Highly tuned, one-point binding chiral iron and ruthenium complexes selectively coordinate and activate α,β-unsaturated aldehydes and ketones toward asymmetric catalytic Diels-Alder cycloaddition reactions. Here we focus on the application of these transition-metal Lewis acids to asymmetric catalytic 1,3-dipolar cycloaddition reaction between enals and cyclic and acyclic nitrones as well as aryl nitrile oxides to give isoxazolidines and isoxazolines, respectivel

Brinkmann, Yasmin

Bădoiu, Andrei

Kündig, E. Peter

Viton, Florian

RERO DOC Digital Library

1013Pure Appl. Chem., Vol. 80, No. 5, pp. 1013–1018, 2008.doi:10.1351/pac200880051013© 2008 IUPACAsymmetric Lewis acid-catalyzed 1,3-dipolarcycloadditions*Andrei Baˇdoiu, Yasmin Brinkmann, Florian Viton, andE. Peter Kündig‡Department of Organic Chemistry, University of Geneva, Sciences II,30 quai Ernest Ansermet, CH-1211 Geneva 4, SwitzerlandAbstract: Highly tuned, one-point binding chiral iron and ruthenium complexes selectivelycoordinate and activate α,β-unsaturated aldehydes and ketones toward asymmetric catalyticDiels–Alder cycloaddition reactions. Here we focus on the application of these transition-metal Lewis acids to asymmetric catalytic 1,3-dipolar cycloaddition reaction between enalsand cyclic and acyclic nitrones as well as aryl nitrile oxides to give isoxazolidines and isoxa-zolines, respectively. Keywords: Lewis acids; asymmetric reactions; 1,3-dipolar cycloadditions; nitrones; nitrileoxides.INTRODUCTIONTransition-metal-mediated and -catalyzed reactions continue to have a high impact on the venerablefield of heterocyclic chemistry. Functionalized chiral N,O-heterocyclic compounds figure prominentlydue to the high versatility of these compounds either on their own or, after the reductive cleavage of theN–O bond, as acyclic chiral amino alcohol building blocks. Asymmetric catalytic cycloaddition reac-tions can afford an efficient access to highly enantiomerically enriched N,O-heterocycles [1].We have developed structurally well-defined, single-point binding chiral transition-metal Lewisacid complexes of Fe(II) (1) and Ru(II) (2) that selectively bind and activate α,β-unsaturated aldehydesand ketones for asymmetric Diels–Alder reactions [2]. Structural and mechanistic studies provided in-sight into the mode of activation, the geometry of the coordinated and activated dienophile, the role ofthe counterion, and the factors governing endo/exo-selectivity of the cycloadditions. *Paper based on a presentation at the 14th International Symposium on Organometallic Chemistry Directed Towards OrganicSynthesis (OMCOS-14), 2–6 August 2007, Nara, Japan. Other presentations are published in this issue, pp. 807–1194.‡Corresponding author: E-mail: peter.kundig@chiorg.unige.chWith its potential for the control of up to three contiguous stereogenic centers, the chiral Lewisacid-catalyzed 1,3-dipolar cycloaddition reaction between nitrones and alkenes is a direct and versatileroute to these compounds. Catalytic asymmetric reactions between nitrones and α,β-unsaturated dicar-bonyl compounds have been shown to be successfully catalyzed by two-point binding chiral Lewisacids [3]. For normal electron-demand cycloadditions, two-point binding of the dipolarophile appeareda necessity because one-point binding Lewis acids were shown to coordinate nitrones preferentiallyover simple α,β-unsaturated