Plan
Comptes Rendus
no. 5

Palladium-catalyzed nucleophilic allylic substitution of Morita–Baylis–Hillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds
Ghalia Bouhalleb1  ; Jalloul Bouajila2 ; Farhat Rezgui1
1 Université de Tunis EL Manar, Faculté des sciences, Laboratoire de chimie organique structurale, Campus universitaire, 2092 Tunis, Tunisia
2 Université de Toulouse-3, Université Paul-Sabatier, Faculté des sciences pharmaceutiques, Laboratoire des IMRCP, UMR CNRS 5623, 35, chemin des Maraichers, 31062 Toulouse cedex 09, France
Comptes Rendus. Chimie, Volume 20 (2017) no. 5, pp. 484-491.

Résumé

An efficient nucleophilic allylic substitution of a variety of Morita–Baylis–Hillman adducts with enamines catalyzed by Pd(OAc)2 in the presence of ZnBr2 as a promoter is described in the present study. The reaction gives SN2-type 1,5-dicarbonyl compounds that may subsequently undergo an intramolecular conjugate addition onto the enone moiety affording the corresponding 1,4-adducts. All the synthesized compounds have been isolated in moderate to good yields and fully characterized.

Supplementary Materials:
Supplementary material for this article is supplied as a separate file:

Métadonnées
Reçu le :
Accepté le :
Publié le :
DOI : 10.1016/j.crci.2016.11.011
Mots clés : Allylic substitution, Palladium, Enamine, 1, 5-Dicarbonyl compounds, Morita–Baylis–Hillman, Conjugate addition
Ghalia Bouhalleb 1 ; Jalloul Bouajila 2 ; Farhat Rezgui 1

1 Université de Tunis EL Manar, Faculté des sciences, Laboratoire de chimie organique structurale, Campus universitaire, 2092 Tunis, Tunisia
2 Université de Toulouse-3, Université Paul-Sabatier, Faculté des sciences pharmaceutiques, Laboratoire des IMRCP, UMR CNRS 5623, 35, chemin des Maraichers, 31062 Toulouse cedex 09, France 
@article{CRCHIM_2017__20_5_484_0,
     author = {Ghalia Bouhalleb and Jalloul Bouajila and Farhat Rezgui},
     title = {Palladium-catalyzed nucleophilic allylic substitution of {Morita{\textendash}Baylis{\textendash}Hillman} adducts with enamines: {Synthesis} of 1,5-dicarbonyl compounds},
     journal = {Comptes Rendus. Chimie},
     pages = {484--491},
     publisher = {Elsevier},
     volume = {20},
     number = {5},
     year = {2017},
     doi = {10.1016/j.crci.2016.11.011},
     language = {en},
}
TY  - JOUR
AU  - Ghalia Bouhalleb
AU  - Jalloul Bouajila
AU  - Farhat Rezgui
TI  - Palladium-catalyzed nucleophilic allylic substitution of Morita–Baylis–Hillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds
JO  - Comptes Rendus. Chimie
PY  - 2017
SP  - 484
EP  - 491
VL  - 20
IS  - 5
PB  - Elsevier
DO  - 10.1016/j.crci.2016.11.011
LA  - en
ID  - CRCHIM_2017__20_5_484_0
ER  - 
%0 Journal Article
%A Ghalia Bouhalleb
%A Jalloul Bouajila
%A Farhat Rezgui
%T Palladium-catalyzed nucleophilic allylic substitution of Morita–Baylis–Hillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds
%J Comptes Rendus. Chimie
%D 2017
%P 484-491
%V 20
%N 5
%I Elsevier
%R 10.1016/j.crci.2016.11.011
%G en
%F CRCHIM_2017__20_5_484_0
Ghalia Bouhalleb; Jalloul Bouajila; Farhat Rezgui. Palladium-catalyzed nucleophilic allylic substitution of Morita–Baylis–Hillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds. Comptes Rendus. Chimie, Volume 20 (2017) no. 5, pp. 484-491. doi : 10.1016/j.crci.2016.11.011. https://comptes-rendus.academie-sciences.fr/chimie/articles/10.1016/j.crci.2016.11.011/

Version originale du texte intégral

1 Introduction

1,5-Diketones are useful precursors to various substituted anilines [1] and heterocyclic compounds including pyridine derivatives [2–5], dihydropyridines [5,6], and pyrazolo[1,5-a] pyrimidines [7]. Moreover, 1,5-diketones with abstractable γ-hydrogen atoms were shown to be highly photoactive cage molecules for the release of fragrances [8]. These dicarbonyl compounds were also used for the synthesis of bicyclic ethers via their annulation reaction with bis (trimethylsilyl) enol ethers [9] and pinacol coupling through their reductive dimerization [10].

