Synthesis of Functionally Substituted Bicyclo[4.2.1]nona-2,4-dienes and Bicyclo[4.2.1]nona-2,4,7-trienes by Cobalt(I)-catalyzed [6π + 2π] Cycloaddition of 2-Tropylcyclohexanone.

The [6π + 2π] cycloaddition of 2-tropylcyclohexanone to allenes and alkynes was accomplished for the first time using the three-component catalytic system Co(acac)2(dppe)/Zn/ZnI2, thus giving previously unknown functionally substituted bicyclo[4.2.1]nona-2,4-dienes and bicyclo[4.2.1]nona-2,4,7-trienes in high yields (70-89%). The structures of the synthesized carbocycles were reliably proved using modern spectral methods and X-ray diffraction. The in vitro cytotoxic activity of the obtained bicyclo[4.2.1]nona-2,4-dienes and bicyclo[4.2.1]nona-2,4,7-trienes against the Jurkat, K562, and U937 tumor cell lines has been studied.

Introduction

The bicyclo[4.2.1]nonane skeleton is a part of biologically active natural compounds such as longifolene, longicamphoric acid, secolongifolenediol, mediterraneols, and culmorin (Figure ).[1] Therefore, development of efficient methods for the design of bicyclo[4.2.1]nonanes is currently an area of interest for many chemists working in the field of organic and medicinal chemistry and pharmacology.[2]

Figure 1

Natural products containing the bicyclo[4.2.1]nonane skeleton.

As shown by analysis of the published data, metal-promoted and metal-catalyzed cycloaddition reactions of 1,3,5-cycloheptatriene (CHT) to various unsaturated compounds are currently used as an alternative and successive approach to the synthesis of bicyclo[4.2.1]nonanes.[2j,3] These reactions are described in the studies devoted to photo- and thermal- induced cyclocodimerization of Fe-, Ru-, Cr-, and Mo-containing CHT carbonyl complexes with alkenes, dienes, and alkynes.[4−7] The catalytic versions of these transformations include Ti-, Co-, Mo-, Rh-, and Pt-catalyzed cycloaddition reactions of CHT and its derivatives.[8−12]

Previously,[2j,8d−8h,9g] we developed efficient methods for the synthesis of a broad spectrum of bicyclo[4.2.1]nona-2,4-dienes and bicyclo[4.2.1]nona-2,4,7-trienes based on the catalytic cyclocodimerization of 1- and 7-substituted CHTs with 1,2-dienes and alkynes. To continue the work on the synthesis of previously unknown bicyclo[4.2.1]nonanes which act as potential block synthons in the targeted design of valuable bioactive compounds, we studied for the first time cobalt(I)-catalyzed [6π + 2π] cycloaddition of 2-tropylcyclohexanone to allenes and alkynes.

It is noteworthy that substituted cyclohexanones possess considerable synthetic potential, as they are used in the synthesis of numerous pharmacologically active heterocyclic compounds, for example, isoquinolines, indazoles, and 3-azabicyclo[3.3.1]nonanes.[13] For this reason, development of synthesis of new bicyclo[4.2.1]nonanes containing a cyclohexanone substituent is especially relevant and practically significant. In addition, no data on the catalytic cycloaddition reactions involving 2-tropylcyclohexanone can be found in the world literature.

Results and Discussion

Initially, we considered the catalytic reaction of 2-tropylcyclohexanone with allenes. The reaction was catalyzed by the efficient three-component system Co(acac)2(dppe)/Zn/ZnI2, which we developed previously and which proved to be active in the cyclocodimerization of 1,3,5-cyclooctatriene,[14] 1,3,5,7-cyclooctatetraene,[15] and 1-substituted CHTs[9g] with alkynes. It was shown that the [6π + 2π] cycloaddition of 2-tropylcyclohexanone 1 to allenes 2 catalyzed by the Co(acac)2(dppe)/Zn/ZnI2 system under the conditions we developed [10 mol % Co(acac)2(dppe), 30 mol % Zn, 20 mol % ZnI2, DCE (1,2-dichloroethane), 20 h, 60 °C] affords substituted (E)-bicyclo[4.2.1]nona-2,4-dienes 3a–c in 79–88% yields as a 1:1 mixture of syn- and anti-stereoisomers (Table ).

Table 1

Cobalt(I)-catalyzed [6π + 2π] Cycloaddition of 2-Tropylcyclohexanone (1) to Allenes (2)a

allene	R	product syn/anti	yieldb (%)
2a	Hex	1:1 (3a)	88
2b	Ph	1:1 (3b)	79
2c	Bn	1:1 (3c)	81

Reaction conditions: 1 (1 mmol), 2 (1.5 mmol), Co(acac)2(dppe) (0.10 mmol), Zn (0.3 mmol), ZnI2 (0.20 mmol), DCE (3 mL), 60 °C, 20 h.

Yields of products isolated by column chromatography.

According to 2D NOESY-GPPH NMR spectroscopy data, both stereoisomers of the cycloadducts 3a–c had an (E)-orientation of the substituent in the side chain. The NOESY-GPPH spectra of compounds 3a–c showed a cross-peak between the C(6,6′)H and C(16,16′)H proton signals, which confirmed the (E)-configuration of the C(7,7′)–C(16,16′) exo-double bond (Table ).

The cross-correlations between the signals of protons on the bridgehead carbons, C(1,1′)H and C(6,6′)H, in the 2D NOESY-GPPH spectrum served as check points for determining the stereochemistry of the obtained bicyclo[4.2.1]nona-2,4-dienes. The NOESY spectra of compounds 3a–c exhibited cross-correlation peaks for C(1)H and C(11)H2 protons, but no correlation was observed between the C(6)H and C(11)H2 proton signals (Figure ). The results unambiguously indicate that this group of signals corresponds to the syn-stereoisomer. Meanwhile, the second stereoisomer of cycloadducts 3a–c showed an opposite pattern of proton correlation: the NOESY spectrum contained cross-peaks between the C(6′)H and C(11′)H2 proton signals, but had no correlation between the C(1′)H and C(11′)H2 signals. These cross-correlations reliably point to the orientation of the cyclohexanone ring in the anti-stereoisomer (Figure ).

Figure 2

Fragment of the 2D NOESY-GPPH spectrum for compound 3a.

Reliable evidence for the molecular structure of (E)-bicyclo[4.2.1]nona-2,4-dienes 3a–c was gained from a single crystal X-ray diffraction study of a phenyl-substituted (E)-bicyclo[4.2.1]nona-2,4-diene 3b. According to the results, the keto group of the cyclohexanone ring points toward the phenyl-substituted part of the bicyclic system in the syn-stereoisomer and, conversely, toward the unsubstituted part of the bicyclic system in the anti-isomer (Figures and 4).

