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Ir-Catalyzed Intramolecular Transannulation/C(sp2)– H Amination of 1,2,3,4-Tetrazoles by Electrocyclization Sandip Kumar Das, Satyajit Roy, Hillol Khatua, and Buddhadeb Chattopadhyay J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b05343 • Publication Date (Web): 28 Jun 2018 Downloaded from http://pubs.acs.org on June 29, 2018
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Journal of the American Chemical Society
Ir-Catalyzed Intramolecular Transannulation/C(sp2)–H Amination of 1,2,3,4-Tetrazoles by Electrocyclization Sandip Kumar Das,† Satyajit Roy,† Hillol Khatua,† and Buddhadeb Chattopadhyay†,* †
Center of Bio-Medical Research, Division of Molecular Synthesis & Drug Discovery, SGPGIMS Campus, Raebareli Road, Lucknow 226014, Uttar Pradesh, India Supporting Information Placeholder On the other hand, owing to the presence in molecules with a ABSTRACT: An efficient strategy for the intramolecular 2 wide range of biological activity, a-carboline ring system has denitrogenative transannulation/C(sp )–H amination of been branded as one of the privileged frameworks9 for drug 1,2,3,4-tetrazoles bearing C8-substituted arenes, heteroarenes discovery (Chart 1, C). Numerous methods10 exist for the and alkenes is described. The process involves the generation assembly of various a-carboline, however, every method is of the metal-nitrene intermediate from tetrazole by the combiassociated with their own restrictions (e.g. selectivity issues, nation of [Cp*IrCl2]2 and AgSbF6. It has been shown that the poor yield, requirement of particular classes of substrate etc.). reaction proceeds via an unprecedented electrocyclization Thus, it is highly desirable to develop new methods to overprocess. The method has been successfully applied for the come the existing shortcomings. Herein, we report a new consynthesis of a diverse array of a-carbolines and 7-azaindoles. cept11 for the intramolecular denitrogenative transannulati1 on/C(sp2)–H amination of 1,2,3,4-tetrazoles by iridium catalyTransition metal-catalyzed denitrogenative transannulation is sis, which undergo likely via the TS-IV (Chart 1, B) for the one of the most efficient methods to construct nitrogencontaining heterocycles. It has been reported that while 1,2,3synthesis of diverse a-carbolines, 7-azaindoles and other imtriazoles readily undergo denitrogenative transannulation with portant classes of heterocycles. transition metal catalysts via either an ionic1,2 or a radical actiTable 1. Evaluation and Reaction Optimizationsa vation mechanism,3 1,2,3,4-tetrazoles remain completely inactive for the transannulation.4 In this context, Wentrup’s pioneering denitrogenative thermal and photochemical nitrene2-20 mol% [M]-cat. + nitrene rearrangement of tetrazoles is remarkable, which pro0-20 mol% AgSbF6, solvent N N N 5 N N 130 oC, 24 h vide various nitrogen heterocycles. Usually, 1,2,3,4-tetrazoles NH2 H N N – N2 gas exist in equilibrium between closed and open form, the posi2a’ 1a 2a 2a/2a’ solvent additive cat. tion of this equilibrium depends on (Chart 1, A) several pa# 0 PhMe – Cu-cat. 1 rameters6 (e.g. temperature, solvents and substituents). Alt0 DCE – Zn-cat. 2 hough, Driver group7 has studied well on metal-nitrene com0 PhH – Co-cat. 3 plexes derived from ortho-substituted aryl azides, however, 0 PhH – Fe-cat. 4 the denitrogenative transannulation of 1,2,3,4-tetrazole via 0 PhH – Mn-cat. 5 metal-nitrene is entirely underdeveloped to date. Thus, it 0 dioxane – Ru-cat. 6 would be highly intriguing to develop this transannulation/C– 0 DCE – Rh-cat. 7 H amination8 chemistry via metal-nitrene formation. 0/40 PhH AgSbF6 [Ir(cod)(Cl)]2 8 Chart 1. Concept for the Transannulation/C–H Amination (A) Proposed hypothesis for the metal-nitrene 7 known FG FG 8 6 [M]-cat. [M] 5 N N N N N1 N N 4 N2 metal-carbene 3 N N2
unknown
N3 N 2
(B) Proposed hypothesis and designed work plan
H
N
N HO Me Neocryptolepin O O HO
N N H HO Mescengricin
O
metal-nitrene
X = SbF6
X
N H α-carboline
N N N3 N N2 N N (C) Selected examples for bioactive molecules Me
N
[M]
N
via N N SbF 6
a Reactions were conducted with 0.25 mmol scale and NMR conversions were determined using 1,3,5-trimethoxybenzene as internal standard; in parenthesis, isolated yield is given.
