DOI: 10.1002/chem.201404859
Communication
& C H Activation
Hydroarylations of Heterobicyclic Alkenes through RhodiumCatalyzed Directed C H Functionalizations of S-Aryl Sulfoximines Wanrong Dong,[a] Kanniyappan Parthasarathy,[a] Ying Cheng,[a] Fangfang Pan,[b] and Carsten Bolm*[a] to heterobicyclic alkenes (hydroarylation) that allow to keep the backbone of the unsaturated starting material [Eq. (2)]. They proceed under rhodium catalysis by utilizing sulfoximidoyl substituents as a directing group. As a result, synthetically valuable products are obtained that can further be derivatized.
Abstract: Rhodium-catalyzed directed CH-functionalizations have been used in hydroarylations of heterobicyclic alkenes with NH-sulfoximines. Unexpectedly, the bicyclic framework is retained, resulting in the formation of addition products being attractive intermediates for functionalized molecules that are difficult to prepare by other means.
Transition-metal-catalyzed direct C H-bond functionalizations have become a powerful alternative to the traditional methodologies that require the use of pre-functionalized starting materials.[1] Applying this principle has led to the development of most valuable and straightforward methods for the construction of C C or C X (X = Cl, Br, N, O, etc.) bond frameworks.[2] Among them, addition reactions stand out owing to their high efficiency and atom economy; hose combining C(sp2) H fragments with alkenes or alkynes have been the focus of many studies.[3] Ever since the first examples of ruthenium-catalyzed selective C H/olefin addition reactions by Lewis[4a] and Murai,[4b,c] various catalysts based on Pd,[3e, 5] Ru,[6] Rh,[7] or other transition metals[8] have been introduced. Commonly, these systems require combinations of substrates with heteroatomcontaining moieties for directing the C H functionalizations[9] and alkynes or substituted alkenes as unsaturated coupling partners [Eq. (1)]. It is worth noting that heterobicyclic alkenes have only been used scarcely in such types of C H addition reactions.[10, 11] A recent example is the rhodium-catalyzed coupling between phenyl pyridines with 7-oxa- or 7-azabenzonorbornadienes, leading to naphthylated arenes or dihydrocarbazoles, respectively, as reported by Qi and Li.[12] To the best of our knowledge, analogous reactions with other substrates undergoing C H functionalizations and, in particular, transformations retaining the heterobicyclic core are unprecedented. Herein, we demonstrate directed C(sp2) H addition reactions
Starting point of our investigation was the recently discovered C H activation of sulfoximidoyl-substituted arenes by rhodium catalysis.[13, 14] Both 1,2-benzothiazines and alkenylsubstituted sulfoximines could selectively be accessed by using adequately functionalized sulfur reagents in combination with alkynes or alkenes, respectively. Assuming analogous reaction pathways, we now submitted a mixture of NH-sulfoximine 1 a and benzo-substituted heterobicyclic olefin 2 a to the previously optimized reaction conditions involving [Cp*Rh(MeCN)3][BF4]2 (5 mol %), Fe(OAc)2 (20 mol %), and dioxygen (1 atm) in toluene at elevated temperature (100 8C). However, in contrast to our expectations, no oxidative olefination occurred, but instead, 1 a added to the heterobicyclic olefin to give saturated benzo-fused 7-oxanorbornane 3 a in 62 % yield (Table 1, entry 1).[15] Because the heterobicyclic core is retained, the reaction opens attractive synthetic opportunities, allowing a more elaborate functionalization at a later stage. Raising the temperature from 100 to 120 8C increased the yield of 3 a to 89 % (Table 1, entry 2). The catalyst loading could be reduced to 2.5 mol %, affording 3 a in almost the same yield as with 5 mol % (87 %, Table 1, entry 3). Reducing the catalyst amount further to 1.0 mol % of [Cp*Rh(MeCN)3][BF4]2 had a negative effect on the yield of the product (63 % as determined by NMR spectroscopy; Table 1, entry 4). With the optimized reaction conditions in hand, the substrate scope was examined. First, various diversely substituted sulfoximines (1 a–l) were reacted with alkene 2 a (Table 2, entries 1–12). In general, all additions proceeded well, providing
[a] Dr. W. Dong, Dr. K. Parthasarathy, Y. Cheng, Prof. Dr. C. Bolm Institute of Organic Chemistry, RWTH Aachen University Landoltweg 1, 52056 Aachen (Germany) Fax: (+ 49) 241-8092-391 E-mail: [email protected] [b] Dr. F. Pan Institute of Inorganic Chemistry, RWTH Aachen University Landoltweg 1, 52056, Aachen (Germany) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201404859. Chem. Eur. J. 2014, 20, 1 – 6
These are not the final page numbers! ÞÞ
1
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
Communication Table 1. Optimization of the addition reaction.
Table 2. (Continued)
Entry
x
Temp. [8C]
Yield [%]
1 2 3 4
5.0 5.0 2.5 1.0
100 120 120 120
62 89 87 63[b]
[a] Reaction conditions: sulfoximine 1 a (0.30 mmol), alkene 2 a (0.36 mmol), [Cp*Rh(MeCN)3][BF4]2 (x mol %), Fe(OAc)2 (0.06 mmol, 20 mol %), and toluene (2.5 mL) under O2 (1 atm) at indicated temperature for 4 h. [b] Determined by 1H NMR spectroscopy.
Entry
1
2
Product 3
Yield [%]
10 11 12
1j 1k 1l
2a 2a 2a
3 j: R4 = iBu 3 k: R4 = iPr 3 l: R4 = cyclo-Pr
78 86 87
13
1a
2b
3m
85
14
1a
2c
3n
82
15
1a
2d
3o
78
16
1a
2e
3p
76
17
1a
2f
3 q: X = NCOOMe
82
18[b]
1a
2g
III
Table 2. Substrate scope of the Rh -catalyzed hydroarylation of heterobicyclic alkenes with sulfoximines.[a]
85 3r
Entry
&
&
1
2
Product 3
1
1a
2a
3 a: R1 = H
87
2
1b
2a
3 b: R1 = Me
86
3
1c
2a
3 c: R1 = MeO
90
4 5 6 7
1d 1e 1f 1g
2a 2a 2a 2a
3 d: R1 = Me 3 e: R1 = NO2 3 f: R1 = Cl 3 g: R1 = Br
89 70 79 80
8
1h
2a
3h
85
9
1i
2a
3 i: R2 = Et
91
Chem. Eur. J. 2014, 20, 1 – 6
[a] Reaction conditions: sulfoximine 1 (0.50 mmol), alkene 2 (0.60 mmol), [Cp*Rh(MeCN)3][BF4]2 (0.0125 mmol, 2.5 mol %), Fe(OAc)2 (0.10 mmol, 20 mol %), and toluene (3.0 mL) at 120 8C for 4 h. [b] The ratio of regioisomers 3 r and 3 r’ was ca. 1:1, as determined by 1H NMR spectroscopy.
