Dzhemilev reaction for the synthesis of spiro[3.3]heptane and spiro[3.4]octanes

Article abstract of DOI:10.1016/j.tetlet.2007.10.065

For the first time cycloalumination of methylenecyclobutane with the aid of Et₃Al in the presence of Cp₂ZrCl₂ leading to 6-ethyl-6-aluminaspiro[3.4]octane has been realized. The latter, without isolation, was converted into spiro[3.3]heptane, 6-thiaspiro[3.4]octane and also spiro[3.4]octan-6-ol and 6-spiro[3.4]octyl formate with high yields and selectivity.

Full text of DOI:10.1016/j.tetlet.2007.10.065

Available online at www.sciencedirect.com
Tetrahedron Letters 48 (2007) 8583–8586
Dzhemilev reaction for the synthesis of spiro[3.3]heptane
and spiro[3.4]octanes
a,
b
a
*
Vladimir A. D’yakonov, Evgeniy Sh. Finkelshtein and Askhat G. Ibragimov
a
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya,
4
50075 Ufa, Russian Federation
A.V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, 29 Leninskii prospekt,
19991 Moscow, Russian Federation
b
1
Received 12 September 2007; revised 1 October 2007; accepted 12 October 2007
Available online 14 October 2007
Abstract—For the first time cycloalumination of methylenecyclobutane with the aid of Et Al in the presence of Cp ZrCl leading to
3
2
2
6
-ethyl-6-aluminaspiro[3.4]octane has been realized. The latter, without isolation, was converted into spiro[3.3]heptane, 6-thia-
spiro[3.4]octane and also spiro[3.4]octan-6-ol and 6-spiro[3.4]octyl formate with high yields and selectivity.
Ó 2007 Elsevier Ltd. All rights reserved.
Methods for the synthesis of strained hydrocarbons such
as spiro[3.3]heptanes and spiro[3.4]octanes are complex
and multistage. These approaches are frequently based
on the transformations of difficult to prepare reagents,
including spiro[3.3]heptane or spiro[3.4]octane frag-
to acyclic hydrocarbons with less active 1,1-disubstituted
double bonds could be implicated in the catalytic reac-
tion with Et Al. Furthermore, we assumed that such a
3
reaction, if successful, may afford aluminacyclopentanes
containing a spirane fragment, which can potentially be
used in the synthesis of spiro hetero(carbo)cycles, and
strained hydrocarbons with a cyclobutane fragment as
well.
1
ments. The above mentioned compounds are of great
interest both from the synthetic point of view and as
2
,3
monomers, which can find use as liquid-crystal systems
as well as for obtaining natural compounds and high-
4
energy components for rocket propellants.
We conducted investigations and established that the
reaction of methylenecyclobutane and Et Al (excess)
3
9
Herein, we propose a new approach to obtain spiro
compounds, which is based on the reaction of methylene-
cyclobutane with Et Al in the presence of Cp ZrCl , that
under previously optimized conditions (5 mol %
Cp ZrCl , 4 h, pentane) led to organoaluminium com-
2
2
pound (OAC) 1. Hydrolysis or deuterolysis converted
1 into 1-ethyl-1-methylcyclobutane 2 or 1-(2-deuterio-
3
2
2
is, the catalytic cycloalumination of unsaturated
5
–8
29
compounds (Dzhemilev reaction).
This reaction has
ethyl)-1-(deuteriomethyl)cyclobutane 3 in 92% yields
9
–17
been widely studied using as examples, a-olefins,
(Scheme 1).
1
8,19
20
21,22
1
,2-dienes,
norbornenes, [60]fullerene
leading to aluminacyclopentanes, alumina-
and acet-
2
3–28
13
ylenes
The structure of compound 1 was established by
C
cyclopentenes and aluminacyclopentadienes under mild
conditions. Efforts to utilize compounds containing a
NMR and mass spectrometry. The structures of 2 and
1
,1-disubstituted double bond failed. We envisaged that
Et
strained cyclic compounds with an activated methylene
bond, for example, methylenecyclobutane, in contrast
2
H O
+
3
3
Me
8
2
1
[
Cp ZrCl ]
4
2
2
+
7
5
CH D
2
-(EtH)
6
Al
Keywords: Catalysis; Organoaluminium compounds; Methylencyclo-
butane; Cycloalumination; Spiro[3.3]heptane; 6-Thiaspiro[3.4]octane;
Spiro[3.4]octane-6-ol.
