Photocycloaddition reactions of 2-(alk-3-en-1-ynyl)cyclohex-2-enones

Article abstract of DOI:10.1002/hlca.200890240

The newly synthesized 2-(alk-3-en-1-ynyl)cyclohex-2-enones 4 undergo photodimerization (chemo- and regio-)selectively at the exocyclic C=C bond to give diastereoisomeric mixtures of 1,2-dialkynyl-1,2-dimethylcyclobutanes. On irradiation of 4 in the presen

Full text of DOI:10.1002/hlca.200890240

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Helvetica Chimica Acta – Vol. 91 (2008)
Photocycloaddition Reactions of 2-(Alk-3-en-1-ynyl)cyclohex-2-enones
by Janne Mçbius and Paul Margaretha*
Chemistry Department, University of Hamburg, Martin-Luther-King Platz 6, D-20146 Hamburg
(phone: þ 4940428384316; fax: þ 4940428385592;
e-mail: Paul.Margaretha@chemie.uni-hamburg.de)
The newly synthesized 2-(alk-3-en-1-ynyl)cyclohex-2-enones 4 undergo photodimerization (chemo-
and regio-)selectively at the exocyclic C¼C bond to give diastereoisomeric mixtures of 1,2-dialkynyl-1,2-
dimethylcyclobutanes. On irradiation of 4 in the presence of 2-chloroacrylonitrile, cyclobutane
formation occurs again (chemo- and regio-)selectively at the exocyclic C¼C bond to afford
diastereoisomeric mixtures of 2-alkynyl-1-chloro-2-methylcyclobutanecarbonitriles. Similarly, com-
pounds 4 undergo photoaddition to 2,3-dimethylbuta-1,3-diene exclusively at the exocyclic C¼C bond
to afford mixtures of [2 þ 2] and [4 þ 2] cycloadducts.
1. Introduction. – Quite recently, we have reported [1] that the (photo)reactivity of
3-alkynylcyclohex-2-enones was completely altered by extending the conjugation of the
side chain at C(3) by an additional C¼C bond. Indeed, we observed that 5,5-dimethyl-
3-(3-methylbut-3-en-1-ynyl)cyclohex-2-enone (1) a) undergoes photocyclodimeriza-
tion selectively at this – additional – exocyclic C¼C bond to afford 2, and b), in the
presence of 2,3-dimethylbuta-1,3-diene, affords a novel [6 þ 4] photocycloadduct 3
containing a buta-1,2,3-triene moiety (Scheme 1). We have now synthesized the two
cyclohex-2-enones 4a and 4b bearing the same alkynenyl side chain at C(2) and
investigated their photochemical behavior.
Scheme 1
ꢀ 2008 Verlag Helvetica Chimica Acta AG, Zꢁrich

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2. Results. – 2-(Alk-3-en-1-ynyl)cyclohex-2-enones 4a and 4b were obtained from 2-
iodocyclohex-2-enones 5a and 5b via a Sonogashira-type coupling [2] with 2-methylbut-
1-en-3-yne in 28 and 61% yield, respectively (Scheme 2).
Scheme 2
Irradiation (350 nm) of a 0.5m solution of 4a in benzene affords a 2.5 :1 mixture of
diastereoisomeric 1,1,2,2-tetrasubstituted cyclobutanes 6a and 7a, respectively. Under
similar conditions, 4b affords only the trans-diastereoisomer 6b. On irradiation in the
presence of a 20-fold molar excess of 2-chloroacrylonitrile, both cyclohexenones 4
afford a – roughly – 1:1 diastereoisomeric mixture of 2-alkynyl-1-chloro-2-methyl-
cyclobutane-1-carbonitriles 8 and 9, respectively. On irradiation in the presence of
excess 2,3-dimethylbuta-1,3-diene, again both cyclohexenones 4 behave alike, affording
– roughly – 4 :3 mixtures of the trans-1,1,2,2-tetraalkylcyclobutane 10 and the (formal)
[4 þ 2] cycloadduct 11, respectively (Scheme 3). The conversion of both cyclohex-
enones 4 to products in all these experiments – as monitored by 1H-NMR – is
significantly slower than that of 1 in the corresponding reactions, and competing
(photo)destruction of the primarily formed products begins at a much earlier stage,
generally limiting the conversion of 4 to ꢀ 50%.
