DOI: 10.1002/chem.201303008
Full Paper
& Organic Synthesis
Rhodium-Catalyzed Intramolecular Hydroarylation of 1-Halo-1alkynes: Regioselective Synthesis of Semihydrogenated Aromatic Heterocycles Hirohiko Murase, Kousuke Senda, Masato Senoo, Takeshi Hata, and Hirokazu Urabe*[a]
cles, such as 4-halo-1,2-dihydroquinolines, 4-halo-3-chromenes, or 4-(halomethylene)chromans, in good to excellent yields. Some synthetic applications taking advantage of the halo-substituents of the products are also illustrated.
Abstract: The regioselective intramolecular hydroarylation of (3-halo-2-propynyl)anilines, (3-halo-2-propynyl) aryl ethers, or (4-halo-3-butynyl) aryl ethers was efficiently catalyzed by Rh2(OCOCF3)4 to give semihydrogenated aromatic heterocy-
Intramolecular Friedel–Crafts reaction and its variants are traditional methods for the preparation of cyclic compounds via electrophilic substitution to various aromatic compounds.[1] Although a wide variety of electrophiles and their equivalents could be used in these reactions, there still exists some limitation on the electrophiles, especially incipient ones such as acetylenes.[2] Recent rapid development in transition-metal catalysts, which are more susceptible to interact with an acetylenic bond than traditional Lewis or Brønsted acids, has made it more reactive toward the aromatic substitution. For this reason, this type of reaction is often called transition-metal-catalyzed hydroarylation of acetylenes, irrespective of its actual mechanism, and has attracted much attention recently.[3] During the course of our studies on the synthetic utility of haloacetylenes,[4] we experienced that the cyclization of (halopropargyl)aniline 1 to 2 with a typical Lewis acid, BF3·OEt2, proved unsuccessful, probably due to the moderately electrondeficient nature of haloacetylenes not permitting the effective interaction with such an activator (Scheme 1, method a). However, to the contrary, we were pleased to find that a Rh catalyst ([Rh2(tfa)4], tfa = CF3CO2)[5] is quite promising for the same cyclization from 1 or 3,[6] nicely giving desired products 2 or 4 in good yields, without being accompanied by isomeric product 5 (method b). The carbon–carbon bond formation exclusively took place at the acetylenic carbon atom a to halogen, yielding the six-membered dihydroquinoline derivatives 2 or 4, the structure of which was verified by the derivatization to known
Scheme 1. Rh-catalyzed hydroarylation of chloroacetylene.
4-chloroquinoline 6. On the other hand, 4-chloroquinoline 6 was not detected as a byproduct in the crude reaction mixture derived from method b, which shows that the aromatization of the product during this cyclization was negligible. A plausible mechanism is shown in Scheme 2, in which the more cationic acetylenic carbon atom a to halogen appears to be preferen-
[a] H. Murase, K. Senda, M. Senoo, Prof. Dr. T. Hata, Prof. Dr. H. Urabe Department of Biomolecular Engineering Graduate School of Bioscience and Biotechnology Tokyo Institute of Technology 4259-B-59 Nagatsuta-cho, Midori-ku, Yokohama Kanagawa 226-8501 (Japan) Fax: (+ 81) (0)45-924-5849 E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201303008. Chem. Eur. J. 2014, 20, 317 – 322
Scheme 2. A proposed mechanism.
317
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper tially attacked by the aromatic ring to exhibit the observed regioselection. Equations (1) and (2) show some scope of the substrates. The above reaction is valid for the conversion of both chloroand bromoacetylenes 3 and 7 to desired products 4 and 9, but not for an iodoacetylene 8, due perhaps to the increasing instability of the acetylenic carbon–iodine bond [Eq. (1)]. The protection of the aniline nitrogen atom is critical: while the sulfonyl derivatization is satisfactory as already shown in Scheme 1, N-acyl protection found in 11 and 12 proved unsuitable, giving virtually no desired products 13 or 14 [Eq. (2)] (Boc = tBuOCO ).
Table 1. Preparation of various 4-chloro-1,2-dihydroquinolines.[a]
Entry
Partially hydrogenated aromatic heterocycles, such as those shown above, are frequently found in naturally occurring products and artificial pharmaceuticals and are also useful intermediates in organic synthesis.[7] The hydrogenation of the corresponding aromatic compounds is one of the most straightforward methods for their preparation, but the regioselective transfer of controlled amounts of hydrogen (or its surrogates) to the aromatic ring is not necessarily a trivial process. In addition, the halogenated structures prepared herein should be quite useful for further functionalization and carbon–carbon bond formation. Thus, we further investigated the generality of this transformation. Table 1 summarizes other results of the dihydroquinoline synthesis. Various p-toluenesulfonylanilines participated in the reaction. A TBS-protected hydroxy group in 17 remained unattacked (Table 1, entry 4), and a sterically congested aniline 18 and a-naphthylamine derivative 19 cyclized as well to give 23 and 24 (entries 5 and 6). As already shown in Equation (1), the corresponding bromoacetylenes could be used as an alternative starting material to give similar products, which are summarized in Table 2. However, bromoacetylenes appear less reactive than chloroacetylenes, as the former requires prolonged reaction periods and more catalyst loading to achieve good product yields. The fact that the carbon atom a to bromide is less cationic than that a to chloride should account for the above observation (cf. Scheme 2). Nonetheless, from various bromoacetylenes 25–29, the desired heterocyclic products 30–34 were obtained in good yields. The TBS ether Chem. Eur. J. 2014, 20, 317 – 322
www.chemeurj.org
Substrate
Product
Isolated yield [%]
1
91
2
74
3
97
4
91
5
96
6
83[b]
[a] Ts = p-TolSO2 , TBS = tBuMe2Si . [b] The reaction was performed for 7 h and with 10 mol % of catalyst.
moiety in 27 again survived the reaction conditions. The anilines in Table 2 were protected with a benzenesulfonyl group rather than the Ts that was used in Table 1, showing variation in sulfonyl protecting groups. 4-Halo-1,2-dihydroquinolines prepared above should be versatile synthetic intermediates for the preparation of substituted heterocyclic compounds.[8] Scheme 3 exemplifies some applications.[8q,r] From a representative product 9, different types of side chains including an sp3, sp2, or sp carbon terminus were successfully introduced to its dihydroquinoline skeleton, illustrating the diverse synthesis from a common starting material. During these transformations, an undesired side reaction, aromatization to the corresponding quinolines like the one mentioned in Scheme 1, was not observed at all. It should be emphasized that the extension of a functional group or a carbon side chain from the halogen substituents may make it possible to prepare the products that could not be obtained by the direct hydroarylation of the corresponding alkynes[6d–g] owing to the lack of either regioselectivity or functional-group compatibility (for example, the hydroxy group in 36). 318
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper After having established the preparation of dihydroquinolines via the intramolecular hydroarylation of haloacetylenes and their synthetic application, we next turned our attention to the preparation of an oxygen heterocycle from a similar halopropargyl aryl ether 39 (Scheme 4). Under analogous con-
Table 2. Preparation of various 4-bromo-1,2-dihydroquinolines.