AlEt3
1
+
CH D
9
D O
2
3
10
3
*
Corresponding author. Tel./fax: +7 347 2312750; e-mail addresses:
Ink@anrb.ru; DyakonovVA@rambler.ru
Scheme 1.
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.065

8584
V. A. D’yakonov et al. / Tetrahedron Letters 48 (2007) 8583–8586
Pd]
[
4
(88%)
Cl
SOCl2
5
6
(62%)
(74%)
S
1
. HCO Me, [Cu]
2
2
. H+
Al
Et
1
OFm
1
. HCO Me, [Cu]
2
7
8
(76%)
(81%)
2
. OH-
OH
1
. n -BuLi-[Cu]
. Cl
2
2
2
Scheme 2.
1
13
octane 5,31 6-spiro[3.4]octyl formate 6,32 spiro[3.4]-
3
were identified from H and C NMR spectra. The
1
3
33
C NMR spectrum of OAC 1 contained nine signals,
octan-6-ol 7 and 5-[1-(3-butenyl)cyclobutyl]pent-1-ene
3
4
with three signals of low intensity at 1.07 C(9), 6.61
C(5) and 17.58 C(7) ppm, for the carbons connected to
Al. The signals were broadened due to the quadrupole
relaxation on the Al (I = 5/2) nuclei. The signals at
4.88, 34.55 and 34.32 ppm were due to the C(1)–C(3)
carbons in the cyclobutane fragment. The signal at
4.22 ppm was due to the central carbon atom of the
spirane fragment. The remaining two signals at 8.27
and 38.91 ppm were due to the terminal C(10) carbon
atom of the ethyl fragment and to C(8) of the alumina-
cyclopentane fragment.
8
according to Scheme 2.
In conclusion, we have shown that methylenecyclo-
butane undergoes a catalytic cycloalumination reaction
with the aid of Et Al in the presence of Cp ZrCl to
2
7
1
3
2
2
afford 6-ethyl-6-aluminaspiro[3.4]octane in a yield of
more than 90%. The latter, without isolation, was con-
verted into spiro hetero(carbo)cyclic compounds and
hydrocarbons containing a cyclobutane fragment. Pres-
ently we are conducting investigations on the catalytic
cycloaluminations of more complex hydrocarbons for
application of this procedure to a wide range of com-
pounds containing an active methylene bond.
4
1
3
The C NMR spectra of compounds 2 and 3 were char-
acterized by the presence of six high-field signals. In the
spectrum of deuterated compound 3, up-field a-isotopic
shifts were observed for C(6) and C(7) (Dd = 0.25 and
0
.31, respectively) with triplet splitting (JCD = 19.1 and
Acknowledgements
JCD = 19.05 Hz for C(6) and C(7), respectively). The
results obtained indicate the formation of a 1,4-dideu-
terated hydrocarbon, so it is reasonable to assume the
presence of two Al–C bonds in starting OAC 1.
The work was financially supported by the Russian
Foundation for Basic Research (Grant No. 05-03-
32367) and by Grants of the RF President (MC-
1
039.2007.3 and Sci.Sh.-7470.2006.3).
The mass spectra showed the presence of the molecular
ions MS 98 (27%) and 100 (21%) for compounds 2 and
3
, respectively. The data obtained for OAC 1 were in full
References and notes
agreement with the proposed structure of 6-ethyl-6-
aluminaspiro[3.4]octane.
1
. Weinstein, B.; Fenselau, A. H.; Thoene, J. G. J. Chem.
Soc. 1965, 2281–2282.