3. Discussion. – Under photodimerization conditions, i.e., irradiation of 0.5m
solutions, cyclohexenones 4 behave very similarly to 1 by reacting almost exclusively
at the exocyclic C¼C bond. The assignment of the trans-configuration to the major-
diastereoisomer 6 was based on the analysis of the vicinal coupling constants of the
AA’XX’ pattern of the two adjacent CH2 groups in the cyclobutane ring [1] and the
chemical shifts of the Me groups in the 13C-NMR spectra, in which the Me C-atoms of
the trans-diastereoisomer resonated at lower field by ca. 5 ppm [3]. Interestingly, 1
gave a 1:1 mixture of diastereoisomers, whereas 4 afforded distinctly higher amounts of
the trans-isomer 6.
The differentiation between cyclobutanecarbonitriles 8 and 9 is straightforward
1
from their H-NMR spectra, as the four H-atoms of the adjacent CH2 groups exhibit
first order signals (and coupling constants). The relative configuration of the Me group
at C(2) was deduced from NOE analysis and that of the Cl-atom at C(1) from the fact
that a vicinal H-atom trans to the Cl-atom was shifted to lower field as compared to the
corresponding cis-oriented H-atom [4][5] . In contrast, the trans-alignment of the
(vicinal) alkynyl and alkenyl groups on the cyclobutane ring in 10 was based on the
NOE analysis of the angular Me groups and the correspondingly adjacent H-atoms, as

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Scheme 3
here the vicinal coupling constants for the CH2 H-atoms cannot be determined due to
conformational changes in the four-membered ring occurring on the NMR-time scale.
Regarding the reaction with 2-chloroacrylonitrile, excited 1 and 4 exhibited a
distinctly different behavior, as only the latter compounds cleanly underwent cyclo-
addition to the unsaturated nitrile, while no such reaction was observed for 1. As for the
reaction with 2,3-dimethylbuta-1,3-diene, both excited 1 and 4 underwent primary
binding between the exocyclic (olefinic) CH2 group of the enone and a diene CH2 C-
atom to afford biradicals 12 and 13, respectively. The fact that 12 then underwent a
novel and unprecedented 1,10-cyclization [1], whereas 13 reacted further via – the
expected – 1,4- and 1,6-cyclization paths is most probably due to the different position
of the acyl substituent in the intermediate pentynenyl radical moiety. Whereas in 12
delocalization extends to the C-atom adjacent to the C¼O group, and thus facilitates
the 1,10-ring closure, this is not the case for – cross-conjugated – intermediate 13
(Scheme 4). In this context, the different behavior of 1 and 4 parallels that of carbonyl-
substituted hexadienes [6], where 2-acylhexa-1,5-dienes were found to cyclize much

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more sluggishly, i.e., with quantum yields by a magnitude lower than the corresponding
1-acylhexa-1,5-dienes.
Scheme 4
Experimental Part
1. General. Photolyses were conducted in a Rayonet RPR-100 photoreactor equipped with 350-nm
lamps and solvents of spectrophotometric grade. Column chromatography (CC): silica gel 60 (Merck;
230 – 400 mesh). 1H- and 13C-NMR spectra (including 2D plots): in CDCl3 as solvent, Bruker WM 500; at
500.13 and 125.8 MHz, resp., d in ppm, J in Hz. GC/EI-MS: at 70 eV. The starting materials, 2-
iodocyclohex-2-enones 5a and 5b, were synthesized according to [7]. Coupling of 5a and 5b with 2-
methylbut-1-en-3-yne was performed according to [2].