Figure 3

Molecular structure of cycloadduct 3b according to X-ray diffraction data. The nonhydrogen atoms are drawn by thermal ellipsoids (p = 50%). The O1, H11a, H11b and O2, H15a, H15b atoms are disordered over two positions with occupancies of 0.7639 and 0.2361, respectively.

Figure 4

Molecular structure of cycloadduct 3b (syn-stereoisomer) according to X-ray diffraction data. The non-hydrogen atoms are drawn by thermal ellipsoids (p = 50%).

In order to prepare new bicyclo[4.2.1]nona-2,4,7-trienes, we studied the catalytic cyclocodimerization of 2-tropylcyclohexanone with terminal alkynes, including those containing nitrile, ester, acetyl, phthalimide, or sulfide functional groups. We found that [6π + 2π] cycloaddition of 2-tropylcyclohexanone 1 to alkynes 4a–l catalyzed by the Co(acac)2(dppe)/Zn/ZnI2 system under the developed conditions (10 mol % Co(acac)2(dppe), 30 mol % Zn, 20 mol % ZnI2, DCE, 20 h, 60 °C) afforded substituted bicyclo[4.2.1]nona-2,4,7-trienes 5a–l in 70–89% yields. Similar to the bicyclo[4.2.1]nonadienes considered above, cycloadducts 5a–l were formed as two syn- and anti-stereoisomers, differing in the orientation of the cyclohexanone substituent at the bridging carbon atom (Table ).

Table 2

Cobalt(I)-catalyzed [6π + 2π] Cycloaddition of 2-Tropylcyclohexanone (1) to Alkynes (4)a

alkyne	R	product syn/anti	yieldb (%)
4a	Bu	1:1.3 (5a)	89
4b	Oct	1:1.3 (5b)	86
4c	(CH2)2CN	1:1 (5c)c	76
4d	(CH2)3CN	1:1 (5d)	87
4e	(CH2)2COOCH3	1:1.2 (5e)	71
4f	(CH2)2COOC2H5	1:1.3 (5f)	75
4g	(CH2)2OCOCH3	1:1 (5g)	73
4h	CH(CH2)2	1:1 (5h)	70
4i	2-phthalimidoethyl	1:1.3 (5i)c	74
4j	2-phthalimidobutyl	1:3 (5j)	88
4k	(CH2)4OTHP	1:1.3 (5k)	85
4l	(CH2)3St-Bu	1:1.2 (5l)	83

Reaction conditions: 1 (1 mmol), 4 (1.5 mmol), Co(acac)2(dppe) (0.10 mmol), Zn (0.3 mmol), ZnI2 (0.20 mmol), DCE (3 mL), 60 °C, 20 h.

Yields of products isolated by column chromatography.

CF3CH2OH as solvent.

The cycloadduct 5j with a 2-phthalimidobutyl substituent is a crystalline compound; this enabled us to obtain additional evidence about its structure by X-ray diffraction. According to the results, the keto group in the cyclohexanone ring pointed toward the substituted part of the bicyclic system in syn-stereoisomer 5j and toward the unsubstituted part in the anti-stereoisomer (Figure ).

Figure 5

Molecular structure of cycloadduct 5j according to X-ray diffraction data. The non-hydrogen atoms are drawn by thermal ellipsoids (p = 50%). The O1, H15a, H15b and O2, H11a, H11b atoms are disordered over two positions with occupancies of 0.5983 and 0.4017, respectively.

We believe that the Co(I)-catalyzed [6π + 2π] cycloaddition of 2-tropylcyclohexanone to allenes and alkynes follows the mechanism of the reaction of CHT with terminal alkynes, as described by Achard et al.(9c)

We have previously found that substituted bicyclo[4.2.1]nona-2,4,7-trienes exhibit a pronounced antitumor effect.[9g] Continuing the search for new bicyclo[4.2.1]nonanes, which are of interest as potential antitumor drugs, we have studied the in vitro cytotoxic activity of synthesized bicyclo[4.2.1]nona-2,4-dienes 3a–c and bicyclo[4.2.1]nona-2,4,7-trienes 5a–i,k,l against the Jurkat, K562, and U937 tumor cell lines. The values of inhibitory concentrations of the tested compounds are presented in Table .

Table 3

In Vitro Cytotoxic Activities IC50 of Bicyclo[4.2.1]nona-2,4-dienes 3a–c and Bicyclo[4.2.1]nona-2,4,7-trienes 5a–i,k,l Measured on Tumor Cell Cultures (Jurkat, K562, U937) and Normal Fibroblasts (μM)

	IC50/μM
compound	Jurkat	K562	U937	fibroblast
3a	0.029 ± 0.003	0.017 ± 0.001	0.034 ± 0.003	0.127 ± 0.011
3b	0.082 ± 0.007	0.059 ± 0.005	0.077 ± 0.007	0.412 ± 0.038
3c	0.061 ± 0.006	0.038 ± 0.003	0.059 ± 0.005	0.267 ± 0.021
5a	0.037 ± 0.004	0.029 ± 0.003	0.035 ± 0.003	0.246 ± 0.019
5b	0.079 ± 0.007	0.041 ± 0.004	0.084 ± 0.008	0.673 ± 0.059
5c	0.075 ± 0.006	0.057 ± 0.005	0.081 ± 0.007	0.629 ± 0.054
5d	0.069 ± 0.007	0.031 ± 0.002	0.074 ± 0.006	0.389 ± 0.034
5e	0.159 ± 0.012	0.062 ± 0.005	0.171 ± 0.014	0.562 ± 0.042
5f	0.048 ± 0.004	0.021 ± 0.002	0.051 ± 0.005	0.318 ± 0.029
5g	0.064 ± 0.006	0.039 ± 0.004	0.167 ± 0.012	0.517 ± 0.048
5h	0.039 ± 0.003	0.017 ± 0.001	0.041 ± 0.004	0.241 ± 0.022
5i	0.026 ± 0.002	0.011 ± 0.001	0.027 ± 0.002	0.196 ± 0.019
5k	0.135 ± 0.012	0.027 ± 0.002	0.143 ± 0.011	0.784 ± 0.072
5l	0.057 ± 0.005	0.028 ± 0.002	0.061 ± 0.006	0.311 ± 0.028

Analysis of the resulting data revealed that among bicyclo[4.2.1]nona-2,4,7-trienes 5a–i,k,l, cycloadduct 5i, containing the 2-phthalimidoethyl moiety, exhibited the greatest antitumor activity (IC50 = 0.011 ± 0.001–0.027 ± 0.002 μM). Bicyclo[4.2.1]nona-2,4,7-trienes bearing butyl and cyclopropyl substituents also showed a high cytotoxic effect (5a IC50 = 0.029 ± 0.003–0.037 ± 0.004 μM, 5h IC50 = 0.017 ± 0.001–0.041 ± 0.004 μM). The lowest antitumor activity among the tested samples was exhibited by the methoxycarbonyl-substituted bicyclic compound 5e (IC50 = 0.062 ± 0.005–0.171 ± 0.014 μM).

