DOI: 10.1002/chem.201405357
Communication
& Synthetic Methods
One-Pot Synthesis of 2,5-Dihydropyrroles from Terminal Alkynes, Azides, and Propargylic Alcohols by Relay Actions of Copper, Rhodium, and Gold Tomoya Miura,* Takamasa Tanaka, Kohei Matsumoto, and Masahiro Murakami*[a] Dedicated to Professor Iwao Ojima (SUNY) on the occasion of his 70th birthday one[4] with regard to the position of unsaturation. Of particular note is that multiple reactions occur stepwise by simply applying the requisite substrate/catalyst to terminal alkynes. A single execution of work-up/purification procedures gave substantial expansion of the structural, as well as functional complexities. The direct synthesis of various 2,5-dihydropyrroles in one pot starting from terminal alkynes is summarized in Table 1. 1Arylethynes 1 a–d having both electron-donating and -withdrawing substituents reacted facilely with tosyl azide (2 a) and propargylic alcohol 3 a to give the corresponding 2,5-dihydropyrroles 4 a–d in yields ranging from 56 to 83 % (entries 1–4). Mesyl azide (2 b) also successfully participated in the reaction (entry 5). Multisubstituted 2,5-dihydropyrroles 4 f and g could be regioselectively synthesized by using a,a-disubstituted and a,a,g-trisubstituted propargylic alcohols 3 b and c, respectively (entries 6 and 7). From the experimental viewpoint, the transformation consists of three operational procedures and a single work-up/purification procedure. In the first procedure, 1-sulfonyl-1,2,3-triazoles were generated from terminal alkynes and sulfonyl azides by the authentic method developed by Fokin;[7] terminal alkynes 1 (1.0 equiv) were treated with sulfonyl azides 2 (1.0 equiv) in the presence of copper(I) thiophene-2-carboxylate (10 mol %, CuTC) in 1,2-dichloroethane (DCE) at room temperature for 6 h. In the second procedure, propargylic alcohols 3 (1.5 equiv) and rhodium(II) pivalate dimer (1.0 mol %) were added to the same reaction vessel, which was heated at 100 8C for 30 min under microwave (MW) irradiation[8] to prompt O H insertion and subsequent sigmatropic rearrangement.[9–12] The resulting a-allenyl-a-amino ketones were then cyclized in the third procedure; [Au(JohnPhos)(CH3CN)][SbF6] (5.0 mol %, JohnPhos = (2-biphenyl)di-tert-butylphosphine)[13] was added to the reaction vessel, which was further stirred at room temperature for 3 h. Finally, the reaction mixture was subjected to a workup/purification procedure to give 2,5-dihydropyrrole products 4. The rhodium-catalyzed O H insertion reaction in the second procedure was not interfered by the copper catalyst used in the first procedure for 1,3-dipolar cycloaddition. Neither the gold-catalyzed cyclization reaction occurring in the third procedure was interfered by the copper and rhodium catalysts used in the first and second procedures. As a result, the whole multistep transformation can be carried out in a same reaction
Abstract: Relay actions of copper, rhodium, and gold formulate a one-pot multistep pathway, which directly gives 2,5-dihydropyrroles starting from terminal alkynes, sulfonyl azides, and propargylic alcohols. Initially, copper-catalyzed 1,3-dipolar cycloaddition of terminal alkynes with sulfonyl azides affords 1-sulfonyl-1,2,3-triazoles, which then react with propargylic alcohols under the catalysis of rhodium. The resulting alkenyl propargyl ethers subsequently undergo the thermal Claisen rearrangement to give a-allenyl-a-amino ketones. Finally, a gold catalyst prompts 5endo cyclization to produce 2,5-dihydropyrroles.
Functionalized pyrrolidines constitute a core structural element broadly found in natural products and pharmaceutically active substances.[1] Dihydropyrroles with an unsaturation available for further functionalization are valuable precursors for their synthesis.[2] Therefore, the development of efficient methods for the synthesis of dihydropyrroles from readily available starting materials has been an active area of research.[3] We have reported the synthesis of 2,3-dihydropyrroles from terminal alkynes, sulfonyl azides, and a,b-unsaturated aldehydes.[4] aImino carbenoid species are involved therein as the key reactive intermediate of electrophilic nature.[5] Herein, we report a new synthetic protocol constituting 2,5-dihydropyrroles from three components including propargylic alcohols (Figure 1). Relay actions of copper, rhodium, and gold catalysts[6] formulate a one-pot multistep pathway, complementing the previous
Figure 1. Constitution of 2,5-dihydropyrroles from terminal alkynes, tosyl azide, and propargylic alcohols.
[a] Prof. Dr. T. Miura, T. Tanaka, K. Matsumoto, Prof. Dr. M. Murakami Department of Synthetic Chemistry and Biological Chemistry Kyoto University, Katsura, Kyoto 615-8510 (Japan) E-mail: [email protected] [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201405357. Chem. Eur. J. 2014, 20, 1 – 6
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Communication Propargylic alcohol 3 undergoes nucleophilic addition to the electrophilic carbenoid carbon of A to give zwitterionic intermediate B. Then, a proton shifts onto the imino nitrogen with release of rhodium(II), forming the (Z)-isomer of alkenyl propargyl ether C. It is probably spontaneous at 100 8C for C to undergo the thermal Claisen-type [3,3]-sigmatropic rearrangement via the six-membered chairlike transition state D (see below) to produce a-allenyl aamino ketone 6.[9–11] The third procedure follows the gold-catalyzed cyclization reaction developed by Krause.[3d] The allenyl group is activated by gold to induce intramolecular addition of the amino group in a 5-endo mode, producing 2,5-dihydropyrrole 4.[15] Entry 1-Alkyne 1 Azide 2 Alcohol 3 Product Yield [%][d] R1 R2 R3 C(R4)2 4 To delineate the scope of the present method, the transformation consisting of the second rhodium(II)1 Ph 1 a p-Tol 2 a H CH2 3a 4a 83 3a 4b 83 2 p-Tol 1 b p-Tol 2 a H CH2 catalyzed and third gold(I)-catalyzed procedures was 1 c p-Tol 2 a H CH2 3a 4c 82 3 p-MeOC6H4 examined by using the propargylic alcohol 3 a and 3a 4d 56 4 p-MeO2CC6H4 1 d p-Tol 2 a H CH2 various isolated 1-tosyltriazoles 5 (Table 2). Triazoles 3a 4e 86 5 Ph 1 a Me 2 b H CH2 5 aa–ga possessing electron-donating and -withdraw6 Ph 1 a p-Tol 2 a H CMe2 3b 4 f 73[e] 7 Ph 1 a p-Tol 2 a Me cyclohexylidene 3 c 4 g 73 ing aryl groups at the fourth positions all gave the corresponding products in good to high yields (en[a] 1 (0.20 mmol), 2 (0.20 mmol), CuTC (20 mmol), 1,2-dichloroethane (DCE, 1 mL). [b] 3 (0.30 mmol), [Rh2(tBuCO2)4] (2.0 mmol), DCE (1 mL). [c] [Au(JohnPhos)(CH3CN)][SbF6] tries 1–6 in Table 2). A similar result was obtained (10 mmol), DCE (1 mL). [d] Isolated yield (average of two runs). [e] Using [Auwhen the reaction of entry 1 was carried out on (JohnPhos)(CH3CN)][SbF6] (20 mmol) for 15 h. a larger scale by using 2.0 mmol of 5 aa. Even alkylsubstituted triazoles 5 ha–ja successfully gave 2,5-dihydropyrroles 4 k–m, despite of the possibility of 1,2hydride shift occurring with the intermediate rhodium(II) carvessel,[14] necessitating only a one-time execution of a workbene complex (entries 7–9 in Table 2).[16] However, the reaction up/purification procedure, which would be most costly in general, consuming a significant amount of time and solvents. Scheme 1 depicts a more detailed mechanistic explanation for the sequential procedures mentioned above. The first opTable 2. Sequential reaction of various triazole 5 with propargyl alcohol erational procedure is for the copper(I)-catalyzed 1,3-dipolar (3 a).[a] [7b] cycloaddition. The resulting triazole 5 equilibrates with adiazo imine 5’, which in the second procedure reacts with the rhodium(II) catalyst to generate a-imino rhodium-carbene complex A.[5] Table 1. Sequential one-pot reaction starting from terminal alkynes 1.
Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
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Ph p-Tol p-MeOC6H4 p-EtO2CC6H4 p-CF3C6H4 3-thienyl Et n-Hex BzO(CH2)4 EtO Ph Ph Ph Ph Ph
p-Tol p-Tol p-Tol p-Tol p-Tol p-Tol p-Tol p-Tol p-Tol p-Tol Me iPr Me3Si(CH2)2 p-MeOC6H4 p-BrC6H4
5 aa 5 ba 5 ca 5 ea 5 fa 5 ga 5 ha 5 ia 5 ja 5 ka 5 ab 5 ac 5 ad 5 ae 5 af
Product 4
Yield [%][b]
4a 4b 4c 4h 4i 4j 4k 4l 4m 4n 4e 4o 4p 4q 4r
89 89 90 84 85 90 80[c] 71[c] 81[c] 51[d] 86 95 81 94 90
[a] 1) 5 (0.20 mmol), 3 a (0.30 mmol), [Rh2(tBuCO2)4] (2.0 mmol), DCE (1 mL); 2) [Au(JohnPhos)(CH3CN)][SbF6] (10 mmol), DCE (1 mL). [b] Isolated yield (average of two runs). [c] Using 3 a (0.60 mmol). [d] 1) 3 a (1.0 mmol), 10 min; 2) [Au(JohnPhos)(CH3CN)][SbF6] (20 mmol).
Scheme 1. Plausible mechanism for the one-pot synthesis of 4 from 1, 2, and 3.
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Communication of the ethoxy-substituted triazole 5 ka was slower to give the product 4 n in 51 % yield,[9a, 17] probably due to the less electrophilic nature of the carbenoid carbon (entry 10). The reaction was efficient with respect to the R2 substituent on the sulfonyl group (entries 11–15 in Table 2). The reaction scope was also examined with respect to propargylic alcohols 3 (Scheme 2). g-Substituted alcohols 3 d and e were regioselectively converted to 3-substituted 2,5-dihydropyroles 4 s and t, respectively. On the other hand, the reaction of a,a-disubstituted alcohols 3 f gave 5,5-disubstituted 2,5-dihydropyroles 4 u. These results are consistent with the occurrence of [3,3]-sigmatropic rearrangement during the transformation.
Scheme 3. Reaction with enantiomerically pure alcohol 3 g. 1) [Rh2(tBuCO2)4] (1.0 mol %), DCE, 100 8C/MW, 30 min; 2) [Au(JohnPhos)(CH3CN)][SbF6] (5.0 mol %), DCE, RT, 3 h.
Scheme 2. Sequential reaction of triazole 5 aa with various substituted propargylic alcohols 3 d–f.
When enantiomerically pure a-substituted alcohol 3 g was used, a 3:1 mixture of trans/cis diastereoisomers was obtained (Scheme 3). Notably, the enantiomeric purity was retained with the both diastereoisomers (trans 99 % ee, cis 99 % ee), the absolute configurations of which were not determined. When the sequential transformation was intercepted before the addition of the gold catalyst, a diastereomeric mixture of a-allenyl-aamino ketones G and H (3:1) was obtained. Based on these results, we assume that the alkenyl moiety of the intermediate alkenyl propargylic ether partially isomerizes under the reaction conditions before the [3,3]-sigmatropic rearrangement, giving a 3:1 mixture of Z/E isomers. The Z and E isomers both undergo the rearrangement via the six-membered chairlike transition states E and F, respectively, with the a-methyl substituent taking the pseudoequatorial position. The chirality of 3 g is transferred to the axial chirality of the allenyl group. Then, the external allenic p bond coordinates to gold(I) from the face cis to the Ht. The nitrogen intramolecularly adds to the activated p bond from the face opposite to the gold(I) in a five-endo mode to form the zwitterionic species K and L, respectively. Finally, protodemetalation affords 4 v with generation of a catalytically active gold(I) complex.[3d, 18] Thus, the original central chirality of 3 g is first transferred to the axial chirality of the allenyl group, and finally back to the central chirality of the fifth position of the dihydropyrroles 4 v. Chem. Eur. J. 2014, 20, 1 – 6
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Further derivatization of the obtained dihydropyrroles are exemplified in Equation (1). Treatment of 4 a with 1,8-diazabicycloundec-7-ene (DBU) induced a sequence of E1cB and prototropy to produce pyrrole 7. The carbon–carbon double bond was stereoselectively dihydroxylated by a simple dihydroxylation protocol by using K2OsO2(OH)2, giving diol 8 in 87 % yield (6:1 d.r.). Monosubstituted pyrrolidine 9 was readily synthesized by hydrogenation using the Crabtree’s catalyst.
