Photocycloaddition of 4-(Alk-1-ynyl)-Substituted Coumarins and Thiocoumarins to 2,3-Dimethylbuta-1,3-diene

Article abstract of DOI:10.1002/hlca.201100112

On irradiation (350a nm) in the presence of 2,3-dimethylbuta-1,3-diene (8), 4-(alk-1-ynyl)coumarins 1 afford mixtures of cyclobuta- and cycloocta-annulated products 9 and 10, respectively. In contrast, the corresponding thiocoumarins 2 react with the same

Full text of DOI:10.1002/hlca.201100112

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Photocycloaddition of 4-(Alk-1-ynyl)-Substituted Coumarins and
Thiocoumarins to 2,3-Dimethylbuta-1,3-diene
by Inga Inhꢀlsen, Karin Chin, Maren Gçwert, and Paul Margaretha*
Department of Chemistry, University of Hamburg, Martin-Luther-King Platz 6, D-20146 Hamburg
(phone: þ 4940-428384316; fax: þ 4940-428385592; e-mail: Paul.Margaretha@chemie.uni-hamburg.de)
On irradiation (350 nm) in the presence of 2,3-dimethylbuta-1,3-diene (8), 4-(alk-1-ynyl)coumarins
1 afford mixtures of cyclobuta- and cycloocta-annulated products 9 and 10, respectively. In contrast, the
corresponding thiocoumarins 2 react with the same diene chemoselectively to give cyclohexa-annulated
products 11.
Introduction. – The thermal isomerization of 1,2-divinylcyclobutanes to either of
their diastereoisomers, to vinylcyclohexenes, or to cycloocta-1,5-dienes has been
intensively studied, and hypothetical octa-1,7-diene-3,6-diyl radicals (I) proposed as
common intermediates for the three possible cyclization modes [1][2]. In contrast, the
much less [3][4] investigated oct-1-en-7-yne-3,6-diyl biradicals (II) can formally
undergo four modes of cyclization, i.e., one 1,4-, two 1,6-, and one 1,8-cyclization, to
afford cyclobutanes, 4-alkynylcyclohexenes and 4-vinylcyclohexa-1,2-dienes, and cyclo-
octa-1,2,5-trienes, respectively (Scheme 1).
Scheme 1
We have recently observed competitive 1,4- vs. 1,8-cyclization of intermediates of
type II in photocycloadditions of 3-(alk-1-ynyl)cyclohept-2-enones to dienes, and
proposed that additional benzylic stabilization of the propargyl radical moiety of the
bis-delocalized 1,4-biradical would favor ꢀend-to-endꢁ, i.e., 1,8-cyclization [5]. We have
now extended these studies to alkynyl-substituted coumarins 1 and thiocoumarins 2,
readily available by Pd-mediated coupling of the corresponding 4-tosyloxy (TsO)
derivatives 3 and 4 (obtained from the 4-OH precursors 5 and 6, resp.) with 3,3-
dimethylbut-1-yne (7) (Scheme 2). Here, we report the results of these reactions.
ꢂ 2011 Verlag Helvetica Chimica Acta AG, Zꢃrich

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Scheme 2
Results. – Irradiation (350 nm) of coumarin (¼2H-1-benzopyran) 1a in the
presence of a 20-fold molar excess of 2,3-dimethylbuta-1,3-diene (8) afforded a 2 :1
mixture of products 9a and 10a. Similarly, irradiation of coumarin 1b gave a 2 :1
mixture of 9b and 10b. In contrast, both thiocoumarins (¼2H-1-benzothiopyrans) 2a
and 2b afforded dibenzothiopyrans 11a and 11b, respectively, as main products,
together with minor amounts of benzothiophenes 12a and 12b, respectively, resulting
from photodecarbonylation (Scheme 3). All products were separated and purified by
column chromatography, and fully characterized by 1D- and 2D-NMR spectroscopy.
Scheme 3
Discussion. – The essential point regarding the results presented above is certainly
the dissimilar behavior of excited heterocycles 1 and 2 towards diene 8, as reflected in