Entry
Substrate
[Rh2(tfa)4] [mol %]
t [h]
Product
Isolated yield [%]
1
3
15.5
86
2
5
4
84
3
10
3
73 Scheme 4. Rh-catalyzed cyclization of chloropropargyl aryl ethers.
4
5
4
70
5
5
4
80
6
10
7
61
ditions as those described above, the desired cyclization gratifyingly proceeded to give exclusively chromene 40 containing an endo-cyclic double bond in good yield.[6, 9] The isomeric fivemembered product 41 was not detected, and the structure of 40 was unambiguously determined by its hydrogenation to known 42 (yield not optimized). It should be noted that the amount of the Rh catalyst could be reduced to 0.5 mol % of the substrate whilst keeping a satisfactory yield. The advantage of the Rh catalyst is again illustrated in Equations (3) and (4). Although the substrates 43 and 45 have an electron-rich aromatic ring, traditional activators, such as CF3CO2H or BF3·OEt2 proved not effective for their cyclization. On the other hand, the Rh catalyst did effect the desired reaction, giving chromenes 44 and 46, which is consistent with the outcome of Scheme 1. Equations (3) and (4) also show a favorable aspect of this Rh-catalyzed reaction that it tolerates the presence of a nitrogen functional group in the substrates.[10] However, to complete the reaction in an acceptable period, a greater amount of the Rh catalyst (10 mol %) is necessary than that for a non-functionalized substrate (0.5 mol % in Scheme 4), which suggests that the catalyst is at least partially deactivated by coordination with the nitrogen functional group. To show the generality of this functional-group compatibility, several protected amino-substituted 4-chlorochromenes obtained by this method are summarized in Table 3. In these re-
Scheme 3. Synthetic application of 4-bromo-1,2-dihydroquinoline. Chem. Eur. J. 2014, 20, 317 – 322
www.chemeurj.org
319
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper Table 4. Preparation of various 4-bromochromenes.
Entry
Table 3. Preparation of various 4-chlorochromenes.
Entry
1 2 3
Substrate
X = COPr Boc Ts
Product
(43) (47) (48)
Isolated yield [%]
(44) (54) (55)
67 95 96
4 5
X = COPr Boc
(45) (49)
(46) (56)
62 94[a]
6 7
X = COPr Ts
(50) (51)
(57) (58)
62 97[a]
8
80
9
69
Substrate
Product
Isolated yield [%]
1
70
2
87
3
84
4
88
5
95
[a] The reaction was performed for 2 h and with 3 mol % of catalyst.
actions, acyl-, Boc-, and Ts-protected aniline derivatives 43, 47, and 48 can be used equally well (Table 3, entries 1–3) and, to our satisfaction, broad substitution patterns on the aromatic ring are also acceptable (entries 4–9). Like the synthesis of dihydroquinolines, this cyclization is not limited to chloroacetylenes, but is also applicable to bromoacetylenes to give 4-bromochromenes, which are listed in Table 4. In these transformations, the amount of the Rh catalyst could again be reduced to as low as 1 mol % of the substrates. It is interesting to compare the above cyclizations with that starting from homologous halobutynyl aryl ether 71 Chem. Eur. J. 2014, 20, 317 – 322
www.chemeurj.org
Scheme 5. Hydroarylation of chlorobutynyl aryl ether.
(Scheme 5). Considering the tendency discussed above that the carbon–carbon bond formation always takes place at the acetylenic carbon atom a to the halogen, we, at first glance, expected that the reaction of Scheme 5 might give preferentially seven-membered product 74. However, what was actually observed was the ring closure at the acetylenic carbon atom b to the halogen, selectively giving a chromene derivative 72 containing an exo-cyclic double bond with Z configuration. 320
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper The olefin geometry of 72 was unambiguously determined by a 1H NMR NOESY study, and another isomeric product 73 and aforementioned 74 were not detected even in a crude reaction mixture. A conventional Lewis acid, BF3·OEt2, again proved useless for this type of substrate. Further structural confirmation of 72 was performed on an alternative product 75 (vide infra), which was led to methylchroman 76 upon hydrogenolysis
Table 5. Preparation of various 4-(halomethylene)chromans.
Entry Substrate
[Rh2(tfa)4] Product [mol %]
Isolated Z/E yield [%]
1
5
70[a]
97:3
2
3
79
97:3
3
3
81
98:2
4
3
83
95:5
5
10
54[b]
> 99:1
6
5
53[c]
> 99:1
7
3
91[d]
95:5
Scheme 6. A proposed mechanism.
(Scheme 5). The reaction course is proposed in Scheme 6, which is consistent with the formation of Z-olefinic products. In addition, the ease of formation of a six-membered ring relative to a seven-membered ring should be a prevailing driving force in this case. As a whole, the direction of the cyclization appears to be controlled under the balance between the electronic (ring closure at the acetylenic carbon atom a or b to halogen) and structural (five-, six-, or seven-membered ring formation) factors. As Z-(chloromethylene)chroman 72 should be also a useful building block, we investigated the cyclization of various halobutynyl aryl ethers and summarized the results in Table 5. In each reaction, more catalyst loading was required than for the cyclization of halopropargyl substrates shown in Scheme 4 and Table 4. The olefin geometry was fixed to be Z with high selectivities in most cases. An additional olefinic bond in the starting material 80 survived the reaction conditions. The double cyclization of 81 took place to give tricyclic products 86 with the defined olefin geometry, although an aromatic regioisomer 88 was also formed in a small amount. A bromo-substituted butynyl ether 82 could be used as well to give sterically congested vinyl bromide 87. In conclusion, the regioselective intramolecular hydroarylation of haloacetylenes was efficiently achieved with [Rh2(tfa)4], which was found to be superior to traditional Brønsted or Lewis acids, to give 4-halo-1,2-dihydroquinolines, 4-halo-3chromenes, or 4-(halomethylene)chromans in good yields.
[a] The reaction was performed for 24 h. [b] The reaction was performed at 90 8C for 15 h. [c] The isomeric product 88 (see below) was also isolated in 17 % yield. [d] The reaction period was 0.5 h and this product is an inseparable 95:5 mixture of 87 and 89 (see below).
with the aid of ethyl acetate. The combined filtrates were concentrated in vacuo to give a crude oil, 1H NMR spectroscopic analysis of which showed the presence of a single olefinic isomer. The crude product was chromatographed on silica gel (hexane/ethyl acetate) to afford the title compound (0.905 g, 86 %) as a paleyellow solid.