Yield [%]
www.chemeurj.org
3 r’
products in yields ranging from 70 to 91 %. Electron-donating substituents on the sulfoximine arene appeared to have a slightly positive effect on the yield. For example, 4-methoxyand 4-methyl-substituted sulfoximines 1 c and 1 d afforded addition products 3 c and 3 d in 90 and 89 % yield, respectively (Table 2, entries 3 and 4). In contrast, using 1 e with an electron-withdrawing nitro group in the 4 position of the arene led to 3 e in only 70 % yield (Table 2, entry 5). Halo substituents were unaffected, giving access to chloro and bromo-substituted products 3 f and 3 g in 79 and 80 % yield, respectively (Table 2, entries 6 and 7). Noteworthy are the results from the addition reactions of 3-methyl-substituted sulfoximine 1 b and naphthyl derivative 1 h onto oxabicyclic alkene 2 a, which led to 3 b and 3 h in 86 and 85 % yield, respectively (Table 2, entries 2 and 8). In both cases, a high regioselectivity was observed, which we attributed to steric factors hampering alternative pathways. Varying the non-aromatic substituent of the sulfoximine sulfur was also possible, as reflected by the results 2
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!
Communication of the additions of 1 i–l onto alkene 2 a, providing 3 i–l in yields ranging from 78 to 91 % (Table 2, entries 9–12). These results are similar to the aforementioned one observed in the coupling of methyl-bearing sulfoximine 1 a, which led to 3 a in 87 % yield (Table 2, entry 1). Under the same catalytic conditions, heterobicyclic alkenes 2 b–g were reacted with sulfoximine 1 a (Table 2, entries 13–18); these transformations also provided the addition products in good yields (up to 85 %). In the series of 7-oxabicycles 2 a–e and 2 g, the substitution pattern on the arene had no apparent effect on the yields of the corresponding products (3 a, 3 m–p, 3 r/r’). Analogously, 1 a added to 7-azabicyclo alkene 2 f to afford product 3 q in 85 % yield (Table 2, entry 17). Bicyclic alkenes 2 h and 2 i did not react. The structure of 3 q was unequivocally determined by single-crystal X-ray diffraction (Figure 1).[16] It is worth noting
The process is initiated by an anion-exchange reaction between [Cp*Rh(MeCN)3][BF4]2 and Fe(OAc)2, providing a [Cp*Rh(OAc)2] species that enters the catalytic cycle. Upon reaction with sulfoximine 1 and concomitant loss of acetic acid, a new rhodium complex I is formed, which undergoes ortho-C Hbond activation to give rhodacycle II (and an additional equivalent of AcOH). The insertion of heterobicyclic alkene 2 into the C Rh bond of II leads to 7-membered rhodacycle IV via coordination compound III. Finally, IV is protonated twice, providing hydroarylated product 3 and the reactive [Cp*Rh(OAc)2] species, which closes the catalytic cycle.[15.18] To get an insight into the reaction mechanism, a kinetic isotope effect (KIE) experiment was carried out by using a mixture of [D1]-1 a and 2 a as the starting materials (Scheme 2). As
Scheme 2. KIE experiment.
a result, a kH/kD ratio of 3.17 was found. Further studies are needed for a careful analysis of these data.[19] Although we assume the formation of AcOD under these conditions, no [D2]-3 a was detected, probably owing to the involvement of other H/D exchange reactions during the metal catalysis. Finally, we focused on demonstrating the synthetic potential of the products. In light of our previous success in applying Nphosphorylated sulfoximines as ligands in asymmetric catalysis[20] and assuming that related compounds could show interesting bioactivities,[21] we wondered about possible N-phosphorylations of products 3. The hetero-dehydrogenative crosscoupling method recently reported by Dhineshkumar and Prabhu[22] appeared most suitable in this context, because it allowed such N,P-couplings without the necessity to use a strong base or acid. Accordingly, 3 a was treated with diphenyl phosphite (4) in the presence of iodine and tert-butyl hydroperoxide (TBHP, as a 5.0–6.0 m solution in decane) and, to our delight, N-phosphorylated product 5 a could be isolated in 54 % yield (Scheme 3). In the same manner, 5 b was obtained from 3 f and 4 in 53 % yield. Realizing the value of products 3 for the synthesis of orthonaphthyl-substituted products that could further be converted to heterocycles that are difficult to prepare by other means,
Figure 1. ORTEP diagram of the X-ray crystal structure of 3 q (thermal ellipsoids are drawn at 50 % probability).[19]
that the addition of 1 a onto unsymmetrically substituted 7-oxabicyclo alkene 2 g led to a mixture of regioisomers 3 r and 3 r’ in a ratio of ca. 1:1 in 85 % yield (Table 2, entry 18). Based on earlier work on rhodium-catalyzed C H-bond activations,[2, 12, 13, 17] a plausible mechanism for the addition reaction can be proposed (Scheme 1).
Scheme 1. Plausible mechanism of the rhodium-catalyzed hydroarylation. Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
These are not the final page numbers! ÞÞ
Scheme 3. N-Phosphorylation of 3 mediated by molecular iodine.
3
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
Communication a ratio of 4:1 as eluent). In this manner, product 3 a was obtained in 87 % yield (130 mg).
the synthetic strategy depicted in Scheme 4 was established. In this sequence, arylated 7-oxa bicycles 3 a, 3 d, and 3 f were applied. When treated with methyl sulfonic acid in chloroform
Acknowledgements W.D., Y.C., and F.P. thank the China Scholarship Council for predoctoral stipends. K.P. acknowledges support by the Alexander von Humboldt Foundation. We also thank Prof. Dr. Jiarong Chen (Central China Normal University, Wuhan, China) for valuable discussions. Keywords: C H activation · heterobicyclic hydroarylation reaction · rhodium · sulfoximines
under reflux, a dehydration occurred to provide the corresponding ortho-naphthylated products 6 a–c in almost quantitative yields. Subsequent palladium-catalyzed oxidative ringclosure, initiated by a combination of Pd(OAc)2 and PhI(OAc)2 in toluene at 120 8C,[23] led to aryl-fused thiazines 7 in good yields.[24] In the conversions of 3 a and 3 b, unequal mixtures of regioisomers were obtained (for structural details, see Scheme 4). Unexpectedly, the resulting main products differed in fusion sites. Whereas the first reaction provided 1,2-naphthyl-fused thiazine 7 a as the major regioisomer, the second led predominantly to 2,3-naphthyl-connected derivative 7 b’. Even more surprising was the fact that, for unknown reasons, the conversion of 4-chloro-substituted 6 c gave only a single product (7 c); the other regioisomer (7 c’) was not observed. In summary, we discovered rhodium-catalyzed hydroarylation reactions of heterobicyclic alkenes with NH-sulfoximines initiated by directing-group-assisted C H functionalizations. The products are synthetically useful, as demonstrated by Nphosphorylations providing potential ligands for metal catalysis and ring-closing reactions leading to aryl-fused thiazine derivatives.