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the formation of cycloadducts 9 and 10 (from 1), and 11 (from 2), respectively. On one
hand, the behavior of excited 4-alkynylcoumarins 13 parallels that of 5-alkynylbenzo-
cyclohept-5-en-7-ones [5] in the reaction with 8 affording two products resulting from
either 1,4- or 1,8-cyclization of biradical 14. On the other hand, there appear two
differences: a) here, the intermediate cyclic allene 15 is not observed; and b) again
here, the 1,3-H shift originates in the a-position to the CO group. Whereas, for
benzocycloheptenones, the cyclooctatriene adduct represented the major (2 :1)
product, it is now not surprising that the less flexible six-membered lactone ring gives
a relatively higher amount (2 :1) of cyclobuta-annulated product. Nevertheless, from
this point of view, we expected that thiocoumarins 2 would again afford cycloocta-
annulated products preferentially due to the – now longer – CꢀS bonds in the
thiolactone ring. Our answer to the question ꢀwhy do thiocoumarins 2 behave
differently?ꢁ is for the moment purely speculative. It is well-known that organic
molecules containing (bivalent) S-atoms react with alkyl radicals to afford sulfuranyl
radicals, i.e., intermediates involving an expansion of the sulfur valence octet [6][7].
Similarly, intramolecular addition/elimination sequences proceeding via sulfuranyl-
alkyl biradicals have been proposed in light-induced rearrangements of S-heterocycles
[8]. If both benzo adducts 11 and benzothiophenes 12 are formed via a common
intermediate stemming from excited thiocoumarins 16, then sufuranyl-alkyl biradicals
17 are indeed highly plausible candidates, as addition to diene 8 would now occur via
the benzylic radical center with formation of biradical 18, whereas concomitant
decarbonylation would afford benzothiophenes 12. Finally, the selective 1,6-cyclization
of 17 to 11 is thermodynamically controlled, reflecting the higher strain in vinyl-
cyclobutanes as compared to that in cyclohexenes [9] (Scheme 4).
Experimental Part
1. General. Photolyses were conducted in a Rayonet RPR-100 photoreactor, equipped with 350-nm
lamps, and with solvents of spectrophotometric grade. Column chromatography (CC): silica gel 60 (SiO2;
Merck; 230 – 400 mesh). 1H- and 13C-NMR spectra (including 2D plots): Bruker WM-500; at 500.13 and
125.8 MHz, resp.; d in ppm rel. to Me4Si as internal standard, J in Hz. GC/EI-MS: Varian MAT-311A at
70 eV.
2. Starting Materials. The syntheses of compounds 1a and 2a have been reported in [10]. The 4-
hydroxy-substituted heterocycles 5b and 6b were synthesized according to [11], and converted into 1b
and 2b, resp., via the 4-TsO derivatives 3b and 4b, resp., according to [12].
4-(3,3-Dimethylbut-1-yn-1-yl)-6-methyl-2H-1-benzopyran (1b). Light-yellow solid. M.p. 103 – 1058.
1H-NMR (CDCl3): 7.57 (s, 1 H); 7.34 (d, J ¼ 7.2, 1 H); 7.20 (d, J ¼ 7.2, 1 H); 6.45 (s, 1 H); 2.43 (s, 3 H); 1.41
(s, 9 H). 13C-NMR (CDCl3): 159.7 (s); 149.9 (s); 136.7 (q); 133.1 (s); 131.0 (d); 130.2 (d); 126.7 (d); 126.1
(s); 117.3 (d); 111.2 (s); 74.2 (s); 30.5 (s); 30.4 (q); 21.2 (q). MS: 240 (100, Mþ).
4-(3,3-Dimethylbut-1-yn-1-yl)-6-methyl-2H-1-benzothiopyran-2-one (2b). Light-yellow solid. M.p.
110 – 1128. 1H-NMR (CDCl3): 8.00 (s, 1 H); 7.33 (s, 2 H); 6.72 (s, 1 H); 2.46 (s, 3 H); 1.41 (s, 9 H).
13C-NMR (CDCl3): 184.3 (s); 148.3 (s); 136.7 (s); 133.1 (s); 131.0 (d); 130.2 (d); 126.7 (d); 126.1 (s); 125.6
(d); 111.2 (s); 76.2 (s); 30.8 (s); 30.5 (q); 21.4 (q). MS: 256 (32, Mþ), 213 (100).
3. Photocycloadditions to 2,3-Dimethylbuta-1,3-diene. Ar-Degassed solns. of 1 or 2 (1 mmol) and 8
(20 mmol) in benzene (10 ml) were irradiated for 12 – 14 h up to 80 – 90% conversion (as monitored by
GC). After evaporation of the solvent and excess diene, the residue was subjected to CC.
3.1. Photocycloaddition of 1a. CC (pentane/Et2O 5 :1) afforded first 139 mg (45%) of (1S,2aS,8bR)-
8b-(3,3-dimethylbut-1-yn-1-yl)-1,2,2a,8b-tetrahydro-1-methyl-1-(prop-1-en-2-yl)-3H-cyclobuta[c]chro-
men-3-one (9a; Rf 0.35). Colorless oil. 1H-NMR (CDCl3): 7.11 – 6.98 (m, 4 H); 4.71 (s, 1 H); 4.50 (s, 1 H);