Experimental Section N-(Benzenesulfonyl)-4-bromo-1,2-dihydroquinoline (9): A mixture of N-(3-bromo-2-propynyl)-N-phenylbenzenesulfonamide (7) (1.05 g, 3.00 mmol) and rhodium trifluoroacetate dimer ([Rh2(tfa)4], 58.9 mg, 0.0895 mmol) in toluene (30 mL) was stirred in an oil bath maintained at 80 8C for 15.5 h. After being cooled to room temperature, the mixture was filtered through a short pad of silica gel Chem. Eur. J. 2014, 20, 317 – 322
www.chemeurj.org
Acknowledgements This work was supported by a Grant-in-Aid for Challenging Exploratory Research (22655014) from JSPS, Japan. 321
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper Keywords: chromene · dihydroquinolines · heterocycles · hydroarylation · rhodium
[7]
[1] For reviews on the Friedel–Crafts reaction, see: a) Friedel – Crafts and Related Reactions, Vols. I – IV (Ed.: G. A. Olah), Wiley, New York, 1963 – 1965; b) G. A. Olah, R. Krishnamurti, G. K. S. Prakash in Comprehensive Organic Synthesis, Vol. 3 (Eds.: B. M. Trost, I. Fleming), Pergamon, Oxford, 1991, pp. 293 – 339; c) M. B. Smith, J. March, March’s Advanced Organic Chemistry, 6th ed., Wiley, Hoboken, 2007, pp. 705 – 733; d) F. A. Carey, R. J. Sundberg, Advanced Organic Chemistry Part B, 5th ed., Springer, New York, 2007, pp. 1014 – 1025. [2] The Friedel – Crafts reaction of aromatic compounds with acetylenes was little documented at the outset: V. Franzen in Friedel – Crafts and Related Reactions, Vol. II, Part 1 (Ed.: G. A. Olah), Wiley, New York, 1964, pp. 413 – 416. [3] As the hydroarylation refers to a formal reaction pattern characterized by its products, its actual mechanism may include the Friedel–Craftstype reaction and the aromatic C H bond activation. For reviews, see: a) M. Bandini, E. Emer, S. Tommasi, A. Umani-Ronchi, Eur. J. Org. Chem. 2006, 3527 – 3544; b) C. Nevado, A. M. Echavarren, Synthesis 2005, 167 – 182; c) T. Kitamura, Eur. J. Org. Chem. 2009, 1111 – 1125; d) X. Wang, L. Zhou, W. Lu, Curr. Org. Chem. 2010, 14, 289 – 307; e) D. A. Capretto, Z. Li, C. He in Handbook of Cyclization Reactions, Vol. 2 (Ed.: S. Ma), WileyVCH, Weinheim, 2010, pp. 991 – 1023; f) R. Hayashi, G. R. Cook in Handbook of Cyclization Reactions, Vol. 2 (Ed.: S. Ma), Wiley-VCH, Weinheim, 2010, pp. 1025 – 1054. [4] For a review on certain synthetic aspects of haloacetylenes, see: a) J. P. Brand, J. Waser, Chem. Soc. Rev. 2012, 41, 4165 – 4179; for our reports on the synthetic applications of haloacetylenes, see: b) Y. Fukudome, H. Naito, T. Hata, H. Urabe, J. Am. Chem. Soc. 2008, 130, 1820 – 1821; c) M. Yamagishi, K. Nishigai, T. Hata, H. Urabe, Org. Lett. 2011, 13, 4873 – 4875; d) M. Yamagishi, J. Okazaki, K. Nishigai, T. Hata, H. Urabe, Org. Lett. 2012, 14, 34 – 37; e) M. Yamagishi, K. Nishigai, A. Ishii, T. Hata, H. Urabe, Angew. Chem. 2012, 124, 6577 – 6580; Angew. Chem. Int. Ed. 2012, 51, 6471 – 6474. [5] For recent reviews on Rh-catalyzed reactions, see: a) F. W. Patureau, J. Wencel-Delord, F. Glorius, Aldrichimica Acta 2012, 45, 31 – 41; b) C. Zhu, R. Wang, J. R. Falck, Chem. Asian J. 2012, 7, 1502 – 1514; c) Eds.: H. M. L. Davies, J. Du Bois, J.-Q. Yu, Chem. Soc. Rev. 2011, 40, 1857 – 2038; d) T. Satoh, M. Miura, Chem. Eur. J. 2010, 16, 11212 – 11222; e) Ed.: R. H. Crabtree, Chem. Rev. 2010, 110, 575 – 1211; f) V. Michelet, P. Y. Toullec, J.-P. GenÞt, Angew. Chem. 2008, 120, 4338 – 4386; Angew. Chem. Int. Ed. 2008, 47, 4268 – 4315; g) J. C. Lewis, R. G. Bergman, J. A. Ellman, Acc. Chem. Res. 2008, 41, 1013 – 1025; h) Y. J. Park, J.-W. Park, C.-H. Jun, Acc. Chem. Res. 2008, 41, 222 – 234; i) Modern Rhodium-Catalyzed Organic Reactions (Ed.: P. A. Evans), Wiley-VHC, Weinheim, 2005; j) H. M. L. Davies, M. S. Long, Angew. Chem. 2005, 117, 3584 – 3586; Angew. Chem. Int. Ed. 2005, 44, 3518 – 3520; k) K. Fagnou, M. Lautens, Chem. Rev. 2003, 103, 169 – 196; l) H. M. L. Davies, R. E. J. Beckwith, Chem. Rev. 2003, 103, 2861 – 2903; m) P. Mller, C. Fruit, Chem. Rev. 2003, 103, 2905 – 2919; n) T. Hayashi, K. Yamasaki, Chem. Rev. 2003, 103, 2829 – 2844; o) V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev. 2002, 102, 1731 – 1769; for our recent reports on Rh-catalyzed activation of acetylenes, see: p) D. Shikanai, H. Murase, T. Hata, H. Urabe, J. Am. Chem. Soc. 2009, 131, 3166 – 3167; q) Y. T. Oh, K. Senda, T. Hata, H. Urabe, Tetrahedron Lett. 2011, 52, 2458 – 2461. [6] As hydroarylation to haloacetylenes is still quite limited, its feasibility and chemo-, regio-, and stereoselective aspects have not been amply elucidated; a) V. Mamane, P. Hannen, A. Frstner, Chem. Eur. J. 2004, 10, 4556 – 4575; b) G. Huang, B. Cheng, L. Xu, Y. Li, Y. Xia, Chem. Eur. J. 2012, 18, 5401 – 5415; an unsuccessful case was also mentioned, see: c) K. Komeyama, R. Igawa, K. Takaki, Chem. Commun. 2010, 46, 1748 – 1750; for the preparation of non-halogenated dihydroquinolines and chromenes via hydroarylation, see: d) S. J. Pastine, S. W. Youn, D. Sames, Org. Lett. 2003, 5, 1055 – 1058; e) B. Martn-Matute, C. Nevado, D. J. Crdenas, A. M. Echavarren, J. Am. Chem. Soc. 2003, 125, 5757 – 5766; f) C. Nieto-Oberhuber, M. P. MuÇoz, E. BuÇuel, C. Nevado, D. J. Crdenas,