Experimental Section Exemplary procedure for the rhodium-catalyzed hydroarylation of heterobicyclic alkenes A Schlenk tube (60 mL) with a stirring bar was loaded with sulfoximine 1 a (78 mg, 0.50 mmol), heterobicyclic alkene 2 a (87 mg, 0.60 mmol), [Cp*Rh(MeCN)3][BF4]2 (6.8 mg, 0.0125 mmol, 2.5 mol %), and Fe(OAc)2 (18 mg, 0.10 mmol, 20 mol %). Under an oxygen atmosphere (1 atm), dry toluene (3.0 mL) was added to the reaction mixture by using a syringe. After stirring at 120 8C for 4 h, the mixture was cooled to room temperature and filtered through a short pad of celite. Washing with dichloromethane (3 20 mL) and concentrating the solution under vacuum was followed by product purification (column chromatography using triethylamine-deactivated silica gel and a mixture of hexane and ethyl acetate in &
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
·
[1] For early overviews, see: a) F. Kakiuchi, S. Murai, Top. Organomet. Chem. 1999, 3, 47; b) G. Dyker, Angew. Chem. Int. Ed. 1999, 38, 1698 – 1712; Angew. Chem. 1999, 111, 1808 – 1822; c) J. A. Kerr, in CRC Handbook of Chemistry and Physics, 71edst ed(Ed.: D. R. Lide), CRC, Boston, 1990, pp: 9-95 – 9-96. [2] For selected reviews, see: a) F. Kakiuchi, S. Murai, Acc. Chem. Res. 2002, 35, 826 – 834; b) V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev. 2002, 102, 1731 – 1770; c) F. Kakiuchi, N. Chatani, Adv. Synth. Catal. 2003, 345, 1077 – 1101; d) Y. J. Park, C. H. Jun, Bull. Korean Chem. Soc. 2005, 26, 871 – 877; e) F. Kakiuchi, T. Kochi, Synthesis 2008, 3013 – 3039; f) J. C. Lewis, R. G. Bergman, J. A. Ellman, Acc. Chem. Res. 2008, 41, 1013 – 1025; g) D. A. Colby, R. G. Bergman, J. A. Ellman, Chem. Rev. 2010, 110, 624 – 655; h) D. A. Colby, A. S. Tsai, R. G. Bergman, J. A. Ellman, Acc. Chem. Res. 2012, 45, 814 – 825. [3] For selected examples of additions to alkenes or alkynes, see: a) R. F. Jordan, D. F. Taylor, J. Am. Chem. Soc. 1989, 111, 778 – 779; b) S. Rodewald, R. F. Jordan, J. Am. Chem. Soc. 1994, 116, 4491 – 4492; c) C. Jia, D. Piao, J. Oyamada, W. Lu, T. Kitamura, Y. Fujiwara, Science 2000, 287, 1992 – 1995; d) S. Cacchi, G. Fabrizi, A. Goggiamani, D. Persiani, Org. Lett. 2008, 10, 1597 – 1600; e) W. Zhou, Y. Yang, Z. Wang, G. J. Deng, Org. Biomol. Chem. 2014, 12, 251 – 254. [4] a) L. N. Lewis, J. K. Smith, J. Am. Chem. Soc. 1986, 108, 2728 – 2735; b) S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M. Sonoda, N. Chatani, Nature 1993, 366, 529 – 531; c) S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M. Sonoda, N. Chatani, Pure Appl. Chem. 1994, 66, 1527 – 1534. [5] a) L. Liao, M. S. Sigman, J. Am. Chem. Soc. 2010, 132, 10209 – 10211; b) T. Kitamura, K. Otsubo, J. Org. Chem. 2012, 77, 2978 – 2982; c) S. Liu, Y. Bai, X. Cao, F. Xiao, G. J. Deng, Chem. Commun. 2013, 49, 7501 – 7503; d) W. Cui, J. Yin, R. Zheng, C. Cheng, Y. Bai, G. Zhu, J. Org. Chem. 2014, 79, 3487 – 3493. [6] a) M. O. Simon, J. P. Genet, S. Darses, Org. Lett. 2010, 12, 3038 – 3041; b) M. C. Reddy, M. Jeganmohan, Chem. Commun. 2013, 49, 481 – 483; c) R. Manikandan, M. Jeganmohan, Org. Lett. 2014, 16, 912 – 915; d) review: S. De Sarkar, W. Liu, S. I. Kozhushkov, L. Ackermann, Adv. Synth. Catal. 2014, 356, 1461 – 1479. [7] a) K. Oguma, M. Miura, T. Satoh, M. Nomura, J. Am. Chem. Soc. 2000, 122, 10464 – 10465; b) T. Hayashi, K. Inoue, N. Taniguchi, M. Ogasawara, J. Am. Chem. Soc. 2001, 123, 9918 – 9919; c) K. L. Tan, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc. 2002, 124, 13964 – 13965; d) J. F. Paquin, C. Defieber, C. R. Stephenson, E. M. Carreira, J. Am. Chem. Soc. 2005, 127, 10850 – 10851; e) R. Jana, J. A. Tunge, Org. Lett. 2009, 11, 971 – 974; f) J. Bexrud, M. Lautens, Org. Lett. 2010, 12, 3160 – 3163; g) D. J. Schipper, M. Hutchinson, K. Fagnou, J. Am. Chem. Soc. 2010, 132, 6910 – 6911; h) Z. M. Sun, J. Zhang, R. S. Manan, P. Zhao, J. Am. Chem. Soc. 2010, 132, 6935 – 6937; i) C. M. So, S. Kume, T. Hayashi, J. Am. Chem. Soc. 2013, 135, 10990 – 10993; j) F. Wang, Z. Qi, J. Sun, X. Zhang, X. Li, Org. Lett. 2013, 15, 6290 – 6293; k) Z. C. Qian, J. Zhou, B. Li, F. Hu, B. F. Shi, Org. Biomol. Chem. 2014, 12, 3594 – 3597. [8] a) T. Matsumoto, R. A. Periana, D. J. Taube, H. Yoshida, J. Mol. Catal. A 2002, 180, 1 – 18; b) R. Dorta, A. Togni, Chem. Commun. 2003, 760 – 761; c) Y. Nakao, K. S. Kanyiva, S. Oda, T. Hiyama, J. Am. Chem. Soc. 2006, 128,
Scheme 4. Dehydration and intramolecular oxidative C N-bond formation by palladium-catalyzed C H activation.
&
alkenes
4
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!
