Letter Cite This: Org. Lett. 2017, 19, 6478−6481
pubs.acs.org/OrgLett
Iodobenzene-Catalyzed Ortho-Dearomatization and AromatizationTriggered Rearrangement of 2‑Allylanilines: Construction of Indolin3-ylmethanols with High Diastereoselectivities Shuo-En Wang,† Qiuqin He,*,† and Renhua Fan*,† †
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China S Supporting Information *
ABSTRACT: An iodobenzene-catalyzed oxidative rearrangement of 2-allylanilines was developed. This process involves an orthooxidative dearomatization mediated by the in situ generated iodine(III) compound and a subsequent aromatization-triggered rearrangement reaction, leading to the formation of functionalized indolin-3-ylmethanols with high diastereoselectivities.
F
Scheme 1. Iodobenzene-Catalyzed Oxidative Rearrangement of 2-Allylanilines
or decades, hypervalent iodine compounds have been widely used in organic synthesis because of their versatility, ready availability, and benign environmental character.1 While a variety of transformations have been proven to be mediated by hypervalent iodine compounds, stoichiometric amounts of or even excess amounts of hypervalent iodine compounds are normally required. Hence, equimolecular amounts of iodoarenes are produced as waste. These issues have apparently been the bottleneck for the application of hypervalent iodine compounds in designing clean and scalable reactions. Therefore, the development of iodoarene-catalyzed reactions has especially attracted the interest of chemists and has become an active research area.2 The first example of such a process, which was realized by using p-methoxyiodobenzene as a catalyst for gem-difluorination of cyclic dithioacetals under anodic conditions, was reported by Fuchigami and Fujita in 1994.3 In 2005, Ochiai and co-workers reported an iodobenzenecatalyzed α-acetoxylation of ketones in the presence of mchloroperbenzoic acid.4 This study presents a significant breakthrough in the iodoarene-catalyzed reaction and has inspired the rapid expansion of the application of such a tactic on various chemical transformations, such as oxidation of alcohols,5 functionalization of alkenes6 and alkynes.7 Recently, enantioselective dearomatization reactions catalyzed by chiral iodoarenes were also achieved by Kita,8 Ishihara,9 Quideau,10 and Birman.11 The elegance of these creative transformations, in association with our ongoing studies on the dearomatization of anilines,12 prompted us to explore the iodobenzene-catalyzed dearomatization reaction of anilines. As depicted in Scheme 1, we conceived that the introduction of a suitable trapping group, such as an allyl group, at the ortho-position of anilines would induce an iodine(III)-catalyzed dearomatization in an ortho manner to generate a spirocyclic intermediate, which might undergo an aromatization-triggered rearrangement to complete the construction of indolin-3-ylmethanols. Here, we report an iodobenzene-catalyzed oxidative rearrangement of 2-allylani© 2017 American Chemical Society
lines that affords functionalized indolin-3-ylmethanols with high diastereoselectivities through an ortho-dearomatization process. As mentioned by Wirth,2b the basic requirement for a successful iodoarene-catalyzed reaction is a selective oxidation condition. Under these conditions, the released iodoarene can be reoxidized to the corresponding hypervalent iodine species, whereas the substrates should be inert to this oxidation condition. Therefore, the key to the implemention of our strategy was the choice of a hypervalent iodine catalytic system to realize the dearomatization of anilines that could tolerate the sensitive nitrogen atom and the allyl group. Moreover, besides the oxidant-mediated epoxidation, another competitive reaction of dearomatization might be the activation of the alkene moiety in the substrates by the in situ generated iodine(III) compounds, which would lead to the formation of indolin-2ylmethanols. To test the possibility of our hypothesis, N-Ms-protected 2(1,3-diphenylallyl)-4-methylaniline 1a was used as the standard substrate for searching for suitable catalytic system and reaction conditions. The representative results are summarized in Table 1. When 0.2 equiv of iodobenzene was used together with 1.2 Received: September 22, 2017 Published: December 1, 2017 6478