Chem. Eur. J. 2014, 20, 317 – 322
www.chemeurj.org
[8]
[9]
[10]
A. M. Echavarren, Angew. Chem. 2004, 116, 2456 – 2460; Angew. Chem. Int. Ed. 2004, 43, 2402 – 2406; g) reference [6c]. For reviews on quinolines and their hydrogenated derivatives, see: a) R. Alajarn, C. Burgos in Modern Heterocyclic Chemistry, Vol. 3 (Eds.: J. Alvarez-Builla, J. J. Vaquero, J. Barluenga), Wiley-VCH, Weinheim, 2011, pp. 1527 – 1570; b) J. A. Joule, K. Mills, Heterocyclic Chemistry, 5th ed., Wiley, Chichester, 2010, pp. 177 – 203; c) Comprehensive Heterocyclic Chemistry, Vol. 2 (Eds.: A. R. Katritzky, C. W. Rees, A. J. Boulton, A. McKillop), Pergamon, Oxford, 1984; d) C. Bhanja, S. Jena, S. Nayak, S. Mohapatra, Beilstein J. Org. Chem. 2012, 8, 1668 – 1694; e) J. Barluenga, F. Rodrguez, F. J. FaÇans, Chem. Asian J. 2009, 4, 1036 – 1048; f) V. V. Kouznetsov, Tetrahedron 2009, 65, 2721 – 2750; g) J. P. Michael, Nat. Prod. Rep. 2008, 25, 166 – 187; h) J. P. Michael, Nat. Prod. Rep. 2007, 24, 223 – 246; i) S. A. Yamashkin, E. A. Oreshkina, Chem. Heterocycl. Compd. 2006, 42, 701 – 718; j) V. V. Kouznetsov, J. Heterocycl. Chem. 2005, 42, 39 – 59; k) H. Water, J. Prakt. Chem. 1998, 340, 309 – 314; l) A. R. Katritzky, S. Rachwal, B. Rachwal, Tetrahedron 1996, 52, 15031 – 15070; m) O. MethCohn, Heterocycles 1993, 35, 539 – 557. Halogenated heterocycles (including even chlorinated ones) are versatile synthetic building blocks: a) J. J. Li, G. W. Gribble, Palladium in Heterocyclic Chemistry, Pergamon, Amsterdam, 2000; b) T. Liu, H. Fu, Synthesis 2012, 2805 – 2824; c) H. Li, C. C. C. J. Seechurn, T. J. Colacot, ACS Catal. 2012, 2, 1147 – 1164; d) S. M. Wong, C. M. So, F. Y. Kwong, Synlett 2012, 23, 1132 – 1153; e) K. C. Majumdar, S. Samanta, B. Sinha, Synthesis 2012, 44, 817 – 847; f) Ed.: S. L. Buchwald, Acc. Chem. Res. 2008, 41, 1439 – 1564; g) E. A. B. Kantchev, C. J. O’Brien, M. G. Organ, Angew. Chem. 2007, 119, 2824 – 2870; Angew. Chem. Int. Ed. 2007, 46, 2768 – 2813; h) R. J. Lundgren, M. Stradiotto, Aldrichimica Acta 2012, 45, 59 – 65; i) D. Maiti, B. P. Fors, J. L. Henderson, Y. Nakamura, S. L. Buchwald, Chem. Sci. 2011, 2, 57 – 68; j) F. Monnier, M. Taillefer, Angew. Chem. 2008, 120, 3140 – 3143; Angew. Chem. Int. Ed. 2008, 47, 3096 – 3099; k) D. S. Surry, S. L. Buchwald, Angew. Chem. 2008, 120, 6438 – 6461; Angew. Chem. Int. Ed. 2008, 47, 6338 – 6361; l) M. C. Willis, Angew. Chem. 2007, 119, 3470 – 3472; Angew. Chem. Int. Ed. 2007, 46, 3402 – 3404; m) S. V. Ley, A. W. Thomas, Angew. Chem. 2003, 115, 5558 – 5607; Angew. Chem. Int. Ed. 2003, 42, 5400 – 5449; n) K. Kunz, U. Scholz, D. Ganzer, Synlett 2003, 2428 – 2439; o) D. Prim, J.-M. Campagne, D. Joseph, B. Andrioletti, Tetrahedron 2002, 58, 2041 – 2075; p) V. V. Grushin, H. Alper in Activation of Unreactive Bonds and Organic Synthesis (Ed.: S. Murai), Springer, Berlin, 1999, pp. 193 – 226. For individual reactions in Scheme 3, see: q) Z. Liang, S. Ma, J. Yu, R. Xu, J. Org. Chem. 2007, 72, 9219 – 9224; r) G. Uray, A.-M. Kelterer, J. Hashim, T. N. Glasnov, C. O. Kappe, W. M. F. Fabian, J. Mol. Struct. 2009, 929, 85 – 96. For reviews on chromenes or chromans, see: a) J. Santamara, C. Valds in Modern Heterocyclic Chemistry, Vol. 3 (Eds.: J. Alvarez-Builla, J. J. Vaquero, J. Barluenga), Wiley-VCH, Weinheim, 2011, pp. 1631 – 1682; b) J. A. Joule, K. Mills, Heterocyclic Chemistry, 5th ed., Wiley, Chichester, 2010, pp. 205 – 207 and 229 – 247; c) P. J. Brogden, C. D. Gabbutt, J. D. Hepworth in Comprehensive Heterocyclic Chemistry, Vol. 3 (Eds.: A. R. Katritzky, C. W. Rees, A. J. Boulton, A. McKillop), Pergamon, Oxford, 1984, pp. 573 – 645; d) G. P. Ellis in Comprehensive Heterocyclic Chemistry, Vol. 3 (Eds.: A. R. Katritzky, C. W. Rees, A. J. Boulton, A. McKillop), Pergamon, Oxford, 1984, pp. 647 – 736; e) J. D. Hepworth in Comprehensive Heterocyclic Chemistry, Vol. 3 (Eds.: A. R. Katritzky, C. W. Rees, A. J. Boulton, A. McKillop), Pergamon, Oxford, 1984, pp. 737 – 883; f) reference [7d]; g) T. E.-S. Ali, M. A. Ibrahim, S. M. Abdel-Kariem, Phosphorus Sulfur Silicon Relat. Elem. 2009, 184, 2358 – 2392; h) S. B. Ferreira, F. de C. da Silva, A. C. Pinto, D. T. G. Gonzaga, V. F. Ferreira, J. Heterocycl. Chem. 2009, 46, 1080 – 1097; i) Y.-L. Shi, M. Shi, Org. Biomol. Chem. 2007, 5, 1499 – 1504; j) A. Lvai, T. Tmr, P. Sebçk, T. Eszenyi, Heterocycles 2000, 53, 1193 – 1203; k) K. C. Majumdar, P. Biswas, Heterocycles 1999, 50, 1227 – 1267; l) Chemistry of Heterocyclic Compounds, Vol. 36 (Ed.: G. P. Ellis), Wiley, New York, 1981. For a relevant note, see: B. M. Trost, Acc. Chem. Res. 1990, 23, 34 – 42.
