t), 31.6 (t), 29.7 (t), 28.6 (t), 23.0 (t), 22.0 (q), 21.8 (q), 12.1 (t), 1.9 (q); HRMS
m/z 363.2352 [M+, C23H48Si4– SiMe3], requires 363.2360. Bicyclic 1,3-diene 10:
In summary, a new and interesting carbon radical cyclisation
into an allenecyclopropane unit has been investigated which pro-
vides access to 5,6- and 6,6-ring-fused 1,3-dienes, for example,
11 and 14. Efforts to extend the scope of the method to the synthe-
sis of smaller and larger ring systems instead led to products, for
example, 21 and 16, resulting from alternative reaction pathways.
IR (CHCl3/cmÀ1 max 2949, 2850; 13C NMR (CDCl3, 67.8 MHz) d (ppm) (rotamer
) m
mixture): 139.7 (s), 133.9 (s), 132.7 (s), 131.7 (s), 131.6 (s), 128.7 (s), 126.8 (d),
125.4 (d), 44.5 (d), 41.6 (d), 39.0 (d), 37.0 (d), 34.0 (t), 33.4 (t), 32.0 (t), 31.3 (t),
30.0 (t), 29.6 (t), 27.3 (t), 25.2 (q), 25.1 (q), 23.9 (t), 23.7 (t), 19.8 (q), 19.6 (q),
14.5 (t), 1.4 (q), 1.2 (q); HRMS m/z 436.2816 [M+], C23H48Si4 requires 436.2833.
Bicyclic hydrocarbon 11: IR (CHCl3/cmÀ1 mmax 2917, 2854; 1H NMR (CDCl3,
)
250 MHz) d (ppm): 5.46 (1H, br s, CH@C(CH3)2), 2.04 (2H, m, allylic CH2), 1.85–
1.14 (10H, m, 4CH2 and 2CH), 1.76 (3H, d, J = 1.2 Hz, @CCH3), 1.53 (3H, s,
@CCH3), 1.51 (3H, s, @CCH3); 13C NMR (CDCl3, 67.8 MHz) d (ppm): 133.0 (s),
132.0 (s), 129.0 (s), 125.9 (d), 44.2 (d), 37.1 (d), 31.7 (t), 31.4 (t), 30.9 (t), 26.9
(t), 25.2 (q), 23.8 (t), 20.6 (q), 19.5 (q); HRMS m/z 190.1711 [M+], C14H22
Acknowledgements
We thank AstraZeneca (formerly Zeneca Specialities) for sup-
port (studentship to N.R.J.), and Dr. Alan Chorlton for his interest
in this work.
requires 190.1722. Alkylsilane 16: IR (film/cmÀ1 mmax 2927, 2852, 2005; 1H
)
NMR (CDCl3, 250 MHz) d (ppm): 1.78 (3H, s, CH3), 1.76 (3H, s, CH3), 1.90–1.20
(17H, m, 8CH2 and cyclopropyl CH), 0.74 (2H, m, CH2Si(TMS)3), 0.16 (27H, s,
3Si(CH3)3); 13C NMR (CDCl3, 67.8 MHz) d (ppm): 185.1 (s), 96.9 (s), 89.6 (s),
39.9 (t), 34.4 (t), 29.3 (t), 28.3 (t), 28.0 (s), 26.0 (t), 24.9 (d), 23.7 (t), 21.8 (t),
21.6 (t), 21.4 (q), 7.5 (t), 1.2 (q); HRMS m/z 464.3177 [M+], C25H52Si4 requires
References and notes
464.3146. Iodide 18: IR (CHCl3/cmÀ1 mmax 2932, 2853, 2008, 1602; 1H NMR
)
(CDCl3, 250 MHz) d (ppm): 3.15 (2H, m, CH2CH2I), 1.77 (6H, s, 2CH3), 2.20–1.10
(11H, m, 5CH2 and cyclopropyl CH); 13C NMR (CDCl3, 67.8 MHz) d (ppm): 186.0
(s), 99.0 (s), 88.0 (s), 44.4 (t), 28.9 (s), 27.5 (t), 24.8 (d), 23.4 (t), 21.4 (t), 21.3
(2 Â C, q), 21.2 (t), 2.2 (t); HRMS m/z 302.0474 [M+], C13H19I requires 302.0532.
1. For a comprehensive review of recent advances in the chemistry of allenes see:
Ma, S. Aldrichim. Acta 2007, 40, 91; See also: Ma, S. Chem. Rev. 2005, 105, 2829.
and references cited therein.
2. For some recent surveys see: Brandi, A.; Cicchi, S.; Cordero, F. M.; Goti, A. Chem.
Rev. 2003, 103, 1213.
Enyne 21: IR (CHCl3/cmÀ1 mmax 2932, 2862; 1H NMR (CDCl3, 250 MHz) d
)
(ppm): 5.43 (1H, m, C@CH), 2.95 (1H, br s, C„CCH), 2.55 (1H, m, CH(CH3)2),
2.15 (2H, m, C@CCH2), 2.00 (2H, m, C@CCHCH2), 1.76 (2H, m, CH2CH3), 1.55
(2H, m, CH2CH2CH2), 1.15 (6H, d, J = 6.8 Hz, CH(CH3)2), 1.03 (3H, t, J = 7.4 Hz,
CH2CH3); 13C NMR (CDCl3, 67.8 MHz) d (ppm): 139.1 (s), 120.4 (d), 86.0 (s),
81.9 (s), 30.4 (t), 30.1 (d), 28.6 (t), 25.1 (t), 23.4 (2 Â C, q), 20.6 (d), 20.0 (t), 12.3
(q); HRMS m/z 176.1552 [M+], C13H20 requires 176.1565.
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2005, 46, 4745.
4. Crandall, J. K.; Tindell, G. L.; Manmade, A. Tetrahedron Lett. 1982, 23, 3769;
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14. The 1H NMR spectra recorded for compounds 9, 10 and 13 could not be
analysed in detail due to the complicated, overlapping, resonances over the
region d 0.74–1.74 ppm.
15. cf. Journet, M.; Malacria, M. Tetrahedron Lett. 1992, 33, 1893; Huang, X. L.;
Dannenburg, J. J. J. Org. Chem. 1991, 56, 5421; For a discussion see: Fossey, J.;
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