Diallylation of 2,2-dialkylbenzodioxoles from TiCl4-mediated allylsilane reaction

Article abstract of DOI:10.1016/j.tetlet.2009.07.033

Reaction of aliphatic ketones with catechol afforded 2,2-dialkylbenzodioxoles. Treatment of these benzodioxoles with allyltrimethylsilane in the presence of titanium tetrachloride led to 4,4-dialkylhepta-1,6-dienes resulting from a diallylation process. R

Full text of DOI:10.1016/j.tetlet.2009.07.033

Tetrahedron Letters 50 (2009) 5238–5240
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Tetrahedron Letters
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Diallylation of 2,2-dialkylbenzodioxoles from TiCl4-mediated
allylsilane reaction
*
Nicolas Galy, Delphine Moraleda, Maurice Santelli
Laboratoire de Synthèse Organique, Equipe ‘Chirosciences’, UMR CNRS 6263, Université d’Aix-Marseille, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Reaction of aliphatic ketones with catechol afforded 2,2-dialkylbenzodioxoles. Treatment of these benzo-
dioxoles with allyltrimethylsilane in the presence of titanium tetrachloride led to 4,4-dialkylhepta-1,6-
dienes resulting from a diallylation process. Ring-closing metathesis gave rise to 4,4-dialkylcyclopentenes.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 19 June 2009
Accepted 1 July 2009
Available online 10 July 2009
Keywords:
Allylsilane
Benzodioxoles
Diallylation
Titanium tetrachloride
Nitromethane
Metathesis
1. Introduction
2. Results
The allylation of electrophilic reagents has gained in importance
since the development from the seventies of the allylsilane chem-
istry.1 In particular, allylation of acetals is well documented and
homoallyl alkyl ethers can be obtained in this case (Hosomi–Saku-
rai reaction).2 Ethylene ketals afforded homoallyl ether of glycol 2
(Scheme 1). These results suggested that the titanium glycolate
ether is not a sufficient leaving group to allow the substitution
reaction with a second allylsilane 1 reagent. Moreover, compound
2 does not lead to further manipulation due to the inactivity of the
aliphatic ether linkage.
We have prepared various benzodioxoles8 to confirm this
hypothesis. With 2,2-dialkyl-1,3-benzodioxoles 3, a clean diallyla-
tion occurred when allyltrimethylsilane (3 equiv) was added to the
complex benzodioxole–TiCl4.9 First, we studied the reaction of ben-
zodioxole 4 derived from the methylisopropylketone (Scheme 3).
Diallylation occurred in good yield (70%) and the structure of 5
was confirmed by a ring-closing metathesis reaction affording
cyclopentene 6.10,11
Diallylation occurred only with aryl aldehydes,3 cyclopropylke-
R1
R2
R1 R2
O
TiCl4
O
O
SiMe3
tones4 or bis-dioxanes.5
The use of more reactive catechol ketals (2,2-dialkylbenzodiox-
oles) 3 could increase the leaving group ability of the titanium spe-
cies and therefore enhance its reactivity.
+
OH
CH2Cl2
1
2
Scheme 1. Allylation of ethylene ketals with allylsilane 1.
Although the chemistry of 2,2-dialkylbenzodioxoles 3 will be
weakly developed, some results confirm the easy substitution of
the ether linkage. In particular, treatment of 3 with boron tribro-
mide exclusively led to gem-dibromo derivatives in excellent
yields,6 and the dichloroalane afforded reductive opening to give
phenolic ether (Scheme 2).7
R1
BBr3 / CH2Cl2
Br
Br
R1
R2
H
O
O
R2
R1
R2
OH
AlCl3 - LiAlH4
3
O
* Corresponding author. Tel.: +33 4 91288825; fax: +33 4 91289112.
E-mail address: m.santelli@univ-cezanne.fr (M. Santelli).