Along with bicycles 5a–i,k,l, bicyclo[4.2.1]nona-2,4-dienes 3a–c exhibited antitumor activity, the inhibitory concentration of which is in the range IC50 = 0.017 ± 0.001–0.082 ± 0.007 μM. Herewith, in this series, the hexyl-substituted bicyclo[4.2.1]nona-2,4-diene 3a has the highest cytotoxicity.

In addition, it was shown that for the tested Jurkat, K562, and U937 tumor cell lines, the therapeutic selectivity index (SI) of cytotoxic activity is 3–14 for normal fibroblasts.

Conclusions

Thus, we performed for the first time [6π + 2π] cycloaddition reactions of 2-tropylcyclohexanone to terminal allenes and alkynes catalyzed by the Co(acac)2(dppe)/Zn/ZnI2 three-component system and thus prepared new functionally substituted bicyclo[4.2.1]nona-2,4-dienes and bicyclo[4.2.1]nona-2,4,7-trienes in high yields (70–89%). The resulting bicyclo[4.2.1]nonadi(tri)enes are of considerable interest as key precursors for the targeted synthesis of promising pharmaceutical drugs and biologically active compounds. Simultaneously, the presence of reactive functional groups, in particular, a cyclohexanone substituent, in the molecules of the synthesized carbocycles opens up more opportunities for their practical use.

Experimental Section

General Information

Chromatographic analysis was performed on a Shimadzu GC-9A instrument using a 2000 × 2 mm column, the SE-30 (5%) stationary phase on Chromaton N-AW-HMDS (0.125–0.160 mm), helium carrier gas (30 mL/min), temperature programming from 50 to 300 °C at an 8 °C/min rate. The 1H and 13C spectra were measured in CDCl3 on a Bruker AVANCE-500 spectrometer (500 MHz for 1H, 125 MHz for 13C). The X-ray diffraction measurements were performed on an XCalibur Eos four-circle diffractometer (graphite monochromator, Mo Kα radiation, λ = 0.71073 Å, ω-scan mode, 2θmax = 62°) at ambient temperature (293–298 K). Collection and processing of the data were performed using the program CrysAlisPro Oxford Diffraction Ltd. Structure determinations were carried out with the OLEX2 program.[16] The structure was solved by direct methods as implemented in the program SHELXS.[17] The refinement was carried out using SHELXL.[18] The structures were refined by a full-matrix least-square technique using anisotropic thermal parameters for non-hydrogen atoms and a riding model for hydrogen atoms. The crystal structures were generated by mercury.[19] Mass spectra were obtained with a Shimadzu GC–MS-QP2010 Plus spectrometer at 70 eV and a working temperature of 200 °C. Mass spectra of compounds 5i,j were recorded on a MALDI TOF/TOF Autoflex-III Bruker mass spectrometer using 2,5-dihydroxybenzoic acid and α-cyano-4-hydroxycinnamic acid as a matrix in positive ion mode. Elemental analyses were measured with a 1106 Carlo Erba apparatus. IR spectra were recorded on a Bruker VE VERTEX 70V spectrometer as liquid films and are reported in wavenumbers (cm–1). All solvents were dried and freshly distilled before use. All reactions were carried out under a dry argon atmosphere. The terminal alkynes, alkynols, and ZnI2 were purchased from commercial sources and used without further purification. Co(acac)2(dppe), allenes, methyl pent-4-ynoate, ethyl pent-4-ynoate, but-3-yn-1-yl acetate, and tert-butyl(pent-4-yn-1-yl)sulfane were synthesized according to procedures described in the literature.[20] 2-Tropylcyclohexanone was prepared according to the literature procedure.[21]

Cycloaddition of Allenes and Alkynes to 2-Tropylcyclohexanone (General Procedure)

Zn powder (30 mol %) was added to a solution of Co(acac)2(dppe) (10 mol %) in DCE (1.5 mL) for 3a–c, 5a,b,d–h,j–l (in CF3CH2OH for 5c,i) in a Schlenk tube under a dry argon atmosphere, and the mixture was stirred at room temperature for 2 min. Next, 2-tropylcyclohexanone (1.0 mmol), the allene (or alkyne) (1.5 mmol) in DCE (1.5 mL) for 3a–c, 5a,b,d–h,j–l (in CF3CH2OH for 5c,i), and dry ZnI2 (20 mol %) (ZnI2 was weighed in a dry weighing bottle) were added successively. The resultant mixture was stirred at 60 °C for 20 h. The reaction was stopped by the addition of petroleum ether and stirring in air for 10 min to deactivate the catalyst. After filtering through a short pad of silica, the volatiles were removed under vacuum. Chromatographic purification over SiO2 (petroleum ether → petroleum ether/ethyl acetate 20:1 as eluent for 3a–c, 5a–h,k,l, petroleum ether → petroleum ether/ethyl acetate 20:1 → 10:1 → 5:1 → 2:1 for 5i,j) afforded the target products 3a–c, 5a–l.