In summary, we have developed the one-pot multistep procedure for the synthesis of 2,5-dihydropyrroles starting from 3
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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[4] T. Miura, T. Tanaka, K. Hiraga, S. G. Stewart, M. Murakami, J. Am. Chem. Soc. 2013, 135, 13652. [5] For reviews on synthetic transformations of triazoles, see: a) A. V. Gulevich, V. Gevorgyan, Angew. Chem. Int. Ed. 2013, 52, 1371; Angew. Chem. 2013, 125, 1411; b) H. M. L. Davies, J. S. Alford, Chem. Soc. Rev. 2014, 43, 5151. For initiative reports, see: c) S. Chuprakov, F. W. Hwang, V. Gevorgyan, Angew. Chem. Int. Ed. 2007, 46, 4757; Angew. Chem. 2007, 119, 4841; d) T. Horneff, S. Chuprakov, N. Chernyak, V. Gevorgyan, V. V. Fokin, J. Am. Chem. Soc. 2008, 130, 14972; e) T. Miura, M. Yamauchi, M. Murakami, Chem. Commun. 2009, 1470. For recent reports, see: f) E. E. Schultz, R. Sarpong, J. Am. Chem. Soc. 2013, 135, 4696; g) B. T. Parr, S. A. Green, H. M. L. Davies, J. Am. Chem. Soc. 2013, 135, 4716; h) J. E. Spangler, H. M. L. Davies, J. Am. Chem. Soc. 2013, 135, 6802; i) T. Miura, Y. Funakoshi, M. Murakami, J. Am. Chem. Soc. 2014, 136, 2272; j) J.-M. Yang, C.-Z. Zhu, X.-Y. Tang, M. Shi, Angew. Chem. Int. Ed. 2014, 53, 5142; Angew. Chem. 2014, 126, 5242; k) H. Shang, Y. Wang, Y. Tian, J. Feng, Y. Tang, Angew. Chem. 2014, 126, 5768; Angew. Chem. Int. Ed. 2014, 53, 5662; l) K. Chen, Z.-Z. Zhu, Y.-S. Zhang, X.-Y. Tang, M. Shi, Angew. Chem. 2014, 126, 6763; Angew. Chem. Int. Ed. 2014, 53, 6645; m) Y. Xing, G. Sheng, J. Wang, P. Lu, Y. Wang, Org. Lett. 2014, 16, 1244; n) A. Boyer, Org. Lett. 2014, 16, 1660; o) C.-E. Kim, S. Park, D. Eom, B. Seo, P. H. Lee, Org. Lett. 2014, 16, 1900; p) D. J. Jung, H. J. Jeon, J. H. Kim, Y. Kim, S. Lee, Org. Lett. 2014, 16, 2208; q) D. Yadagiri, P. Anbarasan, Org. Lett. 2014, 16, 2510; r) T. Miura, Y. Funakoshi, T. Tanaka, M. Murakami, Org. Lett. 2014, 16, 2760; s) F. Medina, C. Besnard, J. Lacour, Org. Lett. 2014, 16, 3232; t) D. J. Lee, J. Shin, E. J. Yoo, Chem. Commun. 2014, 50, 6620; u) T. Miura, T. Nakamuro, K. Hiraga, M. Murakami, Chem. Commun. 2014, 50, 10474; v) D. J. Lee, H. S. Han, J. Shin, E. J. Yoo, J. Am. Chem. Soc. 2014, 136, 11606; w) E. E. Schultz, V. N. G. Lindsay, R. Sarpong, Angew. Chem. 2014, 126, 10062; Angew. Chem. Int. Ed. 2014, 53, 9904. [6] For one-pot sequential reactions involving gold catalysts, see: a) M. D. Milton, Y. Inada, Y. Nishibayashi, S. Uemura, Chem. Commun. 2004, 2712; b) J. T. Binder, S. F. Kirsch, Org. Lett. 2006, 8, 2151; c) . AksinArtok, N. Krause, Adv. Synth. Catal. 2011, 353, 385; d) M. N. Pennell, M. G. Unthank, P. Turner, T. D. Sheppard, J. Org. Chem. 2011, 76, 1479; e) H. Wang, J. R. Denton, H. M. L. Davies, Org. Lett. 2011, 13, 4316; f) A. S. K. Hashmi, M. Ghanbari, M. Rudolph, F. Rominger, Chem. Eur. J. 2012, 18, 8113; g) M. M. Hansmann, A. S. K. Hashmi, M. Lautens, Org. Lett. 2013, 15, 3226. [7] a) E. J. Yoo, M. Ahlquist, S. H. Kim, I. Bae, V. V. Fokin, K. B. Sharpless, S. Chang, Angew. Chem. Int. Ed. 2007, 46, 1730; Angew. Chem. 2007, 119, 1760; b) J. Raushel, V. V. Fokin, Org. Lett. 2010, 12, 4952; c) Y. Liu, X. Wang, J. Xu, Q. Zhang, Y. Zhao, Y. Hu, Tetrahedron 2011, 67, 6294. [8] We used a microwave synthesizer in to safely handle a low-boilingpoint solvent at high temperature. When a toluene solution of triazole 5 aa and propargylic alcohol 3 a (1.5 equiv) was simply heated at 100 8C in the presence of [Rh2(tBuCO2)4] (1.0 mol %) for 30 min without microwave irradiation, 6 aa was formed also in high yield. [9] It is possible to isolate the intermediate a-allenyl-a-amino ketones. For the previous reports on the rhodium-catalyzed reaction of triazoles with propargylic alcohols forming a-allenyl-a-amino ketones, see: a) T. Miura, T. Tanaka, T. Biyajima, A. Yada, M. Murakami, Angew. Chem. Int. Ed. 2013, 52, 3883; Angew. Chem. 2013, 125, 3975; b) S. Chuprakov, B. T. Worrell, N. Selander, R. K. Sit, V. V. Fokin, J. Am. Chem. Soc. 2014, 136, 195. [10] The reaction of rhodium carbene complexes with propargylic alcohols induces analogous [2,3]- and [3,3]-sigmatropic rearrangement: a) M. E. Jung, J. Pontillo, Org. Lett. 1999, 1, 367; b) J. L. Wood, G. A. Moniz, Org. Lett. 1999, 1, 371; c) G. A. Moniz, J. L. Wood, J. Am. Chem. Soc. 2001, 123, 5095; d) Z. Li, V. Boyarskikh, J. H. Hansen, J. Autschbach, D. G. Musaev, H. M. L. Davies, J. Am. Chem. Soc. 2012, 134, 15497. [11] A review on the Claisen rearrangement of propargyl vinyl ethers: D. Tejedor, G. Mndez-Abt, L. Cotos, F. Garca-Tellado, Chem. Soc. Rev. 2013, 42, 458. [12] A review on the use of propargyl vinyl ethers for the synthesis of heterocycles: Z.-B. Zhu, S. F. Kirsch, Chem. Commun. 2013, 49, 2272. [13] C. Nieto-Oberhuber, S. Lpez, M. P. MuÇoz, D. J. C rdenas, E. BuÇuel, C. Nevado, A. M. Echavarren, Angew. Chem. Int. Ed. 2005, 44, 6146; Angew. Chem. 2005, 117, 6302.