Michael addition of ketone enolates or their surrogates onto α,β-enones is one of the common methods for the synthesis of 1,5-diketones [11–13]. These compounds can also be prepared by a cross-coupling reaction of aryl methyl ketones with either aromatic aldehydes [14] or acetohydrazones [15], as well as by dimerization of α,β-enones in the presence of a quaternary ammonium salt as a phase-transfer catalyst [16]. In addition, the cross-metathesis of olefins was found to be a rapid access to such dicarbonyl derivatives [1,3]. In another synthetic protocol, Zard et al. reported a free radical approach for the synthesis of 1,5-diketones from alkenylacylphosphonates and keto-xanthates [2].

On the other hand, during the last decades, the nucleophilic behavior of enamines has been explored in palladium-catalyzed nucleophilic substitution of allylic compounds. Indeed, the reaction of allylic acetates with enamines worked well in the presence of Pd(II)/metallocene-based ligands, affording the corresponding allylation products [17]. Such a nucleophilic allylic substitution was used to prepare γ,δ-unsaturated ketones through the reaction of allylic benzotriazoles with enamines under the action of Pd(0)/PPh3 in the presence of ZnBr2 [18].

Furthermore, it was shown that the one-pot reaction of functionalized acyclic Morita–Baylis–Hillman (MBH) acetates with various enamino β-ketoesters in the presence of NaH afforded a series of trisubstituted 2-pyridones [19,20]. Nevertheless, it is worth noting that up to now, no Pd-catalyzed nucleophilic reaction of enamines with acyclic or cyclic MBH adducts has been reported. In our previous studies on the MBH chemistry, we have reported a Pd-free Tsuji-Trost–type reaction of MBH alcohols or acetates with β-dicarbonyl compounds, affording γ,δ-unsaturated 1,5-diketones [21,22]. In continuation of our interest in the allylic substitution of MBH derivatives with various nucleophiles [23,24], we report herein the first examples of a Pd-catalyzed allylic nucleophilic substitution of both cyclic and acyclic MBH adducts, as functionalized allylic substrates, with ketoenamines, providing a new series of saturated and γ,δ-unsaturated 1,5-dicarbonyl compounds.

2 Results and discussion

For this purpose, we have initially prepared the enamines 2a–c in 60–70% yields (Table 1) from the reaction of cyclic ketones 1a–c with morpholine using conventional reaction conditions [25].

Table 1

Synthesis of enamines 2a–c from the reaction of ketones 1a–c with morpholine.a

Table 1
EntryEnamine 2Reaction time (days)Yield 2 (%)b
12aImage 2360
22bImage 3470
32cImage 4165

a The reaction was performed using ketones 1a–c (1 equiv), morpholine (1.5 equiv), p-toluenesulfonic acid (2 equiv) in toluene.

b Isolated yield.

Next, upon treatment of the enamine 2a with the MBH acetate 3a [21], at room temperature (rt), under solvent-free conditions, and without any additive, the starting materials were recovered within 48 h (Table 2, entry 1). The same result was also obtained when toluene was used as a solvent in the same reaction at rt or at reflux for 72 h (Table 2, entries 2 and 3). Interestingly, in dichloromethane at rt, the 1,5-dicarbonyl compound 4a was obtained, within 72 h, but in only 30% yield (Scheme 1, Table 2, entry 4). To improve the reaction yield and reduce the reaction time, our subsequent experiment was conducted in refluxing dichloromethane. Under these conditions, the 1,5-keto ester 4a was produced in the same yield within 72 h (Scheme 1, Table 2, entry 5).