DOI: 10.1021/acs.orglett.7b02986 Org. Lett. 2017, 19, 6478−6481
Letter
Organic Letters Table 1. Evaluation of Catalysts and Conditions
Scheme 2. Effect of the Nitrogen Protecting Groups
entry
ArI (equiv)
oxidant (equiv)
2aa (%)
b
PhI (0.2) PhI (0.2) PhI (0.2) PhI (0.2) PhI (0.2) PhI (0.2) PhI (0.1) PhI (0.2) 2-MeC6H4I (0.2) 2-PhC6H4I (0.2) 2,6-diMeC6H3I (0.2) 4-MeC6H4I (0.2) 4-OMeC6H4I (0.2) 4-BrC6H4I (0.2) 4-IC6H4I (0.2) 4-CH3COC6H4I (0.2) 1-Naph-I (0.2)
m-CPBA (1.2) m-CPBA (1.2) H2O2 (1.2) CH3CO3H (1.2) m-CPBA (1.2) m-CPBA (2.5) m-CPBA (2.5) m-CPBA (2.5) m-CPBA (2.5) m-CPBA (2.5) m-CPBA (2.5) m-CPBA (2.5) m-CPBA (2.5) m-CPBA (2.5) m-CPBA (2.5) m-CPBA (2.5) m-CPBA (2.5)
8 21 0 0 36 59 50 73 65 58 59 47 46 29 29 36 34
1 2c 3c 4c 5d 6d 7d 8e 9e 10e 11e 12e 13e 14e 15e 16e 17e
Table 2. Reaction Scope Investigation
entry
R1
R2
R3
producta (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph 2-MeC6H4 4-MeC6H4 4-MeC6H4 4-MeC6H4 4-ClC6H4 4-ClC6H4 4-ClC6H4 4-ClC6H4 4-BrC6H4 4-BrC6H4 4-BrC6H4 4-BrC6H4 4-CNC6H4 4-Pyrimidyl Me iPr Bn
Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph 2-MeC6H4 4-MeC6H4 4-MeC6H4 4-MeC6H4 4-ClC6H4 4-ClC6H4 4-ClC6H4 4-ClC6H4 4-BrC6H4 4-BrC6H4 4-BrC6H4 4-BrC6H4 4-CNC6H4 4-Pyrimidyl Ph Ph Ph
H 4-Et 4-iPr 4-nBu 4-tBu 4-allyl 4-cyclohexyl 4-Br 4,5-diMe 6-Me 4-Me 4-Et 4-iPr 4-nBu 4-Et 4-iPr 4-nBu 4-tBu H 4-Et 4- iPr 4-tBu 4-Me 4-Me 4-Me 4-Me 4-Me
3 (46) 4 (67) 5 (50) 6 (61) 7 (63) 8 (65) 9 (49) 10 (53) 11 (40) 12 (35) 13 (36) 14 (56) 15 (61) 16 (61) 17 (59) 18 (75) 19 (68) 20 (82) [80]b 21 (50) 22 (62) 23 (77) 24 (72) 25 (0) 26 (0) 27(58)c 28 (31) 29 (36)
Isolated yields. bReaction in CF3CH2OH at 25 °C. cReaction in (CF3)2CHOH at 25 °C. dReaction in (CF3)2CHOH/H2O (2:1) at 25 °C. eReaction in (CF3)2CHOH/H2O (2:1) at 0 °C.
a
equiv of m-chloroperoxybenzoic acid (m-CPBA), the formation of the desired indolin-3-ylmethanol 2a was only observed in the reaction using 2,2,2-trifluoroethanol (TFE) or 1,1,1,3,3,3hexafluoro-2-propanol (HFIP) as solvent, albeit in low yields (Table 1, entries 1 and 2). When hydrogen peroxide (H2O2) or peroxyacetic acid (CH3CO3H) was used instead of m-CPBA, the formation of compound 2a was not observed (Table 1, entries 3 and 4). Further investigation revealed that the addition of water could promote the formation of compound 2a. The best ratio of HFIP and water was 2:1, increasing the yield to 36% (Table 1, entry 5). The best ratio of the substrate, iodobenzene, and m-chloroperoxybenzoic acid was 1:0.2:2.5, improving the yield to 59% (Table 1, entry 6). When the reaction was conducted at 0 °C, compound 2a was formed in 73% yield with a high diastereoselectivity (dr >95:5, determined by 1H NMR) (Table 1, entry 8). The catalytic activity of a range of iodoarenes was examined (Table 1, entries 9−17). Iodoarenes bearing slightly electron-donating groups at the ortho position afforded better results than those bearing a para substituent. The use of p-bromo-, p-iodo-, and pacetyliodobenzene and 1-iodonaphthalene significantly decreased the catalytic efficiency. Among all of the tested iodoarenes, iodobenzene proved to be the best catalyst for the generation of indolin-3-ylmethanol. Moreover, the nature of the nitrogen protecting group had a great influence on the transformation (Scheme 2). N-Sulfonyl-protected substrates worked well, but the desired product was not observed in the reactions of N-acetyl- or N-benzoyl-protected substrates. The generality of this iodobenzene-catalyzed oxidative rearrangement was then investigated (Table 2). The reaction showed broad substrate compatibility, and a range of substituents on the aromatic ring could be tolerated. For example, a second allyl group at the C-4 position remained unaffected under the oxidizing conditions, leading to the
a
Isolated yields of reactions performed on 0.2 mmol scale, unless noted. bIsolated yield of reaction performed on 1 mmol scale. cTrans/ cis = 76:24, determined by 1H NMR.