Experimental Section Typical procedure for the one-pot synthesis of 2,5-dihydropyrroles from terminal alkynes (Table 1, entry 1): Phenylethyne (1 a, 20.4 mg, 0.20 mmol), TsN3 (2 a, 39.4 mg, 0.20 mmol), CuTC (3.8 mg, 20 mmol), and 1,2-dichloroethane (1 mL) were added to an ovendried 0.5–2 mL Biotage microwave vial equipped with a stirrer bar in a glovebox. The vial was sealed with a Teflon pressure cap. The reaction mixture was stirred at RT for 6 h. Then, propargylic alcohol 3 a (16.8 mg, 0.30 mmol) and [Rh2(tBuCO2)4] (1.2 mg, 2.0 mmol) in 1,2-dichloroethane (1 mL) were added. The mixture was heated at 100 8C for 30 min under microwave irradiation. After the resulting mixture was cooled, the solution of [Au(JohnPhos)(CH3CN)][SbF6] (7.7 mg, 10 mmol)) in 1,2-dichloroethane (1 mL) was added. The reaction mixture was stirred at RT for 3 h, and it was concentrated under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography (CHCl3/ethyl acetate 30:1) to give the 2,5-dihydropyrrole 4 a (55.7 mg, 0.17 mmol, 83 %) as a white solid.
Acknowledgements This work was supported by MEXT (Grant-in-Aid for Scientific Research on Innovative Areas nos. 22105005 and 24106718, Young Scientists (A) no. 23685019, Scientific Research (B) no. 23350041) and JST (ACT-C). Keywords: copper · gold · rhodium · terminal alkynes · triazoles [1] a) A. R. Pinder, Nat. Prod. Rep. 1992, 9, 491; b) A. B. Mauger, J. Nat. Prod. 1996, 59, 1205; c) D. O’Hagan, Nat. Prod. Rep. 2000, 17, 435. [2] a) Y. Tsuzuki, K. Chiba, K. Mizuno, K. Tomita, K. Suzuki, Tetrahedron: Asymmetry 2001, 12, 2989; b) E. S. Greenwood, P. J. Parsons, Synlett 2002, 167; c) A. L. L. Garcia, M. J. S. Carpes, A. C. B. M. de Oca, M. A. G. dos Santos, C. C. Santana, C. R. D. Correia, J. Org. Chem. 2005, 70, 1050; d) F. A. Davis, T. Ramachandar, J. Chai, E. Skucas, Tetrahedron Lett. 2006, 47, 2743; e) M. Sampath, P.-Y. B. Lee, T.-P. Loh, Chem. Sci. 2011, 2, 1988; f) Y. Luo, A. J. Carnell, H. W. Lam, Angew. Chem. Int. Ed. 2012, 51, 6762; Angew. Chem. 2012, 124, 6866; g) V. Dhand, J. A. Draper, J. Moore, R. Britton, Org. Lett. 2013, 15, 1914. [3] For a review, see: a) M. Brichacek, J. T. Njardarson, Org. Biomol. Chem. 2009, 7, 1761. By ruthenium-catalyzed ring-closing metathesis: b) R. Martn, M. Alcn, M. A. Perics, A. Riera, J. Org. Chem. 2002, 67, 6896; c) H. Kim, W. Lim, D. Im, D. Kim, Y. H. Rhee, Angew. Chem. Int. Ed. 2012, 51, 12055; Angew. Chem. 2012, 124, 12221. By gold-catalyzed cyclization of a-aminoallenes: d) N. Morita, N. Krause, Org. Lett. 2004, 6, 4121; e) P. H. Lee, H. Kim, K. Lee, M. Kim, K. Noh, H. Kim, D. Seomoon, Angew. Chem. Int. Ed. 2005, 44, 1840; Angew. Chem. 2005, 117, 1874; f) A. C. Breman, J. Dijkink, J. H. van Maarseveen, S. S. Kinderman, H. Hiemstra, J. Org. Chem. 2009, 74, 6327; g) N. Krause, C. Winter, Chem. Rev. 2011, 111, 1994. By silver- and base-promoted cyclization of a-aminoallenes: h) M. A. Chowdhury, H.-U. Reissig, Synlett 2006, 2383; i) H. Ohno, Y. Kadoh, N. Fujii, T. Tanaka, Org. Lett. 2006, 8, 947. For other preparative methods, see: j) B. Cekavicus, K. Kore, L. Jakovele, A. Plotniece, K. Pajuste, M. Petrova, S. Belyakov, A. Sobolev, Tetrahedron Lett. 2011, 52, 6246; k) M. Brichacek, M. N. Villalobos, A. Plichta, J. T. Njardarson, Org. Lett. 2011, 13, 1110; l) A. Viso, R. F. de La Pradilla, M. UreÇa, R. H. Bates, M. A. del guila, I. Colomer, J. Org. Chem. 2012, 77, 525.
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Communication [19] When the isolated a-allenyl-a-amino ketone 6 a was treated with [Au(JohnPhos)(CH3CN)][SbF6] (0.5 mol %) at RT for 5 min, the corresponding 2,5-dihydropyrroles 4 a was formed in 68 % yield (NMR) and the starting material was recovered in 26 % yield (NMR). The same reaction in the presence of both the gold catalyst and [Rh2(tBuCO2)4] (1.0 mol %) gave a similar result, suggesting no interference of the rhodium(II) catalyst on the gold(I)-catalyzed cyclization reaction.
[14] We carried out the all-in-one-pot reaction by mixing all substrates and catalysts at once and heating the mixture. However, no reaction occurred, and terminal alkynes remained unchanged. [15] T. J. Brown, D. Weber, M. R. Gagn, R. A. Widenhoefer, J. Am. Chem. Soc. 2012, 134, 9134. [16] a) T. Miura, Y. Funakoshi, M. Morimoto, T. Biyajima, M. Murakami, J. Am. Chem. Soc. 2012, 134, 17440; b) N. Selander, B. T. Worrell, V. V. Fokin, Angew. Chem. Int. Ed. 2012, 51, 13054; Angew. Chem. 2012, 124, 13231. [17] J. S. Alford, H. W. L. Davies, J. Am. Chem. Soc. 2014, 136, 10266. [18] a) C. Deutsch, B. Gockel, A. Hoffmann-Rçder, N. Krause, Synlett 2007, 1790; b) T. Miura, M. Shimada, P. de Mendoza, C. Deutsch, N. Krause, M. Murakami, J. Org. Chem. 2009, 74, 6050.
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COMMUNICATION & Synthetic Methods T. Miura,* T. Tanaka, K. Matsumoto, M. Murakami* && – && One-Pot Synthesis of 2,5Dihydropyrroles from Terminal Alkynes, Azides, and Propargylic Alcohols by Relay Actions of Copper, Rhodium, and Gold
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Trio works! Relay actions of copper, rhodium, and gold formulate a one-pot multistep pathway, which directly gave 2,5-dihydropyrroles starting from terminal alkynes, sulfonyl azides, and propar-
gylic alcohols. A single execution of work-up/purification procedures gives substantial expansion of the structural, as well as functional complexities (see scheme).