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Scheme 4
3.54 (dd, J ¼ 9.3, 9.3, 1 H); 2.53 (dd, J ¼ 9.3, 11.3, 1 H); 2.10 (dd, J ¼ 9.3, 11.3, 1 H); 1.59 (s, 3 H); 1.55 (s,
3 H); 1.22 (s, 9 H). 13C-NMR (CDCl3): 162.1 (s); 150.1 (s); 146.2 (s); 130.3 (d); 128.9 (d); 125.5 (d); 124.1
(d); 121.7 (s); 117.0 (d); 112.8 (t); 94.6 (s); 80.3 (s); 53.1 (s); 43.2 (s); 39.1 (d); 32.8 (t); 30.1 (s); 29.8 (q);
24.1 (q); 20.5 (q). EI-MS: 308 (41, Mþ); 226 (100).
The second fraction consisted of 77 mg (25%) of 11-(tert-butyl)-8,9-dimethyl-6H-cycloocta[c]chro-
1
men-6-one (10a; Rf 0.24). Viscous yellow oil. H-NMR (CDCl3): 7.48 – 7.43 (m, 2 H); 7.32 (d, J ¼ 8.2,
1 H); 6.54 (s, 1 H); 3.27 (s, 2 H); 2.67 (s, 2 H); 1.93 (s, 3 H); 1.79 (s, 3 H); 1.20 (s, 9 H). 13C-NMR (CDCl3):
160.9 (s); 152.5 (s); 151.0 (s); 147.6 (s); 129.4 (d); 124.8 (s); 124.5 (d); 122.8 (d); 119.4 (s); 118.3 (s); 130.4
(s); 116.7 (d); 115.6 (d); 36.2 (t); 35.3 (t); 32.9 (s); 28.7 (q); 22.3 (q); 22.1 (q). EI-MS: 308 (11, Mþ), 224
(100).
3.2. Photocycloaddition of 1b. CC (pentane/Et2O/toluene 25 :2 :2) afforded first 138 mg (43%) of
(1S,2aS,8bR)-8b-(3,3-dimethylbut-1-yn-1-yl)-1,2,2a,8b-tetrahydro-1,7-dimethyl-1-(prop-1-en-2-yl)-3H-
cyclobuta[c]chromen-3-one (9b; Rf 0.27). Colorless oil. 1H-NMR (CDCl3): 7.05 (s, 1 H); 7.02 (d, J ¼ 8.2,
1 H); 6.68 (d, J ¼ 8.2, 1 H); 4.71 (s, 1 H); 4.50 (s, 1 H); 3.51 (dd, J ¼ 9.3, 9.3, 1 H); 2.52 (dd, J ¼ 9.3, 11.1,
1 H); 2.29 (s, 3 H); 2.08 (dd, J ¼ 9.3, 11.1, 1 H); 1.58 (s, 3 H); 1.54 (s, 3 H); 1.23 (s, 9 H). 13C-NMR
(CDCl3): 165.7 (s); 148.1 (s); 146.3 (s); 133.3 (s); 130.3 (d); 129.3 (d); 121.1 (s); 116.5 (d); 112.8 (t); 94.5
(s); 78.9 (s); 53.0 (s); 45.5 (s); 38.9 (d); 32.8 (t); 30.9 (q); 29.6 (s); 23.8 (q); 20.6 (q); 20.1 (q). EI-MS: 322
(23, Mþ); 240 (100).