Scheme 2. Reactivity of 2,2-dialkylbenzodioxoles 3.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.033

N. Galy et al. / Tetrahedron Letters 50 (2009) 5238–5240
5239
Similar results are observed with benzodioxole 11 derived from
(R)-(+)-3-methylcyclohexanone.18 At low temperatures (ꢀ90 °C,
4 h) and in the presence of nitromethane, (1R,3R)-1-allyl-3-meth-
ylcyclohexanol 1319 and (1S,3R)-1-allyl-3-methylcyclohexanol 14
are the major products.20,21 In contrast, at ꢀ60 °C, the diallyl deriv-
ative 1222 was obtained in 55% yield (Scheme 6). The ring-closing
metathesis afforded the spiro alkene 15.23
camphorsulfonic
acid
HO
OH
O
O
+
toluene
Dean-Stark, 24 h
O
4, 60%
TiCl4
4 equiv
Cyclopentanone-derived benzodioxole 1624 afforded diallyl-
cyclopentane 1725 in a fair yield (Scheme 7).
SiMe3
+
4
5
CH2Cl2
The diallylation to give 1926 can be performed in the good yield
of 65% even with the strained norcamphor-derived benzodioxole
18.27 The corresponding spiro tricyclic hydrocarbon 2028 is easily
obtained by ring-closing metathesis (Scheme 8).
1, 3 equiv
−
90 ºC, 4 h
5, 70%
6, 60%
1st generation Grubb's catalyst (5 mol%)
CH2Cl2 (0.05M), rt, 5 h
3. Conclusion
Scheme 3. Synthesis of the methylisopropyl ketone-derived benzodioxole 4, its
diallylation followed by a ring-closing metathesis.
To the best of our knowledge, the titanium tetrachloride-medi-
ated diallylation with allylsilane of ketone-derived benzodioxole
constitutes the only one-step method. Gratefully, metathesis easily
gave rise to 4,4-dialkylcyclopentenes.
−
Cl( )
SiMe3
O
+
Me SiCl
3
5
2
O
TiCl4
O
Cl
O
Ti(IV)
Ti(IV)
O
TiCl4
2 equiv
+
OH
OH
Cl
O
1
+
+
+
O
O
7
MeNO2
CH2Cl2
3 equiv
Scheme 4. Allylsilane substitution of the titanium catecholate.
−
90 ºC, 4 h
11
12, 7%
13, 54%
14, 8%
TiCl4 (2 equiv)
+ MeNO2 (4 equiv)
1st generation Grubb's catalyst
The diallylation of 4 involved the formation of the titanium
complex which underwent an allylsilane substitution. The result-
ing complex titanium dichloride catecholate 7 could be more sta-
ble than the glycolate counterpart. Complex 7 is a stable well-
known compound (CAS number, 13523-46-1) (Scheme 4).12
Under the same experimental conditions, the diallylation of the
cyclohexanone-derived benzodioxole 8 gave the 1,1-diallylcyclo-
hexane 9 in a low yield (20%),13 and the formation of a by-product
10 (25% yield) resulting from a participation reaction (Scheme
5).14,15
−
60 ºC, 36 h, 55%
15
, 80%
Scheme 6. Diallylation of the 3-methylcyclohexanone-derived benzodioxole 11
followed by a ring-closing metathesis.
However, the yield of diallylcyclohexane 9 was increasing to
55% by the addition of nitromethane (4 M equiv), a higher temper-
ature (ꢀ75 °C) and with only 2 equiv of TiCl4 (allylcyclohexanol, 7%
yield, was also isolated). The presence of nitromethane reduced or
prevented the formation of by-products which result from a partic-
ipation reaction.16,17
TiCl4
2 equiv
+
1
O
O
MeNO2
CH2Cl2
3 equiv
16
17, 50%
−
−
75 to 45 ºC, 20 h
Scheme 7. Diallylation of the cyclopentanone-derived benzodioxole 16.