2-{7-[(E)-Heptylidene]bicyclo[4.2.1]nona-2,4-dien-9-yl}cyclohexanone (3a)

Yield 88% (0.275 g), yellowish oil, ratio syn/anti = 1:1. R = 0.48 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 5.61–5.89 (m, 8H, syn, anti), 5.10 (t, J = 7 Hz, 2H, syn, anti), 3.63 (t, J = 7 Hz, 1H, syn), 3.16 (t, J = 7 Hz, 1H, anti), 3.04–3.10 (m, 1H, anti), 2.42–2.65 (m, 9H, syn, anti), 2.26–2.38 (m, 4H, syn, anti), 2.01–2.11 (m, 4H, syn, anti), 1.81–1.92 (m, 6H, syn, anti), 1.59–1.76 (m, 4H, syn, anti), 1.44–1.58 (m, 2H, syn, anti), 1.19–1.35 (m, 16H, syn, anti), 0.88 (t, J = 6.9 Hz, 6H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 214.1, 214.0, 151.1 (syn), 150.3 (anti), 136.6 (anti), 135.5 (syn), 135.2 (syn), 134.1 (anti), 125.3, 125.0, 124.9, 124.7, 121.3, 120.9, 49.8, 49.7, 47.6 (syn), 47.1 (anti), 43.0, 42.7, 42.66, 42.2, 40.3 (anti), 39.6, 39.5, 39.3, 34.8, 34.1, 31.8 (2C, syn, anti), 29.4 (2C, syn, anti), 29.0, 28.9 (3C, syn, anti), 28.88, 28.8, 25.3 (2C, syn, anti), 22.7 (2C, syn, anti), 14.1 (2C, syn, anti) ppm. IR (liquid film): 3017, 2927, 2855, 1710, 1448, 1378, 1310, 1223, 1126, 1061, 1025. MS (EI, 70 eV): 312 [M]+ (59), 283 (7), 241 (24), 214 (31), 163 (8), 143 (46), 129 (92), 117 (49), 91 (100), 79 (28), 67 (24), 55 (24), 41 (42). Anal. Calcd for C22H32O: C, 84.56; H, 10.32. Found: C, 84.42; H, 10.25.

2-{7-[(E)-Phenylmethylidene]bicyclo[4.2.1]nona-2,4-dien-9-yl}cyclohexanone (3b)

Yield 79% (0.240 g), yellowish needles, mp 149–150 °C, ratio syn/anti = 1:1. R = 0.51 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 7.14–7.37 (m, 10H, syn, anti), 6.19–6.23 (m, 2H, syn, anti), 5.80–5.96 (m, 4H, syn, anti), 5.69–5.79 (m, 4H, syn, anti), 3.89 (t, J = 7 Hz, 1H, syn), 3.39 (t, J = 7 Hz, 1H, anti), 3.23 (dd, J = 13.5 Hz, J = 7.5 Hz, 1H, anti), 2.92–3.04 (m, 3H, syn, anti), 2.84 (ddd, J = 17.4 Hz, J = 8.1 Hz, J = 2.8 Hz, 1H, syn), 2.56–2.77 (m, 5H, syn, anti), 2.30–2.43 (m, 4H, syn, anti), 2.03–2.18 (m, 4H, syn, anti), 1.85–1.93 (m, 2H, syn, anti), 1.49–1.78 (m, 6H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 214.0, 213.9, 154.3 (syn), 153.3 (anti), 138.4, 138.3, 136.6 (anti), 135.2 (syn), 134.6 (syn), 133.2 (anti), 128.1 (8C), 125.9, 125.8 (2C, syn, anti), 125.6, 125.4, 125.2, 121.3, 120.9, 49.9, 49.8, 49.7, 49.4 (anti), 44.9 (anti), 44.1 (syn), 42.8, 42.7, 40.9 (anti), 40.3 (syn), 38.7, 38.6, 34.8, 34.1, 28.9, 28.8, 25.4 (2C, syn, anti) ppm. IR (liquid film): 3021, 2934, 2859, 1706, 1447, 1386, 1310, 1221, 1129, 1028. MS (EI, 70 eV) (%): 304 [M]+ (61), 206 (31), 179 (10), 167 (16), 115 (24), 91 (100), 77 (8), 65 (6), 41 (6). Anal. Calcd for C22H24O: C, 86.80; H, 7.95. Found: C, 86.65; H, 7.87.

2-{7-[(E)-2-Phenylethylidene]bicyclo[4.2.1]nona-2,4-dien-9-yl}cyclohexanone (3c)

Yield 81% (0.258 g), yellowish oil, ratio syn/anti = 1:1. R = 0.53 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 7.29 (dd, J = 9.5 Hz, J = 5.4 Hz, 4H, syn, anti), 7.19 (dd, J = 13.7 Hz, J = 7.5 Hz, 6H, syn, anti), 5.66–5.96 (m, 8H, syn, anti), 5.31–5.38 (m, 2H, syn, anti), 3.76 (t, J = 7 Hz, 1H, syn), 3.23–3.32 (m, 5H, anti), 3.12–3.18 (m, 1H, anti), 2.71–2.77 (m, 3H, syn, anti), 2.55–2.70 (m, 6H, syn, anti), 2.32–2.40 (m, 4H, syn, anti), 2.05–2.14 (m, 4H, syn, anti), 1.84–1.91 (m, 2H, syn, anti), 1.63–1.76 (m, 4H, syn, anti), 1.48–1.60 (m, 2H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 214.1, 214.0, 152.5 (syn), 151.5 (anti), 141.3 (2C, syn, anti), 136.6 (anti), 135.2 (syn), 135.16 (syn), 133.8 (anti), 128.3 (8C), 125.8, 125.75, 125.5, 125.3, 125.0, 124.97, 119.6, 119.3, 49.8, 49.7, 47.6 (syn), 47.1 (anti), 43.1, 42.8, 42.7, 42.3, 40.3 (anti), 39.7 (syn), 39.6, 39.4, 35.2 (2C, syn, anti), 34.8, 34.1, 28.9, 28.8, 25.4, 25.37 ppm. IR (liquid film): 3023, 2926, 2858, 1706, 1450, 1385, 1310, 1223, 1129, 1028. MS (EI, 70 eV) (%): 318 [M]+ (95), 264 (4), 227 (33), 181 (10), 141 (13), 129 (69), 91 (100), 77 (12), 65 (10), 41 (11). Anal. Calcd for C23H26O: C, 86.75; H, 8.23. Found: C, 86.64; H, 8.13.

