Letter Cite This: Org. Lett. 2017, 19, 5764-5767
pubs.acs.org/OrgLett
Rh(II)-Catalyzed Denitrogenative Reaction of N‑Sulfonyl-1,2,3triazoles with Isatins for the Construction of Indigoids Kuntal Pal, Rahul K. Shukla, and Chandra M. R. Volla* Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai-400076, India S Supporting Information *
ABSTRACT: A convenient, Rh(II)-catalyzed, denitrogenative reaction of N-sulfonyl-1,2,3-triazoles and isatins to access (E)-2-(1-amino-2-oxo2-phenylethylidene)indolin-3-ones, the core structure of indigo dyes, was achieved under operationally simple conditions with high levels of diastereoselectivity. Moreover, photophysical and electrochemical studies were conducted to understand their applicability in optoelectronic applications.
I
Scheme 1. Overview of the Work
ndigoids are important and widely used natural dyes having a rich historical background.1 Around 50 kilotons of indigo dye are produced industrially per year for dyeing cotton yarn, wool, and silk.2 Furthermore, they are also used as nematicide and antiseptics and for treating ovarian and stomach cancer.3 Various indigo and bay-annulated indigo (BAI) derivatives found applications in field effect transistors due to their excellent electron-accepting properties.4 Other indigoids such as tyrian purple, ciba blue, indigo carmine, and indirubin also gained much interest for their significant pharmaceutical and medicinal activities,5 as well as their applications in the food industry (Figure 1).6
Figure 1. Widely utilized 3-oxoindolin-2-ylidene derivatives.
Since the seminal work of Fokin and Gevorgyan in 2008, Rh(II)-catalyzed denitrogenative ring opening of N-sulfonyl1,2,3-triazoles was extensively studied for synthesizing a variety of biologically active heterocycles.7,8 Rh-azavinyl carbene (RhAVC) derived from N-sulfonyl-1,2,3-triazoles was established as a versatile reactive intermediate and was broadly used in a series of organic transformations.9 The reactivity of Rh-carbenoid revolves around the carbenoid carbon (C1, δ+), iminium carbon (C2, δ+), and nitrogen center (N, δ−) (Scheme 1a). Insertion reactions of metal carbenoids are one of the most powerful class of transformations.10 In these reactions, Rh-AVC exhibits reactivity similar to metallocarbene derived from diazo compounds (Path A), where C1 displays an ambipolar behavior and has been employed in a 1,1-insertion.11 On the other hand, due to its dipolar nature (C1 as δ+ and N as δ−), it can also undergo 1,3insertion (Path B).12 For example, a formal 1,3-insertion of the O−H bond of water into α-imino Rh-carbenoid was reportd by © 2017 American Chemical Society
Murakami and co-workers (Scheme 1b).13 Fokin and co-workers also exploited the reactivity of Rh-AVC to achieve highly regioand stereoselective 1,3-insertions of O−H and N−H bonds of alcohols, amides, and carboxylic acids.14 Interestingly, in the case of sterically hindered secondary amides, an O−H insertion followed by a rearrangement was observed to afford α-amino ketones. While these two reactivity modes involving C1 and N of Rh-AVC are widely studied, harnessing the reactivity of the iminium carbon center (C2) in X−H insertion are much less explored (Path C). On the other hand isatin, due to its easy availability and high reactivity, was used in the synthesis of a variety of heterocyclic frameworks of biological significance.15 The most common Received: August 29, 2017 Published: October 23, 2017 5764
DOI: 10.1021/acs.orglett.7b02697 Org. Lett. 2017, 19, 5764−5767
Letter
Organic Letters reactions of isatin are the nucleophilic addition to the prochiral C3 carbonyl group.16 In contrast, the reactions of a more electronrich amide group are largely underdeveloped. Activation of less reactive amides is of great interest, and various metalmediated17,18 and electrophilic activation19 methods were developed. Herein we report the successful implementation of a Rh(II)-catalyzed method for the selective reaction of the amide carbonyl of isatin to gain efficient and expedient access to the structurally important 3-oxoindolin-2-ylidene scaffold (Scheme 1c). Remarkably, Rh−azavinyl carbene undergoes a formal change in its inherent reactivity at carbon-2 (C2) from electrophilic (δ+) to nucleophilic (δ−). We commenced our study by subjecting a mixture of readily accessible isatin 1a (0.1 mmol) and N-tosyl-4-phenyl-triazole 2a (0.12 mmol) to 2 mol % of Rh2(Oct)4 in 1,2-DCE at room temperature for 2 h. However, no product was detected even after a prolonged reaction time (Supporting Information). To our delight, increasing the temperature to 60 °C resulted in the selective formation of N-tosyl-(E)-2-(1-amino-2-oxo-2-phenylethylidene)indolin-3-one 3a in 67% NMR yield. The high diastereoselectivity of the reaction is likely due to the double hydrogen bonding present in 3a, analogous to