Rhodium-Catalyzed Cycloadditions between 3-Diazoindolin-2-imines

Mar 30, 2017 - Hualong Ding , Zaibin Wang , Songlin Bai , Ping Lu , and Yanguang Wang ... Anni Ren , Bo Lang , Jialun Lin , Ping Lu , and Yanguang Wan...
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Rhodium-Catalyzed Cycloadditions between 3‑Diazoindolin-2-imines and 1,3-Dienes Bo Lang, Huangtianzhi Zhu, Chen Wang, Ping Lu,* and Yanguang Wang* Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China S Supporting Information *

ABSTRACT: Azepino[2,3-b]indoles were regioselectively prepared through rhodium-catalyzed formal aza-[4 + 3] cycloaddition between 3-diazoindolin-2-imines and 1,3-dienes in moderate to good yields. Using 2-[(trimethylsilyl)oxy]-1,3butadiene as the diene component, azepino[2,3-b]indol4(1H)-ones were constructed. Furthermore, the reactions of cyclic dienes, such as 1,3-cyclohexadiene and 1,3-cyclopentadiene, furnished the corresponding [3 + 2] cycloaddition products.

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oth indole1 and azepine2 are privileged scaffolds in medicinal science. Compounds containing an azepino[2,3-b]indole skeleton were discovered to possess sedative activity and function as tranquilizers.3 Therefore, development of new and efficient methods for the construction of this class of fused heterocyclic rings could be important in both synthetic chemistry and drug discovery. Since the fragile N-sulfonyl-1,2,3-triazoles have been successfully approached through copper-catalyzed alkyne azide cycloaddition (CuAAC) by applying the appropriate base and ligand,4 their utility as precursors of α-imino rhodium carbenes (called α-azavinyl rhodium carbenes) has been reported by the leading groups of Fokin,5 Davies,6 Gevorgyan,7 Murakami,8 Shi,9 Sarpong,10 and Tang.11 By trapping the in situ generated α-imino rhodium carbenes, a series of reactions including C−H insertion,12 X−H insertion (X = N, O, Si),13 cyclopropanation,14 transannulation,15 and expansions/rearrangements16 have been developed. These reactions provided efficient methods for the formation of C−C or C−X bonds and the construction of carbocycles or heterocycles. Recently, we reported two approaches for the preparation of 3-diazoindolin-2-imines and demonstrated their applications as precursors of α-amidino metal carbenes.17 The rhodium- or copper-catalyzed reactions of 3-diazoindolin-2-imines with several nucleophilic partners, such as alkynes,17 alkenes,17 electron-rich arenes,17 enol ethers,18 and amines,19 were developed. In this way, many indole-containing compounds were prepared. Inspired by these results and interested in the potential utilities of indole derivatives in medicinal chemistry, here we report a rhodium-catalyzed formal [4 + 3] cycloaddition between 3-diazoindolin-2-imines and 1,3-dienes, leading to facile construction of azepino[2,3-b]indoles. Our first trial was conducted between 3-diazoindolin-2-imine (1a) and isoprene (2a) in the presence of Rh2(Oct)4 in toluene © XXXX American Chemical Society

under N2 (Scheme 1). Fortunately, a [4 + 3] annulation occurred, and azepino[2,3-b]indole 3a was prepared in 30% Scheme 1. Initial Trial of Rh-Catalyzed Reaction of 1a and 2a

yield. The structure of 3a was established from its single-crystal analysis.20 Compound 3a was obtained in excellent regioselectivity without any isolation of isomer 3a′. Delighted by this result, we screened the reaction conditions (Table 1). When the reaction was conducted at 120 °C for 12 h, 3b was isolated in 38% yield. Decreasing the reaction temperature to 110 °C increased the yield of 3b (Table 1, entries 1−3). Adding a certain amount of AgOTf (Table 1, entries 2 and 4) significantly increased the yield. The optimal solvent was screened to be toluene among others, such as 1,2-dichloroethane (DCE), acetonitrile, tetrahydrofuran (THF), chlorobenzene, and dichloromethane (Table 1, entries 4−9). Furthermore, it was observed that Rh2(Oct)4 was the optimal catalyst compared with Rh2(OAc)4 and Rh2(s-dosp)4 (Table 1, entries 4, 10−12). Finally, the optimal reaction time was determined to be 12 h (Table 1, entries 4, 13−15). Received: February 13, 2017