Me3Si
Cl
TiCl4
4 equiv
+
+
1
O
O
TiCl4
CH2Cl2
90 ºC, 4 h
3 equiv
2 equiv
O
−
9, 20%
10, 25%
+
1
MeNO2
CH2Cl2
8
TiCl4 (2 equiv)
+ MeNO2 (4 equiv)
O
3 equiv
−
75 to 0 ºC, 20 h
18
19, 65%
20, 80%
−
75 ºC, 20 h, 55%
−
)
Cl(
1st generation Grubb's catalyst
Me3Si
Me3Si
(+)
(+)
Scheme 8. Diallylation of the norcamphor-derived benzodioxole 18 followed by a
Scheme 5. Diallylation of the cyclohexanone-derived benzodioxole 8.
ring-closing metathesis.

5240
N. Galy et al. / Tetrahedron Letters 50 (2009) 5238–5240
1H); 13C NMR (75 MHz, CDCl3): d = 57.2 (d), 48.1 (t), 47.4 (t), 45.8 (t), 41.7 (t),
Acknowledgements
36.3 (s), 33.2 (t), 29.6 (d), 26.8 (t), 25.3 (t), 21.8 (t), 21.7 (t), ꢀ0.40 (q) (3C).
15. Monti, H.; Piras, P.; Afshari, M.; Faure, R. J. Mol. Struct. 1991, 242, 31–35.
16. (a) Tubul, A.; Santelli, M. Tetrahedron 1988, 44, 3975–3982; (b) Santelli, M.;
Tubul, A.; Morel-Fourrier, C. In Selectivities in Lewis Acid Promoted Reactions, D.
Schinzer, Ed.; NATO ASI Series C; Kluwer Academic: Dordrecht, 1989; Vol. 289,
pp 127–145.; (c) Pellissier, H.; Toupet, L.; Santelli, M. J. Org. Chem. 1994, 59,
1709–1713.
D.M. is grateful to the MEN for a grant and N.G. is grateful to the
CNRS and the Région Provence-Alpes-Côte d’Azur for a grant. This
work has been financially supported by the CNRS and the Ministère
de l’Education Nationale.
17. Titanium tetrachloride and nitromethane give
a 1:1 complex with the
nitromethane acting as a bidentate ligand, see: Norbury, A. H.; Sinha, A. I. P.
References and notes
J. Chem. Soc. (A) 1966, 1814–1816.
18. Compound 11: mp 76 °C (CH2Cl2–pentane), ½a D20
ꢁ
ꢀ31.4 (c 5.1, CHCl3). 1H NMR
1. (a) Weber, W. P. Silicon Reagents for Organic Synthesis, 1983; (b) Fleming, I.;
Dunoguès, J.; Smithers, R. Org. React. 1989, 37, 57–575; (c) Santelli, M.; Pons, J.
M. Lewis Acids and Selectivity in Organic Synthesis; CRC Press: Boca-Raton, 1995.;
(d) Yamamoto, H. Lewis Acids Reagents; Oxford Univ. Press: New York, 1999.
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3. Durand, A.-C.; Brahmi, L.; Lahrech, M.; Hacini, S.; Santelli, M. Synth. Commun.
2005, 35, 1825–1833.
4. Piras, P.; Afshari, M.; Léandri, G.; Monti, H. J. Organomet. Chem. 1990, 384, C9–
C11.
5. (a) Pellissier, H.; Santelli, M. J. Chem. Soc., Chem. Commun. 1995, 607–608; (b)
Mariet, N.; Ibrahim-Ouali, M.; Santelli, M. Tetrahedron Lett. 2003, 44, 5315–
5317.
6. (a) Napolitano, E.; Fiaschi, R.; Mastrorilli, E. Synthesis 1986, 122–125; (b)
Debroy, P.; Shukla, R.; Lindeman, S. V.; Rathore, R. J. Org. Chem. 2007, 72, 1765–
1769.