. Chan, L. K. M.; Gemmell, P. A.; Gray, G. W.; Lacey, D.;
Toyne, K. J. Mol. Cryst. Liq. Cryst. 1989, 168, 229–245.
. Feuerbacher, N.; Vogtle, F.; Windscheidt, J.; Poetsch, E.;
Nieger, M. Synthesis 1999, 117–120.
For additional confirmation of the structure of OAC 1,
and also to demonstrate the potential of the developed
procedure in the synthesis of spiro[3.3]heptane and
spiro[3.4]octanes as well as hydrocarbons containing a
cyclobutane fragment, we have realized the transfor-
2
3
4. Koch, S. D. U.S. Patent 3,113,421, 1963; Chem. Abstr.
1964, 60, 9083d.
3
0
mations of 1 into spiro[3.3]heptane 4, 6-thiaspiro[3.4]-

V. A. D’yakonov et al. / Tetrahedron Letters 48 (2007) 8583–8586
8585
5
6
. Dzhemilev, U. M.; Ibragimov, A. G. Russ. Chem. Rev.
000, 69, 121–135.
. Dzhemilev, U. M.; Ibragimov, A. G. Russ. Chem. Bull.,
Int. Ed. 1998, 47, 786–794.
solution of HCl 2 (or DCl, 10–12% solution in D
The crude products 2 or 3, respectively, were extracted
2
O, 3).
2
with Et O or pentane, quenched with an 8–10% (aq)
2
solution of HCl or DCl. The layers were separated and the
7
8
. Dzhemilev, U. M. Tetrahedron 1995, 51, 4333–4346.
. Dzhemilev, U. M.; Ibragimov, A. G. J. Organomet. Chem.
2
aqueous phase was extracted with Et O or hexane. The
combined organic extracts were washed with water,
saturated aqueous NaHCO , dried (CaCl ), filtered and
1
994, 466, 1–4.
3
2
1
3
9
. Dzhemilev, U. M.; Ibragimov, A. G.; Zolotarev, A. P.;
Musluhov, R. R.; Tolstikov, G. A. Bull. Acad. Sci. USSR,
Div. Chem. Sci. 1989, 38, 194–195.
distilled. 6-Ethyl-6-aluminaspiro[3.4]octane (1). C NMR
(75 MHz, CDCl ): d 1.07, 6.61, 8.27, 14.88, 17.58, 34.32,
34.55, 38.91, 44.22. 1-Ethyl-1-methylcyclobutane (2). Bp
3
1
1
0. Dzhemilev, U. M.; Ibragimov, A. G.; Zolotarev, A. P.;
88–89 °C. H NMR (100 MHz, CDCl
J = 6.0 Hz, 3H, CH ), 1.04 (s, 3H, CH ), 1.48 (m, 2H,
CH ), 1.71 (m, 6H, CH ring); C NMR (75 MHz,
3
): d 0.81 (t,
Tolstikov, G. A. Bull. Acad. Sci. USSR, Div. Chem. Sci.
3
3
1
3
1
990, 39, 2570–2578.
2
2
1
1. Dzhemilev, U. M.; Ibragimov, A. G.; Morozov, A. B.;
Musluhov, R. R.; Tolstikov, G. A. Bull. Acad. Sci. USSR,
Div. Chem. Sci. 1991, 40, 1425–1427.
CDCl ): d 8.49, 14.84, 25.68, 32.84, 34.8, 39.1. MS (m/z,
%): 98 (27, M ), 70 (66), 69 (37), 56 (26), 55 (76), 42 (25),
3
+
41 (100). Anal. Calcd for C
7
H14: C, 85.63; H, 14.37.
1
2. Dzhemilev, U. M.; Ibragimov, A. G.; Morozov, A. B.
Mendeleev Commun. 1992, 26–28.
3. Dzhemilev, U. M.; Ibragimov, A. G.; Morozov, A. B.;
Musluhov, R. R.; Tolstikov, G. A. Bull. Russ. Acad. Sci.,
Div. Chem. Sci. 1992, 41, 1089–1093.