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DOI: 10.1021/acs.orglett.7b00438 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters Table 1. Optimization of the Reaction Conditionsa

entry

catalyst

solvent

time (h)

yieldb (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Rh2(Oct)4 Rh2(Oct)4 Rh2(Oct)4 Rh2(Oct)4 Rh2(Oct)4 Rh2(Oct)4 Rh2(Oct)4 Rh2(Oct)4 Rh2(Oct)4 Rh2(OAc)4 Rh2(s-ptad)4 Rh2(s-dosp)4 Rh2(Oct)4 Rh2(Oct)4 Rh2(Oct)4

PhCH3 PhCH3 PhCH3 PhCH3 DCE CH3CN THF PhCl CH2Cl2 PhCH3 PhCH3 PhCH3 PhCH3 PhCH3 PhCH3

12 12 12 12 12 12 12 12 12 12 12 12 2 6 24

38c 50 49d 63e 38e tracee tracee 23e tracee 18e 11e 30e 52e 56e 59e

a

Reaction conditions: 1b (0.2 mmol), 2a (1 mmol), Rh2(Oct)4 (0.002 mmol), solvent (2 mL) 110 °C, N2, in sealed tube. bIsolated yield. c 120 °C. d100 °C. eAgOTf (0.01 mmol) was added.

With the optimized conditions in hand (Table 1, entry 4), we examined the scope of 3-diazoindolin-2-imines (1) (Figure 1). In general, we smoothly obtained the products 3a−m in moderate yields varying from 40% to 74%, regardless of the functional group (R1, R2, or R3). A wide range of alkyl and aryl groups on the 1-position of indole, such as methyl, isopropyl, phenyl, benzyl, and allyl, tolerated these reaction conditions and afforded 3a−e in yields varying from 40% to 63%. Neither N−H insertion product nor cyclopropanation product was observed during the formation of 3f and 3c. With an electronwithdrawing group (F, Cl, Br) on the 5-position of indole, 3h−j were obtained in higher yields than with an electron-donating group (3g, OMe). The sulfonyl group could be arenesulfonyl (3a−l) or alkanesulfonyl (3m). To further extend the substrate scope, we paid attention to 1,3-dienes. Myrcene, with both diene and alkene functional groups, provided 3n in 35% yield. The cyclopropanation product was not observed. When (E)-penta-1,3-diene was used, 2-methylazepino[2,3-b]indoles (3o−v) were obtained in yields varying from 46% to 74% without the observation of 2mehtylazepino[2,3-b]indole. The excellent regioselectivity was supported by the NOESY spectrum of 3p (see the SI). However, we failed to obtain the enantiomeric excess in these cases by applying chiral catalysts, such as Rh2(s-ptad)4 and Rh2(s-dosp)4. Similar regioselectivity was observed by applying (E)-1-phenylbuta-1,3-diene as starting material. Thus, 3w and 3x were prepared in 71% and 66% yields, respectively. With 2,3dimethylbutadiene, we achieved the corresponding products 3y-3A. Finally, a high yield (84%) of 3B was obtained when the electron-rich 1-TMSO-1,3-butadiene was used as substrate. When cyclohexa-1,3-diene (4) was subjected to the reaction with 3-diazoindolin-2-imines 1, hexahydroindolo[2,3-b]indoles 5a−g were obtained the moderate yields (Figure 2). Their structures were confirmed by the single-crystal analysis of product 5g.20 Similarly, the reaction between cyclopentadiene (6) and 1j provided 7 in 35% yield (Figure 3).

Figure 1. Preparation of azepino[2,3-b]indoles 3.

Figure 2. Preparation of hexahydroindolo[2,3-b]indoles 5.