formation of compound 8 in 65% yield. Reaction of the substrate bearing a bromo group afforded 10 in 53% yield. Substrates with an o-methyl substituent (1k or 1l) led to the formation of products 12 or 13 in lower yields possibly due to steric hindrance. Halogen atoms, such as bromo and chloro atoms, were compatible with the reaction conditions. However, with the substrate containing two cyan groups, the reaction did not give the corresponding product because the dearomatization occurred in a para-manner of the substrate and thus could not induce the following rearrangement. The transformation of the substrate featuring two 4-pyrimidyl moieties to form 26 also failed because of the consumption of hypervalent iodine with the 4-pyrimidyl moieties. When the R1 group is an alkyl group, the reaction still proceeded smoothly and gave rise to the 6479
DOI: 10.1021/acs.orglett.7b02986 Org. Lett. 2017, 19, 6478−6481
Letter
Organic Letters
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
corresponding product in acceptable yields. For example, the reaction of 4-methyl-2-(4-phenylbut-3-en-2-yl)aniline produced compound 27, in which the phenyl group was located at the C2 position and the methyl group was located at the C-3 side chain. The structure and its relative stereochemistry were determined by single-crystal diffraction analysis and 1H NMR chromatography. A plausible reaction pathway for the oxidative rearrangement is shown in Scheme 3. Ligand exchange of the in situ generated
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AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected]. *E-mail:
[email protected]. ORCID
Renhua Fan: 0000-0001-7398-3368
Scheme 3. Tentative Pathway for the Iodine(III)-Mediated Oxidative Rearrangement
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We are grateful to the National Natural Science Foundation of China (21332009, 21572033) and the Shanghai Science and Technology Committee (14431901402) for support of this research.
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iodine(III) compound with the nitrogen atom of substrates through a tricoordinated iodine intermediate would produce intermediate I. Dearomatization of the benzene ring is trapped by the o-alkenyl group to afford a spirocyclic intermediate II after reductive elimination of iodobenzene. The conformer II-b is more favorable than II-a due to the lack of the steric repulsion between the R2 group and the three-membered ring. Aromatization of II-b might be the driving force to promote the opening of the three-membered ring with water attack and the closure of five-membered ring in a concerted fashion, affording indolin-3-ylmethylium with high diastereoselectivity. In summary, on the basis of an ortho-trapping strategy, we have developed an iodobenzene-catalyzed oxidative rearrangement of 2-allylanilines. This process involves an in situ generated iodine(III) compound-mediated ortho-oxidative dearomatization and a subsequent aromatization-triggered tandem rearrangement, leading to the formation of functionalized indolin-3-ylmethanols with high diastereoselectivities. Studies to elucidate the detailed mechanism are currently in progress.
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REFERENCES
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b02986. Experimental procedures, characterization data, copies of 1 H NMR and 13C NMR of new compounds, and X-ray diffraction structure and crystallographic data of compounds 2a and 27b (PDF) Accession Codes
CCDC 1575967 and 1575972 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
[email protected], or by contacting The 6480
DOI: 10.1021/acs.orglett.7b02986 Org. Lett. 2017, 19, 6478−6481
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Organic Letters (12) (a) Song, R.; Han, Z.; He, Q.; Fan, R. Org. Lett. 2016, 18, 5328. (b) Han, D.; He, Q.; Fan, R. Angew. Chem., Int. Ed. 2015, 54, 14013. (c) Han, Z.; Zhang, L.; Li, Z.; Fan, R. Angew. Chem., Int. Ed. 2014, 53, 6805. (d) Feng, X.; Wang, H.; Yang, B.; Fan, R. Org. Lett. 2014, 16, 3600. (e) Zheng, C.; Chen, J. J.; Fan, R. Org. Lett. 2014, 16, 816. (f) Yang, M.; Tang, J.; Fan, R. Org. Lett. 2013, 15, 3464.
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DOI: 10.1021/acs.orglett.7b02986 Org. Lett. 2017, 19, 6478−6481