Received: July 31, 2013 Published online on December 2, 2013
322
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper
& Organic Synthesis
Rhodium-Catalyzed Intramolecular Hydroarylation of 1-Halo-1alkynes: Regioselective Synthesis of Semihydrogenated Aromatic Heterocycles Hirohiko Murase, Kousuke Senda, Masato Senoo, Takeshi Hata, and Hirokazu Urabe*[a]
cles, such as 4-halo-1,2-dihydroquinolines, 4-halo-3-chromenes, or 4-(halomethylene)chromans, in good to excellent yields. Some synthetic applications taking advantage of the halo-substituents of the products are also illustrated.
Abstract: The regioselective intramolecular hydroarylation of (3-halo-2-propynyl)anilines, (3-halo-2-propynyl) aryl ethers, or (4-halo-3-butynyl) aryl ethers was efficiently catalyzed by Rh2(OCOCF3)4 to give semihydrogenated aromatic heterocy-
Intramolecular Friedel–Crafts reaction and its variants are traditional methods for the preparation of cyclic compounds via electrophilic substitution to various aromatic compounds.[1] Although a wide variety of electrophiles and their equivalents could be used in these reactions, there still exists some limitation on the electrophiles, especially incipient ones such as acetylenes.[2] Recent rapid development in transition-metal catalysts, which are more susceptible to interact with an acetylenic bond than traditional Lewis or Brønsted acids, has made it more reactive toward the aromatic substitution. For this reason, this type of reaction is often called transition-metal-catalyzed hydroarylation of acetylenes, irrespective of its actual mechanism, and has attracted much attention recently.[3] During the course of our studies on the synthetic utility of haloacetylenes,[4] we experienced that the cyclization of (halopropargyl)aniline 1 to 2 with a typical Lewis acid, BF3·OEt2, proved unsuccessful, probably due to the moderately electrondeficient nature of haloacetylenes not permitting the effective interaction with such an activator (Scheme 1, method a). However, to the contrary, we were pleased to find that a Rh catalyst ([Rh2(tfa)4], tfa = CF3CO2)[5] is quite promising for the same cyclization from 1 or 3,[6] nicely giving desired products 2 or 4 in good yields, without being accompanied by isomeric product 5 (method b). The carbon–carbon bond formation exclusively took place at the acetylenic carbon atom a to halogen, yielding the six-membered dihydroquinoline derivatives 2 or 4, the structure of which was verified by the derivatization to known
Scheme 1. Rh-catalyzed hydroarylation of chloroacetylene.
4-chloroquinoline 6. On the other hand, 4-chloroquinoline 6 was not detected as a byproduct in the crude reaction mixture derived from method b, which shows that the aromatization of the product during this cyclization was negligible. A plausible mechanism is shown in Scheme 2, in which the more cationic acetylenic carbon atom a to halogen appears to be preferen-
[a] H. Murase, K. Senda, M. Senoo, Prof. Dr. T. Hata, Prof. Dr. H. Urabe Department of Biomolecular Engineering Graduate School of Bioscience and Biotechnology Tokyo Institute of Technology 4259-B-59 Nagatsuta-cho, Midori-ku, Yokohama Kanagawa 226-8501 (Japan) Fax: (+ 81) (0)45-924-5849 E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201303008. Chem. Eur. J. 2014, 20, 317 – 322
Scheme 2. A proposed mechanism.
317
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper tially attacked by the aromatic ring to exhibit the observed regioselection. Equations (1) and (2) show some scope of the substrates. The above reaction is valid for the conversion of both chloroand bromoacetylenes 3 and 7 to desired products 4 and 9, but not for an iodoacetylene 8, due perhaps to the increasing instability of the acetylenic carbon–iodine bond [Eq. (1)]. The protection of the aniline nitrogen atom is critical: while the sulfonyl derivatization is satisfactory as already shown in Scheme 1, N-acyl protection found in 11 and 12 proved unsuitable, giving virtually no desired products 13 or 14 [Eq. (2)] (Boc = tBuOCO ).
Table 1. Preparation of various 4-chloro-1,2-dihydroquinolines.[a]
Entry
Partially hydrogenated aromatic heterocycles, such as those shown above, are frequently found in naturally occurring products and artificial pharmaceuticals and are also useful intermediates in organic synthesis.[7] The hydrogenation of the corresponding aromatic compounds is one of the most straightforward methods for their preparation, but the regioselective transfer of controlled amounts of hydrogen (or its surrogates) to the aromatic ring is not necessarily a trivial process. In addition, the halogenated structures prepared herein should be quite useful for further functionalization and carbon–carbon bond formation. Thus, we further investigated the generality of this transformation. Table 1 summarizes other results of the dihydroquinoline synthesis. Various p-toluenesulfonylanilines participated in the reaction. A TBS-protected hydroxy group in 17 remained unattacked (Table 1, entry 4), and a sterically congested aniline 18 and a-naphthylamine derivative 19 cyclized as well to give 23 and 24 (entries 5 and 6). As already shown in Equation (1), the corresponding bromoacetylenes could be used as an alternative starting material to give similar products, which are summarized in Table 2. However, bromoacetylenes appear less reactive than chloroacetylenes, as the former requires prolonged reaction periods and more catalyst loading to achieve good product yields. The fact that the carbon atom a to bromide is less cationic than that a to chloride should account for the above observation (cf. Scheme 2). Nonetheless, from various bromoacetylenes 25–29, the desired heterocyclic products 30–34 were obtained in good yields. The TBS ether Chem. Eur. J. 2014, 20, 317 – 322
www.chemeurj.org
Substrate
Product
Isolated yield [%]
1
91
2
74
3
97
4
91
5
96
6
83[b]
[a] Ts = p-TolSO2 , TBS = tBuMe2Si . [b] The reaction was performed for 7 h and with 10 mol % of catalyst.
moiety in 27 again survived the reaction conditions. The anilines in Table 2 were protected with a benzenesulfonyl group rather than the Ts that was used in Table 1, showing variation in sulfonyl protecting groups. 4-Halo-1,2-dihydroquinolines prepared above should be versatile synthetic intermediates for the preparation of substituted heterocyclic compounds.[8] Scheme 3 exemplifies some applications.[8q,r] From a representative product 9, different types of side chains including an sp3, sp2, or sp carbon terminus were successfully introduced to its dihydroquinoline skeleton, illustrating the diverse synthesis from a common starting material. During these transformations, an undesired side reaction, aromatization to the corresponding quinolines like the one mentioned in Scheme 1, was not observed at all. It should be emphasized that the extension of a functional group or a carbon side chain from the halogen substituents may make it possible to prepare the products that could not be obtained by the direct hydroarylation of the corresponding alkynes[6d–g] owing to the lack of either regioselectivity or functional-group compatibility (for example, the hydroxy group in 36). 318
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper After having established the preparation of dihydroquinolines via the intramolecular hydroarylation of haloacetylenes and their synthetic application, we next turned our attention to the preparation of an oxygen heterocycle from a similar halopropargyl aryl ether 39 (Scheme 4). Under analogous con-
Table 2. Preparation of various 4-bromo-1,2-dihydroquinolines.