aldehydes. Thus, addition of a nitrose to a Lewis acid gives a 1:1 complexand this coordination is often irreversible. Any nitrone/enal cycloaddition would then be due to the non-catalyzed background reaction. This changed in 2002 when Kanemasa et al. showed that a stericallyhindered Lewis acid prevents the bulky nitrone from coordinating at the metal and that α,β-unsaturatedaldehydes can thus be activated and used in the 1,3-dipolar cycloaddition [4]. In the same year, we pro-vided the first examples of one-point binding asymmetric catalytic 1,3-dipolar cycloaddition reactionsof nitrones with α,β-unsaturated aldehydes [5], and Yamada et al., using β-ketoiminato Co(II) com-plexes, also published their first results shortly thereafter [6]. A subsequent full study showed the effi-ciency and versatility of these complexes as catalysts for the reaction of diarylnitrones and α,β-unsatu-rated aldehydes [7,8]. Carmona’s dicationic, half-sandwich, Rh and Ir aqua complexes containingdiphosphine or PN ligands also proved good catalysts for this transformation [9–12]. The same grouprecently provided the first examples of asymmetric catalytic cycloaddition reactions of nitrones withmethacrylonitrile [13]. In situ prepared complexes of Ni, Zn, and Mg with DBFOX ligands also werefound to be highly efficient and selective catalysts [14,15]. In elegant work, Maruoka et al. recently re-ported BINOL Ti-complexes to catalyze very efficiently the reaction of the less reactive N-benzyl andN-diphenylmethyl, aryl nitrones providing an access to isoxazoldines bearing readily cleavable groupsat the nitrogen atom [16,17]. Preceding the asymmetric transition-metal-catalyzed dipolar nitrone cycloadditions, and stimu-lating this research in the first place, are the organocatalyzed reactions reported by McMillan et al. in2000 [18]. This field also has seen much recent progress [19–23]. In this short article, we review our recent results in asymmetric Lewis acid-catalyzed 1,3-dipolarcycloaddition reactions of enals with acyclic nitrones [24] and the extension of these reactions to nitrileoxides [25].A. BAˇ DOIU et al.© 2008 IUPAC, Pure and Applied Chemistry 80, 1013–10181014DIARYL NITRONESAs mentioned above, the Lewis acid-catalyzed cycloaddition reaction between enals and nitrones waslong thought impossible to realize since nitrones are better ligands than aldehydes and they thereforeprevent enal activation by Lewis acids and poison the catalyst. We found that judicious choice of metalligand environment and Lewis acidity can overcome this preference. Both (R,R)-1 and (R,R)-2 are effi-cient catalysts for the asymmetric cycloaddition reaction of enals with a variety of cyclic nitrones. Thecycloadducts were obtained in excellent yields and high enantiomeric purity when the reaction was per-formed in the presence of 5 mol % of (R,R)-1 [5]. Acyclic nitrones are generally more difficult substrates due to the possibility of forming two re-gioisomeric products. Initial results with diphenylnitrone confirmed the ability of (R,R)-1 and (R,R)-2to efficiently catalyze the reaction with methacrolein [5]. Only the endo-products were obtained, but re-gioselectivity was poor (3:2 mixture). While the catalyst of choice for the cyclic nitrones was the Fecomplex (R,R)-1, the Ru analog (R,R)-2 proved better in the case of the diaryl nitrones. Despite giving good results in terms