7. Saccomano, N. A.; Vinick, F. J.; Koe, B. K.; Nielsen, J. A.; Whalen, W. M.; Meltz,
M.; Phillips, D.; Thadieo, P. F.; Jung, S.; Chapin, D. S.; Lebel, L. A.; Russo, L. L.;
Helweg, D. A.; Johnson, J. L.; Ives, J. L.; Williams, I. H. J. Med. Chem. 1991, 34,
291–298.
8. (a) McCain, N. B.; Helliwell, M.; Hassan, B. M.; Hayhurst, D.; Li, H.; Thompson,
N.; Teat, S. J. Chem. Eur. J. 2007, 228–234; (b) Li, T.-S.; Li, L.-J.; Lu, B.; Yang, F. J.
Chem. Soc., Perkin Trans. 1 1998, 3561–3564; (c) Butkus, E.; Berg, U.; Stoncius,
A.; Rimkus, A. J. Chem. Soc., Perkin Trans. 2 1998, 2547–2551; (d) Cole, E. R.;
Crank, G.; Minh, H. T. H. Aust. J. Chem. 1980, 33, 675–680.
9. A three-necked flask equipped with a thermometer, a septum cap, a magnetic
stirring bar and argon outlet was charged with anhydrous CH2Cl2 (30 mL) and
anhydrous nitromethane (2.1 mL, 40 mmol). The solution was cooled to
ꢀ75 °C, and TiCl4 was added (2.2 mL, 20 mmol) followed by the dioxole
(10 mmol) in CH2Cl2 (10 mL) and then allylsilane (3.42 g, 30 mmol) in CH2Cl2
(20 mL). The completion of the reaction was followed by TLC. Then, the
solution was poured onto aqueous saturated NH4Cl solution and extracted with
CH2Cl2. The extract was washed until neutrality and possibly filtrated on
CeliteÒ. The solution was dried over MgSO4, and concentrated under vacuum.
The residue was purified by chromatography on silica gel, eluting with a
gradient of pentane–diethyl ether.
(300 MHz, CDCl3): d = 6.81 (br s, 4H), 2.18 (m, 2H), 1.85–1.65 (m, 6H), 1.42 (t,
J = 12.8 Hz, 1H), 1.2 (d, J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d = 147.5 (s),
147.4 (s), 121.0 (d) (2C), 118.6 (s), 108.6 (d), 108.5 (d), 43.4 (t), 34.7 (t), 33.4 (t),
30.0 (d), 22.6 (t), 22.1 (q).
19. (1R,3R)-1-Allyl-3-methylcyclohexanol (13): ½a D20
ꢁ
3.5 (c 3.85, CHCl3). 1H NMR
(300 MHz, CDCl3): d = 5.95 (ddt, J = 16.8, 10.4, 7.1 Hz, 1H), 5.16–5.03 (m, 2H),
2.49 (dt, J = 7.1, 1.0 Hz, 2H), 1.95–1.85 (m, 3H), 1.75–1.30 (m, 5H), 1.08 (½AB,
J = 12.4 Hz, 1H), 1.02 (½AB, J = 12.4 Hz, 1H), 0.87 (d, J = 6.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d = 133.5 (d), 118.6 (t), 75.1 (s), 50.9 (t), 47.8 (t), 39.0 (t), 34.5
(t), 28.1 (d), 22.2 (q), 22.1 (t).
20. (1S,3R)-1-Allyl-3-methylcyclohexanol (14): ½ ꢁ
a 2D0 3.7 (c 3.4, CHCl3). 1H NMR
(300 MHz, CDCl3): d = 5.85 (ddt, J = 16.9, 10.3, 7.5 Hz, 1H), 5.12–5.02 (m, 2H),
2.14 (d, J = 7.5 Hz, 2H), 1.70–1.50 (m, 5H), 1.25–1.10 (m, 2H), 1.0–0.72 (m, 2H),
0.84 (d, J = 6.45 Hz, 3H); 13C NMR (75 MHz, CDCl3): d = 133.8 (d), 118.7 (t), 71.5
(s), 49.0 (t), 45.8 (t), 36.7 (t), 34.8 (t), 27.9 (d), 22.7 (q), 21.6 (t).