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One-Pot Synthesis of 2,5-Dihydropyrroles from Terminal Alkynes, Azides, and Propargylic Alcohols by Relay Actions of Copper, Rhodium, and Gold Tomoya Miura,* Takamasa Tanaka, Kohei Matsumoto, and Masahiro Murakami*[a] Dedicated to Professor Iwao Ojima (SUNY) on the occasion of his 70th birthday one[4] with regard to the position of unsaturation. Of particular note is that multiple reactions occur stepwise by simply applying the requisite substrate/catalyst to terminal alkynes. A single execution of work-up/purification procedures gave substantial expansion of the structural, as well as functional complexities. The direct synthesis of various 2,5-dihydropyrroles in one pot starting from terminal alkynes is summarized in Table 1. 1Arylethynes 1 a–d having both electron-donating and -withdrawing substituents reacted facilely with tosyl azide (2 a) and propargylic alcohol 3 a to give the corresponding 2,5-dihydropyrroles 4 a–d in yields ranging from 56 to 83 % (entries 1–4). Mesyl azide (2 b) also successfully participated in the reaction (entry 5). Multisubstituted 2,5-dihydropyrroles 4 f and g could be regioselectively synthesized by using a,a-disubstituted and a,a,g-trisubstituted propargylic alcohols 3 b and c, respectively (entries 6 and 7). From the experimental viewpoint, the transformation consists of three operational procedures and a single work-up/purification procedure. In the first procedure, 1-sulfonyl-1,2,3-triazoles were generated from terminal alkynes and sulfonyl azides by the authentic method developed by Fokin;[7] terminal alkynes 1 (1.0 equiv) were treated with sulfonyl azides 2 (1.0 equiv) in the presence of copper(I) thiophene-2-carboxylate (10 mol %, CuTC) in 1,2-dichloroethane (DCE) at room temperature for 6 h. In the second procedure, propargylic alcohols 3 (1.5 equiv) and rhodium(II) pivalate dimer (1.0 mol %) were added to the same reaction vessel, which was heated at 100 8C for 30 min under microwave (MW) irradiation[8] to prompt O H insertion and subsequent sigmatropic rearrangement.[9–12] The resulting a-allenyl-a-amino ketones were then cyclized in the third procedure; [Au(JohnPhos)(CH3CN)][SbF6] (5.0 mol %, JohnPhos = (2-biphenyl)di-tert-butylphosphine)[13] was added to the reaction vessel, which was further stirred at room temperature for 3 h. Finally, the reaction mixture was subjected to a workup/purification procedure to give 2,5-dihydropyrrole products 4. The rhodium-catalyzed O H insertion reaction in the second procedure was not interfered by the copper catalyst used in the first procedure for 1,3-dipolar cycloaddition. Neither the gold-catalyzed cyclization reaction occurring in the third procedure was interfered by the copper and rhodium catalysts used in the first and second procedures. As a result, the whole multistep transformation can be carried out in a same reaction
Abstract: Relay actions of copper, rhodium, and gold formulate a one-pot multistep pathway, which directly gives 2,5-dihydropyrroles starting from terminal alkynes, sulfonyl azides, and propargylic alcohols. Initially, copper-catalyzed 1,3-dipolar cycloaddition of terminal alkynes with sulfonyl azides affords 1-sulfonyl-1,2,3-triazoles, which then react with propargylic alcohols under the catalysis of rhodium. The resulting alkenyl propargyl ethers subsequently undergo the thermal Claisen rearrangement to give a-allenyl-a-amino ketones. Finally, a gold catalyst prompts 5endo cyclization to produce 2,5-dihydropyrroles.
Functionalized pyrrolidines constitute a core structural element broadly found in natural products and pharmaceutically active substances.[1] Dihydropyrroles with an unsaturation available for further functionalization are valuable precursors for their synthesis.[2] Therefore, the development of efficient methods for the synthesis of dihydropyrroles from readily available starting materials has been an active area of research.[3] We have reported the synthesis of 2,3-dihydropyrroles from terminal alkynes, sulfonyl azides, and a,b-unsaturated aldehydes.[4] aImino carbenoid species are involved therein as the key reactive intermediate of electrophilic nature.[5] Herein, we report a new synthetic protocol constituting 2,5-dihydropyrroles from three components including propargylic alcohols (Figure 1). Relay actions of copper, rhodium, and gold catalysts[6] formulate a one-pot multistep pathway, complementing the previous
Figure 1. Constitution of 2,5-dihydropyrroles from terminal alkynes, tosyl azide, and propargylic alcohols.
[a] Prof. Dr. T. Miura, T. Tanaka, K. Matsumoto, Prof. Dr. M. Murakami Department of Synthetic Chemistry and Biological Chemistry Kyoto University, Katsura, Kyoto 615-8510 (Japan) E-mail: [email protected] [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201405357. Chem. Eur. J. 2014, 20, 1 – 6
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Communication Propargylic alcohol 3 undergoes nucleophilic addition to the electrophilic carbenoid carbon of A to give zwitterionic intermediate B. Then, a proton shifts onto the imino nitrogen with release of rhodium(II), forming the (Z)-isomer of alkenyl propargyl ether C. It is probably spontaneous at 100 8C for C to undergo the thermal Claisen-type [3,3]-sigmatropic rearrangement via the six-membered chairlike transition state D (see below) to produce a-allenyl aamino ketone 6.[9–11] The third procedure follows the gold-catalyzed cyclization reaction developed by Krause.[3d] The allenyl group is activated by gold to induce intramolecular addition of the amino group in a 5-endo mode, producing 2,5-dihydropyrrole 4.[15] Entry 1-Alkyne 1 Azide 2 Alcohol 3 Product Yield [%][d] R1 R2 R3 C(R4)2 4 To delineate the scope of the present method, the transformation consisting of the second rhodium(II)1 Ph 1 a p-Tol 2 a H CH2 3a 4a 83 3a 4b 83 2 p-Tol 1 b p-Tol 2 a H CH2 catalyzed and third gold(I)-catalyzed procedures was 1 c p-Tol 2 a H CH2 3a 4c 82 3 p-MeOC6H4 examined by using the propargylic alcohol 3 a and 3a 4d 56 4 p-MeO2CC6H4 1 d p-Tol 2 a H CH2 various isolated 1-tosyltriazoles 5 (Table 2). Triazoles 3a 4e 86 5 Ph 1 a Me 2 b H CH2 5 aa–ga possessing electron-donating and -withdraw6 Ph 1 a p-Tol 2 a H CMe2 3b 4 f 73[e] 7 Ph 1 a p-Tol 2 a Me cyclohexylidene 3 c 4 g 73 ing aryl groups at the fourth positions all gave the corresponding products in good to high yields (en[a] 1 (0.20 mmol), 2 (0.20 mmol), CuTC (20 mmol), 1,2-dichloroethane (DCE, 1 mL). [b] 3 (0.30 mmol), [Rh2(tBuCO2)4] (2.0 mmol), DCE (1 mL). [c] [Au(JohnPhos)(CH3CN)][SbF6] tries 1–6 in Table 2). A similar result was obtained (10 mmol), DCE (1 mL). [d] Isolated yield (average of two runs). [e] Using [Auwhen the reaction of entry 1 was carried out on (JohnPhos)(CH3CN)][SbF6] (20 mmol) for 15 h. a larger scale by using 2.0 mmol of 5 aa. Even alkylsubstituted triazoles 5 ha–ja successfully gave 2,5-dihydropyrroles 4 k–m, despite of the possibility of 1,2hydride shift occurring with the intermediate rhodium(II) carvessel,[14] necessitating only a one-time execution of a workbene complex (entries 7–9 in Table 2).[16] However, the reaction up/purification procedure, which would be most costly in general, consuming a significant amount of time and solvents. Scheme 1 depicts a more detailed mechanistic explanation for the sequential procedures mentioned above. The first opTable 2. Sequential reaction of various triazole 5 with propargyl alcohol erational procedure is for the copper(I)-catalyzed 1,3-dipolar (3 a).[a] [7b] cycloaddition. The resulting triazole 5 equilibrates with adiazo imine 5’, which in the second procedure reacts with the rhodium(II) catalyst to generate a-imino rhodium-carbene complex A.[5] Table 1. Sequential one-pot reaction starting from terminal alkynes 1.
Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
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Ph p-Tol p-MeOC6H4 p-EtO2CC6H4 p-CF3C6H4 3-thienyl Et n-Hex BzO(CH2)4 EtO Ph Ph Ph Ph Ph
p-Tol p-Tol p-Tol p-Tol p-Tol p-Tol p-Tol p-Tol p-Tol p-Tol Me iPr Me3Si(CH2)2 p-MeOC6H4 p-BrC6H4
5 aa 5 ba 5 ca 5 ea 5 fa 5 ga 5 ha 5 ia 5 ja 5 ka 5 ab 5 ac 5 ad 5 ae 5 af
Product 4
Yield [%][b]
4a 4b 4c 4h 4i 4j 4k 4l 4m 4n 4e 4o 4p 4q 4r
89 89 90 84 85 90 80[c] 71[c] 81[c] 51[d] 86 95 81 94 90
[a] 1) 5 (0.20 mmol), 3 a (0.30 mmol), [Rh2(tBuCO2)4] (2.0 mmol), DCE (1 mL); 2) [Au(JohnPhos)(CH3CN)][SbF6] (10 mmol), DCE (1 mL). [b] Isolated yield (average of two runs). [c] Using 3 a (0.60 mmol). [d] 1) 3 a (1.0 mmol), 10 min; 2) [Au(JohnPhos)(CH3CN)][SbF6] (20 mmol).
Scheme 1. Plausible mechanism for the one-pot synthesis of 4 from 1, 2, and 3.
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Communication of the ethoxy-substituted triazole 5 ka was slower to give the product 4 n in 51 % yield,[9a, 17] probably due to the less electrophilic nature of the carbenoid carbon (entry 10). The reaction was efficient with respect to the R2 substituent on the sulfonyl group (entries 11–15 in Table 2). The reaction scope was also examined with respect to propargylic alcohols 3 (Scheme 2). g-Substituted alcohols 3 d and e were regioselectively converted to 3-substituted 2,5-dihydropyroles 4 s and t, respectively. On the other hand, the reaction of a,a-disubstituted alcohols 3 f gave 5,5-disubstituted 2,5-dihydropyroles 4 u. These results are consistent with the occurrence of [3,3]-sigmatropic rearrangement during the transformation.
Scheme 3. Reaction with enantiomerically pure alcohol 3 g. 1) [Rh2(tBuCO2)4] (1.0 mol %), DCE, 100 8C/MW, 30 min; 2) [Au(JohnPhos)(CH3CN)][SbF6] (5.0 mol %), DCE, RT, 3 h.
Scheme 2. Sequential reaction of triazole 5 aa with various substituted propargylic alcohols 3 d–f.
When enantiomerically pure a-substituted alcohol 3 g was used, a 3:1 mixture of trans/cis diastereoisomers was obtained (Scheme 3). Notably, the enantiomeric purity was retained with the both diastereoisomers (trans 99 % ee, cis 99 % ee), the absolute configurations of which were not determined. When the sequential transformation was intercepted before the addition of the gold catalyst, a diastereomeric mixture of a-allenyl-aamino ketones G and H (3:1) was obtained. Based on these results, we assume that the alkenyl moiety of the intermediate alkenyl propargylic ether partially isomerizes under the reaction conditions before the [3,3]-sigmatropic rearrangement, giving a 3:1 mixture of Z/E isomers. The Z and E isomers both undergo the rearrangement via the six-membered chairlike transition states E and F, respectively, with the a-methyl substituent taking the pseudoequatorial position. The chirality of 3 g is transferred to the axial chirality of the allenyl group. Then, the external allenic p bond coordinates to gold(I) from the face cis to the Ht. The nitrogen intramolecularly adds to the activated p bond from the face opposite to the gold(I) in a five-endo mode to form the zwitterionic species K and L, respectively. Finally, protodemetalation affords 4 v with generation of a catalytically active gold(I) complex.[3d, 18] Thus, the original central chirality of 3 g is first transferred to the axial chirality of the allenyl group, and finally back to the central chirality of the fifth position of the dihydropyrroles 4 v. Chem. Eur. J. 2014, 20, 1 – 6
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Further derivatization of the obtained dihydropyrroles are exemplified in Equation (1). Treatment of 4 a with 1,8-diazabicycloundec-7-ene (DBU) induced a sequence of E1cB and prototropy to produce pyrrole 7. The carbon–carbon double bond was stereoselectively dihydroxylated by a simple dihydroxylation protocol by using K2OsO2(OH)2, giving diol 8 in 87 % yield (6:1 d.r.). Monosubstituted pyrrolidine 9 was readily synthesized by hydrogenation using the Crabtree’s catalyst.
In summary, we have developed the one-pot multistep procedure for the synthesis of 2,5-dihydropyrroles starting from 3
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Communication terminal alkynes. The three different catalysts operate in relay without any serious catalyst deactivation,[19] making this sequential transformation work out.