2. Starting Materials. 5,5-Dimethyl-2-(3-methylbut-3-en-1-ynyl)cyclohex-2-enone (4a) was obtained
in 28% yield as yellow oil after purification by CC (SiO2; AcOEt/hexane 1:6). 1H-NMR: 7.13 (t, J ¼ 4.5);
5.38, 5.28 (br. s); 2.36 (s, 2 H); 2.35 (d, J ¼ 4.5, 2 H); 1.95 (br. s, 3 H); 1.06 (s, 6 H). 13C-NMR: 195.7 (s);
151.7 (d); 126.5 (s); 124.5 (s); 122.6 (t); 93.5 (s); 82.6 (s); 51.7 (t); 40.5 (t); 33.9 (s); 28.3 (q); 23.4 (q).
EI-MS: 188 (93, Mþ), 104 (100).
4,4-Dimethyl-2-(3-methylbut-3-en-1-ynyl)cyclohex-2-enone (4b) was obtained in 61% yield as light
orange oil after purification by CC (SiO2, AcOEt/hexane 1:6). 1H-NMR: 6.95 (s); 5.37, 5.27 (br. s); 2.53
(t, J ¼ 6.8, 2 H); 1.94 (br. s, 3 H); 1.88 (t, J ¼ 6.8, 2 H); 1.20 (s, 6 H). 13C-NMR: 195.8 (s); 163.2 (d); 126.9
(s); 126.5 (s); 123.0 (t); 93.5 (s); 82.6 (s); 36.0 (t); 34.7 (t); 34.1 (s); 28.1 (q); 23.7 (q). EI-MS: 188 (100,
Mþ).
3. Photochemical Reactions. Ar-Degassed solns. of 4a or 4b were irradiated (concentration, solvent,
added reaction partner, duration, degree of conversion, and workup as described).
3.1. Photodimerization of 4a. A soln. of 4a (188 mg, 1 mmol) in benzene (2 ml) was irradiated for
40 h up to 40% conversion; dimers 6a and 7a were formed in a 2.5 :1 ratio. A first CC (SiO2; pentane/
Et2O 1:1) afforded first 4a (63 mg) and then the mixture 6a/7a. This fraction was subjected to a second
CC (SiO2; pentane/Et2O 2 :1) to afford first 38 mg (10%) of trans-2,2’-[(1,2-Dimethylcyclobutane-1,2-
diyl)diethyne-2,1-diyl]bis(5,5-dimethylcyclohex-2-en-1-one) (6a). Light yellow oil. Rf 0.29. 1H-NMR:
7.06 (t, J ¼ 4.4, 2 H); 2.32 (s, 4 H); 2.31 (d, J ¼ 4.4, 4 H); 2.30, 1.92 (AA’XX’, JAX ¼ 11.0, JAA’ ¼ JXX’ ¼ 7.0,
JAX’ ¼ 10.0, 4 H); 1.57 (s, 6 H); 1.05 (s, 12 H). 13C-NMR: 195.9 (s); 150.5 (d); 124.4 (s); 96.8 (s); 77.8 (s);
51.9 (t); 40.6 (t); 39.7 (s); 33.8 (t); 31.9 (t); 27.9 (q); 25.3 (q). Compound 6a was followed by 9 mg (3%) of
cis-2,2’[(1,2-dimethylcyclobutane-1,2-diyl)diethyne-2,1-diyl]bis(5,5-dimethylcyclohex-2-en-1-one (7a).
1
Light yellow oil. Rf 0.14. H-NMR: 7.14 (t, J ¼ 4.4, 2 H); 2.36, 1.91 (AA’XX’, JAX ¼ 11.0, JAA’ ¼ JXX’
¼

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Helvetica Chimica Acta – Vol. 91 (2008)
10.0, JAX’ ¼ 7.0, 4 H); 2.32 (s, 4 H); 2.31 (d, J ¼ 4.4, 4 H); 1.36 (s, 6 H); 1.04 (s, 12 H). 13C-NMR: 196.0 (s);
51.3 (d); 124.6 (s); 98.3 (s); 77.0 (s); 51.8 (t); 40.5 (t); 39.7 (s); 34.0 (t); 32.2 (t); 28.3 (q); 21.8 (q).