Communication
[9]
[10]
[11]
[12] [13] [14] [15]
8146 – 8147; d) S. Haldar, S. Koner, J. Org. Chem. 2010, 75, 6005 – 6008; e) J. Mo, P. H. Lee, Org. Lett. 2010, 12, 2570 – 2573; f) K. Gao, N. Yoshikai, J. Am. Chem. Soc. 2011, 133, 400 – 402; g) D. Kang, J. Kim, S. Oh, P. H. Lee, Org. Lett. 2012, 14, 5636 – 5639; h) N. K. Lee, S. Y. Yun, P. Mamidipalli, R. M. Salzman, D. Lee, T. Zhou, Y. Xia, J. Am. Chem. Soc. 2014, 136, 4363 – 4368. a) F. Kakiuchi, M. Yamauchi, N. Chatani, S. Murai, Chem. Lett. 1996, 111 – 112; b) S. Busch, W. Leitner, Adv. Synth. Catal. 2001, 343, 192 – 195; c) F. Kakiuchi, T. Sato, K. Igi, N. Chatani, S. Murai, Chem. Lett. 2001, 386 – 387; d) C.-H. Jun, C. W. Moon, J.-B. Hong, S.-G. Lim, K.-Y. Chung, Y.-H. Kim, Chem. Eur. J. 2002, 8, 485 – 492; e) R. Martinez, R. Chevalier, S. Darses, J.P. Genet, Angew. Chem. Int. Ed. 2006, 45, 8232 – 8235; Angew. Chem. 2006, 118, 8412 – 8415; f) R. Martinez, J. P. Genet, S. Darses, Chem. Commun. 2008, 3855 – 3857; g) K. Gao, P. S. Lee, T. Fujita, N. Yoshikai, J. Am. Chem. Soc. 2010, 132, 12249 – 12251; h) J. Kwak, Y. Ohk, Y. Jung, S. Chang, J. Am. Chem. Soc. 2012, 134, 17778 – 17788. For selected examples of catalyzed addition reactions of preformed organometallic reagents onto heterobicyclic dienes leading to ringopened products, see: a) M. Lautens, P. Chiu, S. Ma, T. Rovis, J. Am. Chem. Soc. 1995, 117, 532 – 533; b) M. Murakami, H. Igawa, Chem. Commun. 2002, 390 – 391; c) X.-J. Pan, G.-B. Huang, Y.-H. Long, X.-J. Zuo, X. Xu, F.-L. Gu, D. Q. Yang, J. Org. Chem. 2014, 79, 187 – 196. For an early example from our group with the focus on rhodium-catalyzed hydroacylations of bicyclic dienes including 4-epoxy-1,4-dihydronaphthalene with salicylaldehydes, see: R. T. Stemmler, C. Bolm, Adv. Synth. Catal. 2007, 349, 1185 – 1198. Z. Qi, X. Li, Angew. Chem. Int. Ed. 2013, 52, 8995 – 9000; Angew. Chem. 2013, 125, 9165 – 9170. W. Dong, L. Wang, K. Parthasarathy, F. Pan, C. Bolm, Angew. Chem. Int. Ed. 2013, 52, 11573 – 11576; Angew. Chem. 2013, 125, 11787 – 11790. K. Parthasarathy, C. Bolm, Chem. Eur. J. 2014, 20, 4896 – 4900. As can be expected from these results, the hydroarylation also proceeds under argon instead of oxygen. These alternative conditions led to essentially the same yield of 3 a starting from 1 a and 2 a. Changing the acetate source from Fe(OAc)2 to Cu(OAc)2, NaOAc, or KOAc (20 mol %) led to lower yields of 3 a (28, 72, and 73 %, respectively).
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
These are not the final page numbers! ÞÞ
[16] CCDC 945223 (3 q) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_ request/cif [17] a) T. Satoh, M. Miura, Chem. Eur. J. 2010, 16, 11212 – 11222; b) J. WencelDelord, T. Droge, F. Liu, F. Glorius, Chem. Soc. Rev. 2011, 40, 4740 – 4761; c) G. Song, F. Wang, X. Li, Chem. Soc. Rev. 2012, 41, 3651 – 3678; d) P. B. Arockiam, C. Bruneau, P. H. Dixneuf, Chem. Rev. 2012, 112, 5879 – 5918; e) L. Ackermann, Acc. Chem. Res. 2014, 47, 281 – 295; f) F. W. Patureau, J. Wencel-Delord, F. Glorius, Aldrichimica Acta 2012, 45, 31 – 41. [18] To our surprise, we did not observe products resulting from a reductive elimination of rhodacycle IV, which would be in analogy to heterocycle formations reported in ref. [16]. Because the oxidation state of rhodium did not change in the new process, oxidative conditions were not essential (as confirmed by the fact that hydroarylated products were also obtained in reactions performed under argon in the absence of oxygen). [19] For an important essay on the interpretation of KIEs, see: E. M. Simmons, J. F. Hartwig, Angew. Chem. Int. Ed. 2012, 51, 3066 – 3072; Angew. Chem. 2012, 124, 3120 – 3126. [20] a) M. T. Reetz, O. G. Bondarev, H.-J. Gais, C. Bolm, Tetrahedron Lett. 2005, 46, 5643 – 5646; b) E. B. Benetskiy, C. Bolm, Tetrahedron: Asymmetry 2011, 22, 373 – 378. [21] For a stimulating article, see: M. Tauro, F. Loiodice, M. Ceruso, C. T. Supuran, P. Tortorelli, Bioorg. Med. Chem. Lett. 2014, 24, 2617 – 2620. [22] J. Dhineshkumar, K. R. Prabhu, Org. Lett. 2013, 15, 6062 – 6065. [23] A. J. Jordan-Hore, C. C. C. Johansson, M. Gulias, E. M. Beck, M. J. Gaunt, J. Am. Chem. Soc. 2008, 130, 16184 – 16186, and references therein. [24] For the use of fused benzothiazine derivatives as fluorescent sensors, see: A. Garimallaprabhakaran, X. Hong, M. Harmata, ARKIVOC (Gainesville, FL, U.S.) 2012, 6, 119 – 128.
Received: August 14, 2014 Published online on && &&, 0000
5
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
Communication
COMMUNICATION &C
H Activation
W. Dong, K. Parthasarathy, Y. Cheng, F. Pan, C. Bolm* && – && Hydroarylations of Heterobicyclic Alkenes through Rhodium-Catalyzed Directed C H Functionalizations of SAryl Sulfoximines
&
&
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
Rhodium-catalyzed hydroarylations of heterobicyclic alkenes with NH-sulfoximines lead to products that can then be converted to aryl-fused thiazines. The initial process involves a C H-func-
tionalization directed by the sulfoximidoyl group. Aryl addition to the alkene is then followed by dehydration and palladium-catalyzed oxidative C N coupling (see scheme).
6
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!