Found: C, 85.42; H, 14.29. Yield 92%. 1-(2-Deuterio-
1
ethyl)-1-(deuteriomethyl)cyclobutane (3).
(100 MHz, CDCl ): d 0.83 (t, J = 6.0 Hz, 2H, CH
1.02 (s, 2H, CH D), 1.45 (m, 2H, CH ), 1.76 (m, 6H, CH
NMR (75 MHz, CDCl3): 8.24 (t,
H
NMR
1
3
2
D),
2
2
2
1
3
ring);
C
d
1
4. Kondakov, D. Y.; Negishi, E. J. Am. Chem. Soc. 1996,
JCD = 19.1 Hz), 14.81, 25.37 (t, JCD = 19.05 Hz), 32.81,
34.76, 39.15. MS (m/z, %): 100 (21, M ), 72 (28), 71 (41),
+
1
18, 1577–1578.
1
5. Dzhemilev, U. M.; Ibragimov, A. G.; Khafizova, L. O.;
70 (34), 57 (30), 56 (48), 55 (20), 44 (69), 43 (27), 42 (63), 41
(64), 40 (100). Anal. Calcd for C H D : C, 83.92; H,
Rusakov, S. V.; Khalilov, L. M. Mendeleev Commun.
7
12
2
1
997, 198–199.
12.07; D, 4.01. Found: C, 83.79; H + D, 15.93. Yield 92%.
1
6. Negishi, E.; Montchamp, J.-L.; Anastasia, L.; Elizarov,
A.; Choueiry, D. Tetrahedron Lett. 1998, 39, 2503–2506.
7. Ibragimov, A. G.; Khafizova, L. O.; Satenov, E. G.;
Khalilov, L. M.; Yakovleva, L. G.; Rusakov, S. V.;
Dzhemilev, U. M. Russ. Chem. Bull., Int. Ed. 1999, 48,
30. Synthesis of spiro[3.3]heptane (4): To crude 1 at 0 °C were
2 3 2
added Et O (5 ml), Ph P (0.5 mmol), Pd(acac) (0.5 mmol)
1
and allyl chloride (30 mmol) dropwise. The reaction
mixture was allowed to warm to ꢀ20 °C and stirred for
8 h. The reaction was quenched with an 8–10% (aq)
solution of HCl. The layers were separated and the
1
574–1580.
1
1
2
2
8. Khafizova, L. O.; Ibragimov, A. G.; Gilfanova, G. N.;
Khalilov, L. M.; Dzhemilev, U. M. Russ. Chem. Bull., Int.
Ed. 2001, 50, 2188–2192.
9. Ibragimov, A. G.; Khafizova, L. O.; Gilfanova, G. N.;
Dzhemilev, U. M. Russ. Chem. Bull., Int. Ed. 2002, 51,
aqueous phase was extracted with Et O or pentane. The
combined organic extracts were washed with water,
2
saturated aqueous NaHCO
3
, dried (CaCl
2
), filtered and
1
distilled. Bp 96–97 °C. H NMR (100 MHz, CDCl ): d
3
1
3
0.92–2.54 (m, 12H, CH
CDCl ): d 16.34, 35.19, 44.21. MS, m/z: 96 (M ). Anal.
Calcd for C 12: C, 87.42; H, 12.58. Found: C, 87.21; H,
2
ring); C NMR (75 MHz,
+
2
255–2260.
3
0. Dzhemilev, U. M.; Ibragimov, A. G.; Zolotarev, A. P.;
Khalilov, L. M.; Musluhov, R. R. Bull. Russ. Acad. Sci.,
Div. Chem. Sci. 1992, 41, 300–305.
1. Dzhemilev, U. M.; Ibragimov, A. G.; Khafizova, L. O.;
Khalilov, L. M.; Vasil’ev, Yu. V.; Tuktarov, R. F.;
Tomilov, Yu. V.; Nefedov, I. M. Russ. Chem. Bull., Int.
Ed. 1999, 48, 567–569.