Figure 3. Preparation of cyclopenta[4,5]pyrrolo[2,3-b]indole 7. B

DOI: 10.1021/acs.orglett.7b00438 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters

electron-donating nature of the double bond. As a result, 5 or 7 is obtained with the surviving double bond at the appropriate position as shown in Scheme 2. In summary, we have developed rhodium-catalyzed cycloadditions between 3-diazoindolin-2-imines and dienes. The linear 1,3-dienes underwent a formal aza-[4 + 3] cycloaddition to furnish azepino[2,3-b]indoles or azepino[2,3-b]indol-4(1H)ones through a cyclopropanation/aza-Cope rearrangement cascade, while the cyclic 1,3-dienes (e.g., cyclohexadiene andcyclopentadiene) underwent formal aza-[3 + 2] annulations to afford hexahydroindolo[2,3-b]indoles or cyclopenta[4,5]pyrrolo[2,3-b]indoles through a sequential cyclopropanation/ 1,3-shift process. The reactions were carried out smoothly with excellent regioselectivities. Further studies on the chemistry of this class of precursors of α-amidino rhodium carbenes are underway in our laboratory.

When we used TMSO-diene (8), instead of obtaining azepino[2,3-b]indoles, we obtained azepino[2,3-b]indol-4(1H)ones 9a−g as major products accompanied by the cleavage of trimethylsilyl group. In these cases, reactions were completed in 12−24 h, determined by TLC analysis. A possible mechanism is proposed in Scheme 2. In the presence of rhodium catalyst, 3-diazoindolin-2-imine 1 is Scheme 2. Plausible Mechanism

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b00438. Detailed synthetic procedures and characterization data for all products (PDF) Crystallographic information for compound 3a (CIF) Crystallographic information for compound 3f (CIF) Crystallographic information for compound 5g (CIF)

converted to α-amidino rhodium carbene A as we previously reported.17 The two double bonds of isoprene possess different electron density. The one with a methyl group has larger electron density and preferentially attacks the electron-deficient rhodium carbene A with excellent regioselectivity. Thus, a formal [2 + 1] cycloaddition intermediate B can form. Subsequent aza-Cope rearrangement provides 3. For TMSOdiene 8, the desilylation of the cycloaddition products occurs to afford 9 with excellent regioselectivity (Figure 4). In cases where cyclohexadiene or cyclopentadiene is used, aza-Cope rearrangement is inhibited because of the unfavorable geometry for aza-Cope rearrangement of C. Instead, the three-membered ring of C undergoes a regioselective 1,3-allyl shift due to the

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Yanguang Wang: 0000-0002-5096-7450 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (Nos. 21472164, 21472173, and 21632003) for financial support.

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REFERENCES

(1) For recent reviews, see: (a) Gribble, G. W. In Heterocyclic Scaffolds II: Reactions and Applications of Indoles; Topics in Heterocyclic Chemistry; Springer: Heidelberg, 2010; Vol. 26. (b) KochanowskaKaramyan, A. J.; Hamann, M. T. Chem. Rev. 2010, 110, 4489. (2) For reviews, see: (a) Kametani, T.; Fukumoto, K. Heterocycles 1975, 3, 931. (b) Renfroe, B.; Harrington, C.; Proctor, G. R. Heterocyclic Compounds: Azepines; Wiley Interscience: New York, 1984. (3) Hester, J. B. U. S. Patent 3595874, 1971. (4) (a) Yoo, E. J.; Ahlquist, M.; Kim, S. H.; Bae, I.; Fokin, V. V.; Sharpless, K. B.; Chang, S. Angew. Chem., Int. Ed. 2007, 46, 1730. (b) Raushel, J.; Fokin, V. V. Org. Lett. 2010, 12, 4952. (5) (a) Chuprakov, S.; Kwok, S. W.; Fokin, V. V. J. Am. Chem. Soc. 2013, 135, 4652. (b) Zibinsky, M.; Fokin, V. V. Angew. Chem., Int. Ed. 2013, 52, 1507. (c) Grimster, N.; Zhang, L.; Fokin, V. V. J. Am. Chem. Soc. 2010, 132, 2510. (6) (a) Davies, H. M. L.; Alford, J. S. Chem. Soc. Rev. 2014, 43, 5151. (b) Alford, J. S.; Spangler, J. E.; Davies, H. M. L. J. Am. Chem. Soc. 2013, 135, 11712.