Communication
& C H Activation
Hydroarylations of Heterobicyclic Alkenes through RhodiumCatalyzed Directed C H Functionalizations of S-Aryl Sulfoximines Wanrong Dong,[a] Kanniyappan Parthasarathy,[a] Ying Cheng,[a] Fangfang Pan,[b] and Carsten Bolm*[a] to heterobicyclic alkenes (hydroarylation) that allow to keep the backbone of the unsaturated starting material [Eq. (2)]. They proceed under rhodium catalysis by utilizing sulfoximidoyl substituents as a directing group. As a result, synthetically valuable products are obtained that can further be derivatized.
Abstract: Rhodium-catalyzed directed CH-functionalizations have been used in hydroarylations of heterobicyclic alkenes with NH-sulfoximines. Unexpectedly, the bicyclic framework is retained, resulting in the formation of addition products being attractive intermediates for functionalized molecules that are difficult to prepare by other means.
Transition-metal-catalyzed direct C H-bond functionalizations have become a powerful alternative to the traditional methodologies that require the use of pre-functionalized starting materials.[1] Applying this principle has led to the development of most valuable and straightforward methods for the construction of C C or C X (X = Cl, Br, N, O, etc.) bond frameworks.[2] Among them, addition reactions stand out owing to their high efficiency and atom economy; hose combining C(sp2) H fragments with alkenes or alkynes have been the focus of many studies.[3] Ever since the first examples of ruthenium-catalyzed selective C H/olefin addition reactions by Lewis[4a] and Murai,[4b,c] various catalysts based on Pd,[3e, 5] Ru,[6] Rh,[7] or other transition metals[8] have been introduced. Commonly, these systems require combinations of substrates with heteroatomcontaining moieties for directing the C H functionalizations[9] and alkynes or substituted alkenes as unsaturated coupling partners [Eq. (1)]. It is worth noting that heterobicyclic alkenes have only been used scarcely in such types of C H addition reactions.[10, 11] A recent example is the rhodium-catalyzed coupling between phenyl pyridines with 7-oxa- or 7-azabenzonorbornadienes, leading to naphthylated arenes or dihydrocarbazoles, respectively, as reported by Qi and Li.[12] To the best of our knowledge, analogous reactions with other substrates undergoing C H functionalizations and, in particular, transformations retaining the heterobicyclic core are unprecedented. Herein, we demonstrate directed C(sp2) H addition reactions
Starting point of our investigation was the recently discovered C H activation of sulfoximidoyl-substituted arenes by rhodium catalysis.[13, 14] Both 1,2-benzothiazines and alkenylsubstituted sulfoximines could selectively be accessed by using adequately functionalized sulfur reagents in combination with alkynes or alkenes, respectively. Assuming analogous reaction pathways, we now submitted a mixture of NH-sulfoximine 1 a and benzo-substituted heterobicyclic olefin 2 a to the previously optimized reaction conditions involving [Cp*Rh(MeCN)3][BF4]2 (5 mol %), Fe(OAc)2 (20 mol %), and dioxygen (1 atm) in toluene at elevated temperature (100 8C). However, in contrast to our expectations, no oxidative olefination occurred, but instead, 1 a added to the heterobicyclic olefin to give saturated benzo-fused 7-oxanorbornane 3 a in 62 % yield (Table 1, entry 1).[15] Because the heterobicyclic core is retained, the reaction opens attractive synthetic opportunities, allowing a more elaborate functionalization at a later stage. Raising the temperature from 100 to 120 8C increased the yield of 3 a to 89 % (Table 1, entry 2). The catalyst loading could be reduced to 2.5 mol %, affording 3 a in almost the same yield as with 5 mol % (87 %, Table 1, entry 3). Reducing the catalyst amount further to 1.0 mol % of [Cp*Rh(MeCN)3][BF4]2 had a negative effect on the yield of the product (63 % as determined by NMR spectroscopy; Table 1, entry 4). With the optimized reaction conditions in hand, the substrate scope was examined. First, various diversely substituted sulfoximines (1 a–l) were reacted with alkene 2 a (Table 2, entries 1–12). In general, all additions proceeded well, providing
[a] Dr. W. Dong, Dr. K. Parthasarathy, Y. Cheng, Prof. Dr. C. Bolm Institute of Organic Chemistry, RWTH Aachen University Landoltweg 1, 52056 Aachen (Germany) Fax: (+ 49) 241-8092-391 E-mail: [email protected] [b] Dr. F. Pan Institute of Inorganic Chemistry, RWTH Aachen University Landoltweg 1, 52056, Aachen (Germany) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201404859. Chem. Eur. J. 2014, 20, 1 – 6
These are not the final page numbers! ÞÞ
1
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
Communication Table 1. Optimization of the addition reaction.
Table 2. (Continued)
Entry
x
Temp. [8C]
Yield [%]
1 2 3 4
5.0 5.0 2.5 1.0
100 120 120 120
62 89 87 63[b]
[a] Reaction conditions: sulfoximine 1 a (0.30 mmol), alkene 2 a (0.36 mmol), [Cp*Rh(MeCN)3][BF4]2 (x mol %), Fe(OAc)2 (0.06 mmol, 20 mol %), and toluene (2.5 mL) under O2 (1 atm) at indicated temperature for 4 h. [b] Determined by 1H NMR spectroscopy.
Entry
1
2
Product 3
Yield [%]
10 11 12
1j 1k 1l
2a 2a 2a
3 j: R4 = iBu 3 k: R4 = iPr 3 l: R4 = cyclo-Pr
78 86 87
13
1a
2b
3m
85
14
1a
2c
3n
82
15
1a
2d
3o
78
16
1a
2e
3p
76
17
1a
2f
3 q: X = NCOOMe
82
18[b]
1a
2g
III
Table 2. Substrate scope of the Rh -catalyzed hydroarylation of heterobicyclic alkenes with sulfoximines.[a]
85 3r
Entry
&
&
1
2
Product 3
1
1a
2a
3 a: R1 = H
87
2
1b
2a
3 b: R1 = Me
86
3
1c
2a
3 c: R1 = MeO
90
4 5 6 7
1d 1e 1f 1g
2a 2a 2a 2a
3 d: R1 = Me 3 e: R1 = NO2 3 f: R1 = Cl 3 g: R1 = Br
89 70 79 80
8
1h
2a
3h
85
9
1i
2a
3 i: R2 = Et
91
Chem. Eur. J. 2014, 20, 1 – 6
[a] Reaction conditions: sulfoximine 1 (0.50 mmol), alkene 2 (0.60 mmol), [Cp*Rh(MeCN)3][BF4]2 (0.0125 mmol, 2.5 mol %), Fe(OAc)2 (0.10 mmol, 20 mol %), and toluene (3.0 mL) at 120 8C for 4 h. [b] The ratio of regioisomers 3 r and 3 r’ was ca. 1:1, as determined by 1H NMR spectroscopy.