Table 2

Optimization of the reaction conditions for the synthesis of 4a from the reaction of 2a with 3a.a

Table 2
EntryT (°C)SolventTime (h)Yield 4ab (%)
1rtNone48–
2rtToluene72–
3110Toluene72–
4rtCH2Cl27230
540CH2Cl27230

a The reaction was performed using the acetate 3a (1 equiv) and enamine 2a (5 equiv) in CH2Cl2.

b Isolated yield.

Scheme 1

Synthesis of ketoesters 4a–c from acyclic MBH 3a and enamines 2a–c.

Taking into account the low yields of the compound 4a and long reaction times recorded in the previous preliminary attempts, we therefore decided to explore a new synthetic approach for 4a under catalytic conditions. In this context, we reacted, under the established conditions, the enamine 2a (5 equiv) with the MBH acetate 3a (1 equiv) in the presence of Pd(OAc)2 (0.04 equiv)/PPh3 (0.16 equiv) and ZnBr2 (2.66 equiv) as a Lewis acid in refluxing dichloromethane. The conversion of the substrate 3a was complete within 6 h, yielding exclusively, after hydrolysis of the reaction mixture, the unsaturated 1,5-keto ester 4a in 70% yield (Scheme 1, Table 3, entry 1). Under the same conditions, the allylic nucleophilic substitution of the substrate 3a was also successfully performed with enamines 2b and 2c, affording similarly the corresponding SN2 and/or SN2′-type products 4b and 4c in 80 and 68% yield, respectively (Scheme 1, Table 3, entries 2 and 3).

Table 3

Synthesis of 1,5-dicarbonyl compounds 4 and 5 through the reaction of substrates 3a–e with enamines 2a–c.a

Table 3
Entry32Time (h)Product 4 and/or 5bRatio 4:5
13a2a6Image 5
4a, 70%		4a/5a = 100:0
23a2b4Image 6
4b, 80%		4b/5b = 100:0
33a2c4Image 7
4c, 68%		4c/5c = 100:0
43b2a24Image 8
5d, 80%		4d/5d = 0:100
53c2a48Image 9
5d, 75%		4d/5d = 0:100
63d2a24Image 10
5d, 75%		4d/5d = 0:100
73e2a37Image 11
5e, 60%		4e/5e = 0:100
83e2b32Image 12
5f, 64%		4f/5f = 0:100
93e2c40Image 13
5g, 57%		4g/5g = 0:100
103b2b7Image 14
4h, 27%		Image 20
5h, 60%		4h/5h = 31:69
113c2b28Image 15
4h, 26%		Image 21
5h, 63%		4h/5h = 29:71
123d2b12Image 16
4h, 35%		Image 22
5h, 57%		4h/5h = 38:62
133b2c24Image 17
4i, 37%		Image 23
5i, 54%		4i/5i = 40:60
143c2c28Image 18
4i, 28%		Image 24
5i, 65%		4i/5i = 30:70
153d2c24Image 19
4i, 27%		Image 25
5i, 64%		4i/5i = 30:70

a The reaction was performed using MBH adducts 3 (1 equiv), ketoenamine 2 (5 equiv), Pd(OAc)2 (0.04 equiv), PPh3 (0.16 equiv), and ZnBr2 (2.66 equiv) in refluxing CH2Cl2.

b Isolated yield.

Next, to establish the substrate scope, we selected the cyclic MBH derivatives 3b–d bearing three different leaving groups (LG = OAc, OMe, OEt), and we explored their behavior toward the nucleophilic enamines 2. First, upon treatment of allylic acetate 3b or allylic ethers 3c and 3d with enamine 2a, under the previous conditions (MBH adduct (1 equiv), ketoenamine (5 equiv), Pd(OAc)2 (0.04 equiv), PPh3 (0.16 equiv), and ZnBr2 (2.66 equiv) in CH2Cl2), the reaction worked well. Nevertheless, the expected SN2-type product 4d was not isolated but we exclusively obtained the same compound 5d, in 75–80% yields (entries 4–6). This derivative was presumably formed through an in situ intramolecular Michael addition on the enone moiety of its precursor 4d (Scheme 2, Table 3, entries 4–6). The best yield (80%) and the shorter reaction time (24 h) were achieved with the allylic acetate 3b that was found to be the most reactive.

Scheme 2

Allylic substitution of MBH adducts 3b–e with enamines 2a–c.