of selectivities, at –20 °C the cycloaddition was slow andsuffered further due to the low solubility of the diphenylnitrone at this temperature (Table 1, entry 1).Raising the temperature to –10 °C and concentrating the reaction mixture led to nearly quantitativeyields and a shortening of the reaction time (entry 2). Moreover, selectivities were perfectly preserved,showing thus that the background reaction, even though present at –10 °C, can be completely sup-pressed by the very active Ru catalyst (R,R)-2. The complex can be efficiently recovered and reusedafter the reaction [24].Table 1 Ru-Lewis acid-catalyzed asymmetric 1,3-dipolar cycloadditions ofmethacrolein with diaryl nitrones.Entry Nitrone T Time Isolated 5a/6aa ee (%)(°C) (h) yield (%) 5a/6ab1 3a, R = H –20 32 84 60/40 75/942 3a, R = H –10 14 >98 67/33 75/943 3b, R = NO2 –10 74 16 95/5 71/–4 3c, R = CF3 –10 64 >98 91/9 74/885 3d, R = Cl –10 64 89 73/27 77/896 3e, R = Me –10 22 >98 41/59 74/957 3f, R = OMe –10 22 >98 21/79 75/92aDetermined by NMR analysis. bDetermined by chiral HPLC analysis of the cycloadduct after reduction to theprimary alcohol.For the 1,3-dipolar cycloaddition reaction, both steric and electronic properties are known to in-fluence regioselectivity. In order to assess the latter, a series of diarylnitrones substituted in the para-position of the C-aryl moiety were probed as substrates in the reaction with methacrolein (entries 3–7).5 mol % of the Ru catalyst (R,R)-2 and the optimized conditions at –10 °C were sufficient to give thedesired cycloadducts in almost quantitative yield, complete endo-selectivity, and high enantiomeric pu-rity. The ee, determined by HPLC analysis after conversion to the primary alcohols, was consistently© 2008 IUPAC, Pure and Applied Chemistry 80, 1013–1018Asymmetric catalyzed 1,3-dipolar cycloadditions 1015higher for the 4-substituted isoxazolidines than for the 5-substituted isomers. The low yield obtainedwith the p-NO2-substituted nitrone is interpreted as resulting from competitive coordination of the nitrogroup at the Ru center, thus interfering with the catalytic cycle (entry 3).The variation of the regioisomeric ratio with the electronic character of the aryl substituent R isa particularly notable feature in this series. Thus, in the case of electron-withdrawing substituents the5-substituted isoxazolidine are the predominant products. On the other hand, electron-donating sub-stituents on the nitrone lead to the formation of the 4-substituted isoxazolidines as the major product[26].ARYL NITRILE OXIDESWhile nitrones have been widely used in catalytic asymmetric 1,3-dipolar cycloaddition reactions [1],this is not the case for nitrile oxides. Synthetically, the 2-isoxazolines are very attractive products, butdevelopment of the use of nitrile oxides in these reactions is hampered by their tendency to dimerize.Not surprisingly, literature reports on efficient catalytic, enantioselective 1,3-dipolar cycloaddition re-actions of nitrile oxides with alkenes are scarce [27–30]. Our initial reactions were carried out using the relatively stable mesityl nitrile oxide. Slow addi-tion of the nitrile oxide by means of a syringe pump to a stirred mixture of methacrolein and 5 mol %of (R,R)-2 in CH2Cl2, at –15 °C, followed by reduction, led to the exclusive formation of 2-isoxazoline9a in 71 % yield and 62 % ee (Table 2, entry 1). In the