Yield [%]
www.chemeurj.org
3 r’
products in yields ranging from 70 to 91 %. Electron-donating substituents on the sulfoximine arene appeared to have a slightly positive effect on the yield. For example, 4-methoxyand 4-methyl-substituted sulfoximines 1 c and 1 d afforded addition products 3 c and 3 d in 90 and 89 % yield, respectively (Table 2, entries 3 and 4). In contrast, using 1 e with an electron-withdrawing nitro group in the 4 position of the arene led to 3 e in only 70 % yield (Table 2, entry 5). Halo substituents were unaffected, giving access to chloro and bromo-substituted products 3 f and 3 g in 79 and 80 % yield, respectively (Table 2, entries 6 and 7). Noteworthy are the results from the addition reactions of 3-methyl-substituted sulfoximine 1 b and naphthyl derivative 1 h onto oxabicyclic alkene 2 a, which led to 3 b and 3 h in 86 and 85 % yield, respectively (Table 2, entries 2 and 8). In both cases, a high regioselectivity was observed, which we attributed to steric factors hampering alternative pathways. Varying the non-aromatic substituent of the sulfoximine sulfur was also possible, as reflected by the results 2
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!
Communication of the additions of 1 i–l onto alkene 2 a, providing 3 i–l in yields ranging from 78 to 91 % (Table 2, entries 9–12). These results are similar to the aforementioned one observed in the coupling of methyl-bearing sulfoximine 1 a, which led to 3 a in 87 % yield (Table 2, entry 1). Under the same catalytic conditions, heterobicyclic alkenes 2 b–g were reacted with sulfoximine 1 a (Table 2, entries 13–18); these transformations also provided the addition products in good yields (up to 85 %). In the series of 7-oxabicycles 2 a–e and 2 g, the substitution pattern on the arene had no apparent effect on the yields of the corresponding products (3 a, 3 m–p, 3 r/r’). Analogously, 1 a added to 7-azabicyclo alkene 2 f to afford product 3 q in 85 % yield (Table 2, entry 17). Bicyclic alkenes 2 h and 2 i did not react. The structure of 3 q was unequivocally determined by single-crystal X-ray diffraction (Figure 1).[16] It is worth noting
The process is initiated by an anion-exchange reaction between [Cp*Rh(MeCN)3][BF4]2 and Fe(OAc)2, providing a [Cp*Rh(OAc)2] species that enters the catalytic cycle. Upon reaction with sulfoximine 1 and concomitant loss of acetic acid, a new rhodium complex I is formed, which undergoes ortho-C Hbond activation to give rhodacycle II (and an additional equivalent of AcOH). The insertion of heterobicyclic alkene 2 into the C Rh bond of II leads to 7-membered rhodacycle IV via coordination compound III. Finally, IV is protonated twice, providing hydroarylated product 3 and the reactive [Cp*Rh(OAc)2] species, which closes the catalytic cycle.[15.18] To get an insight into the reaction mechanism, a kinetic isotope effect (KIE) experiment was carried out by using a mixture of [D1]-1 a and 2 a as the starting materials (Scheme 2). As
Scheme 2. KIE experiment.
a result, a kH/kD ratio of 3.17 was found. Further studies are needed for a careful analysis of these data.[19] Although we assume the formation of AcOD under these conditions, no [D2]-3 a was detected, probably owing to the involvement of other H/D exchange reactions during the metal catalysis. Finally, we focused on demonstrating the synthetic potential of the products. In light of our previous success in applying Nphosphorylated sulfoximines as ligands in asymmetric catalysis[20] and assuming that related compounds could show interesting bioactivities,[21] we wondered about possible N-phosphorylations of products 3. The hetero-dehydrogenative crosscoupling method recently reported by Dhineshkumar and Prabhu[22] appeared most suitable in this context, because it allowed such N,P-couplings without the necessity to use a strong base or acid. Accordingly, 3 a was treated with diphenyl phosphite (4) in the presence of iodine and tert-butyl hydroperoxide (TBHP, as a 5.0–6.0 m solution in decane) and, to our delight, N-phosphorylated product 5 a could be isolated in 54 % yield (Scheme 3). In the same manner, 5 b was obtained from 3 f and 4 in 53 % yield. Realizing the value of products 3 for the synthesis of orthonaphthyl-substituted products that could further be converted to heterocycles that are difficult to prepare by other means,
Figure 1. ORTEP diagram of the X-ray crystal structure of 3 q (thermal ellipsoids are drawn at 50 % probability).[19]
that the addition of 1 a onto unsymmetrically substituted 7-oxabicyclo alkene 2 g led to a mixture of regioisomers 3 r and 3 r’ in a ratio of ca. 1:1 in 85 % yield (Table 2, entry 18). Based on earlier work on rhodium-catalyzed C H-bond activations,[2, 12, 13, 17] a plausible mechanism for the addition reaction can be proposed (Scheme 1).
Scheme 1. Plausible mechanism of the rhodium-catalyzed hydroarylation. Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
These are not the final page numbers! ÞÞ
Scheme 3. N-Phosphorylation of 3 mediated by molecular iodine.
3
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
Communication a ratio of 4:1 as eluent). In this manner, product 3 a was obtained in 87 % yield (130 mg).
the synthetic strategy depicted in Scheme 4 was established. In this sequence, arylated 7-oxa bicycles 3 a, 3 d, and 3 f were applied. When treated with methyl sulfonic acid in chloroform
Acknowledgements W.D., Y.C., and F.P. thank the China Scholarship Council for predoctoral stipends. K.P. acknowledges support by the Alexander von Humboldt Foundation. We also thank Prof. Dr. Jiarong Chen (Central China Normal University, Wuhan, China) for valuable discussions. Keywords: C H activation · heterobicyclic hydroarylation reaction · rhodium · sulfoximines
under reflux, a dehydration occurred to provide the corresponding ortho-naphthylated products 6 a–c in almost quantitative yields. Subsequent palladium-catalyzed oxidative ringclosure, initiated by a combination of Pd(OAc)2 and PhI(OAc)2 in toluene at 120 8C,[23] led to aryl-fused thiazines 7 in good yields.[24] In the conversions of 3 a and 3 b, unequal mixtures of regioisomers were obtained (for structural details, see Scheme 4). Unexpectedly, the resulting main products differed in fusion sites. Whereas the first reaction provided 1,2-naphthyl-fused thiazine 7 a as the major regioisomer, the second led predominantly to 2,3-naphthyl-connected derivative 7 b’. Even more surprising was the fact that, for unknown reasons, the conversion of 4-chloro-substituted 6 c gave only a single product (7 c); the other regioisomer (7 c’) was not observed. In summary, we discovered rhodium-catalyzed hydroarylation reactions of heterobicyclic alkenes with NH-sulfoximines initiated by directing-group-assisted C H functionalizations. The products are synthetically useful, as demonstrated by Nphosphorylations providing potential ligands for metal catalysis and ring-closing reactions leading to aryl-fused thiazine derivatives.