3.2 . Photodimerization of 4b. A soln. of 4b (188 mg, 1 mmol) in benzene (2 ml) was irradiated for
40 h up to 28% conversion: dimer 6b was formed selectively. CC (SiO2; pentane/Et2O 1:1) afforded first
4b (78 mg) and then 54 mg (14%) of trans-2,2’-[(1,2-dimethylcyclobutane-1,2-diyl)diethyne-2,1-diyl]-
bis(4,4-dimethylcyclohex-2-en-1-one) (6b). Light yellow oil. Rf 0.25. 1H-NMR: 6.87 (s, 2 H); 2.50 (t, J ¼
6.7, 4 H); 2.30, 1.92 (AA’XX’, JAX ¼ 11.0, JAA’ ¼ JXX’ ¼ 7.0, JAX’ ¼ 10.0, 4 H); 1.86 (t, J ¼ 6.7, 4 H); 1.57 (s,
6 H); 1.18 (s, 12 H). 13C-NMR: 195.6 (s); 161.8 (d); 122.7 (s); 96.7 (s); 78.0 (s); 39.8 (s); 35.7 (t); 34.3 (t);
33.8 (s); 32.2 (t); 27.8 (q); 25.2 (q).
3.3 Photocycloaddition of 4a to 2-Chloroacrylonitrile. A soln. of 4a (94 mg, 0.5 mmol) and 2-
chloroacrylonitrile (870 mg, 10 mmol) in benzene (5 ml) was irradiated for 17 h up to 65% conversion.
The 1:1 mixture was subjected to CC (SiO2; pentane/Et2O 4 :3) to afford first 8 mg (7%) of cis-1-chloro-
2-methyl-2-[(4,4-dimethyl-6-oxocyclohex-1-enyl)ethynyl]cyclobutane-1-carbonitrile (8a). Rf 0.29. Color-
less oil. 1H-NMR: 7.18 (t, J ¼ 4.4); 2.82 (ddd, J ¼ 5.2, 8.4, 12.4); 2.68 (ddd, J ¼7.9, 9.5, 12.5); 2.58 (ddd, J ¼
5.2, 9.5, 11.1); 2.35 (s, 2 H); 2.34 (d, J ¼ 4.4, 2 H); 2.16 (ddd, J ¼7.9, 8.4, 11.1); 1.68 (s, 3 H); 1.07 (s, 6 H).
13C-NMR: 195.5 (s); 152.8 (d); 123.6 (s); 117.7 (CN); 92.0 (s); 81.0 (s); 57.3 (s); 52.0 (t); 46.0 (s); 40.2 (t);
34.8 (t); 33.8 (s); 32.0 (t); 28.3 (q); 24.3 (q). Compound 8a was followed by 9 mg (7%) of trans-1-chloro-
2-methyl-2-[4,4-dimethyl-6-oxocyclohex-1-enyl)ethynyl]cyclobutane-1-carbonitrile (9a). Rf 0.22. Color-
less oil. 1H-NMR: 7.27 (t, J ¼ 4.6); 2.90 (ddd, J ¼ 6.7, 8.5, 12.6); 2.55 (m, 1 H); 2.50 (m, 1 H); 2.35 (s, 2 H);
2.34 (d, J ¼ 4.6, 2 H); 2.21 (m, 1 H); 1.59 (s, 3 H); 1.06 (s, 6 H). 13C-NMR: 195.5 (s); 153.5 (d); 123.7 (s);
118.4 (CN); 92.3 (s); 81.0 (s); 59.0 (s); 51.6 (t); 43.6 (s); 40.5 (t); 34.6 (t); 33.8 (s); 31.6 (t); 28.3 (q); 23.1
(q).