following, the study was extended to other arylnitrile as shown below [25]. In all cases, reactions afforded the 3,5-substituted isoxazolines as singleregioisomers.Table 2 Asymmetric catalyzed 1,3-dipolar cycloadditionsbetween methacrolein and aryl nitrile oxides.Entry Nitrile oxide T Time Isolated ee (%)a(°C) (h) yield (%)1 7a, 2,4,6-Me –15 72 75 602 7b, 4-CF3 –20 16 60 933 7c, 4-F –20 24 38 774 7d, 3,5-CF3 –20 16 40 825 7e, 4-OMe –5 39 57 656 7f, 4-iPr –5 38 65 63aDetermined by chiral HPLC analysis.Two main trends arise from the results shown above. For the aromatic nitrile oxides bearing elec-tron-poor substituents, the best results were obtained at –20 °C (entries 2–4), while in the case of elec-tron-rich substitution, results of reactions carried out at –5 °C were better (entries 5, 6). Electron-with-drawing aryl groups at the nitrile oxide gave products with higher ee (up to 93 %) than those withelectron-releasing groups. As in the case of nitrones, the absolute configuration is in perfect agreementwith an approach of the nitrile oxide on the accessible Cα-Si face of the methacrolein bound at the Ruin an anti s-trans conformation [5,24,25].A. BAˇ DOIU et al.© 2008 IUPAC, Pure and Applied Chemistry 80, 1013–10181016In summary, using 5 mol % of the [Ru(acetone)(R,R-BIPHOP-F)Cp][SbF6] complex 2 and care-fully optimized reaction conditions, the asymmetric 1,3-dipolar cycloaddition reaction between diarylnitrones and methacrolein can be efficiently catalyzed. Moreover, the mild Lewis acid character of thisRu complex allows for a unique reversal of the regioisomeric ratio as a function of the electronic natureof the dipole. The same catalyst has been successfully used in the first asymmetric, single-point bind-ing, catalytic 1,3-dipolar cycloaddition between aryl nitrile oxides and methacrolein. High asymmetricinductions can be achieved, although yields leave room for improvement.ACKNOWLEDGMENTSFinancial support of this work by the Swiss National Science Foundation and the University of Genevais gratefully acknowledged. REFERENCES1. Reviews: (a) K. V. Gothelf, K. A. Jørgensen. Chem. Rev. 98, 863 (1998); (b) S. Kobayashi, K. A.Jørgensen. Cycloaddition Reactions in Organic Synthesis, Wiley-VCH, Weinheim (2002).2. (a) E. P. Kündig, B. Bourdin, G. Bernardinelli. Angew. Chem., Int. Ed. Engl. 33, 1856 (1994); (b)E. P. Kündig, A. Quattropani, M. Inage, A. Ripa, C. Dupre, A. F. Cunningham Jr., B. Bourdin.Pure Appl. Chem. 68, 97 (1996); (c) M. E. Bruin, E. P. Kundig. Chem. Commun. 2635 (1998); (d)E. P. Kündig, M. S. Saudan, G. Bernardinelli. Angew. Chem., Int. Ed. 38, 1220 (1999); (e) E. P.Kündig, M. S. Saudan, F. Viton. Adv. Synth. Catal. 343, 51 (2001); (f) E. P. Kündig, M. S. Saudan,V. Alezra, F. Viton, G. Bernardinelli. Angew. Chem., Int. Ed. 40, 4481 (2001); (g) P. G. AnilKumar, P. S. Pregosin, M. Vallet, G. Bernardinelli, R. F. Jazzar, F. Viton, E. P. Kündig.Organometallics 23, 5410 (2004); (h) A. Alezra, G. Bernadinelli, C. Corminboeuf, U. Frey, E. P.Kündig, A. E. Merbach, C. M. Saudan, F. Viton, J. T. Weber. J. Am. Chem. Soc. 126, 4843 (2004);(i) J. Rickerby, M. Vallet, G. Bernardinelli, F. Viton, E. P. Kündig. Chem.