Thus, we started our initial investigations with substrate 1a using a variety of transition metal catalysts (Table 1, entries 1Me 7, see: SI, for detail optimization) based on the proposed hypothesis that in presence of metal catalysts tetrazole would COMe first generate the metal-nitrene intermediate and subsequently HOHN undergo intramolecular transannulation/C(sp2)–H amination.12 N N N OH N H To our surprise, none of the metal catalysts afforded desired OMe Food-derived carcinogen O product and the tetrazole remain completely unreacted under Cl O OMe the employed reaction conditions. For this extreme inertness13 N O S OMe N N of the tetrazole, we reasoned that metal catalysts such as Cu, N Me CH3 H Cytotoxicity against Zn, Co, Fe, Mn, Ru and Rh might be strongly coordinating Antioxidant HL-60 cell line ACS Paragon Plus Environment [M]-cat.
H
N
[M]-cat.
100 (96) PhH AgSbF6 [Cp*IrCl2]2 9 0 PhH – [Cp*IrCl2]2 10 Cu-cat. = Cu(MeCN)4•PF6, CuI, CuBr, CuBr•Me2S, Cu(acac)2, Cu(OTf)•C6H6; Zn-cat. = ZnI2; Co-cat. = Co(TPP), Fe-cat. = FeBr2, Fe(TPP)Cl; Mn-cat. = Mn(TPP)Cl, Ru-cat. = [Ru(p-cymene)Cl]2; Rh-cat. = Rh2(OAc)4, Rh2(oct)4, Rh2(O2CC3F7)4, Rh2(esp)4, Rh2(s-dosp)4
Me
Ir(III)Me
Me Me TS-IV
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with both the nitrogen atoms of the tetrazole (i.e. pyridine and azide nitrogen) and inhibiting the catalytic process for the generation of the metal-nitrene intermediate.14 Next, considering the unique reactivity of Chang’s amidation,15 we turned our attention towards iridium-based catalytic systems. Thus, transannulation was carried out by the combination of [Ir(cod)Cl]2 and AgSbF6, which gave 40% reduced product (2a¢, entry 8). Remarkably, when the same reaction was performed in presence of [Cp*IrCl2]2 and AgSbF6 in benzene solution, we observed quantitative conversion of the starting tetrazole into the desired transannulation product (2a) in 96% isolated yield (entry 9). In order to verify the role of the AgSbF6, same reaction was carried out without AgSbF6, which resulted in no reaction (entry 10). Moreover, conducting the reaction with only AgSbF6, no product formation observed. With these encouraging results, transannulations/C(sp2)–H aminations were performed for a series of 1,2,3,4-tetrazoles (Table 2). Irrespective of the substituents present in the C8 arene, for example, alkyl, alkoxy, phenyl, vinyl, ester, trifluoromethyl, and ketone were well tolerated under the reaction conditions (Table 2, A). Remarkably, in case of the metasubstituted C8-arene, the reaction produced exclusively one regioisomer out of the possible two regioisomers (entries 2h2l, 2v). Moreover, various disubstituted arenes at C8 position (2q-2t) including a bulky naphthyl group (2u) led to the acarbolines in good yield. For further elaboration, we examined various substitutions at the pyridine moiety of the 1,2,3,4tetrazoles (Table 2, B). Thus, 1,2,3,4-tetrazoles with different substituents at pyridine such as, 5-methyl (2w), 6-phenyl-7methyl (2x), 6-methyl (2y) and 6-phenyl (2z) were found to be compatible. Moreover, 5-hexenyl (2ab) and 5-pentenyl (2ac) also tolerated in the reaction conditions delivering acarbolines in excellent yield.16 Next, we explored the substrate scope with respect to the different types of heteroaromatic systems for C8 substituted 1,2,3,4-tetrazoles (Table 2, C). A range of heterocyclic systems smoothly underwent transannulation/amination to afford the desired multiple-nitrogen-containing molecules in excellent yields. For example, variously substituted pyridines (2ad-2ag), quinoline (2ah) and N-methylindole (2ai) gave the corresponding products in excellent yields. In this context, it deserves mentioning that in case of C8-substituted heterocycle (2ae), out of two possible regioisomers, we observed only the aforementioned isomer as the sole products. For further application of this newly developed strategy, we have demonstrated that the alkaloid Neocryptolepin (4) and an important molecule, which exhibits cytotoxicity against HL-60 cell line (5) can be synthesized efficiently with excellent yields from the corresponding tetrazoles (Chart 2). Towards this end, we were interested in the further development of this method with respect to the C8-substituted alkenes. Pleasingly, the developed method was found to be equally efficient with numerous alkenes and the results are summarized in Table 3. Performing the reactions with electronically neutral alkene (6a), electron-deficient alkenes (6b-c) and electron-rich alkenes (6d-e) provided the corresponding 7azaindoles (7a-e) with excellent yields. Moreover, transannulations of cyclic alkenes-bearing 1,2,3,4-tetrazoles were also found to be compatible delivering consistently in good yields (7f-g). Furthermore, substitution at the pyridine ring of the tetrazole-bearing styrene type of alkenes smoothly underwent denitrogenative transannulation/C(sp2)–H amination to give the substituted 7-azaindole derivatives.