Experimental Section Exemplary procedure for the rhodium-catalyzed hydroarylation of heterobicyclic alkenes A Schlenk tube (60 mL) with a stirring bar was loaded with sulfoximine 1 a (78 mg, 0.50 mmol), heterobicyclic alkene 2 a (87 mg, 0.60 mmol), [Cp*Rh(MeCN)3][BF4]2 (6.8 mg, 0.0125 mmol, 2.5 mol %), and Fe(OAc)2 (18 mg, 0.10 mmol, 20 mol %). Under an oxygen atmosphere (1 atm), dry toluene (3.0 mL) was added to the reaction mixture by using a syringe. After stirring at 120 8C for 4 h, the mixture was cooled to room temperature and filtered through a short pad of celite. Washing with dichloromethane (3 20 mL) and concentrating the solution under vacuum was followed by product purification (column chromatography using triethylamine-deactivated silica gel and a mixture of hexane and ethyl acetate in &
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
·
[1] For early overviews, see: a) F. Kakiuchi, S. Murai, Top. Organomet. Chem. 1999, 3, 47; b) G. Dyker, Angew. Chem. Int. Ed. 1999, 38, 1698 – 1712; Angew. Chem. 1999, 111, 1808 – 1822; c) J. A. Kerr, in CRC Handbook of Chemistry and Physics, 71edst ed(Ed.: D. R. Lide), CRC, Boston, 1990, pp: 9-95 – 9-96. [2] For selected reviews, see: a) F. Kakiuchi, S. Murai, Acc. Chem. Res. 2002, 35, 826 – 834; b) V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev. 2002, 102, 1731 – 1770; c) F. Kakiuchi, N. Chatani, Adv. Synth. Catal. 2003, 345, 1077 – 1101; d) Y. J. Park, C. H. Jun, Bull. Korean Chem. Soc. 2005, 26, 871 – 877; e) F. Kakiuchi, T. Kochi, Synthesis 2008, 3013 – 3039; f) J. C. Lewis, R. G. Bergman, J. A. Ellman, Acc. Chem. Res. 2008, 41, 1013 – 1025; g) D. A. Colby, R. G. Bergman, J. A. Ellman, Chem. Rev. 2010, 110, 624 – 655; h) D. A. Colby, A. S. Tsai, R. G. Bergman, J. A. Ellman, Acc. Chem. Res. 2012, 45, 814 – 825. [3] For selected examples of additions to alkenes or alkynes, see: a) R. F. Jordan, D. F. Taylor, J. Am. Chem. Soc. 1989, 111, 778 – 779; b) S. Rodewald, R. F. Jordan, J. Am. Chem. Soc. 1994, 116, 4491 – 4492; c) C. Jia, D. Piao, J. Oyamada, W. Lu, T. Kitamura, Y. Fujiwara, Science 2000, 287, 1992 – 1995; d) S. Cacchi, G. Fabrizi, A. Goggiamani, D. Persiani, Org. Lett. 2008, 10, 1597 – 1600; e) W. Zhou, Y. Yang, Z. Wang, G. J. Deng, Org. Biomol. Chem. 2014, 12, 251 – 254. [4] a) L. N. Lewis, J. K. Smith, J. Am. Chem. Soc. 1986, 108, 2728 – 2735; b) S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M. Sonoda, N. Chatani, Nature 1993, 366, 529 – 531; c) S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M. Sonoda, N. Chatani, Pure Appl. Chem. 1994, 66, 1527 – 1534. [5] a) L. Liao, M. S. Sigman, J. Am. Chem. Soc. 2010, 132, 10209 – 10211; b) T. Kitamura, K. Otsubo, J. Org. Chem. 2012, 77, 2978 – 2982; c) S. Liu, Y. Bai, X. Cao, F. Xiao, G. J. Deng, Chem. Commun. 2013, 49, 7501 – 7503; d) W. Cui, J. Yin, R. Zheng, C. Cheng, Y. Bai, G. Zhu, J. Org. Chem. 2014, 79, 3487 – 3493. [6] a) M. O. Simon, J. P. Genet, S. Darses, Org. Lett. 2010, 12, 3038 – 3041; b) M. C. Reddy, M. Jeganmohan, Chem. Commun. 2013, 49, 481 – 483; c) R. Manikandan, M. Jeganmohan, Org. Lett. 2014, 16, 912 – 915; d) review: S. De Sarkar, W. Liu, S. I. Kozhushkov, L. Ackermann, Adv. Synth. Catal. 2014, 356, 1461 – 1479. [7] a) K. Oguma, M. Miura, T. Satoh, M. Nomura, J. Am. Chem. Soc. 2000, 122, 10464 – 10465; b) T. Hayashi, K. Inoue, N. Taniguchi, M. Ogasawara, J. Am. Chem. Soc. 2001, 123, 9918 – 9919; c) K. L. Tan, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc. 2002, 124, 13964 – 13965; d) J. F. Paquin, C. Defieber, C. R. Stephenson, E. M. Carreira, J. Am. Chem. Soc. 2005, 127, 10850 – 10851; e) R. Jana, J. A. Tunge, Org. Lett. 2009, 11, 971 – 974; f) J. Bexrud, M. Lautens, Org. Lett. 2010, 12, 3160 – 3163; g) D. J. Schipper, M. Hutchinson, K. Fagnou, J. Am. Chem. Soc. 2010, 132, 6910 – 6911; h) Z. M. Sun, J. Zhang, R. S. Manan, P. Zhao, J. Am. Chem. Soc. 2010, 132, 6935 – 6937; i) C. M. So, S. Kume, T. Hayashi, J. Am. Chem. Soc. 2013, 135, 10990 – 10993; j) F. Wang, Z. Qi, J. Sun, X. Zhang, X. Li, Org. Lett. 2013, 15, 6290 – 6293; k) Z. C. Qian, J. Zhou, B. Li, F. Hu, B. F. Shi, Org. Biomol. Chem. 2014, 12, 3594 – 3597. [8] a) T. Matsumoto, R. A. Periana, D. J. Taube, H. Yoshida, J. Mol. Catal. A 2002, 180, 1 – 18; b) R. Dorta, A. Togni, Chem. Commun. 2003, 760 – 761; c) Y. Nakao, K. S. Kanyiva, S. Oda, T. Hiyama, J. Am. Chem. Soc. 2006, 128,
Scheme 4. Dehydration and intramolecular oxidative C N-bond formation by palladium-catalyzed C H activation.
&
alkenes
4
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!