Figure 4. Preparation of azepino[2,3-b]indol-4(1H)-ones 9. C

DOI: 10.1021/acs.orglett.7b00438 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters (7) (a) Gulevich, A. V.; Gevorgyan, V. Angew. Chem., Int. Ed. 2013, 52, 1371. (b) Chuprakov, S.; Hwang, F. W.; Gevorgyan, V. Angew. Chem., Int. Ed. 2007, 46, 4757. (8) (a) Miura, T.; Funakoshi, Y.; Murakami, M. J. Am. Chem. Soc. 2014, 136, 2272. (b) Miura, T.; Tanaka, T.; Biyajima, T.; Yada, A.; Murakami, M. Angew. Chem., Int. Ed. 2013, 52, 3883. (c) Miura, T.; Yamauchi, M.; Murakami, M. Chem. Commun. 2009, 1470. (9) (a) Yang, J. M.; Zhu, C. Z.; Tang, X. Y.; Shi, M. Angew. Chem., Int. Ed. 2014, 53, 5142. (b) Jiang, Y.; Tang, X. Y.; Shi, M. Chem. Commun. 2015, 51, 2122. (10) (a) Schultz, E. E.; Sarpong, R. J. Am. Chem. Soc. 2013, 135, 4696. (b) Schultz, E. E.; Lindsay, V. N. G.; Sarpong, R. Angew. Chem., Int. Ed. 2014, 53, 9904. (11) Shang, H.; Wang, Y.; Tian, Y.; Feng, J.; Tang, Y. Angew. Chem., Int. Ed. 2014, 53, 5662−5666. (12) Chuprakov, S.; Malik, J. A.; Zibinsky, M.; Fokin, V. V. J. Am. Chem. Soc. 2011, 133, 10352. (13) (a) Chuprakov, S.; Worrell, B. T.; Selander, N.; Sit, R. K.; Fokin, V. V. J. Am. Chem. Soc. 2014, 136, 195. (b) Li, Z.; Davies, H. M. L. J. Am. Chem. Soc. 2010, 132, 396. (c) Wang, H.; Qiao, H.; Zhang, H.; Yang, H.; Zhao, Y.; Fu, H. Eur. J. Org. Chem. 2015, 2015, 4471. (14) (a) Chuprakov, S.; Kwok, S. W.; Zhang, L.; Lercher, L.; Fokin, V. V. J. Am. Chem. Soc. 2009, 131, 18034. (b) Parr, B. T.; Davies, H. M. L. Angew. Chem., Int. Ed. 2013, 52, 10044. (15) Miura, T.; Tanaka, T.; Hiraga, K.; Stewart, S. G.; Murakami, M. J. Am. Chem. Soc. 2013, 135, 13652. (16) Parr, B. T.; Green, S. A.; Davis, H. M. L. J. Am. Chem. Soc. 2013, 135, 4716. (17) (a) Xing, Y. P.; Sheng, G. R.; Wang, J.; Lu, P.; Wang, Y. G. Org. Lett. 2014, 16, 1244. (b) Sheng, G. R.; Huang, K.; Chi, Z. H.; Ding, H. L.; Xing, Y. P.; Lu, P.; Wang, Y. G. Org. Lett. 2014, 16, 5096. (18) Wang, C.; Zhang, H.; Lang, B.; Ren, A.; Lu, P.; Wang, Y. Org. Lett. 2015, 17, 4412. (19) Sheng, G. R.; Huang, K.; Ma, S. C.; Qian, J.; Lu, P.; Wang, Y. G. Chem. Commun. 2015, 51, 11056. (20) CCDC 1413914 (3a), CCDC 1413915 (3f) and CCDC 1524525 (5g) contain supplementary crystallographic data for this paper.

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DOI: 10.1021/acs.orglett.7b00438 Org. Lett. XXXX, XXX, XXX−XXX