Thermodecarbonylation of α-substituted cycloalkanones: A convenient one-carbon ring contraction method

Article abstract of DOI:10.1016/j.tetlet.2004.08.149

A new and very convenient one-carbon ring contraction method is reported. Pyrolysis of α-substituted cycloalkanones at 600-650°C under flow conditions produces the ring contracted compounds under loss of carbon monoxide. Substrates varying in ring size and nature of the α-substituent have been investigated.

Full text of DOI:10.1016/j.tetlet.2004.08.149

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 7887–7889
Thermodecarbonylation of a-substituted cycloalkanones:
a convenient one-carbon ring contraction method
Georg Ruedi,* Matthias A. Oberli and Hans-Jurgen Hansen
¨
¨
Organisch-chemisches Institut der Universita¨t Zu¨rich, Winterthurerstrasse 190, CH-8057 Zu¨rich, Switzerland
Received 23 July 2004; accepted 24 August 2004
Available online 11 September 2004
Abstract—A new and very convenient one-carbon ring contraction method is reported. Pyrolysis of a-substituted cycloalkanones at
600–650ꢀC under flow conditions produces the ring contracted compounds under loss of carbon monoxide. Substrates varying in
ring size and nature of the a-substituent have been investigated.
ꢁ 2004 Elsevier Ltd. All rights reserved.
In recent years, much attention has been paid to the
photochemical reaction of cyclic ketones, which upon
irradiation undergo Norish type-I cleavage to give acy-
clic 1,x-enals by disproportionation.1 On the other
hand, it is well known that appropriate substitution in
2-position allows for ring expansion reactions.2 Thus,
2-cyano-2-methylcycloalkanones 1 are reported to yield
upon irradiation (n + 2) ring expanded N-acylketen-
imine derivatives 2,3 besides the principal products,
being a,b-unsaturated cyanoaldehydes 3 (Scheme 1).4
cyanocycloalkanones. The instigating question of the
present study was directed at whether 1 undergoes clean
a-cleavage upon FVP, and if this was the case, whether
recombination within the generated a-acyl x-cyanoalkyl
diradical A provides access to cyclic N-acylketenimines
of type 2.8
In a test run 2-cyano-2-methylcyclododecanone (1,
n = 12) was heated in a flow reactor system at 550ꢀC
to afford a 2:1 mixture of two compounds, which were
readily purified by column chromatography. To our sur-
prise, no traces of the expected (n + 2) ring expanded
ketenimine 2 and cyanoaldehyde 3, respectively, could
be detected. Instead, the major component turned out
to be (n À 1) ring contracted 1-methylcycloundecanecar-
bonitrile (4) (60%) while the minor component proved
In connection with our investigations aimed at the de-
sign and development of novel diradical-mediated ring
expansion5 and ring opening reactions6 by means of
flash vacuum pyrolysis (FVP),7 we were interested to ex-
plore the hitherto unknown thermal behavior of 2-
O
O
N
H
C
+
+
n+2
hν
O
O
CN
2
3
CN
hν /∆
C N
n
NC
1
A
CH3
∆
n–1
CN
4
5
Scheme 1. Photochemical reaction (reported) versus thermal gas-phase reaction (new) of 2-cyano-2-methylcycloalkanones 1.
Keywords: Ring contraction; Flash vacuum pyrolysis; Diradical intermediates; Hydrogen abstraction.
*
Corresponding author. Tel.: +41 1 635 42 48; fax: +41 1 635 68 53; e-mail: georg@access.unizh.ch
0040-4039/$ - see front matter ꢁ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.08.149