21. Maruoka, K.; Itoh, T.; Yamamoto, H. J. Am. Chem. Soc. 1985, 107, 4573–4576.
22. (3R)-(+)-1,1-Diallyl-3-methylcyclohexane (12): ½a D20
ꢁ
6.0 (c 1.20, CHCl3). 1H NMR
(300 MHz, CDCl3): d = 5.94–5.68 (m, 2H), 5.06–4.94 (m, 4H), 2.11 (d, J = 7.4 Hz,
2H), 1.92 (d, J = 7.5 Hz, 2H), 1.70–1.42 (m, 6H), 1.1–0.7 (m, 3H), 0.84 (d,
J = 6.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d = 135.3 (d), 135.1 (d), 117.1 (t),
116.9 (t), 46.5 (t), 44.5 (t), 38.1 (t), 36.7 (s), 35.4 (t), 35.0 (t), 27.6 (d), 23.3 (q),
21.8 (t).
23. (7R)-(ꢀ)-7-Methylspiro[4.5]dec-2-ene (15): ½a D20
ꢁ
ꢀ3.6 (c 1.0, CHCl3). 1H NMR
(300 MHz, CDCl3): d = 5.60 (½AB, t, J = 5.86, 2.1 Hz, 1H), 5.55 (½AB, t, J = 5.86,
2.1 Hz, 1H), 2.15 (quint., J = 2.1 Hz, 2H), 2.10 (quint., J = 2.1 Hz, 2H), 1.57 (AB, m,
J = 16.0 Hz, 2H), 1.50–1.35 (m, 6H), 0.84 (d, J = 6.5 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d = 129.2 (d), 129.1 (d), 49.4 (t), 48.0 (t), 42.7 (t), 42.5 (s), 38.4 (t), 35.1
(t), 29.7 (d), 23.6 (t), 23.1 (q).
24. Compound 16: 1H NMR (300 MHz, CDCl3): d = 6.84–6.80 (m, 4H), 2.18–2.12 (m,
4H), 1.91–1.86 (m, 4H); 13C NMR (75 MHz, CDCl3): d = 147.5 (s), 127.2 (s),
121.1 (d), 108.3 (d), 37.2 (t), 23.3 (t).
25. 1,1-Diallylcyclopentane (17): 1H NMR (300 MHz, CDCl3): d = 5.82 (ddt, J = 15.8,
11.2, 7.4 Hz, 2H), 5.04 (br s, 2H), 5.02–4.98 (m, 2H), 2.06 (d, J = 7.5 Hz, 4H),
1.65–1.55 (m, 4H), 1.45–1.37 (m, 4H) ppm. 13C NMR (75 MHz, CDCl3): d = 136.2
(d), 116.8 (t), 45.2 (s), 43.6 (t) (2C), 36.9 (t) (2C), 24.9 (t) (2C).
26. 2,2-Diallylbicyclo[3.3.1]heptane (19): 1H NMR (300 MHz, CDCl3): d = 5.77 (ddt,
J = 17.0, 10.4, 7.2 Hz, 2H), 5.06–4.96 (m, 4H), 2.2–2.06 (m, 4H), 2.0 (q, J = 7.1 Hz,
1H), 1.7–1.22 (m, 6H), 1.2–1.02 (m, 2H), 0.85 (dd, J = 12.0, 2.6 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d = 136.6 (d), 135.6 (d), 116.9 (t), 116.6 (t), 44.6 (d), 43.6 (t),
43.1 (s), 42.7 (t), 40.3 (t), 37.7 (t), 37.7 (d), 28.7 (t), 24.6 (t).