—Eur. J. 13, 3354(2007).3. (a) K. V. Gothelf, K. A. Jørgensen. J. Org. Chem. 59, 5687 (1994); (b) D. Seebach, R. E. Marti,T. Hintermann. Helv. Chim. Acta. 79, 1710 (1996); (c) K. Hori, H. Kodama, T. Ohta, I. Furukawa.Tetrahedron Lett. 37, 5947 (1996); (d) K. Jensen, R. G. Hazell, K. V. Gothelf, K. A. Jørgensen. J.Org. Chem. 62, 2471 (1997); (e) S. Kobayashi, M. Kawamura. J. Am. Chem. Soc. 120, 5840(1998); (f) S. Kanemasa, Y. Oderatoshi, J. Tanaka, E. Wada. J. Am. Chem. Soc. 120, 12355(1998); (g) K. Hori, H. Kodama, T. Ohta, I. Furukawa. J. Org. Chem. 64, (1999) 5017; (h)G. Desimoni, G. Faita, A. Mortoni, P. Righetti. Tetrahedron Lett. 40, 2001 (1999); (i) H. Kodama,J. Ito, K. Hori, I. Furukawa. J. Organomet. Chem. 603, 6 (2000); (j) S. Iwasa, S. Tsushima,T. Shimada, H. Nishiyama. Tetrahedron Lett. 42, 6715 (2001).4. S. Kanemasa, N. Ueno, M. Shirahase. Tetrahedron Lett. 43, 657 (2002).5. F. Viton, G. Bernardinelli, E. P. Kündig. J. Am. Chem. Soc. 124, 4968 (2002).6. T. Mita, N. Ohtsuki, T. Ikeno, T. Yamada. Org. Lett. 4, 2457 (2002).7. S. Kezuka, N. Ohtsuki, T. Mita, Y. Kogami, T. Ashizawa, T. Ikeno, T. Yamada. Bull. Chem. Soc.Jan. 76, 2197 (2003).8. N. Ohtsuki, S. Kezuka, Y. Kogami, T. Mita, T. Ashizawa, T. Ikeno, T. Yamada. Synthesis-Stuttgart1462 (2003).9. D. Carmona, M. P. Lamata, F. Viguri, R. Rodriguez, L. A. Oro, A. I. Balana, F. J. Lahoz, T. Tejero,P. Merino, S. Franco, I. Montesa. J. Am. Chem. Soc. 126, 2716 (2004).10. D. Carmona, M. P. Lamata, F. Viguri, R. Rodriguez, L. A. Oro, F. J. Lahoz, A. I. Balana, T. Tejero,P. Merino. J. Am. Chem. Soc. 127, 13386 (2005).11. D. Carmona, M. P. Lamata, F. Viguri, J. Ferrer, N. Garcia, F. J. Lahoz, M. L. Martin, L. A. Oro.Eur. J. Inorg. Chem. 3155 (2006).© 2008 IUPAC, Pure and Applied Chemistry 80, 1013–1018Asymmetric catalyzed 1,3-dipolar cycloadditions 101712. D. Carmona, M. P. Lamata, F. Viguri, R. Rodriguez, T. Fischer, F. J. Lahoz, I. T. Dobrinovitch,L. A. Oro. Adv. Synth. Catal. 349, 1751 (2007).13. D. Carmona, M. Pilar Lamata, F. Viguri, R. Rodriguez, F. J. Lahoz, L. A. Oro. Chem.—Eur. J. 13,9746 (2007).14. M. Shirahase, S. Kanemasa, M. Hasegawa. Tetrahedron Lett. 45, 4061 (2004).15. M. Shirahase, S. Kanemasa, Y. Oderaotoshi. Org. Lett. 6, 675 (2004).16. T. Kano, T. Hashimoto, K. Maruoka. J. Am. Chem. Soc. 127, 11926 (2005).17. T. Hashimoto, M. Omote, T. Kano, K. Maruoka. Org. Lett. 9, 4805 (2007).18. W. S. Jen, J. J. M. Wiener, D. W. C. MacMillan. J. Am. Chem. Soc. 122, 9874 (2000).19. S. Karlsson, H. E. Hogberg. Tetrahedron: Asymmetry 13, 923 (2002).20. S. Karlsson, H. E. Hogberg. Eur. J. Org. Chem. 2782 (2003).21. A. Puglisi, M. Benaglia, M. Cinquini, F. Cozzi, G. Celentano. Eur. J. Org. Chem. 567 (2004).22. M. Lemay, J. Trant, W. W. Ogilvie. Tetrahedron 63, 11644 (2007).23. S. S. Chow, M. Nevalainen, C. A. Evans, C. W. Johannes. Tetrahedron Lett. 48, 277 (2007).24. A. Bădoiu, G. Bernardinelli, J. Mareda, E. P. Kündig, F. Viton. Chem. Asian J. (2008). In press.25. Y. Brinkmann, R. J. Madhushaw, R. Jazzar, G. Bernardinelli, E. P. Kündig. Tetrahedron 63, 8413(2007).26. C. G. Swain, E. C. Lupton. J. Am. Chem. Soc. 90, 4328 (1968).27. Y. Ukaji, K. Sada, K. Inomata. Chem. Lett. 1847 (1993).28. M. Shimizu, Y. Ukaji, K. Inomata. Chem. Lett. 455 (1996).29. M. Tsuji, Y. Ukaji, K. Inomata. Chem. Lett. 1112 (2002).30. M. P. Sibi, K. Itoh, C. P. Jasperse. J. Am. Chem. Soc. 126, 5366 (2004).A. BAˇ DOIU et al.© 2008 IUPAC, Pure and Applied Chemistry 80, 1013–10181018

Asymmetric Lewis acid-catalyzed 1,3-dipolar cycloadditions

Abstract

Similar works

Full text

Available Versions

RERO DOC Digital Library