the indigo framework. Increasing the temperature to 100 °C led to further improvement in the yield, and 3a was isolated in 92% yield (95% NMR yield). When the reaction was carried out in DCM, CHCl3, or toluene under refluxing conditions, 3a was observed in 78%, 63%, and 84% NMR yield, respectively. Finally, screening different Rh-salts for the reaction indicated that Rh2(OAc)4 and Rh2(esp)2 display similar reactivity to that of Rh2(Oct)4 and provided the product 3a in 88% and 91% NMR yield, respectively. With the optimized reaction conditions in hand, the generality of the Rh(II)-catalyzed reaction was then evaluated with various triazoles 2 using isatin 1a as the reaction partner (Scheme 2). Gratifyingly, under the standard conditions, irrespective of the electronic and steric factors, all the examined triazoles 2 performed smoothly to provide the corresponding 3-oxoindolin-2-ylidene derivatives 3 in good to excellent yields. The structure and E geometry of the double bond were confirmed by the single-crystal X-ray diffraction analysis of 3g. Triazoles having either a heteroaryl or an alkyl group were also found to be useful substrates to afford the corresponding 3-oxoindolin-2-ylidene in excellent yields (91% and 96%). In addition, other sulfonyl protected triazoles 2n−2s were also compatible and provided the corresponding products 3n−3s in good to excellent yields (85− 95%). In all cases, excellent diastereoselectivities were observed, consistent with the selective formation of (E)-isomer resulting from the double hydrogen bonding. Subsequently, as shown in Scheme 3, the scope of isatin derivatives in the Rh(II)-catalyzed denitrogenative reaction was also tested. As expected, 5-methylisatin 1b exhibited similar reactivity and produced the desired 3-oxoindolin-2ylidene derivatives 3t−3v in 86−92% yields. Also, we were pleased to find that other mono- and dihalo-substituted isatins underwent this transformation smoothly, although in some cases the yields were relatively lower. To illustrate the practicality of the above transformations, we developed a one-pot protocol for the synthesis of 3-oxoindolin-2ylidene derivatives 3 by combining Cu(I)-catalyzed 1,3-dipolar cycloaddition of terminal alkynes and N-sulfonyl azides and Rh(II)-catalyzed denitrogenative reaction of in situ generated triazoles with isatins (Scheme 4). Isatin 1a was treated with 1.2 equiv of phenylacetylene 4a and 1.2 equiv of tosylazide 5a in the presence of 10 mol % CuTC and 2 mol % Rh2(Oct)4 in 1,2-DCE
Scheme 2. Scope of the Reaction with Different Triazoles
Scheme 3. Scope of the Reaction with Different Isatins
Scheme 4. One-Pot Cu(I)/Rh(II)-Catalyzed Tandem Reaction
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DOI: 10.1021/acs.orglett.7b02697 Org. Lett. 2017, 19, 5764−5767
Letter
Organic Letters
The emission spectra of these derivatives showed a maxima in the visible region around 610 nm (Figure 3). Interestingly, a large Stokes shift was observed for these indigoid moieties. The Stoke shifts were around 80 nm for 3a, 92 nm for 3t, and 58 nm for 3w.
to isolate 3a in 85% yield. In general, the one-pot protocol provided satisfactory yields that are comparable to those acquired in the stepwise pathway. The operational simplicity of this Rh(II)-catalyzed denitrogenative reaction was demonstrated by performing the reaction with 1.0 g of isatin 1a using only 0.5 mol % of Rh2(Oct)4 in DCE to isolate 2.08 g of 3a (73% yield) (Scheme 5a). To gain some Scheme 5. Gram-Scale Synthesis and Control Experiments
Figure 3. Emission spectra of 3a, 3t, and 3w in CHCl3. Concentration 5.0 × 10−5 M.
The electrochemical properties were studied by measuring the cyclic voltammetry of 3a, which indicated its ambipolar character showing both oxidation and reduction peaks (Figure 4). The
insights into the reaction mechanism, N-methyl isatin 6 was treated with triazole 2a under the standard reaction conditions. No expected product was seen in the 1H NMR of the crude reaction mixture, indicating the importance of the free N−H of isatin for the facile reaction with Rh-azavinyl carbene intermediate (Scheme 5b). Furthermore, another control experiment was carried out using phthalimide 8 instead of isatin 1a and no reaction was observed, suggesting the reaction was selective for more electron-rich amides. Due to their strong electron-withdrawing nature, indigo derivatives show promising broad absorption in the visible region and favorable electrochemical and photophysical properties. Thus, we have carried out the photophysical and electrochemical studies on the indigo frameworks with different substituents in order to analyze their applicability in optoelectronic applications. The absorption spectra of three compounds, 3a, 3t, and 3w, having different substituents on the isatin moiety were measured in CHCl3, as shown in Figure 2.