Entry
Substrate
[Rh2(tfa)4] [mol %]
t [h]
Product
Isolated yield [%]
1
3
15.5
86
2
5
4
84
3
10
3
73 Scheme 4. Rh-catalyzed cyclization of chloropropargyl aryl ethers.
4
5
4
70
5
5
4
80
6
10
7
61
ditions as those described above, the desired cyclization gratifyingly proceeded to give exclusively chromene 40 containing an endo-cyclic double bond in good yield.[6, 9] The isomeric fivemembered product 41 was not detected, and the structure of 40 was unambiguously determined by its hydrogenation to known 42 (yield not optimized). It should be noted that the amount of the Rh catalyst could be reduced to 0.5 mol % of the substrate whilst keeping a satisfactory yield. The advantage of the Rh catalyst is again illustrated in Equations (3) and (4). Although the substrates 43 and 45 have an electron-rich aromatic ring, traditional activators, such as CF3CO2H or BF3·OEt2 proved not effective for their cyclization. On the other hand, the Rh catalyst did effect the desired reaction, giving chromenes 44 and 46, which is consistent with the outcome of Scheme 1. Equations (3) and (4) also show a favorable aspect of this Rh-catalyzed reaction that it tolerates the presence of a nitrogen functional group in the substrates.[10] However, to complete the reaction in an acceptable period, a greater amount of the Rh catalyst (10 mol %) is necessary than that for a non-functionalized substrate (0.5 mol % in Scheme 4), which suggests that the catalyst is at least partially deactivated by coordination with the nitrogen functional group. To show the generality of this functional-group compatibility, several protected amino-substituted 4-chlorochromenes obtained by this method are summarized in Table 3. In these re-
Scheme 3. Synthetic application of 4-bromo-1,2-dihydroquinoline. Chem. Eur. J. 2014, 20, 317 – 322
www.chemeurj.org
319
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper Table 4. Preparation of various 4-bromochromenes.
Entry
Table 3. Preparation of various 4-chlorochromenes.
Entry
1 2 3
Substrate
X = COPr Boc Ts
Product
(43) (47) (48)
Isolated yield [%]
(44) (54) (55)
67 95 96
4 5
X = COPr Boc
(45) (49)
(46) (56)
62 94[a]
6 7
X = COPr Ts
(50) (51)
(57) (58)
62 97[a]
8
80
9
69
Substrate
Product
Isolated yield [%]
1
70
2
87
3
84
4
88
5
95
[a] The reaction was performed for 2 h and with 3 mol % of catalyst.
actions, acyl-, Boc-, and Ts-protected aniline derivatives 43, 47, and 48 can be used equally well (Table 3, entries 1–3) and, to our satisfaction, broad substitution patterns on the aromatic ring are also acceptable (entries 4–9). Like the synthesis of dihydroquinolines, this cyclization is not limited to chloroacetylenes, but is also applicable to bromoacetylenes to give 4-bromochromenes, which are listed in Table 4. In these transformations, the amount of the Rh catalyst could again be reduced to as low as 1 mol % of the substrates. It is interesting to compare the above cyclizations with that starting from homologous halobutynyl aryl ether 71 Chem. Eur. J. 2014, 20, 317 – 322
www.chemeurj.org
Scheme 5. Hydroarylation of chlorobutynyl aryl ether.
(Scheme 5). Considering the tendency discussed above that the carbon–carbon bond formation always takes place at the acetylenic carbon atom a to the halogen, we, at first glance, expected that the reaction of Scheme 5 might give preferentially seven-membered product 74. However, what was actually observed was the ring closure at the acetylenic carbon atom b to the halogen, selectively giving a chromene derivative 72 containing an exo-cyclic double bond with Z configuration. 320
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper The olefin geometry of 72 was unambiguously determined by a 1H NMR NOESY study, and another isomeric product 73 and aforementioned 74 were not detected even in a crude reaction mixture. A conventional Lewis acid, BF3·OEt2, again proved useless for this type of substrate. Further structural confirmation of 72 was performed on an alternative product 75 (vide infra), which was led to methylchroman 76 upon hydrogenolysis
Table 5. Preparation of various 4-(halomethylene)chromans.
Entry Substrate
[Rh2(tfa)4] Product [mol %]
Isolated Z/E yield [%]
1
5
70[a]
97:3
2
3
79
97:3
3
3
81
98:2
4
3
83
95:5
5
10
54[b]
> 99:1
6
5
53[c]
> 99:1
7
3
91[d]
95:5
Scheme 6. A proposed mechanism.
(Scheme 5). The reaction course is proposed in Scheme 6, which is consistent with the formation of Z-olefinic products. In addition, the ease of formation of a six-membered ring relative to a seven-membered ring should be a prevailing driving force in this case. As a whole, the direction of the cyclization appears to be controlled under the balance between the electronic (ring closure at the acetylenic carbon atom a or b to halogen) and structural (five-, six-, or seven-membered ring formation) factors. As Z-(chloromethylene)chroman 72 should be also a useful building block, we investigated the cyclization of various halobutynyl aryl ethers and summarized the results in Table 5. In each reaction, more catalyst loading was required than for the cyclization of halopropargyl substrates shown in Scheme 4 and Table 4. The olefin geometry was fixed to be Z with high selectivities in most cases. An additional olefinic bond in the starting material 80 survived the reaction conditions. The double cyclization of 81 took place to give tricyclic products 86 with the defined olefin geometry, although an aromatic regioisomer 88 was also formed in a small amount. A bromo-substituted butynyl ether 82 could be used as well to give sterically congested vinyl bromide 87. In conclusion, the regioselective intramolecular hydroarylation of haloacetylenes was efficiently achieved with [Rh2(tfa)4], which was found to be superior to traditional Brønsted or Lewis acids, to give 4-halo-1,2-dihydroquinolines, 4-halo-3chromenes, or 4-(halomethylene)chromans in good yields.
[a] The reaction was performed for 24 h. [b] The reaction was performed at 90 8C for 15 h. [c] The isomeric product 88 (see below) was also isolated in 17 % yield. [d] The reaction period was 0.5 h and this product is an inseparable 95:5 mixture of 87 and 89 (see below).
with the aid of ethyl acetate. The combined filtrates were concentrated in vacuo to give a crude oil, 1H NMR spectroscopic analysis of which showed the presence of a single olefinic isomer. The crude product was chromatographed on silica gel (hexane/ethyl acetate) to afford the title compound (0.905 g, 86 %) as a paleyellow solid.