It is noteworthy that the monitoring of the reaction progress by thin layer chromatography, from the beginning of our experiment, showed only the formation of the compound 5d with no trace of its precursor 4d (Table 3, entries 4–6), suggesting that the conversion of this intermediate into 5d was kinetically faster than that of substrates 3b–d into the intermediate 4d.

Correlatively, an interesting example on Michael–Stork addition of enamine 2a to allenyl ketones and esters was previously reported by Lepore et al. [26]. They showed that a Michael addition onto the title substrates provided an iminium ion intermediate, which could further undergo hydrolysis to afford the 1,4-adducts 6. Alternatively, the corresponding enamines can undergo an intramolecular cyclization to yield the bicyclic compounds 7 (Scheme 3).

Scheme 3

Michael–Stork addition of an enamine to allenyl ketones and esters.

Furthermore, we explored the scope of this allylic nucleophilic substitution reaction involving the five-membered MBH acetate 3e with enamines 2a–c. Under the previous conditions (Pd(OAc)2/ZnBr2), adducts 5e–g were exclusively obtained in 57–64% yields (Scheme 2, Table 3, entries 7–9).

Finally, the nucleophilic allylic substitution of substrates 3b–d with six-membered enamines 2b and 2c has been investigated (Scheme 2, Table 3, entries 10–15). We observed that these substrates did not have the same behavior toward the five-membered enamine 2a (vide supra) and the six-membered enamines 2b and 2c (Scheme 2, Table 3, entries 10–15). Indeed, the reaction with enamine 2a gave exclusively the adduct 5d (Scheme 2, Table 3, entries 4–6), whereas the use of 2b and 2c gave predominantly adducts 5h and 5i along with their corresponding precursors 4h and 4i (Scheme 2, Table 3, entries 10–15) in high overall yields.

Compounds 5h and 5i and the corresponding precursors 4h and 4i were easily separated by column chromatography (petroleum ether/ether = 60:40) and fully characterized. Polycyclic compounds 5d–i were unequivocally elucidated by 1H NMR and high-resolution mass spectra (HRMS).

It is notable that, under the catalysis of both Pd(0) and ZnBr2, we did not observe any SN2′ product along with the SN2-type products 4d–i using cyclic MBH adducts 3b–e and enamines 2a–c. We believe that this allylic substitution is under thermodynamic control, affording exclusively the α-products [27,28].

To explain the formation of the 1,5-dicarbonyl compounds 4 and 5, we propose an initial departure of the leaving group on adducts 3, which would be assisted by the Lewis acid ZnBr2 [29–31]. Indeed, the resulting intermediate 7 undergoes an oxidative addition to Pd(0) to form a cationic Π–allyl Pd(II) complex 8 (i) that is further attacked by the enamines 2, yielding an iminium intermediate 9 (ii). After that, there is either the hydrolysis of the intermediate 9 to give the δ-diketones 4 (iii), or alternatively the carbanion derived from the tautomeric form 9′ of 9 undergoes an intramolecular Michael addition on the enone moiety to finally provide, after hydrolysis, the δ-diketones 5 (iv) (Scheme 4).

Scheme 4

Proposed reaction mechanism for 1,5-dicarbonyl compounds 4 and 5.

3 Conclusion

We have reported the first examples of an efficient ZnBr2-promoted Pd-catalyzed allylic substitution reactions of cyclic and acyclic MBH adducts with cyclic ketoenamines in refluxing dichloromethane. These reactions afford a series of SN2-type unsaturated 1,5-dicarbonyl compounds, which can further undergo an intramolecular Michael addition on the enone moiety, yielding the corresponding 1,4-adducts. All the newly synthesized compounds were isolated in moderate to good yields and fully characterized.

4 Experimental section

4.1 General comments

1H NMR and 13C NMR spectra were recorded either on a 300 MHz Bruker for 1H or 75 MHz in CDCl3, using tetramethylsilane as an internal standard (chemical shifts in δ values and J in Hz). HRMS were recorded as ESI-HRMS on an Auto Spec Ultima/micromass mass spectrometer. Mass spectra (EI) were obtained at 70 eV on a Hewlett–Packard HP-5890. Analytical thin layer chromatography was performed using Fluka Kieselgel 60 F254 precoated silica gel plates. Visualization was achieved by UV light (254 nm). Flash chromatography was performed using silica gel 60 and a gradient solvent system (petroleum ether/ether). Compounds 3 and enamines 2 were prepared according to the literature methods [21,25].