7888
G. Ru¨edi et al. / Tetrahedron Letters 45 (2004) 7887–7889
to be acrylonitrile 5 (30%) (Scheme 1).9 This finding
intimates a mechanism involving the expulsion of car-
bon monoxide within intermediate A. The resulting
decarbonylated a-alkyl x-cyanoalkyl diradical may
relax either way, giving 4 by recombination or 5 by
intramolecular disproportionation. In contrast to the
photochemical reaction, the formation of the thermody-
namically less favored terminal olefin 5 involves hydro-
gen abstraction from the more readily accessible methyl
group. It is noteworthy to state that no traces of the
decarbonylated form of 3 could be detected.
arises through initial b-cleavage and subsequent hydro-
gen abstraction within the resulting diradical species
C. Notwithstanding the high reactor temperatures the
spectroscopic data provided no evidence for the pres-
ence of the decarbonylated form of 8a. Furthermore,
the product ratio proved to be unaffected by varying
the reactor temperatures. However, temperatures above
700ꢀC adversely affected the overall yield due to increas-
ing amounts of low boiling fragmentation products.
To study the generality of this new ring contraction pro-
cedure, we examined the reaction of 2-cyanocycloalka-
nones, which differed in the ring size (Table 1). In
agreement with the results obtained with 6a, FVP of
the large-ring substrates 6b,c produced the correspond-
ing ring contracted nitriles 7b,c in good-to-excellent
yields (entries 2 and 3). Passing to the medium ring sub-
strate 6d provided the corresponding nitrile 7d in only
63% yield while the yields of the acyclic side products
appeared to be unaffected (entry 4). This trend was even
more pronounced in the case of the eight-membered 6e,
which upon FVP at 640ꢀC afforded equal amounts of
ring contracted and ring opened products (entry 5). In
remarkable contrast, 2-cyanocyclohexanone produced
only trace amounts of the desired cyclopentanecarbonit-
rile when heated in the range of 600–750ꢀC.
Given the ready availability of 2-cyanocycloalkanones10
and the promising performance of 1 in the above-men-
tioned thermal reaction, we next turned our interest to
the scope of this simple but preparatively very useful
ring contraction methodology. In order to suppress
competing hydrogen transfer reactions we subjected a
number of substrates lacking the additional methyl
group at C2 to FVP. As exemplified in the case of 2-
cyanocyclododecanone (6a), FVP at 600ꢀC proceeded
smoothly to afford the desired one-carbon ring con-
tracted nitrile 7a in good yield along with trace amounts
of (E/Z)-1,13-cyanoaldehyde 8a and 1,3-cyanoketone
9a. As indicated in Scheme 2, the latter presumably
In order to extend the general applicability of the ring
contraction method we extended our investigations to
substrates bearing different a-substituents. Thus, 2-
methoxy- and 2-trimethylsilyloxy ketones 6f and 6g,
respectively, reacted in a similar manner to give the cor-
responding ring contracted compounds as the sole prod-
ucts besides considerable amounts of recovered starting
material (entries 6 and 7). Fortunately, the conversion
rate of either reaction could be improved by resubjecting
the crude pyrolyzate to the same reaction conditions
(recycling procedure). For reasons of decreasing radical
stabilizing ability, FVP of 6h,i proceeded rather slug-
gishly (entries 8 and 9). However, the desired 11-mem-
bered products could be isolated in moderate yields
O
O
O
CN
CN
CN
α-cleavage
β-cleavage
12
B
6a
C
–CO,
recombination
H-transfer
H-transfer
O
O
H
CN
CN
CN
11
7a (88%)
8a (2%)
9a (4%)
Scheme 2.
Table 1. Effect of ring size and a-substitution on FVP-mediated ring contraction of cycloalkanones 6
O
O
O
R
H
R
R
R
FVP
+
+
n
n–1
6
7
8
9
Entry
n
R
Compound
Temperature (ꢀC)a
7 (%Yield)b
8 (%Yield)c
9 (%Yield)c
1
2
3
4
5
6
7
8
9
12
14
15
10
8
CN
CN
CN
a
b
c
d
e
f
600
62082
600
88
2
4
2
3
89
1
3
CN
62063
64024
61070
61058
65042
63051
2
8
4
b
CN
16b
d
12
12
12
12
OMe
OSiMe3
Me
(43)
(34)
00
00
00
0
d
g
h
i
d
(27)
(30)
d
CH2SiMe3
0
a Optimized temperatures.
b Yield of isolated material.
c Yield determined by GC.
d Via recycling procedure. Numbers in parentheses indicate the yields obtained after the first run.