Experimental Section N-(Benzenesulfonyl)-4-bromo-1,2-dihydroquinoline (9): A mixture of N-(3-bromo-2-propynyl)-N-phenylbenzenesulfonamide (7) (1.05 g, 3.00 mmol) and rhodium trifluoroacetate dimer ([Rh2(tfa)4], 58.9 mg, 0.0895 mmol) in toluene (30 mL) was stirred in an oil bath maintained at 80 8C for 15.5 h. After being cooled to room temperature, the mixture was filtered through a short pad of silica gel Chem. Eur. J. 2014, 20, 317 – 322
www.chemeurj.org
Acknowledgements This work was supported by a Grant-in-Aid for Challenging Exploratory Research (22655014) from JSPS, Japan. 321
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Full Paper Keywords: chromene · dihydroquinolines · heterocycles · hydroarylation · rhodium
[7]
[1] For reviews on the Friedel–Crafts reaction, see: a) Friedel – Crafts and Related Reactions, Vols. I – IV (Ed.: G. A. Olah), Wiley, New York, 1963 – 1965; b) G. A. Olah, R. Krishnamurti, G. K. S. Prakash in Comprehensive Organic Synthesis, Vol. 3 (Eds.: B. M. Trost, I. Fleming), Pergamon, Oxford, 1991, pp. 293 – 339; c) M. B. Smith, J. March, March’s Advanced Organic Chemistry, 6th ed., Wiley, Hoboken, 2007, pp. 705 – 733; d) F. A. Carey, R. J. Sundberg, Advanced Organic Chemistry Part B, 5th ed., Springer, New York, 2007, pp. 1014 – 1025. [2] The Friedel – Crafts reaction of aromatic compounds with acetylenes was little documented at the outset: V. Franzen in Friedel – Crafts and Related Reactions, Vol. II, Part 1 (Ed.: G. A. Olah), Wiley, New York, 1964, pp. 413 – 416. [3] As the hydroarylation refers to a formal reaction pattern characterized by its products, its actual mechanism may include the Friedel–Craftstype reaction and the aromatic C H bond activation. For reviews, see: a) M. Bandini, E. Emer, S. Tommasi, A. Umani-Ronchi, Eur. J. Org. Chem. 2006, 3527 – 3544; b) C. Nevado, A. M. Echavarren, Synthesis 2005, 167 – 182; c) T. Kitamura, Eur. J. Org. Chem. 2009, 1111 – 1125; d) X. Wang, L. Zhou, W. Lu, Curr. Org. Chem. 2010, 14, 289 – 307; e) D. A. Capretto, Z. Li, C. He in Handbook of Cyclization Reactions, Vol. 2 (Ed.: S. Ma), WileyVCH, Weinheim, 2010, pp. 991 – 1023; f) R. Hayashi, G. R. Cook in Handbook of Cyclization Reactions, Vol. 2 (Ed.: S. Ma), Wiley-VCH, Weinheim, 2010, pp. 1025 – 1054. [4] For a review on certain synthetic aspects of haloacetylenes, see: a) J. P. Brand, J. Waser, Chem. Soc. Rev. 2012, 41, 4165 – 4179; for our reports on the synthetic applications of haloacetylenes, see: b) Y. Fukudome, H. Naito, T. Hata, H. Urabe, J. Am. Chem. Soc. 2008, 130, 1820 – 1821; c) M. Yamagishi, K. Nishigai, T. Hata, H. Urabe, Org. Lett. 2011, 13, 4873 – 4875; d) M. Yamagishi, J. Okazaki, K. Nishigai, T. Hata, H. Urabe, Org. Lett. 2012, 14, 34 – 37; e) M. Yamagishi, K. Nishigai, A. Ishii, T. Hata, H. Urabe, Angew. Chem. 2012, 124, 6577 – 6580; Angew. Chem. Int. Ed. 2012, 51, 6471 – 6474. [5] For recent reviews on Rh-catalyzed reactions, see: a) F. W. Patureau, J. Wencel-Delord, F. Glorius, Aldrichimica Acta 2012, 45, 31 – 41; b) C. Zhu, R. Wang, J. R. Falck, Chem. Asian J. 2012, 7, 1502 – 1514; c) Eds.: H. M. L. Davies, J. Du Bois, J.-Q. Yu, Chem. Soc. Rev. 2011, 40, 1857 – 2038; d) T. Satoh, M. Miura, Chem. Eur. J. 2010, 16, 11212 – 11222; e) Ed.: R. H. Crabtree, Chem. Rev. 2010, 110, 575 – 1211; f) V. Michelet, P. Y. Toullec, J.-P. GenÞt, Angew. Chem. 2008, 120, 4338 – 4386; Angew. Chem. Int. Ed. 2008, 47, 4268 – 4315; g) J. C. Lewis, R. G. Bergman, J. A. Ellman, Acc. Chem. Res. 2008, 41, 1013 – 1025; h) Y. J. Park, J.-W. Park, C.-H. Jun, Acc. Chem. Res. 2008, 41, 222 – 234; i) Modern Rhodium-Catalyzed Organic Reactions (Ed.: P. A. Evans), Wiley-VHC, Weinheim, 2005; j) H. M. L. Davies, M. S. Long, Angew. Chem. 2005, 117, 3584 – 3586; Angew. Chem. Int. Ed. 2005, 44, 3518 – 3520; k) K. Fagnou, M. Lautens, Chem. Rev. 2003, 103, 169 – 196; l) H. M. L. Davies, R. E. J. Beckwith, Chem. Rev. 2003, 103, 2861 – 2903; m) P. Mller, C. Fruit, Chem. Rev. 2003, 103, 2905 – 2919; n) T. Hayashi, K. Yamasaki, Chem. Rev. 2003, 103, 2829 – 2844; o) V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev. 2002, 102, 1731 – 1769; for our recent reports on Rh-catalyzed activation of acetylenes, see: p) D. Shikanai, H. Murase, T. Hata, H. Urabe, J. Am. Chem. Soc. 2009, 131, 3166 – 3167; q) Y. T. Oh, K. Senda, T. Hata, H. Urabe, Tetrahedron Lett. 2011, 52, 2458 – 2461. [6] As hydroarylation to haloacetylenes is still quite limited, its feasibility and chemo-, regio-, and stereoselective aspects have not been amply elucidated; a) V. Mamane, P. Hannen, A. Frstner, Chem. Eur. J. 2004, 10, 4556 – 4575; b) G. Huang, B. Cheng, L. Xu, Y. Li, Y. Xia, Chem. Eur. J. 2012, 18, 5401 – 5415; an unsuccessful case was also mentioned, see: c) K. Komeyama, R. Igawa, K. Takaki, Chem. Commun. 2010, 46, 1748 – 1750; for the preparation of non-halogenated dihydroquinolines and chromenes via hydroarylation, see: d) S. J. Pastine, S. W. Youn, D. Sames, Org. Lett. 2003, 5, 1055 – 1058; e) B. Martn-Matute, C. Nevado, D. J. Crdenas, A. M. Echavarren, J. Am. Chem. Soc. 2003, 125, 5757 – 5766; f) C. Nieto-Oberhuber, M. P. MuÇoz, E. BuÇuel, C. Nevado, D. J. Crdenas,