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The second fraction consisted of 81 mg (25%) of 11-(tert-butyl)-3,8,9-trimethyl-6H-cycloocta[c]-
chromen-6-one (10b; Rf 0.11). Viscous yellow oil. 1H-NMR (CDCl3): 7.29 – 7.19 (m, 2 H); 7.21 (s, 1 H);
6.52 (s, 1 H); 3.26 (s, 2 H); 2.66 (s, 2 H); 2.40 (s, 3 H); 1.93 (s, 3 H); 1.78 (s, 3 H); 1.21 (s, 9 H). 13C-NMR
(CDCl3): 162.1 (s); 153.5 (s); 149.9 (s); 148.6 (s); 134.5 (s); 133.2 (s); 131.3 (d); 125.5 (s); 125.3 (s); 124.9
(d); 120.2 (s); 117.0 (d); 116.3 (d); 39.7 (t); 36.2 (t); 31.1 (s); 29.5 (q); 23.2 (q); 22.9 (q); 20.6 (q). EI-MS:
322 (18, Mþ), 238 (100).
3.3. Photocycloaddition of 2a. CC (pentane/Et2O/toluene 20 :2 :1) afforded first 43 mg (20%) of 3-
(3,3-dimethylbut-1-yn-1-yl)-1-benzothiophene (12a; Rf 0.7). Colorless oil. 1H-NMR (CDCl3): 7.90 (d, J ¼
7.3, 1 H); 7.82 (d, J ¼ 7.5, 1 H); 7.48 (s, 1 H); 7.43 (dd, J ¼ 7.3, J ¼ 7.5, 1 H); 7.37 (dd, J ¼ 7.3, J ¼ 7.5, 1 H);
1.39 (s, 9 H). 13C-NMR (CDCl3): 139.3 (s); 139.0 (s); 128.0 (d); 124.9 (d); 124.4 (d); 122.6 (d); 122.4 (d);
119.1 (s); 101.1 (s); 79.1 (s); 31.1 (s); 28.0 (q). EI-MS: 214 (60, Mþ), 199 (100).
The second fraction consisted of 120 mg (37%) of (6aS,10aR)-10a-(3,3-Dimethylbut-1-yn-1-yl)-
6a,7,10,10a-tetrahydro-8,9-dimethyl-6H-benzo[c][1]benzothiopyran-6-one (11a; Rf 0.5). Yellow oil.
1H-NMR (CDCl3): 7.26 – 7.20 (m, 2 H); 7.17 – 7.14 (m, 2 H); 2.95 (dd, J ¼ 5.8, 5.8, 1 H); 2.78 (d, J ¼
17.3, 1 H); 2.35 – 2.27 (m, 2 H); 2.19 (d, J ¼ 17.3, 1 H); 1.62 (s, 3 H); 1.59 (s, 3 H); 1.19 (s, 9 H).
13C-NMR (CDCl3): 199.1 (s); 135.8 (s); 130.4 (s); 127.8 (d); 127.1 (d); 126.5 (d); 126.1 (d); 124.1 (s); 122.6
(s); 94.5 (s); 80.3 (s); 52.9 (d); 40.6 (s); 40.3 (t); 30.9 (q); 30.3 (t); 27.3 (s); 18.9 (q); 18.3 (q). EI-MS: 324
(40, Mþ), 214 (100).
3.4. Photocycloaddition of 2b. CC (pentane/Et2O/toluene 12 :2 :1) afforded first 13 mg (6%) of 3-
(3,3-dimethylbut-1-yn-1-yl)-5-methyl-1-benzothiophene (12b; Rf 0.27). Colorless oil. 1H-NMR (CDCl3):
7.70 (d, J ¼ 8.3, 1 H); 7.65 (d, J ¼ 8.3, 1 H); 7.54 (s, 1 H); 7.32 (s, 1 H); 2.51 (s, 3 H); 1.40 (s, 9 H). 13C-NMR
(CDCl3): 139.8 (s); 137.6 (s); 134.3 (s); 133.6 (s); 126.3 (d); 125.6 (d); 122.5 (d); 121.8 (d); 111.3 (s); 86.4
(s); 31.2 (q); 30.9 (q); 20.9 (q). EI-MS: 228 (56, Mþ), 213 (100).
The second fraction consisted of 125 mg (37%) of (6aS,10aR)-10a-(3,3-Dimethylbut-1-yn-1-yl)-
6a,7,10,10a-tetrahydro-2,8,9-trimethyl-6H-benzo[c][1]benzothiopyran-6-one (11b; Rf 0.11). Yellow oil.
1H-NMR (CDCl3): 7.07 (d, J ¼ 8.0, 1 H); 7.06 – 7.03 (m, 2 H); 2.92 (dd, J ¼ 5.7, 5.7, 1 H); 2.77 (d, J ¼ 17.4,
1 H); 2.42 – 2.32 (m, 2 H); 2.36 (s, 3 H); 2.15 (d, J ¼ 17.3, 1 H); 1.62 (s, 3 H); 1.60 (s, 3 H); 1.20 (s, 9 H).
13C-NMR (CDCl3): 199.4 (s); 136.8 (s); 135.7 (s); 130.5 (s); 128.3 (d); 128.0 (d); 126.4 (d); 123.9 (s); 122.6
(s); 92.6 (s); 80.5 (s); 52.5 (d); 40.4 (s); 40.3 (t); 30.6 (s); 29.9 (t); 27.4 (q); 20.9 (q); 18.3 (q); 17.6 (q). EI-
MS: 338 (32, Mþ), 228 (100).
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Received March 15, 2011