2-(7-Butylbicyclo[4.2.1]nona-2,4,7-trien-9-yl)cyclohexanone (5a)

Yield 89% (0.241 g), yellowish oil, ratio syn/anti = 1:1.3. R = 0.44 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 6.04 (dd, J = 11.7 Hz, J = 6.8 Hz, 1H, syn), 5.94–6.00 (m, 2H, anti), 5.82–5.93 (m, 5H, syn, anti), 5.09 (s, 1H, anti), 5.06 (s, 1H, syn), 3.44 (t, J = 6.1 Hz, 1H, syn), 3.24 (dd, J = 8.6 Hz, J = 4.3 Hz, 1H, anti), 2.94 (t, J = 6.5 Hz, 1H, anti), 2.78 (dd, J = 8.4 Hz, J = 4.4 Hz, 1H, syn), 2.36 (ddd, J = 16.3 Hz, J = 10.8 Hz, J = 5.9 Hz, 2H, syn, anti), 2.21–2.31 (m, 4H, syn, anti), 1.95–2.12 (m, 9H, syn, anti), 1.87–1.93 (m, 1H, syn), 1.77–1.84 (m, 2H, syn, anti), 1.54–1.68 (m, 4H, syn, anti), 1.21–1.48 (m, 10H, syn, anti), 0.86 (t, J = 7.3 Hz, 6H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 214.2, 214.1, 143.5 (anti), 141.4 (syn), 137.8, 137.7, 136.3, 136.2, 126.3, 126.0, 125.3, 125.1, 121.1 (syn), 119.2 (anti), 49.4 (2C, syn, anti), 48.0 (anti), 47.1 (syn), 44.8 (syn), 44.0 (anti), 42.6, 42.56, 38.03, 38.0, 33.9, 33.6, 30.7 (2C, syn, anti), 28.7, 28.66 (2C, syn, anti), 28.5, 25.2 (2C, syn, anti), 22.5, 22.4, 13.9 (2C, syn, anti) ppm. IR (liquid film): 3015, 2929, 2859, 1710, 1448, 1379, 1297, 1227, 1127, 1062, 1026. MS (EI, 70 eV) (%): 270 [M]+ (11), 207 (9), 173 (5), 148 (57), 129 (55), 122 (51), 117 (74), 105 (65), 91 (100), 77 (18), 57 (16), 40 (41). Anal. Calcd for C19H26O: C, 84.39; H, 9.69. Found: C, 84.27; H, 9.64.

2-(7-Octylbicyclo[4.2.1]nona-2,4,7-trien-9-yl)cyclohexanone (5b)

Yield 86% (0.281 g), yellowish oil, ratio syn/anti = 1:1.3. R = 0.43 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 6.01–6.07 (m, 1H, syn), 5.94–6.00 (m, 2H, anti), 5.82–5.93 (m, 5H, syn, anti), 5.08–5.10 (m, 1H, anti), 5.05–5.07 (m, 1H, syn), 3.45 (t, J = 6.2 Hz, 1H, syn), 3.22–3.27 (m, 1H, anti), 2.94 (t, J = 6.5 Hz, 1H, anti), 2.75–2.80 (m, 1H, syn), 2.19–2.41 (m, 6H, syn, anti), 1.86–2.12 (m, 10H, syn, anti), 1.76–1.84 (m, 2H, syn, anti), 1.52–1.72 (m, 4H, syn, anti), 1.18–1.49 (m, 26H, syn, anti), 0.87 (t, J = 7.3 Hz, 6H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 214.1, 214.0, 143.5 (syn), 141.4 (anti), 137.8, 137.7, 136.3, 136.2, 126.3, 126.0, 125.3, 125.1, 121.1 (anti), 119.2 (syn), 49.4 (2C, syn, anti), 48.0 (syn), 47.1 (anti), 44.8 (anti), 44.0 (syn), 42.6, 42.56, 38.04, 38.0, 33.9, 33.6, 31.9 (2C, syn, anti), 29.4 (3C, syn, anti), 29.3, 29.25 (2C, syn, anti), 29.1, 28.8, 28.7 (2C, syn, anti), 28.6 (2C, syn, anti), 25.2 (2C, syn, anti), 22.6 (2C, syn, anti), 14.1 (2C, syn, anti) ppm. IR (liquid film): 3015, 2925, 2855, 1709, 1463, 1378, 1310, 1226, 1127, 1062, 1026. MS (EI, 70 eV) (%): 326 [M]+ (14), 204 (42), 185 (4), 143 (14), 129 (40), 122 (50), 106 (100), 92 (78), 57 (26), 41 (26). Anal. Calcd for C23H34O: C, 84.60; H, 10.50. Found: C, 84.45; H, 10.42.

3-[9-(2-Oxocyclohexyl)bicyclo[4.2.1]nona-2,4,7-trien-7-yl]propanenitrile (5c)

Yield 76% (0.203 g), yellowish oil, ratio syn/anti = 1:1. R = 0.48 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 6.05 (dd, J = 11.1 Hz, J = 7.4 Hz, 1H) (syn), 5.86–6.02 (m, 7H, syn, anti), 5.23 (s, 2H, syn, anti), 3.50 (t, J = 6.8 Hz, 1H, syn), 3.32–3.37 (m, 1H, anti), 2.99 (t, J = 6.3 Hz, 1H, anti), 2.83–2.87 (m, 1H, syn), 2.35–2.50 (m, 10H, syn, anti), 2.19–2.33 (m, 4H, syn, anti), 1.94–2.10 (m, 5H, syn, anti), 1.91 (ddd, J = 8.4 Hz, J = 5.4 Hz, J = 2.4 Hz, 1H, syn), 1.77–1.85 (m, 2H, syn, anti), 1.51–1.69 (m, 4H, syn, anti), 1.33–1.48 (m, 2H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 213.8, 213.6, 138.1 (syn), 137.3, 136.4, 136.3 (anti), 136.0, 135.0, 127.3, 127.1, 125.8, 125.6, 123.3 (anti), 121.5 (syn), 119.4, 119.36, 49.2 (2C, syn, anti), 47.5 (syn), 46.9 (anti), 44.8 (anti), 44.1 (syn), 42.6, 42.58, 37.9, 37.8, 33.9, 33.6, 28.6, 28.57, 25.3, 25.2, 25.0, 24.8, 16.8, 16.7 ppm. IR (liquid film): 3020, 2929, 2858, 2247, 1704, 1446, 1372, 1297, 1225, 1125, 1063, 1028. MS (EI, 70 eV) (%): 267 [M]+ (3), 207 (1), 170 (5), 148 (5), 129 (26), 122 (100), 105 (13), 91 (14), 77 (5), 65 (4), 41 (6). Anal. Calcd for C18H21NO: C, 80.86; H, 7.92; N, 5.24. Found: C, 80.76; H, 7.88; N, 5.19.