Chem. Eur. J. 2014, 20, 317 – 322
www.chemeurj.org
[8]
[9]
[10]
A. M. Echavarren, Angew. Chem. 2004, 116, 2456 – 2460; Angew. Chem. Int. Ed. 2004, 43, 2402 – 2406; g) reference [6c]. For reviews on quinolines and their hydrogenated derivatives, see: a) R. Alajarn, C. Burgos in Modern Heterocyclic Chemistry, Vol. 3 (Eds.: J. Alvarez-Builla, J. J. Vaquero, J. Barluenga), Wiley-VCH, Weinheim, 2011, pp. 1527 – 1570; b) J. A. Joule, K. Mills, Heterocyclic Chemistry, 5th ed., Wiley, Chichester, 2010, pp. 177 – 203; c) Comprehensive Heterocyclic Chemistry, Vol. 2 (Eds.: A. R. Katritzky, C. W. Rees, A. J. Boulton, A. McKillop), Pergamon, Oxford, 1984; d) C. Bhanja, S. Jena, S. Nayak, S. Mohapatra, Beilstein J. Org. Chem. 2012, 8, 1668 – 1694; e) J. Barluenga, F. Rodrguez, F. J. FaÇans, Chem. Asian J. 2009, 4, 1036 – 1048; f) V. V. Kouznetsov, Tetrahedron 2009, 65, 2721 – 2750; g) J. P. Michael, Nat. Prod. Rep. 2008, 25, 166 – 187; h) J. P. Michael, Nat. Prod. Rep. 2007, 24, 223 – 246; i) S. A. Yamashkin, E. A. Oreshkina, Chem. Heterocycl. Compd. 2006, 42, 701 – 718; j) V. V. Kouznetsov, J. Heterocycl. Chem. 2005, 42, 39 – 59; k) H. Water, J. Prakt. Chem. 1998, 340, 309 – 314; l) A. R. Katritzky, S. Rachwal, B. Rachwal, Tetrahedron 1996, 52, 15031 – 15070; m) O. MethCohn, Heterocycles 1993, 35, 539 – 557. Halogenated heterocycles (including even chlorinated ones) are versatile synthetic building blocks: a) J. J. Li, G. W. Gribble, Palladium in Heterocyclic Chemistry, Pergamon, Amsterdam, 2000; b) T. Liu, H. Fu, Synthesis 2012, 2805 – 2824; c) H. Li, C. C. C. J. Seechurn, T. J. Colacot, ACS Catal. 2012, 2, 1147 – 1164; d) S. M. Wong, C. M. So, F. Y. Kwong, Synlett 2012, 23, 1132 – 1153; e) K. C. Majumdar, S. Samanta, B. Sinha, Synthesis 2012, 44, 817 – 847; f) Ed.: S. L. Buchwald, Acc. Chem. Res. 2008, 41, 1439 – 1564; g) E. A. B. Kantchev, C. J. O’Brien, M. G. Organ, Angew. Chem. 2007, 119, 2824 – 2870; Angew. Chem. Int. Ed. 2007, 46, 2768 – 2813; h) R. J. Lundgren, M. Stradiotto, Aldrichimica Acta 2012, 45, 59 – 65; i) D. Maiti, B. P. Fors, J. L. Henderson, Y. Nakamura, S. L. Buchwald, Chem. Sci. 2011, 2, 57 – 68; j) F. Monnier, M. Taillefer, Angew. Chem. 2008, 120, 3140 – 3143; Angew. Chem. Int. Ed. 2008, 47, 3096 – 3099; k) D. S. Surry, S. L. Buchwald, Angew. Chem. 2008, 120, 6438 – 6461; Angew. Chem. Int. Ed. 2008, 47, 6338 – 6361; l) M. C. Willis, Angew. Chem. 2007, 119, 3470 – 3472; Angew. Chem. Int. Ed. 2007, 46, 3402 – 3404; m) S. V. Ley, A. W. Thomas, Angew. Chem. 2003, 115, 5558 – 5607; Angew. Chem. Int. Ed. 2003, 42, 5400 – 5449; n) K. Kunz, U. Scholz, D. Ganzer, Synlett 2003, 2428 – 2439; o) D. Prim, J.-M. Campagne, D. Joseph, B. Andrioletti, Tetrahedron 2002, 58, 2041 – 2075; p) V. V. Grushin, H. Alper in Activation of Unreactive Bonds and Organic Synthesis (Ed.: S. Murai), Springer, Berlin, 1999, pp. 193 – 226. For individual reactions in Scheme 3, see: q) Z. Liang, S. Ma, J. Yu, R. Xu, J. Org. Chem. 2007, 72, 9219 – 9224; r) G. Uray, A.-M. Kelterer, J. Hashim, T. N. Glasnov, C. O. Kappe, W. M. F. Fabian, J. Mol. Struct. 2009, 929, 85 – 96. For reviews on chromenes or chromans, see: a) J. Santamara, C. Valds in Modern Heterocyclic Chemistry, Vol. 3 (Eds.: J. Alvarez-Builla, J. J. Vaquero, J. Barluenga), Wiley-VCH, Weinheim, 2011, pp. 1631 – 1682; b) J. A. Joule, K. Mills, Heterocyclic Chemistry, 5th ed., Wiley, Chichester, 2010, pp. 205 – 207 and 229 – 247; c) P. J. Brogden, C. D. Gabbutt, J. D. Hepworth in Comprehensive Heterocyclic Chemistry, Vol. 3 (Eds.: A. R. Katritzky, C. W. Rees, A. J. Boulton, A. McKillop), Pergamon, Oxford, 1984, pp. 573 – 645; d) G. P. Ellis in Comprehensive Heterocyclic Chemistry, Vol. 3 (Eds.: A. R. Katritzky, C. W. Rees, A. J. Boulton, A. McKillop), Pergamon, Oxford, 1984, pp. 647 – 736; e) J. D. Hepworth in Comprehensive Heterocyclic Chemistry, Vol. 3 (Eds.: A. R. Katritzky, C. W. Rees, A. J. Boulton, A. McKillop), Pergamon, Oxford, 1984, pp. 737 – 883; f) reference [7d]; g) T. E.-S. Ali, M. A. Ibrahim, S. M. Abdel-Kariem, Phosphorus Sulfur Silicon Relat. Elem. 2009, 184, 2358 – 2392; h) S. B. Ferreira, F. de C. da Silva, A. C. Pinto, D. T. G. Gonzaga, V. F. Ferreira, J. Heterocycl. Chem. 2009, 46, 1080 – 1097; i) Y.-L. Shi, M. Shi, Org. Biomol. Chem. 2007, 5, 1499 – 1504; j) A. Lvai, T. Tmr, P. Sebçk, T. Eszenyi, Heterocycles 2000, 53, 1193 – 1203; k) K. C. Majumdar, P. Biswas, Heterocycles 1999, 50, 1227 – 1267; l) Chemistry of Heterocyclic Compounds, Vol. 36 (Ed.: G. P. Ellis), Wiley, New York, 1981. For a relevant note, see: B. M. Trost, Acc. Chem. Res. 1990, 23, 34 – 42.
Received: July 31, 2013 Published online on December 2, 2013
322
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