[4] T. Miura, T. Tanaka, K. Hiraga, S. G. Stewart, M. Murakami, J. Am. Chem. Soc. 2013, 135, 13652. [5] For reviews on synthetic transformations of triazoles, see: a) A. V. Gulevich, V. Gevorgyan, Angew. Chem. Int. Ed. 2013, 52, 1371; Angew. Chem. 2013, 125, 1411; b) H. M. L. Davies, J. S. Alford, Chem. Soc. Rev. 2014, 43, 5151. For initiative reports, see: c) S. Chuprakov, F. W. Hwang, V. Gevorgyan, Angew. Chem. Int. Ed. 2007, 46, 4757; Angew. Chem. 2007, 119, 4841; d) T. Horneff, S. Chuprakov, N. Chernyak, V. Gevorgyan, V. V. Fokin, J. Am. Chem. Soc. 2008, 130, 14972; e) T. Miura, M. Yamauchi, M. Murakami, Chem. Commun. 2009, 1470. For recent reports, see: f) E. E. Schultz, R. Sarpong, J. Am. Chem. Soc. 2013, 135, 4696; g) B. T. Parr, S. A. Green, H. M. L. Davies, J. Am. Chem. Soc. 2013, 135, 4716; h) J. E. Spangler, H. M. L. Davies, J. Am. Chem. Soc. 2013, 135, 6802; i) T. Miura, Y. Funakoshi, M. Murakami, J. Am. Chem. Soc. 2014, 136, 2272; j) J.-M. Yang, C.-Z. Zhu, X.-Y. Tang, M. Shi, Angew. Chem. Int. Ed. 2014, 53, 5142; Angew. Chem. 2014, 126, 5242; k) H. Shang, Y. Wang, Y. Tian, J. Feng, Y. Tang, Angew. Chem. 2014, 126, 5768; Angew. Chem. Int. Ed. 2014, 53, 5662; l) K. Chen, Z.-Z. Zhu, Y.-S. Zhang, X.-Y. Tang, M. Shi, Angew. Chem. 2014, 126, 6763; Angew. Chem. Int. Ed. 2014, 53, 6645; m) Y. Xing, G. Sheng, J. Wang, P. Lu, Y. Wang, Org. Lett. 2014, 16, 1244; n) A. Boyer, Org. Lett. 2014, 16, 1660; o) C.-E. Kim, S. Park, D. Eom, B. Seo, P. H. Lee, Org. Lett. 2014, 16, 1900; p) D. J. Jung, H. J. Jeon, J. H. Kim, Y. Kim, S. Lee, Org. Lett. 2014, 16, 2208; q) D. Yadagiri, P. Anbarasan, Org. Lett. 2014, 16, 2510; r) T. Miura, Y. Funakoshi, T. Tanaka, M. Murakami, Org. Lett. 2014, 16, 2760; s) F. Medina, C. Besnard, J. Lacour, Org. Lett. 2014, 16, 3232; t) D. J. Lee, J. Shin, E. J. Yoo, Chem. Commun. 2014, 50, 6620; u) T. Miura, T. Nakamuro, K. Hiraga, M. Murakami, Chem. Commun. 2014, 50, 10474; v) D. J. Lee, H. S. Han, J. Shin, E. J. Yoo, J. Am. Chem. Soc. 2014, 136, 11606; w) E. E. Schultz, V. N. G. Lindsay, R. Sarpong, Angew. Chem. 2014, 126, 10062; Angew. Chem. Int. Ed. 2014, 53, 9904. [6] For one-pot sequential reactions involving gold catalysts, see: a) M. D. Milton, Y. Inada, Y. Nishibayashi, S. Uemura, Chem. Commun. 2004, 2712; b) J. T. Binder, S. F. Kirsch, Org. Lett. 2006, 8, 2151; c) . AksinArtok, N. Krause, Adv. Synth. Catal. 2011, 353, 385; d) M. N. Pennell, M. G. Unthank, P. Turner, T. D. Sheppard, J. Org. Chem. 2011, 76, 1479; e) H. Wang, J. R. Denton, H. M. L. Davies, Org. Lett. 2011, 13, 4316; f) A. S. K. Hashmi, M. Ghanbari, M. Rudolph, F. Rominger, Chem. Eur. J. 2012, 18, 8113; g) M. M. Hansmann, A. S. K. Hashmi, M. Lautens, Org. Lett. 2013, 15, 3226. [7] a) E. J. Yoo, M. Ahlquist, S. H. Kim, I. Bae, V. V. Fokin, K. B. Sharpless, S. Chang, Angew. Chem. Int. Ed. 2007, 46, 1730; Angew. Chem. 2007, 119, 1760; b) J. Raushel, V. V. Fokin, Org. Lett. 2010, 12, 4952; c) Y. Liu, X. Wang, J. Xu, Q. Zhang, Y. Zhao, Y. Hu, Tetrahedron 2011, 67, 6294. [8] We used a microwave synthesizer in to safely handle a low-boilingpoint solvent at high temperature. When a toluene solution of triazole 5 aa and propargylic alcohol 3 a (1.5 equiv) was simply heated at 100 8C in the presence of [Rh2(tBuCO2)4] (1.0 mol %) for 30 min without microwave irradiation, 6 aa was formed also in high yield. [9] It is possible to isolate the intermediate a-allenyl-a-amino ketones. For the previous reports on the rhodium-catalyzed reaction of triazoles with propargylic alcohols forming a-allenyl-a-amino ketones, see: a) T. Miura, T. Tanaka, T. Biyajima, A. Yada, M. Murakami, Angew. Chem. Int. Ed. 2013, 52, 3883; Angew. Chem. 2013, 125, 3975; b) S. Chuprakov, B. T. Worrell, N. Selander, R. K. Sit, V. V. Fokin, J. Am. Chem. Soc. 2014, 136, 195. [10] The reaction of rhodium carbene complexes with propargylic alcohols induces analogous [2,3]- and [3,3]-sigmatropic rearrangement: a) M. E. Jung, J. Pontillo, Org. Lett. 1999, 1, 367; b) J. L. Wood, G. A. Moniz, Org. Lett. 1999, 1, 371; c) G. A. Moniz, J. L. Wood, J. Am. Chem. Soc. 2001, 123, 5095; d) Z. Li, V. Boyarskikh, J. H. Hansen, J. Autschbach, D. G. Musaev, H. M. L. Davies, J. Am. Chem. Soc. 2012, 134, 15497. [11] A review on the Claisen rearrangement of propargyl vinyl ethers: D. Tejedor, G. Mndez-Abt, L. Cotos, F. Garca-Tellado, Chem. Soc. Rev. 2013, 42, 458. [12] A review on the use of propargyl vinyl ethers for the synthesis of heterocycles: Z.-B. Zhu, S. F. Kirsch, Chem. Commun. 2013, 49, 2272. [13] C. Nieto-Oberhuber, S. Lpez, M. P. MuÇoz, D. J. C rdenas, E. BuÇuel, C. Nevado, A. M. Echavarren, Angew. Chem. Int. Ed. 2005, 44, 6146; Angew. Chem. 2005, 117, 6302.