G. Ru¨edi et al. / Tetrahedron Letters 45 (2004) 7887–7889
7889
Org. Lett. 2004, 6, 2989; (g) Ruedi, G.; Oberli, M. A.;
¨
Nagel, M.; Hansen, H. J. Org. Lett. 2004, 6,
when the recycling procedure was applied. Interestingly,
substrates 6f–i produced no open-chain disproportiona-
tion products.
3179.
6. (a) Ruedi, G.; Nagel, M.; Hansen, H.-J. Synlett 2003,
¨
1210; (b) Ruedi, G.; Nagel, M.; Hansen, H.-J. Org. Lett.
¨
2003, 5, 2691.
In summary, we have developed a convenient one-car-
bon ring contraction methodology based on thermal
decarbonylation. In the case of 2-cyanocycloalkanones,
the corresponding ring contracted nitriles are produced
in good-to-excellent yields, accompanied with trace
amounts of acyclic disproportionation products. This
procedure appears to be fairly general, as variations in
ring size and a-substitution are well tolerated. In parti-
cular, the ready availability of low-priced C-12 sub-
strates allows for the preparation of common but
otherwise difficult-to-achieve 11-membered carbocyclic
systems. Further studies are in progress.
7. For recent reviews on FVP, see: (a) McNab, H. Contemp.
Org. Synth. 1996, 3, 373; (b) Wiersum, U. E.; Jenneskens,
´
L. W. In Gas-Phase Reactions in Organic Synthesis; Valle,
Y., Ed.; Gordon and Breach: Amsterdam, 1997; pp 143–
194; (c) McNab, H. Aldrichim. Acta 2004, 37, 19.
8. To the best of our knowledge, the class of N-acylketeni-
mines has been limited to very few acyclic examples, cyclic
N-acylketenimines have not been reported thus far: (a)
Schweng, J.; Zbiral, E. Monatsh. Chem. 1976, 107, 537; (b)
Eckhardt, H. H.; Perst, H. Tetrahedron Lett. 1979, 20,
2125; (c) Berstermann, H.-M.; Harder, R.; Winter, H.-W.;
Wentrup, C. Angew. Chem., Int. Ed. 1980, 19, 564; (d)
Capuano, L.; Djokar, K. Chem. Ber. 1981, 114, 1976; (e)
Meier, S.; Wurthwein, E.-U. Chem. Ber. 1990, 123, 2339;
¨
Acknowledgement
(f) Adams, G. W.; Bowie, J. H.; Hayes, R. N. J. Chem.
Soc., Perkin Trans. 2 1991, 1809; (g) Sung, K. J. Chem.
Soc., Perkin Trans. 2 2000, 847; (h) Finnerty, J.; Mitschke,
U.; Wentrup, C. J. Org. Chem. 2002, 67, 1084.
This work was generously supported by the Swiss
National Science Foundation (SNF).
9. FVP reactions were performed in a flow reactor system
using a quartz tube (1m long) heated by a tube furnace
(1m with six different temperature zones, which can be
separately adjusted). After evacuation of the apparatus
with a high-vacuum oil pump (2–4 · 10À2 mbar), 2-cyano-
2-methylcyclododecanone (1, n = 12; 5.0g, 22.6mmol) was
directly distilled through the preheated reactor tube
(550ꢀC; estimated contact time <1s). A flow of nitrogen
gas was adjusted from 1.5L/h. At the end of the reactor
unit the isomerization products were collected in a trap,
which was cooled with liquid N2. After all of the starting
material had been distilled (ca. 45min), the apparatus was
vented and the frozen products were transferred to a bulb
using Et2O as solvent. The resulting solution was dried
over anhydrous MgSO4, filtered, and evaporated under
reduced pressure. Purification by flash chromatography on
silica gel (hexane/AcOEt 50:1) afforded 4 (2.62g, 60%) and
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1
5 (1.31g, 30%). Data of 4: IR (film): 2254, 2233cmÀ1; H
NMR (300MHz, CDCl3): d 1.86–1.76 (m, 2H), 1.70–1.61
(m, 2H), 1.59–1.32 (m, 16H), 1.30(s, 3H); 13C NMR
(75MHz, CDCl3): d 125.4, 36.0, 23.6, 26.8, 26.1, 25.6,
25.2, 21.6. Data of 5: IR (film): 2255, 2225cmÀ1; 1H NMR
(300MHz, CDCl3): d 5.82 (br s, 1H), 5.69 (br s, 1H), 2.24
(t, J = 7.4Hz, 2H), 1.55 (quint., J = 7.2Hz, 2H), 1.30–1.27
(m, 14H), 0.88 (t, J = 6.7Hz, 3H); 13C NMR (75MHz,
CDCl3): d 129.9, 123.5, 118.7, 34.6, 31.8, 29.4, 29.3, 29.2,
29.1, 28.6, 27.5, 22.6, 14.1.
´
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¨