Communication
[9]
[10]
[11]
[12] [13] [14] [15]
8146 – 8147; d) S. Haldar, S. Koner, J. Org. Chem. 2010, 75, 6005 – 6008; e) J. Mo, P. H. Lee, Org. Lett. 2010, 12, 2570 – 2573; f) K. Gao, N. Yoshikai, J. Am. Chem. Soc. 2011, 133, 400 – 402; g) D. Kang, J. Kim, S. Oh, P. H. Lee, Org. Lett. 2012, 14, 5636 – 5639; h) N. K. Lee, S. Y. Yun, P. Mamidipalli, R. M. Salzman, D. Lee, T. Zhou, Y. Xia, J. Am. Chem. Soc. 2014, 136, 4363 – 4368. a) F. Kakiuchi, M. Yamauchi, N. Chatani, S. Murai, Chem. Lett. 1996, 111 – 112; b) S. Busch, W. Leitner, Adv. Synth. Catal. 2001, 343, 192 – 195; c) F. Kakiuchi, T. Sato, K. Igi, N. Chatani, S. Murai, Chem. Lett. 2001, 386 – 387; d) C.-H. Jun, C. W. Moon, J.-B. Hong, S.-G. Lim, K.-Y. Chung, Y.-H. Kim, Chem. Eur. J. 2002, 8, 485 – 492; e) R. Martinez, R. Chevalier, S. Darses, J.P. Genet, Angew. Chem. Int. Ed. 2006, 45, 8232 – 8235; Angew. Chem. 2006, 118, 8412 – 8415; f) R. Martinez, J. P. Genet, S. Darses, Chem. Commun. 2008, 3855 – 3857; g) K. Gao, P. S. Lee, T. Fujita, N. Yoshikai, J. Am. Chem. Soc. 2010, 132, 12249 – 12251; h) J. Kwak, Y. Ohk, Y. Jung, S. Chang, J. Am. Chem. Soc. 2012, 134, 17778 – 17788. For selected examples of catalyzed addition reactions of preformed organometallic reagents onto heterobicyclic dienes leading to ringopened products, see: a) M. Lautens, P. Chiu, S. Ma, T. Rovis, J. Am. Chem. Soc. 1995, 117, 532 – 533; b) M. Murakami, H. Igawa, Chem. Commun. 2002, 390 – 391; c) X.-J. Pan, G.-B. Huang, Y.-H. Long, X.-J. Zuo, X. Xu, F.-L. Gu, D. Q. Yang, J. Org. Chem. 2014, 79, 187 – 196. For an early example from our group with the focus on rhodium-catalyzed hydroacylations of bicyclic dienes including 4-epoxy-1,4-dihydronaphthalene with salicylaldehydes, see: R. T. Stemmler, C. Bolm, Adv. Synth. Catal. 2007, 349, 1185 – 1198. Z. Qi, X. Li, Angew. Chem. Int. Ed. 2013, 52, 8995 – 9000; Angew. Chem. 2013, 125, 9165 – 9170. W. Dong, L. Wang, K. Parthasarathy, F. Pan, C. Bolm, Angew. Chem. Int. Ed. 2013, 52, 11573 – 11576; Angew. Chem. 2013, 125, 11787 – 11790. K. Parthasarathy, C. Bolm, Chem. Eur. J. 2014, 20, 4896 – 4900. As can be expected from these results, the hydroarylation also proceeds under argon instead of oxygen. These alternative conditions led to essentially the same yield of 3 a starting from 1 a and 2 a. Changing the acetate source from Fe(OAc)2 to Cu(OAc)2, NaOAc, or KOAc (20 mol %) led to lower yields of 3 a (28, 72, and 73 %, respectively).
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
These are not the final page numbers! ÞÞ
[16] CCDC 945223 (3 q) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_ request/cif [17] a) T. Satoh, M. Miura, Chem. Eur. J. 2010, 16, 11212 – 11222; b) J. WencelDelord, T. Droge, F. Liu, F. Glorius, Chem. Soc. Rev. 2011, 40, 4740 – 4761; c) G. Song, F. Wang, X. Li, Chem. Soc. Rev. 2012, 41, 3651 – 3678; d) P. B. Arockiam, C. Bruneau, P. H. Dixneuf, Chem. Rev. 2012, 112, 5879 – 5918; e) L. Ackermann, Acc. Chem. Res. 2014, 47, 281 – 295; f) F. W. Patureau, J. Wencel-Delord, F. Glorius, Aldrichimica Acta 2012, 45, 31 – 41. [18] To our surprise, we did not observe products resulting from a reductive elimination of rhodacycle IV, which would be in analogy to heterocycle formations reported in ref. [16]. Because the oxidation state of rhodium did not change in the new process, oxidative conditions were not essential (as confirmed by the fact that hydroarylated products were also obtained in reactions performed under argon in the absence of oxygen). [19] For an important essay on the interpretation of KIEs, see: E. M. Simmons, J. F. Hartwig, Angew. Chem. Int. Ed. 2012, 51, 3066 – 3072; Angew. Chem. 2012, 124, 3120 – 3126. [20] a) M. T. Reetz, O. G. Bondarev, H.-J. Gais, C. Bolm, Tetrahedron Lett. 2005, 46, 5643 – 5646; b) E. B. Benetskiy, C. Bolm, Tetrahedron: Asymmetry 2011, 22, 373 – 378. [21] For a stimulating article, see: M. Tauro, F. Loiodice, M. Ceruso, C. T. Supuran, P. Tortorelli, Bioorg. Med. Chem. Lett. 2014, 24, 2617 – 2620. [22] J. Dhineshkumar, K. R. Prabhu, Org. Lett. 2013, 15, 6062 – 6065. [23] A. J. Jordan-Hore, C. C. C. Johansson, M. Gulias, E. M. Beck, M. J. Gaunt, J. Am. Chem. Soc. 2008, 130, 16184 – 16186, and references therein. [24] For the use of fused benzothiazine derivatives as fluorescent sensors, see: A. Garimallaprabhakaran, X. Hong, M. Harmata, ARKIVOC (Gainesville, FL, U.S.) 2012, 6, 119 – 128.
Received: August 14, 2014 Published online on && &&, 0000
5
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
Communication
COMMUNICATION &C
H Activation
W. Dong, K. Parthasarathy, Y. Cheng, F. Pan, C. Bolm* && – && Hydroarylations of Heterobicyclic Alkenes through Rhodium-Catalyzed Directed C H Functionalizations of SAryl Sulfoximines
&
&
Chem. Eur. J. 2014, 20, 1 – 6
www.chemeurj.org
Rhodium-catalyzed hydroarylations of heterobicyclic alkenes with NH-sulfoximines lead to products that can then be converted to aryl-fused thiazines. The initial process involves a C H-func-
tionalization directed by the sulfoximidoyl group. Aryl addition to the alkene is then followed by dehydration and palladium-catalyzed oxidative C N coupling (see scheme).
6
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!