3.4 Photocycloaddition of 4b to 2-Chloroacrylonitrile. A soln. of 4b (188 mg, 1.0 mmol) and 2-
chloroacrylonitrile (1740 mg, 20 mmol) in benzene (10 ml) was irradiated for 26 h up to 62% conversion.
The 1:1 mixture was subjected to CC (SiO2, pentane/Et2O 4 :3) to afford first 32 mg (12 %) of cis-1-
chloro-2-methyl-2-[(3,3-dimethyl-6-oxocyclohex-1-enyl)ethynyl]cyclobutane-1-carbonitrile (8b). Rf 0.26.
Colorless oil. 1H-NMR: 6.98 (s); 2.82 (ddd, J ¼ 5.2, 8.4, 12.4); 2.69 (ddd, J ¼ 8.1, 9.7, 12.4); 2.56 (ddd, J ¼
5.2, 9.7, 11.1); 2.52 (t, J ¼ 6.7, 2 H); 2.14 (ddd, J ¼ 8.1, 8.4, 11.1); 1.88 (t, J ¼ 6.7, 2 H); 1.68 (s, 3 H); 1.21 (s,
6 H). 13C-NMR: 195.2 (s); 163.5 (d); 122.0 (s); 117.7 (CN); 91.7 (s); 81.1 (s); 57.4 (s); 46.3 (s); 35.5 (t);
34.8 (t); 34.5 (s); 33.8 (t); 31.9 (t); 27.7 (q); 24.3 (q). Compound 8b was followed by 50 mg (20%) of trans-
1-chloro-2-methyl-2-[(3,3-dimethyl-6-oxocyclohex-1-enyl)ethynyl]cyclobutane-1-carbonitrile (9b). Rf
1
0.20. Colorless oil. H-NMR: 7.06 (s); 2.90 (ddd, J ¼ 4.9, 8.5, 12.5); 2.55 (ddd, J ¼ 9.1, 9.2, 12.5); 2.51 (t,
J ¼ 6.7, 2 H); 2.50 (m, 1 H); 2.21 (ddd, J ¼ 4.9, 9.2, 10.4); 1.87 (t, J ¼ 6.7, 2 H); 1.59 (s, 3 H); 1.20 (s, 6 H).
13C-NMR: 195.2 (s); 164.1 (d); 121.8 (s); 118.3 (CN); 92.0 (s); 81.0 (s); 59.0 (s); 43.9 (s); 35.5 (t); 34.8 (t);
34.5 (s); 34.3 (t); 33.8 (t); 31.6 (t); 27.7 (q); 23.2 (q).
3.5 Photocycloaddition of 4a to 2,3-Dimethylbuta-1,3-diene. A soln. of 4a (376 mg, 2.0 mmol) and
2,3-dimethylbuta-1,3-diene (3.28 g, 40 mmol) in benzene (20 ml) was irradiated for 100 h up to 65%
conversion. A first CC (SiO2; pentane/Et2O 4 :1) allowed the isolation of the 4 :3 mixture 10a/11a (Rf
0.25). This mixture was subjected to a further CC (SiO2; hexane/AcOEt 12 :1) to afford first 36.2 mg
(18%) of 5,5-dimethyl-2-{2-[trans-1,2-dimethyl-2-(1-methylethynyl)cyclobutyl]ethynyl}cyclohex-2-enone
(10a). Rf 0.29). Light yellow liquid. 1H-NMR: 7.03 (t, J ¼ 4.6); 4.80 (br. s); 4.63 (br. s); 2.33 (s, 2 H); 2.32
(d, J ¼ 4.6, 2 H); 2.30 (m, 1 H); 2.28 (m, 1 H); 1.68 (s, 3 H); 1.63 (m, 1 H); 1.52 (m, 1 H); 1.42 (s, 3 H);
1.26 (s, 3 H); 1.06 (s, 6 H). 13C-NMR: 195.3 (s); 150.3 (d); 150.2 (s); 124.2 (s); 109.5 (t); 98.2 (s); 77.4 (s);
51.8 (t); 50.2 (s); 40.4 (t); 37.4 (s); 34.0 (s); 30.4 (t); 28.4 (q); 27.3 (t); 24.4 (q); 23.1 (q); 18.8 (q).