Figure 4. Cyclic voltammogram of 3a in acetonitrile containing 0.1 M Bu4NPF6 at a scan rate of 100 mVs−1.
HOMO level of 3a was calculated from the first oxidation potential (Eox), i.e. −5.95 eV. As the HOMO−LUMO gap, the Eg from the UV/vis spectrum is 2.1 eV, and the ELUMO was estimated to be at −3.85 eV (EHOMO − Eg) which is in good agreement with the reduction potential peak (−3.82 eV) obtained from CV. With the crystal structure of 3g known, the electronic properties were examined by the time dependent density functional theory (TD-DFT) without further optimizing the structure. The electron distribution of the HOMO and LUMO of 3g was shown in Figure 5. The energy of the HOMO (−6.12 eV) calculated for 3g is in the range of the measured EHOMO (−5.95 eV) of 3a. Computed isodensity surfaces of molecular orbitals of 3g (Supporting Information) indicate that the electron density is distributed throughout the whole moiety, which supports the high conjugation as well as high λmax value of these derivatives. Based
Figure 2. UV−vis spectra of 3a, 3t, and 3w in CHCl3. Concentration 5.0 × 10−5 M.
All of these compounds have a relatively broad and intense absorption in the ultraviolet and visible region. The absorption bands between 280−400 nm (εmax = 10 000 M−1 cm−1) are ascribed to the π−π* transitions of the conjugated systems, while the bands in the range of 400−620 nm (εmax = 4200 M−1 cm−1) are assigned to the intramolecular charge transfer (ICT). Substituent variations resulted in a slight change in the absorption maxima. With the more donating methyl substituent, the absorption maxima shifted toward the red, from 505 nm (3a) to 520 nm (3t).
Figure 5. HOMO and LUMO of 3g calculated at B3LYP/6-311G(d,p) level of theory in gas phase. 5766
DOI: 10.1021/acs.orglett.7b02697 Org. Lett. 2017, 19, 5764−5767
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Organic Letters
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on these photophysical and electrochemical studies, these derivatives are expected to be potential candidates for harvesting solar energy. Finally, based on the control experiments and previous reports, a plausible mechanism for the title reaction is proposed (Supporting Information). The highly electrophilic α-imino Rh(II)-carbenoid A generated by the catalytic addition of Rh(II)salts onto triazoles is trapped by the O−H tautomer of istain 1′ to form oxonium ylide B. Release of the Rh-catalyst and hydrogen transfer generate the intermediate C. Intramolecular nucleophilic addition followed by ring opening of the strained four-membered zwitterion intermediate leads to E, which after tautomerization provides the selective formation of (E)-3. In summary, a highly efficient O−H insertion reaction of Rh(II)-azavinyl carbenes, exploiting the distinct reactivity of these highly reactive intermediates, was reported for the facile construction of indigoid skeletons from easily accessible isatin and N-sulfonyl triazole precursors. The reaction proceeds via a formal 1,3-insertion followed by an intramolecular rearrangement leading to a highly diastereoselective synthesis of indigo analogues. Reaction conditions are compatible with a wide range of functional groups and amenable to scale up. Various photophysical and electrochemical studies such as UV−vis, fluorescence, and cyclic voltametry indicated the applicability of these materials in harvesting solar energy, and further efforts will be focused in this direction.
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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.7b02697. Additional experimental procedures, X-ray crystallographic analysis, and spectroscopic data for synthesized compounds (PDF) Crystallographic data for 3g (CCDC no. 1534511) (CIF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Kuntal Pal: 0000-0002-9005-0874 Chandra M. R. Volla: 0000-0002-8497-1538 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This activity is supported by SERB (funding to CMRV, EMR/ 2015/002047). K.P. thanks the Council of Scientific & Industrial Research (C.S.I.R.), and R.K.S. thanks the University Grants Commission (U.G.C.) for a fellowship.
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REFERENCES
(1) (a) Gaboriaud-Kolar, N.; Nam, S.; Skaltsounis, A. L.A Colorful History: The Evolution of Indigoids. In Progress in the Chemistry of Organic Natural Products; Kinghorn, A. D., Falk, D., Kobayashi, J., Eds.; Springer: Cham, 2014; Vol. 99, pp 69−145. (b) Steingruber, E. Indigo and Indigo Colorants. Ullmann’s Encylopedia of Industrial Chemistry; Wiley-VCH: Weinheim, 2004. (2) (a) Ferreira, E. S. B.; Hulme, A. N.; McNab, H.; Quye, A. Chem. Soc. Rev. 2004, 33, 329. (b) Padden, A. N.; Dillon, V. M.; John, P.; Edmonds, J.; Collins, M. D.; Alvarez, N. Nature 1998, 396, 225. 5767
DOI: 10.1021/acs.orglett.7b02697 Org. Lett. 2017, 19, 5764−5767