Experimental Section Typical procedure for the one-pot synthesis of 2,5-dihydropyrroles from terminal alkynes (Table 1, entry 1): Phenylethyne (1 a, 20.4 mg, 0.20 mmol), TsN3 (2 a, 39.4 mg, 0.20 mmol), CuTC (3.8 mg, 20 mmol), and 1,2-dichloroethane (1 mL) were added to an ovendried 0.5–2 mL Biotage microwave vial equipped with a stirrer bar in a glovebox. The vial was sealed with a Teflon pressure cap. The reaction mixture was stirred at RT for 6 h. Then, propargylic alcohol 3 a (16.8 mg, 0.30 mmol) and [Rh2(tBuCO2)4] (1.2 mg, 2.0 mmol) in 1,2-dichloroethane (1 mL) were added. The mixture was heated at 100 8C for 30 min under microwave irradiation. After the resulting mixture was cooled, the solution of [Au(JohnPhos)(CH3CN)][SbF6] (7.7 mg, 10 mmol)) in 1,2-dichloroethane (1 mL) was added. The reaction mixture was stirred at RT for 3 h, and it was concentrated under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography (CHCl3/ethyl acetate 30:1) to give the 2,5-dihydropyrrole 4 a (55.7 mg, 0.17 mmol, 83 %) as a white solid.
Acknowledgements This work was supported by MEXT (Grant-in-Aid for Scientific Research on Innovative Areas nos. 22105005 and 24106718, Young Scientists (A) no. 23685019, Scientific Research (B) no. 23350041) and JST (ACT-C). Keywords: copper · gold · rhodium · terminal alkynes · triazoles [1] a) A. R. Pinder, Nat. Prod. Rep. 1992, 9, 491; b) A. B. Mauger, J. Nat. Prod. 1996, 59, 1205; c) D. O’Hagan, Nat. Prod. Rep. 2000, 17, 435. [2] a) Y. Tsuzuki, K. Chiba, K. Mizuno, K. Tomita, K. Suzuki, Tetrahedron: Asymmetry 2001, 12, 2989; b) E. S. Greenwood, P. J. Parsons, Synlett 2002, 167; c) A. L. L. Garcia, M. J. S. Carpes, A. C. B. M. de Oca, M. A. G. dos Santos, C. C. Santana, C. R. D. Correia, J. Org. Chem. 2005, 70, 1050; d) F. A. Davis, T. Ramachandar, J. Chai, E. Skucas, Tetrahedron Lett. 2006, 47, 2743; e) M. Sampath, P.-Y. B. Lee, T.-P. Loh, Chem. Sci. 2011, 2, 1988; f) Y. Luo, A. J. Carnell, H. W. Lam, Angew. Chem. Int. Ed. 2012, 51, 6762; Angew. Chem. 2012, 124, 6866; g) V. Dhand, J. A. Draper, J. Moore, R. Britton, Org. Lett. 2013, 15, 1914. [3] For a review, see: a) M. Brichacek, J. T. Njardarson, Org. Biomol. Chem. 2009, 7, 1761. By ruthenium-catalyzed ring-closing metathesis: b) R. Martn, M. Alcn, M. A. Perics, A. Riera, J. Org. Chem. 2002, 67, 6896; c) H. Kim, W. Lim, D. Im, D. Kim, Y. H. Rhee, Angew. Chem. Int. Ed. 2012, 51, 12055; Angew. Chem. 2012, 124, 12221. By gold-catalyzed cyclization of a-aminoallenes: d) N. Morita, N. Krause, Org. Lett. 2004, 6, 4121; e) P. H. Lee, H. Kim, K. Lee, M. Kim, K. Noh, H. Kim, D. Seomoon, Angew. Chem. Int. Ed. 2005, 44, 1840; Angew. Chem. 2005, 117, 1874; f) A. C. Breman, J. Dijkink, J. H. van Maarseveen, S. S. Kinderman, H. Hiemstra, J. Org. Chem. 2009, 74, 6327; g) N. Krause, C. Winter, Chem. Rev. 2011, 111, 1994. By silver- and base-promoted cyclization of a-aminoallenes: h) M. A. Chowdhury, H.-U. Reissig, Synlett 2006, 2383; i) H. Ohno, Y. Kadoh, N. Fujii, T. Tanaka, Org. Lett. 2006, 8, 947. For other preparative methods, see: j) B. Cekavicus, K. Kore, L. Jakovele, A. Plotniece, K. Pajuste, M. Petrova, S. Belyakov, A. Sobolev, Tetrahedron Lett. 2011, 52, 6246; k) M. Brichacek, M. N. Villalobos, A. Plichta, J. T. Njardarson, Org. Lett. 2011, 13, 1110; l) A. Viso, R. F. de La Pradilla, M. UreÇa, R. H. Bates, M. A. del guila, I. Colomer, J. Org. Chem. 2012, 77, 525.
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Communication [19] When the isolated a-allenyl-a-amino ketone 6 a was treated with [Au(JohnPhos)(CH3CN)][SbF6] (0.5 mol %) at RT for 5 min, the corresponding 2,5-dihydropyrroles 4 a was formed in 68 % yield (NMR) and the starting material was recovered in 26 % yield (NMR). The same reaction in the presence of both the gold catalyst and [Rh2(tBuCO2)4] (1.0 mol %) gave a similar result, suggesting no interference of the rhodium(II) catalyst on the gold(I)-catalyzed cyclization reaction.
[14] We carried out the all-in-one-pot reaction by mixing all substrates and catalysts at once and heating the mixture. However, no reaction occurred, and terminal alkynes remained unchanged. [15] T. J. Brown, D. Weber, M. R. Gagn, R. A. Widenhoefer, J. Am. Chem. Soc. 2012, 134, 9134. [16] a) T. Miura, Y. Funakoshi, M. Morimoto, T. Biyajima, M. Murakami, J. Am. Chem. Soc. 2012, 134, 17440; b) N. Selander, B. T. Worrell, V. V. Fokin, Angew. Chem. Int. Ed. 2012, 51, 13054; Angew. Chem. 2012, 124, 13231. [17] J. S. Alford, H. W. L. Davies, J. Am. Chem. Soc. 2014, 136, 10266. [18] a) C. Deutsch, B. Gockel, A. Hoffmann-Rçder, N. Krause, Synlett 2007, 1790; b) T. Miura, M. Shimada, P. de Mendoza, C. Deutsch, N. Krause, M. Murakami, J. Org. Chem. 2009, 74, 6050.
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COMMUNICATION & Synthetic Methods T. Miura,* T. Tanaka, K. Matsumoto, M. Murakami* && – && One-Pot Synthesis of 2,5Dihydropyrroles from Terminal Alkynes, Azides, and Propargylic Alcohols by Relay Actions of Copper, Rhodium, and Gold
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Trio works! Relay actions of copper, rhodium, and gold formulate a one-pot multistep pathway, which directly gave 2,5-dihydropyrroles starting from terminal alkynes, sulfonyl azides, and propar-
gylic alcohols. A single execution of work-up/purification procedures gives substantial expansion of the structural, as well as functional complexities (see scheme).
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