4-[9-(2-Oxocyclohexyl)bicyclo[4.2.1]nona-2,4,7-trien-7-yl]butanenitrile (5d)

Yield 87% (0.245 g), yellowish oil, ratio syn/anti = 1:1. R = 0.50 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 6.02–6.08 (m, 1H, syn), 5.82–6.00 (m, 7H, syn, anti), 5.12–5.18 (m, 2H, syn, anti), 3.42–3.47 (m, 1H, syn), 3.26–3.32 (m, 1H, anti), 2.92 (t, J = 6.2 Hz, 1H, anti), 2.78–2.83 (m, 1H, syn), 2.31–2.40 (m, 2H, syn, anti), 2.23 (dd, J = 9.2 Hz, J = 5.3 Hz, 12H, syn, anti), 1.86–2.08 (m, 6H, syn, anti), 1.70–1.84 (m, 6H, syn, anti), 1.50–1.66 (m, 4H, syn, anti), 1.31–1.46 (m, 2H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 213.9, 213.7, 139.7 (syn), 137.8 (anti), 137.6, 136.8, 136.3, 135.4, 126.8, 126.6, 125.5, 125.3, 123.0 (anti), 121.4 (syn), 119.7 (2C, syn, anti), 49.2 (2C, syn, anti), 47.8 (syn), 47.1 (anti), 44.9 (anti), 44.1 (syn), 42.6, 42.59, 38.0, 37.9, 33.9, 33.6, 28.62, 28.6, 28.0, 27.8, 25.2 (2C, syn, anti), 24.5 (2C, syn, anti), 16.2 (2C, syn, anti) ppm. IR (liquid film): 3016, 2935, 2858, 2245, 1705, 1447, 1295, 1227, 1126, 1062, 1026. MS (EI, 70 eV) (%): 281 [M]+ (4), 184 (12), 159 (34), 129 (22), 122 (100), 105 (35), 91 (26), 77 (8), 65 (6), 41 (10). Anal. Calcd for C19H23NO: C, 81.10; H, 8.24; N, 4.98. Found: C, 80.93; H, 8.18; N, 4.90.

Methyl 3-[9-(2-Oxocyclohexyl)bicyclo[4.2.1]nona-2,4,7-trien-7-yl]propanoate (5e)

Yield 71% (0.213 g), yellowish oil, ratio syn/anti = 1:1.2. R = 0.48 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 5.81–6.06 (m, 8H, syn, anti), 5.11 (s, 1H, anti), 5.09 (s, 1H, syn), 3.62–3.67 (m, 6H, syn, anti), 3.43–3.47 (m, 1H, syn), 3.22–3.28 (m, 1H, anti), 2.94 (t, J = 6.5 Hz, 1H, anti), 2.75–2.81 (m, 1H, syn), 2.18–2.58 (m, 14H, syn, anti), 1.92–2.09 (m, 5H, syn, anti), 1.89 (d, J = 12.5 Hz, 1H, syn), 1.75–1.83 (m, 2H, syn, anti), 1.49–1.72 (m, 4H, syn, anti), 1.33–1.48 (m, 2H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 214.1, 214.0, 173.6 (2C, syn, anti), 140.9 (syn), 139.0 (anti), 137.5, 137.2, 136.1, 135.8, 126.7, 126.5, 125.5, 125.3, 121.8 (anti), 119.9 (syn), 51.6 (2C, syn, anti), 49.3 (2C, syn, anti), 47.9 (syn), 47.2 (anti), 44.8 (anti), 44.0 (syn), 42.6 (2C, syn, anti), 37.9, 37.8, 33.9, 33.6, 33.1 (2C, syn, anti), 28.6 (2C, syn, anti), 25.2 (2C, syn, anti), 24.2, 24.0 ppm. IR (liquid film): 3015, 2929, 2857, 1739, 1707, 1438, 1310, 1161, 1039. MS (EI, 70 eV) (%): 300 [M]+ (11), 269 (7), 213 (7), 178 (42), 146 (74), 129 (59), 122 (61), 104 (100), 91 (50), 55 (12), 41 (13). Anal. Calcd for C19H24O3: C, 75.97; H, 8.05. Found: C, 75.84; H, 7.96.

Ethyl 3-[9-(2-Oxocyclohexyl)bicyclo[4.2.1]nona-2,4,7-trien-7-yl]propanoate (5f)

Yield 75% (0.236 g), yellowish oil, ratio syn/anti = 1:1.3. R = 0.49 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 5.81–6.06 (m, 8H, syn, anti), 5.12 (s, 1H, anti), 5.09 (s, 1H, syn), 4.10 (dd, J = 14.1 Hz, J = 7.1 Hz, 4H, syn, anti), 3.43–3.49 (m, 1H, syn), 3.22–3.29 (m, 1H, anti), 2.95 (t, J = 7.0 Hz, 1H, anti), 2.75–2.81 (m, 1H, syn), 2.20–2.48 (m, 14H, syn, anti), 1.86–2.10 (m, 6H, syn, anti), 1.76–1.84 (m, 2H, syn, anti), 1.51–1.70 (m, 4H, syn, anti), 1.33–1.48 (m, 2H, syn, anti), 1.16–1.31 (m, 6H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 214.1, 214.0, 173.2 (2C, syn, anti), 141.0 (syn), 139.1 (anti), 137.5, 137.3, 136.1, 135.8, 126.7, 126.5, 125.5, 125.3, 121.7 (anti), 119.9 (syn), 60.3, 60.29, 49.3 (2C, syn, anti), 47.9 (syn), 47.2 (anti), 44.8 (anti), 44.0 (syn), 42.6 (2C, syn, anti), 37.9, 37.8, 33.9, 33.6, 33.4 (2C, syn, anti), 28.6 (2C, syn, anti), 25.2 (2C, syn, anti), 24.3, 24.1, 14.2 (2C, syn, anti) ppm. IR (liquid film): 3016, 2935, 2860, 1732, 1709, 1447, 1307, 1161, 1041. MS (EI, 70 eV) (%): 314 [M]+ (15), 269 (8), 213 (10), 192 (33), 146 (63), 129 (89), 122 (90), 118 (100), 104 (73), 91 (61), 77 (16), 55 (14), 41 (22). Anal. Calcd for C20H26O3: C, 76.40; H, 8.34. Found: C, 76.27; H, 8.28.