7
H
12.39. Yield 88%.
31. Synthesis of 6-thiaspiro[3.4]octane (5): To crude 1 at
À40 °C, thionyl chloride (30 mmol) was added dropwise,
the reaction stirred for 8 h and then treated with an 8–10%
(aq) solution of HCl. The crude was extracted with diethyl
ether or hexane and purified by distillation in vacuo. Bp
1
2
2. Dzhemilev, U. M.; Ibragimov, A. G.; Khafizova, L. O.;
Khalilov, L. M.; Vasil’ev, Yu. V.; Tomilov, Yu. V. Russ.
Chem. Bull., Int. Ed. 2001, 50, 297–299.
92–93 °C (20 Torr). H NMR (400 MHz, CDCl
3
): d 1.1–
1.23 (m, 2H, C(1)H , C(3)H ), 1.31–2.15 (m, 7H, C(1)H ,
a
a
b
C(2)H , C(3)H , C(5)H , C(8)H ), 2.21–3.24 (m, 3H,
2
b
a
2
1
3
2
2
2
2
3. Dzhemilev, U. M.; Ibragimov, A. G.; Zolotarev, A. P.
Mendeleev Commun. 1992, 135–136.
4. Negishi, E.; Kondakov, D. Y. Chem. Soc. Rev. 1996, 26,
C(5)H
b
, C(7)H
2
); C NMR (125 MHz, CDCl
3
): d 15.29,
30.60, 32.75, 40.95, 42.19, 42.64. MS (m/z, %): 128 (56,
+
M ), 100 (74), 99 (54), 85 (100), 79 (13), 72 (14), 67 (22), 65
4
17–426.
(10), 54 (11), 53 (12), 45 (18), 41 (15). Anal. Calcd for
C H12S: C, 65.56; H, 9.43; S, 25.01. Found: C, 65.34; H,
7
9.21; S, 24.89. Yield 62%.
5. Negishi, E.; Kondakov, D. Y.; Choueiry, D.; Kasai, K.;
Takahashi, T. J. Am. Chem. Soc. 1996, 118, 9577–9588.
6. Dzhemilev, U. M.; Ibragimov, A. G.; Ramazanov, I. R.;
Khalilov, L. M. Russ. Chem. Bull., Int. Ed. 1997, 46, 2150–
32. Synthesis of spiro[3.4]oct-6-yl ester formic acid (6): To
crude 1 at À15 °C were added CuCl (1 mmol) and
methylformate (30 mmol) dropwise. The reaction mixture
was allowed to warm to ꢀ20 °C and stirred for 8 h. The
reaction was quenched with an 8–10% (aq) solution of
HCl. The layers were separated and the aqueous phase
2
152.
2
2
2
7. Dzhemilev, U. M.; Ibragimov, A. G.; Ramazanov, I. R.;
Lukyanova, M. P.; Sharipova, A. Z. Russ. Chem. Bull.,
Int. Ed. 2001, 50, 484–487.
8. Dzhemilev, U. M.; Ibragimov, A. G.; Khafizova, L. O.;
Yakupova, L. R.; Khalilov, L. M. Russ. J. Org. Chem.
005, 41, 667–672.
9. Synthesis of compounds 1–3: A 50 mL glass reactor was
charged with Cp ZrCl (0.5 mmol) in dry pentane (3 mL),
was extracted with Et
extracts were washed with water and saturated aqueous
NaHCO , dried (CaCl ), filtered and concentrated in
2
O or hexane. The combined organic
2
3
2
vacuo. The products were isolated by column chromato-
graphy on silica gel (40–100 mesh grade) with hexane/
2
2
1
methylenecyclobutane (10 mmol) and AlEt3 (12 mmol)
under a dried argon atmosphere at 0 °C. The resulting
solution was raised to ambient temperature and stirred for
EtOAc = 10:1 as eluent. Bp 91–92 °C (10 Torr). H NMR
(400 MHz, CDCl
C(5)H , C(7)H
3
): d 1.35–1.71 (m, 5H, C(1)H
a
, C(3)H
a
,
,
a
a
, C(8)H
a
), 1.75–2.13 (m, 7H, C(1)H
b
4
h. The reaction was quenched with an 8–10% aqueous
C(2)H , C(3)H , C(5)H , C(7)H , C(8)H ), 4.37–4.42 (m,
2 b b b b

8586
V. A. D’yakonov et al. / Tetrahedron Letters 48 (2007) 8583–8586
1
3
CH–OFm), 6.68 (s, 1H, OAC(@O)H);
125 MHz, CDCl ): d 16.24, 31.35, 33.82, 33.89, 37.11,
9.55, 45.87, 76.02, 160.84. Anal. Calcd for C H O : C,
C
NMR
(100), 69 (92), 67 (24), 57 (20), 56 (83), 55 (50), 54 (15), 53
(21), 43 (30), 42 (14), 41 (52). Anal. Calcd for C 14O: C,
76.14; H, 11.18; O, 12.68. Found: C, 76.01; H, 11.13; O,
12.46.Yield 76%.