10. (a) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446–452; (b)
Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18–29.
11. 4-Methyl-4-isopropylcyclopentene (6): 1H NMR (300 MHz, CDCl3): d = 5.00–4.96
(m, 2H), 1.32–1.25 (m, 4H), 0.87 (t, J = 6.9 Hz, 6H), 0.87 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3): d = 130.0 (d), 128.1 (d), 34.3 (t), 29.2 (d), 22.5 (t), 14.2 (q) (2C).
12. (a) Flamini, A.; Cole-Hamilton, D. J.; Wilkinson, G. J. Chem. Soc., Dalton 1978,
454–459; (b) Gómez-Carrera, A.; Mena, M.; Royo, P.; Serrano, R. J. Organomet.
Chem. 1986, 315, 329–335; (c) Funk, H.; Schlegel, A.; Zimmermann, K. J. Prakt.
Chem. 1956, 3, 320–332.
27. Compound 18: mp 37 °C (subl.). 1H NMR (300 MHz, CDCl3): d = 6.75 (m, 4H),
2.44 (d, J = 3.2 Hz), 2H), 2.37 (t, J = 3.8 Hz, 2H), 2.12 (dd, J = 4.4, 3.9 Hz, 1H), 2.07
(dd, J = 4.4, 3.0 Hz, 1H), 1.88–1.80 (m, H), 1.78–1.75 (m, H), 1.72 (d, J = 3.4 Hz,
1H), 1.63–1.55 (m, H), 1.50 (t, J = 4.15 Hz, 1H), 1.46 (t, J = 4.03 Hz, 1H), 1.42 (br
d, J = 2.5 Hz, 1H), 1.38 (quint., J = 1.6 Hz, 1H), 1.35 (quint., J = 1.7 Hz); 13C NMR
(75 MHz, CDCl3): d = 147.7 (s), 147.3 (s), 125.3 (s), 121.1 (d), 121.0 (d), 108.3
(d), 108.2 (d), 45.6 (d), 44.9 (t), 37.6 (t), 36.1 (d), 28.1 (t), 21.3 (t).
13. 1,1-Diallylcyclohexane (9): 1H NMR (300 MHz, CDCl3): d = 5.80 (ddt, J = 15.9,
11.3, 7.4 Hz, 2H), 5.05–4.94 (m, 4H), 2.01 (d, J = 7.4 Hz, 4H), 1.6–1.2 (m, 10H);
13C NMR (75 MHz, CDCl3): d = 135.2 (d), 117.0 (t), 41.9 (t), 35.9 (s), 35.4 (t), 26.5
(t), 21.8 (t).
28. Compound 20: 1H NMR (300 MHz, CDCl3): d = 5.67–5.58 (m, 2H), 2.47 (d, quint.
J = 16.1, 2.50 Hz, 1H), 2.32 (d, quint., J = 16.1, 2.25 Hz, 1H), 2.2–2.08 (m, 3H),
1.92 (br d, J = 3.6 Hz, 1H), 1.64–1.34 (m, 6H), 1.20–1.10 (m, 4H); 13C NMR
(75 MHz, CDCl3): d = 130.0 (d), 129.5 (d), 50.3 (t), 50.2 (t), 49.6 (s), 47.6 (d), 43.7
(t), 39.0 (t), 37.9 (t), 29.2 (t), 25.2 (t).
14. 2-Chloro-4-(trimethylsilylmethyl)spiro[5.5]undecane (8): 1H NMR (300 MHz,
CDCl3): d = 4.00 (tt, J = 12.15, 4.16 Hz, 1H), 2.2–2.08 (m, 2H), 1.7–1.6 (m, 2H),
1.42–1.30 (m, 6H), 1.25–1.08 (m, 4H), 0.65 (t, J = 13.4 H, 1H), 0.49 (t, J = 6.2 Hz,