4.2 General procedure for the synthesis of 1,5-dicarbonyl compounds 4a–i and 5a–i

Under nitrogen, a mixture of MBH acetate 3 (1.5 mmol), Pd(OAc)2 (13 mg, 0.06 mmol), PPh3 (63 mg, 0.24 mmol), and ZnBr2 (0.90 g, 4 mmol) was refluxed in CH2Cl2 (10 mL) for 15 min. Then the solution of enamine 2 (7.5 mmol) in CH2Cl2 (5 mL) was added, and the reaction mixture was refluxed for 4–48 h. After evaporation of CH2Cl2, water (10 mL) was added with NaOH (1 M, 30 mL), and the mixture was extracted with CH2Cl2 (3 × 30 mL). The organic phase was washed with a saturated solution of ammonium chloride (10 mL) and dried over magnesium sulfate. After removal of the solvent, the residue was subjected to column chromatography (petroleum ether/ether = 60:40) to produce pure unsaturated 1,5-dicarbonyl compounds 4a–i and 5a–i.

4.3 Ethyl 2-((2-oxocyclopentyl)methyl)acrylate (4a)

Yield 70%; colorless oil. 1H NMR (CDCl3, 300 MHz): δ 6.19 (d, J = 3 Hz, 1H), 5.59 (d, J = 3 Hz, 1H), 4.21 (q, J = 7.5 Hz, 2H), 2.91–2.85 (m, 1H), 2.38–2.34 (m, 2H), 2.33–2.21 (m, 4H), 1.99–1.86 (m, 1H), 1.54–1.50 (m, 1H), 1.32 (t, J = 7.5 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 219.5, 166.9, 138.9, 126.1, 60.7, 48.1, 37.8, 32.1, 29.7, 20.6, 14.2. MS (m/z), 55 (53), 68 (50), 96 (100), 151 (21), 168 (51), 196 (M+, 39); HRMS calcd for C11H16O3+ [M−H]+ 195.1021, found 195.1020.

4.4 Ethyl 2-((2-oxocyclohexyl)methyl)acrylate (4b)

Yield 80%; colorless oil. 1H NMR (CDCl3, 300 MHz): δ 6.19 (d, J = 3 Hz, 1H), 5.57 (d, J = 3 Hz, 1H), 4.20 (q, J = 7.5 Hz, 2H), 2.36–2.32 (m, 4H), 2.12–2.08 (m, 2H), 1.89–1.85 (m, 4H), 1.74–1.68 (m, 1H), 1.30 (t, J = 7.5 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 212.1, 166.9, 138.4, 126.6, 60.5, 49.1, 41.8, 33.5, 31.8, 27.9, 26.9, 14.0. MS (m/z), 55 (39), 67 (34), 97 (41), 136 (100), 165 (32), 210 (M+, 8); HRMS calcd for C12H18O3+ [M+H]+ 211.1327, found 211.1325.

4.5 Ethyl 2-((5-methyl-2-oxocyclohexyl)methyl)acrylate (4c)

Yield 68%; colorless oil. 1H NMR (CDCl3, 300 MHz): δ 6.20 (s, 1H), 5.56 (d, J = 3 Hz, 1H), 4.20 (q, J = 8 Hz, 2H), 2.87–2.80 (m, 1H), 2.71–2.67 (m, 1H), 2.42–2.27 (m, 3H), 2.14–2.04 (m, 2H), 1.70 (t, J = 6 Hz, 2H), 1.65–1.55 (m, 1H), 1.30 (t, J = 8 Hz, 3H), 1.08 (d, J = 6 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 213.3, 166.8, 138.3, 126.4, 60.7, 46.5, 39.3, 37.9, 34.2, 32.9, 26.6, 19.5, 14.1. MS (m/z), 55 (89), 67 (42), 136 (28), 151 (100), 179 (62), 224 (M+, 10); HRMS calcd for C13H20O3+ [M+H]+ 225.1484, found 225.1486.