2-[9-(2-Oxocyclohexyl)bicyclo[4.2.1]nona-2,4,7-trien-7-yl]ethyl acetate (5g)

Yield 73% (0.219 g), yellowish oil, ratio syn/anti = 1:1. R = 0.47 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 5.86–6.07 (m, 8H, syn, anti), 5.18 (s, 1H, anti), 5.15 (s, 1H, syn), 4.06–4.17 (m, 4H, syn, anti), 3.49 (t, J = 5.3 Hz, 1H, syn), 3.28–3.33 (m, 1H, anti), 2.98 (t, J = 6.4 Hz, 1H, anti), 2.79–2.85 (m, 1H, syn), 2.20–2.50 (m, 10H, syn, anti), 1.88–2.12 (m, 12H, syn, anti), 1.77–1.86 (m, 2H, syn, anti), 1.52–1.72 (m, 4H, syn, anti), 1.34–1.49 (m, 2H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 213.9, 213.8, 171.1 (2C, syn, anti), 137.7 (syn), 137.4, 136.9, 136.0, 135.7 (anti), 135.4, 126.9, 126.6, 125.6, 125.4, 123.3 (anti), 121.2 (syn), 63.5, 63.3, 49.3 (2C, syn, anti), 48.0 (syn), 47.0 (anti), 44.9 (anti), 44.1 (syn), 42.6 (2C, syn, anti), 37.8, 37.7, 33.9, 33.7, 28.6 (2C, syn, anti), 28.4, 28.3, 25.2 (2C, syn, anti), 21.0 (2C, syn, anti) ppm. IR (liquid film): 3016, 2935, 2859, 1739, 1707, 1447, 1366, 1240, 1127, 1036. MS (EI, 70 eV) (%): 300 [M]+ (4), 240 (6), 178 (6), 142 (26), 122 (55), 118 (100), 91 (19), 55 (6), 43 (27). Anal. Calcd for C19H24O3: C, 75.97; H, 8.05. Found: C, 75.86; H, 7.98.

2-(7-Cyclopropylbicyclo[4.2.1]nona-2,4,7-trien-9-yl)cyclohexanone (5h)

Yield 70% (0.178 g), yellowish oil, ratio syn/anti = 1:1. R = 0.41 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 5.83–6.08 (m, 8H, syn, anti), 5.10 (dd, J = 5.7 Hz, J = 2.8 Hz, 2H, syn, anti), 3.39 (t, J = 5.0 Hz, 1H, syn), 3.22–3.27 (m, 1H, anti), 2.88 (t, J = 6.5 Hz, 1H, anti), 2.75–2.80 (m, 1H, syn), 2.20–2.41 (m, 6H, syn, anti), 1.87–2.11 (m, 6H, syn, anti), 1.77–1.85 (m, 2H, syn, anti), 1.52–1.71 (m, 4H, syn, anti), 1.32–1.49 (m, 4H, syn, anti), 0.43–0.74 (m, 6H, syn, anti), 0.28–0.35 (m, 2H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 214.0, 213.8, 145.6 (syn), 143.5 (anti), 137.7, 137.68, 136.3 (2C, syn, anti), 126.2, 126.0, 125.4, 125.2, 119.7 (anti), 118.0 (syn), 49.3 (2C, syn, anti), 46.4 (syn), 45.9 (anti), 44.6 (anti), 43.8 (syn), 42.6, 42.56, 38.1, 38.0, 33.9, 33.6, 28.6 (2C, syn, anti), 25.2 (2C, syn, anti), 10.4, 10.2, 8.5, 8.2, 6.8, 6.7 ppm. IR (liquid film): 3012, 2934, 2859, 1707, 1447, 1310, 1227, 1127, 1021. MS (EI, 70 eV) (%): 254 [M]+ (9), 225 (6), 155 (19), 141 (29), 132 (68), 117 (100), 104 (16), 91 (52), 65 (8), 41 (14). Anal. Calcd for C18H22O: C, 84.99; H, 8.72. Found: C, 84.82; H, 8.67.

2-{2-[9-(2-Oxocyclohexyl)bicyclo[4.2.1]nona-2,4,7-trien-7-yl]ethyl}-1H-isoindole-1,3(2H)-dione (5i)

Yield 74% (0.287 g), yellowish oil, ratio syn/anti = 1:1.3. R = 0.60 (petroleum ether/ethyl acetate 2:1). 1H NMR (500 MHz, CDCl3): δ 7.81–7.89 (m, 4H, syn, anti), 7.68–7.76 (m, 4H, syn, anti), 5.98–6.05 (m, 2H, syn, anti), 5.77–5.97 (m, 6H, syn, anti), 5.18 (d, J = 5.7 Hz, 2H, syn, anti), 3.68–3.92 (m, 4H, syn, anti), 3.54 (t, J = 6.5 Hz, 1H, syn), 3.21–3.27 (m, 1H, anti), 3.11 (t, J = 6.5 Hz, 1H, anti), 2.77–2.82 (m, 1H, syn), 2.52 (d, J = 6.6 Hz, 4H, syn, anti), 2.17–2.44 (m, 6H, syn, anti), 1.96–2.09 (m, 5H, syn, anti), 1.76–1.93 (m, 3H, syn, anti), 1.36–1.74 (m, 6H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 213.9 (2C, syn, anti), 168.3 (4C, syn, anti), 138.0 (syn), 137.4, 137.0, 136.1 (anti), 135.9, 135.6, 133.9 (2C), 133.8 (2C), 132.2 (2C), 132.1 (2C), 126.9, 126.7, 125.6, 125.3, 123.5 (anti), 123.2 (2C), 123.1 (2C), 121.1 (syn), 49.3 (2C, syn, anti), 47.8 (syn), 46.6 (anti), 44.9 (anti), 44.1 (syn), 42.6, 42.5, 37.8, 37.6, 37.1, 36.9, 33.8, 33.4, 28.6, 28.55, 27.8, 27.5, 25.2, 25.1 ppm. IR (liquid film): 3017, 2926, 2856, 1771, 1712, 1467, 1397, 1245, 1188, 1046. MS (MALDI-TOF): calcd for C25H25NO3 + Na+ [M + Na]+, 410.173; found, 410.311. Anal. Calcd for C25H25NO3: C, 77.49; H, 6.50; N, 3.61. Found: C, 77.33; H, 6.42; N, 3.52.

2-{4-[9-(2-Oxocyclohexyl)bicyclo[4.2.1]nona-2,4,7-trien-7-yl]butyl}-1H-isoindole-1,3(2H)-dione (5j)