(
3
8
H
3
7
2
9
14
2
0.10; H, 9.15; O, 20.75. Found: C, 70.02; H, 9.07; O,
0.51.Yield 74%.
34. Synthesis of 5-[1-(3-butenyl)cyclobutyl]pent-1-ene (8): To
crude 1 at À78 °C was added n-BuLi (10 mmol) and the
reaction mixture was stirred for 15 min then CuCl
(1 mmol) and allyl chloride (30 mmol) were added drop-
wise. The reaction mixture was allowed to warm to
ꢀ20 °C and stirred for 6 h. The reaction was quenched
with an 8–10% (aq) solution of HCl. The layers were
3
3. Synthesis of spiro[3.4]octan-6-ol (7): To crude 1 at À15 °C
were added CuCl (1 mmol) and methylformate (30 mmol)
dropwise. The reaction mixture was allowed to warm to
ꢀ
20 °C and stirred for 8 h. The reaction was quenched
with a 15–20% (aq) solution of NaOH. The layers were
separated and the aqueous phase was extracted with Et
or hexane. The combined organic extracts were washed
with water and saturated aqueous NaHCO dried
CaCl ), filtered and concentrated in vacuo. The products
2
O
2
separated and the aqueous phase was extracted with Et O
or hexane. The combined organic extracts were washed
3
,
(
with water and saturated aqueous NaHCO , dried
2
3
were isolated by column chromatography on silica gel (40–
(CaCl
(8 Torr). H NMR (400 MHz, CDCl
6H, CH ), 1.41–2.23 (m, 10H, CH ACH@CH
4.75–5.25 (m, 4H, CH @CHA), 5.34–6.05 (m, 2H,
2
), filtered and distilled in vacuo.Bp 87–88 °C
1
1
9
1
1
00 mesh grade) with hexane/EtOAc = 10:1 as eluent. Bp
3
): d 1.11–1.39 (m,
, CH ring),
1
4–95 °C (10 Torr). H NMR (400 MHz, CDCl
3
): d 1.39–
2
2
2
2
.68 (m, 5H, C(1)H , C(3)H , C(5)H , C(7)H , C(8)H ),
a
a
a
a
a
2
1
3
.73–2.07 (m, 7H, C(1)H
b
, C(2)H
2
, C(3)H
b
, C(5)H
b
,
2 3
ACH@CH ); C NMR (125 MHz, CDCl ): d 15.16,
1
3
C(7)H
b
, C(8)H
b
), 4.23–4.30 (m, CH–OH); C NMR
23.34, 28.45, 31.81, 34.47, 37.86, 37.99, 41.41, 113.89,
+
(
4
125 MHz, CDCl ): d 16.74, 34.76, 34.81, 35.06, 37.87,
5.80, 49.56, 73.55. MS (m/z, %): 126 (2, M ), 125 (3), 111
114.38, 139.12, 139.68. MS, m/z: 178 (M ). Anal. Calcd
3
+
for C H : C, 87.56; H, 12.44. Found: C, 87.36; H, 12.18.
1
3
22
(
6), 108 (3), 98 (26), 97 (28), 83 (81), 80 (54), 79 (42), 70
Yield 81%.