4.6 Decahydro-1H-5,8-methanobenzo[7]annulene-1,10-dione (5d)

Yield 80% from (6-oxocyclohex-1-en-1-yl)methyl acetate 3b, 75% from 2-(methoxymethyl)cyclohex-2-enone 3c, and 75% from 2-(ethoxymethyl)cyclohex-2-enone 3d; white solid; mp 128–130 °C. 1H NMR (CDCl3, 300 MHz): δ 2.66–2.57 (m, 1H), 2.40–2.32 (m, 3H), 2.19–1.92 (m, 7H), 180–1.60 (m, 4H), 1.25–1.16 (m, 1H). 13C NMR (CDCl3, 75 MHz): δ 219.4, 210.6, 51.4, 49.2, 47.1, 43.4, 41.3, 34.7, 29.7, 26.0, 23.1, 18.5. MS (m/z), 96 (48), 110 (40), 164 (31), 192 (M+, 100); HRMS calcd for C12H16O2+ [M+H]+ 193.1229, found 193.1230.

4.7 Octahydro-4,7-methanoazulene-1,9(2H)-dione (5e)

Yield 60%; white solid; mp 122–126 °C. 1H NMR (CDCl3, 300 MHz): δ 2.37–2.00 (m, 4H), 1.81–1.43 (m, 4H), 1.39–1.23 (m, 4H), 0.91–0.83 (m, 2H). 13C NMR (CDCl3, 75 MHz): δ 220.8, 220.7, 47.1, 46.8, 38.0, 30.2, 30.1, 29.9, 29.7, 29.6, 20.7. MS (m/z), 150 (100), 178 (M+, 60); HRMS calcd for C11H14O2+ [M+H]+ 179.1072, found 179.1071.

4.8 Decahydro-1H-4,8-methanocyclopenta[8]annulene-1,10-dione (5f)

Yield 64%; white solid; mp 119–121 °C. 1H NMR (CDCl3, 300 MHz): δ 3.04–2.95 (m, 1H), 2.82–2.74 (m, 1H), 2.43–2.31 (m, 3H), 2.19–2.05 (m, 9H), 1.77–1.63 (m, 2H). 13C NMR (CDCl3, 75 MHz): δ 219.3, 219.2, 50.3, 47.4, 45.7, 45.2, 36.9, 35.1, 34.3, 32.2, 27.0, 20.1. MS (m/z), 96 (48), 110 (40), 164 (31), 192 (M+, 100); HRMS calcd for C12H16O2+ [M+H]+ 193.1229, found 193.1241.

4.9 6-Methyldecahydro-1H-4,8-methanocyclopenta[8]annulene-1,10-dione (5g)

Yield 57%; white solid; mp 120–123 °C. 1H NMR (CDCl3, 300 MHz): δ 2.47–2.42 (m, 1H), 2.26–1.96 (m, 4H), 1.94–1.83 (m, 4H), 1.76–1.27 (m, 6H), 0.96 (d, J = 9 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 219.2, 213.0, 51.8, 47.8, 47.5, 46.8, 37.9, 34.5, 34.1, 33.6, 27.9, 24.5, 20.0. MS (m/z) 96 (90), 110 (88), 164 (89), 206 (M+, 98); HRMS calcd for C13H18O2+ [M+H]+ 207.1385, found 207.1389.

4.10 2-((2-Oxocyclohexyl)methyl)cyclohex-2-enone (4h)

Yield 27% from (6-oxocyclohex-1-en-1-yl)methyl acetate 3b, 26% from 2-(methoxymethyl)cyclohex-2-enone 3c, and 35% from 2-(ethoxymethyl)cyclohex-2-enone 3d; colorless oil. 1H NMR (CDCl3, 300 MHz): δ 6.79 (t, J = 4.5 Hz, 1H), 1.76–1.70 (m, 1H), 2.60–2.50 (m, 1H), 2.43–2.28 (m, 6H), 2.08–1.95 (m, 5H), 1.86–1.81 (m, 1H), 1.68–1.59 (m, 2H), 1.21–1.36 (m, 1H). 13C NMR (CDCl3, 75 MHz): δ 212.9, 199.7, 147.8, 137.5, 49.2, 42.2, 38.5, 34.0, 30.3, 28.1, 26.3, 25.0, 23.0. MS (m/z) 55 (100), 67 (71), 95 (52), 110 (31), 122 (83), 206 (M+, 92); HRMS calcd for C13H18O2+ [M+H]+ 207.1385, found 207.1389.