Yield 88% (0.366 g), yellowish needles, mp 137–138 °C, ratio syn/anti = 1:3. R = 0.65 (petroleum ether/ethyl acetate 2:1). 1H NMR (500 MHz, CDCl3): δ 7.85 (dd, J = 5.4 Hz, J = 3.1 Hz, 4H, syn, anti), 7.72 (dd, J = 5.5 Hz, J = 2.9 Hz, 4H, syn, anti), 6.05 (dd, J = 12.1 Hz, J = 7.0 Hz, 1H, syn), 5.94–6.01 (m, 2H, anti), 5.83–5.93 (m, 5H, syn, anti), 5.11–5.13 (m, 1H, anti), 5.10 (s, 1H, syn), 3.67 (t, J = 7.2 Hz, 4H, syn, anti), 3.44 (t, J = 6.4 Hz, 1H, syn), 3.23–3.29 (m, 1H, anti), 2.94 (t, J = 6.5 Hz, 1H, anti), 2.77–2.82 (m, 1H, syn), 1.87–2.44 (m, 16H, syn, anti), 1.78–1.86 (m, 2H, syn, anti), 1.54–1.73 (m, 8H, syn, anti), 1.37–1.53 (m, 6H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ (syn) 213.9, 168.4 (2C), 137.5, 136.3, 133.9 (2C), 132.2 (2C), 126.2, 125.4, 123.2 (2C), 119.8, 49.3, 48.0, 44.1, 42.6, 38.0, 37.9, 33.6, 28.7, 28.4, 28.2, 25.9, 25.2 ppm; δ (anti) 213.93, 168.42 (2C), 140.4, 137.7, 136.0, 133.85 (2C), 132.17 (2C), 126.5, 125.2, 123.16 (2C), 121.8, 49.33, 47.1, 44.9, 42.58, 38.02, 37.85, 33.9, 28.65, 28.37, 28.18, 25.85, 25.21 ppm. IR (liquid film): 3018, 2936, 2861, 1770, 1712, 1467, 1397, 1229, 1188, 1038. MS (MALDI-TOF): calcd for C27H29NO3 + Na+ [M + Na]+, 438.205; found, 438.172. Anal. Calcd for C27H29NO3: C, 78.04; H, 7.03; N, 3.37. Found: C, 77.92; H, 6.99; N, 3.31.

2-{7-[4-(Tetrahydro-2H-pyran-2-yloxy)butyl]bicyclo[4.2.1]nona-2,4,7-trien-9-yl}cyclohexanone (5k)

Yield 85% (0.315 g), yellowish oil, ratio syn/anti = 1:1.3. R = 0.57 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 6.04 (dd, J = 11.7 Hz, J = 7.0 Hz, 1H, syn), 5.94–6.00 (m, 2H, anti), 5.83–5.93 (m, 5H, syn, anti), 5.11 (s, 1H, anti), 5.08 (s, 1H, syn), 4.56 (s, 2H, syn, anti), 3.84 (dd, J = 13.3 Hz, J = 5.5 Hz, 2H, syn, anti), 3.67–3.78 (m, 2H, syn, anti), 3.32–3.54 (m, 5H, syn, anti), 3.22–3.27 (m, 1H, anti), 2.95 (t, J = 6.5 Hz, 1H, anti), 2.75–2.81 (m, 1H, syn), 2.19–2.42 (m, 6H, syn, anti), 1.94–2.18 (m, 9H, syn, anti), 1.90 (dd, J = 12.8 Hz, J = 3.0 Hz, 1H, syn), 1.76–1.87 (m, 4H, syn, anti), 1.33–1.75 (m, 24H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 214.1 (syn), 214.0 (anti), 143.0 (syn), 141.0 (anti), 138.8 (anti), 137.6 (syn), 136.3 (syn), 136.1 (anti), 126.4 (anti), 126.1 (syn), 125.4 (syn), 125.2 (anti), 121.4 (anti), 119.5 (syn), 98.8 (2C, syn, anti), 67.4 (2C, syn, anti), 62.3, 62.2, 49.4 (2C, syn, anti), 47.9 (syn), 47.1 (anti), 44.8 (anti), 44.0 (syn), 42.6 (2C, syn, anti), 38.0 (anti), 37.99 (syn), 33.9 (anti), 33.6 (syn), 30.7 (2C, syn, anti), 29.4, 29.36, 29.3, 28.8, 28.7 (2C, syn, anti), 28.6 (2C, syn, anti), 25.5 (2C, syn, anti), 25.2 (2C, syn, anti), 19.6 (2C, syn, anti) ppm. IR (liquid film): 3015, 2937, 2862, 1707, 1448, 1352, 1200, 1136, 1076, 1033. MS (EI, 70 eV) (%): 370 [M]+ (3), 355 (7), 309 (7), 281 (22), 207 (88), 163 (24), 117 (17), 85 (100), 73 (21), 57 (21), 41 (26). Anal. Calcd for C24H34O3: C, 77.80; H, 9.25. Found: C, 77.61; H, 9.17.

2-{7-[3-(tert-Butylsulfanyl)propyl]bicyclo[4.2.1]nona-2,4,7-trien-9-yl}cyclohexanone (5l)

Yield 83% (0.286 g), yellowish oil, ratio syn/anti = 1:1.2. R = 0.59 (petroleum ether/ethyl acetate 20:1). 1H NMR (500 MHz, CDCl3): δ 5.84–6.09 (m, 8H, syn, anti), 5.14 (d, J = 1.2 Hz, 1H, anti), 5.12 (s, 1H, syn), 3.46 (dd, J = 7.8 Hz, J = 5.7 Hz, 1H, syn), 3.26–3.31 (m, 1H, anti), 2.95 (t, J = 6.5 Hz, 1H, anti), 2.78–2.83 (m, 1H, syn), 2.43–2.50 (m, 4H, syn, anti), 2.35–2.42 (m, 2H, syn, anti), 2.16–2.33 (m, 8H, syn, anti), 1.78–2.13 (m, 8H, syn, anti), 1.53–1.73 (m, 8H, syn, anti), 1.36–1.49 (m, 2H, syn, anti), 1.28–1.35 (m, 18H, syn, anti) ppm. 13C NMR (125 MHz, CDCl3): δ 214.0 (2C, syn, anti), 142.0 (syn), 140.0 (anti), 137.7 (anti), 137.4 (syn), 136.3 (syn), 135.9 (anti), 126.5 (anti), 126.3 (syn), 125.4 (syn), 125.2 (anti), 121.9 (anti), 120.0 (syn), 49.3 (2C, syn, anti), 48.0 (syn), 47.2 (anti), 44.9 (anti), 44.1 (syn), 42.6 (2C, syn, anti), 41.9 (2C, syn, anti), 38.0, 37.98, 33.9 (anti), 33.7 (syn), 31.0 (6C, syn, anti), 28.9, 28.8, 28.7 (3C, syn, anti), 28.4, 27.8, 27.7, 25.2 (2C, syn, anti) ppm. IR (liquid film): 3014, 2933, 2860, 1708, 1448, 1377, 1295, 1164, 1127, 1061, 1027. MS (EI, 70 eV) (%): 344 [M]+ (4), 287 (100), 222 (7), 189 (42), 165 (24), 129 (29), 118 (33), 91 (30), 57 (53), 41 (25). Anal. Calcd for C22H32OS: C, 76.69; H, 9.36. Found: C, 76.54; H, 9.32.