Compound 10a was followed by 10 mg (5%) of 5,5-dimethyl-2-[2-(1,3,4-trimethylcyclohex-3-en-1-
yl)ethynyl]cyclohex-2-enone (11a). Rf 0.22. Colorless liquid. 1H-NMR: 7.00 (t, J ¼ 4.6); 2.33 (s, 2 H); 2.32
(d, J ¼ 4.6, 2 H); 2.10 (m, 2 H); 1.79 (m, 2 H); 1.62 (s, 3 H); 1.59 (s, 3 H); 1.50 (m, 2 H); 1.26 (s, 3 H); 1.04
(s, 6 H). 13C-NMR: 195.5 (s); 150.3 (d); 124.8 (s); 122.9 (s); 122.7 (s); 100.2 (s); 73.9 (s); 51.3 (t); 44.8 (s);
40.3 (t); 35.3 (t); 35.2 (t); 35.1 (t); 33.6 (s); 27.7 (q); 23.1 (q); 19.9 (q); 18.2 (q).
3.6 Photocycloaddition of 4b to 2,3-Dimethylbuta-1,3-diene. A soln. of 4b (282 mg, 1.5 mmol) and
2,3-dimethylbuta-1,3-diene (2.46 g, 30 mmol) in benzene (15 ml) was irradiated for 74 h up to 52%
conversion to afford mainly a 4 :3 mixture 10b /11b. CC (SiO2; pentane/Et2O 7:2) afforded first 25 mg
(7%) of 4,4-dimethyl-2-{2-[trans-1,2-dimethyl-2-(1-methylethynyl)cyclobutyl]ethynyl}cyclohex-2-enone

Helvetica Chimica Acta – Vol. 91 (2008)
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(10b). Rf 0.32. Light yellow liquid. 1H-NMR: 6.84 (s); 4.80 (br. s); 4.63 (br. s); 2.50 (t, J ¼ 6.8, 2 H); 2.30
(m, 1 H); 2.26 (m, 1 H); 1.86 (t, J ¼ 6.8, 2 H); 1.69 (s, 3 H); 1.63 (m, 1 H); 1.52 (m, 1 H); 1.43 (s, 3 H); 1.26
(s, 3 H); 1.18 (s, 6 H). 13C-NMR: 195.7 (s); 161.1 (d); 150.0 (s); 122.9 (s); 109.5 (d); 98.0 (s); 76.9 (s); 49.8
(s); 37.7 (s); 35.7 (t); 34.5 (t); 33.6 (s); 30.5 (t); 27.8 (q); 27.3 (t); 24.4 (q); 23.1 (q); 18.8 (q). Compound
10b was followed by 6 mg (2.2%) of 4,4-dimethyl-2-[2’-(1,3,4-trimethylcyclohex-3-en-1-yl)ethynyl]cyclo-
hex-2-enone (11b). Rf 0.28. Colorless liquid. 1H-NMR: 6.82 (s); 2.50 (t, J ¼ 6.6, 2 H); 2.10 (m, 2 H); 1.86
(t, J ¼ 6.6, 2 H); 1.78 (m, 2 H); 1.63 (s, 3 H); 1.59 (s, 3 H); 1.50 (m, 2 H); 1.26 (s, 3 H); 1.18 (s, 6 H).
13C-NMR: 195.5 (s); 161,3 (d); 124.8 (s); 122.9 (s); 122.7 (s); 100.2 (s); 73.9 (s); 44.8 (s); 35.4 (t); 35.3 (t);
35.2 (t); 35.1 (t); 34.5 (t); 33.6 (s); 27.3 (q); 23.1 (q); 19.9 (q); 18.2 (q).
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Received August 4, 2008