4.11 Decahydro-5,9-methanobenzo[8]annulene-1,11(2H)-dione (5h)

Yield 60% from (6-oxocyclohex-1-en-1-yl)methyl acetate 3b, 57% from 2-(methoxymethyl)cyclohex-2-enone 3c, and 63% from 2-(ethoxymethyl)cyclohex-2-enone 3d; white solid; mp 113–116 °C. 1H NMR (CDCl3, 300 MHz): δ 3.44–3.35 (m, 1H), 2.58–2.53 (m, 2H), 2.46–2.22 (m, 4H), 2.15–1.98 (m, 7H), 1.74–1.54 (m, 4H). 13C NMR (CDCl3, 75 MHz): δ 219.2, 213.0, 51.8, 47.8, 47.5, 46.8, 37.9, 34.5, 34.1, 33.6, 27.9, 24.5, 20.0. MS (m/z): 55 (77), 95 (52), 110 (34), 150 (34), 178 (21), 206 (M+, 100); HRMS calcd for C13H18O2+ [M+H]+ 207.1385, found 207.1383.

4.12 2-((5-Methyl-2-oxocyclohexyl)methyl)cyclohex-2-enone (4i)

Yield 37% from (6-oxocyclohex-1-en-1-yl)methyl acetate 3b, 28% from 2-(methoxymethyl)cyclohex-2-enone 3c, and 27% from 2-(ethoxymethyl)cyclohex-2-enone 3d; colorless oil. 1H NMR (CDCl3, 300 MHz): δ 6.80 (t, J = 4.5 Hz, 1H), 2.77–2.37 (m, 2H), 2.34–2.31 (m, 6H), 2.02–1.92 (m, 7H), 1.90–1.28 (m, 1H), 0.96 (d, J = 6 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 220.9, 199.7, 147.8, 137.5, 47.9, 42.1, 41.6, 38.5, 36.1, 31.9, 30.2, 26.2, 23.0, 21.2. MS (m/z), 55 (79), 110 (47), 203 (88), 220 (M+, 100); HRMS calcd for C14H20O2+ [M+H]+ 221.1542, found 221.1544.

4.13 7-Methyldecahydro-5,9-methanobenzo[8]annulene-1,11(2H)-dione (5i)

Yield 54% from (6-oxocyclohex-1-en-1-yl)methyl acetate 3b, 65% from 2-(methoxymethyl)cyclohex-2-enone 3c, and 64% from 2-(ethoxymethyl)cyclohex-2-enone 3d; white solid; mp 106–108 °C. 1H NMR (CDCl3, 300 MHz): δ 3.46–3.38 (m, 1H), 2.56–2.23 (m, 7H), 2.18–2.12 (m, 4H), 1.69–1.40 (m, 4H), 1.35–1.17 (m, 1H), 0.89 (d, J = 6 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 219.4, 212.9, 51.9, 48.4, 47.8, 45.8, 43.2, 42.8, 37.4, 33.6, 27.6, 26.4, 24.4, 22.4. MS (m/z), 55 (100), 110 (77), 163 (42), 220 (M+, 59); HRMS calcd for C14H20O2+ [M+H]+ 221.1542, found 221.1546.

Bibliographie

[1] M.R. Tatton; I. Simpson; T.J. Donohoe Org. Lett., 16 (2014), pp. 1920-1923

[2] K.K.K. Goh; S. Kim; S.Z. Zard Org. Lett., 15 (2013), pp. 4818-4821

[3] T.J. Donohoe; J.A. Basutto; F.J. Bower; A. Rathi Org. Lett., 13 (2011), pp. 1036-1039

[4] L.A. Hardegger; J. Habegger; T.J. Donohoe Org. Lett., 17 (2015), pp. 3222-3225

[5] V.G. Kharchenko; L.I. Markova; O.V. Fedotova; N.V. Pchelintseva Chem. Heterocycl. Compd., 39 (2003), pp. 1121-1141

[6] H.L. Zhiping He; X. Guo; W. Li; X. Zhao; Z. Li Org. Lett., 11 (2009), pp. 4176-4179

[7] P. Saikia; S. Gogoi; R. Browah J. Org. Chem., 80 (2015), pp. 6885-6889

[8] A.G. Griesbeck; O. Hinze; H. Görner; U. Huchel; C. Kropf; U. Sundermeier; T. Gerke Photochem. Photobiol. Sci., 11 (2012), pp. 587-592

[9] G.A. Molander; P.R. Eastwood J. Org. Chem., 61 (1996), pp. 1910-1911

[10] Y. Chen; J. Wan; C. Wang; C. Sun Molecules, 13 (2008), pp. 2652-2658

[11] L.A. Hardegger; J. Habegger; T.J. Donohoe Org. Lett., 12 (2010), pp. 1484-1487

[12] S.-J. Ji; Z.-L. Shen; D.-G. Gu; S.-Y. Wang J. Organomet. Chem., 689 (2004), pp. 1843-1848

[13] T.P. Kumar; M.A. Sattar; V.U.M. Sarma Tetrahedron: Asymmetry, 24 (2013), pp. 1615-1619

[14] A. Yanagisawa; H. Takahashi; T. Arai Tetrahedron, 63 (2007), pp. 8581-8585

[15] B. Lui; J. Wang; Y. Pang; Z. Ge; R. Li Tetrahedron, 70 (2014), pp. 9240-9244

[16] F. Zhang; E. Corey J. Org. Lett., 6 (2004), pp. 3397-3399

[17] X. Zhao; D. Liu; F. Xie; W. Zhang Tetrahedron, 65 (2009), pp. 512-517

[18] A.R. Katritzky; Z. Huang; F. Fang J. Org. Chem., 64 (1999), pp. 7625-7627

[19] M. Ravinder; B. Mahendar; S. Mattapally; K.V. Hamsini; T.N. Reddy; C. Rohit; S.K. Banergiee; V.J. Rao Bioorg. Med. Chem. Lett., 22 (2012), pp. 6010-6015

[20] M. Ravinder; P.S. Sadhu; V.J. Rao Tetrahedron Lett., 50 (2009), pp. 4229-4232

[21] F. Rezgui; M.M. El Gaied Tetrahedron, 53 (1997), pp. 15711-15716

[22] O. Mhasni; F. Rezgui Tetrahedron Lett., 51 (2010), pp. 586-587

[23] H. Elleuch; M. Ayadi; J. Bouajila; F. Rezgui J. Org. Chem., 81 (2016), pp. 1757-1761

[24] I. Erray; J. Oble; G. Poli; F. Rezgui J. Sulfur. Chem., 35 (2014), pp. 128-136

[25] B.M. Trost; T.R. Verhoeven Compr. Org. Metal. Chem., 8 (1982), pp. 799-983

[26] M.A. Silvestri; D.C. Bromfield; S.D. Lepore J. Org. Chem., 70 (2005), pp. 8239-8241

[27] S. Rajesh; B. Banerji; J. Iqbal J. Org. Chem., 67 (2002), pp. 7852-7857

[28] Y.-L. Liu; L. Liu; D. Wang; Y.-J. Chen Tetrahedron, 65 (2009), pp. 3473-3479

[29] A.R. Katritzky; H. Wu; L. Xie; S. Rachwal; B. Rachwal; J. Jiang; G. Zhang; H. Lang Synthesis, 10 (1995), pp. 1315-1323

[30] A.R. Katritzky; J. Chen; S.A. Belyakov Tetrahedron Lett., 37 (1996), pp. 6631-6634

[31] A.R. Katritzky; X. Wang; L. Xie; D. Toader J. Org. Chem., 63 (1998), pp. 3445-3449

Commentaires - Politique

Ces articles pourraient vous intéresser

Iron salts catalyzed synthesis of β-N-substituted aminoacrylates

Hania Hebbache; Zakia Hank; Sultana Boutamine; ...

C. R. Chim (2008)

New functionalized scaffolds from hydroxymethylfurfural and glucosyloxymethylfurfural by Morita–Baylis–Hillman reaction with cycloalkenones

Lianjie Wang; Jia-Neng Tan; Mohammed Ahmar; ...

C. R. Chim (2019)

Organocatalyzed tandem process involving asymmetric protonations as a stereo-defining step

Angelo Frongia; Francesco Secci; Nicola Melis

C. R. Chim (2015)