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Table 2. Scope of Reaction with Diverse Substrates R1 R N N 1b-v N N
5.0 mol% [Cp*IrCl2]2 20 mol% AgSbF6, PhH 130 oC, 12-24 h – N2 gas
R1
R N
N H
2b-v
(A) scope of C-8 arene with diverse substitutions
Me
N
N H 2b: 85% Cl N H 2e: 80% Me
N
N
N H 2h: 80%
N
N
N
N H 2g: 83%
OMe
CO2Et
N H 2j: 69% Me
N
N H 2l: 82%
N
N
N H 2o: 67% OMe OMe
N H 2r: 92%
N
CF3
N
N
F N H 2t: 71%
N H 2d: 93%
F
N Me H 2q: 91% F
N
N H 2i: 89%
CHO
N H 2n: 96% Me
N
Ph N H 2f: 90%
F
N
N H 2c: 90%
N
N
N H 2k: 76% MeO
N
OMe
N
N H 2p: 83% CF 3
N
N CF3 H 2s: 74% COMe
N
N H 2u: 84%
N H 2m: 77% Ph
N H 2v: 88%
(B) scope of pyridine ring of the tetrazoles
Me
Ph Me
N
N
N H 2w: 82%b
Ph
N
Me
N
N H 2x: 71%
N H 2y: 86%
N
N H 2z: 85%
N
N H 2ab: 80%b
N H 2ac: 83%b
(C) scope of C-8 heteroarene with various substitutions
N
N N
N
N H 2ad: 95% N N Me H 2ag: 92%
N
N
N N H 2ae: 76% N N H 2ah: 89%
N
Me N H 2af: 89%
N
N N Me H 2ai: 66%
a Reactions were conducted with 0.5 mmol scale; isolated yields were reported after purification. bReaction completed within 12 h.
Chart 2. Short Synthesis of Important Molecules – N2 gas i) 5.0 mol% [Cp*IrCl2]2, 20 mol% AgSbF6, PhH, 130 oC, 24 h ii) 3.0 equiv. MeI, THF, 80 oC, 12 h
N N N N
3
– N2 gas
H
H N N N N 1v
i) 5.0 mol% [Cp*IrCl2]2, 20 mol% O AgSbF6, PhH, 130 oC, 24 h Me ii) 1.1 equiv. FG–Br, 2.0 equiv KOH, THF, 70 oC, 30 min FG = 3,4,5-trimethoxybenzyl
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N N Me 4, 96% Neocryptolepin COMe N
N FG 5, 80% Cytotoxicity against HL-60 cell line
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Journal of the American Chemical Society Table 3. Scope of Transannulation with Alkenesa R/Ar
5.0 mol% [Cp*IrCl2]2 20 mol% AgSbF6, PhH 130 oC, 24 h – N2 gas
R1 N N N N 6a-i
N
R1
Chart 4. Mechanistic Studies/Control Experiments N
Ph N H 7b: 89%
N H 7a-i
R/Ar
A) control experiments with nonconjugated alkene and conjugated Z-alkene:
CO2Me N H 7c: 79%
N
N H 7d: 93% Me
N
N
N H 7h: 88%
N H 7g: 87%
N
N H 7e: 90%
OMe Me
OMe
N
Ph
N H 7i: 91%
X Me
Ir(v)
Me
Me Me
Me
TS-I: C-H Activation
N
N H X Me
N SbF6 Ir(v) Me
Me
Me Me
TS-II: C-H Insertion
Me
Me Me
TS-III: EAS
X Me Me
D/H Me
developed conditions
N N N N 1c
+
N
OMe N H 2c: conv. 38% @4 h N
N H 2i: conv. 6% @4 h
Chart 5. Proposed Electrocyclization Mechanism [Cp*IrCl2]2 2AgSbF6
2AgCl N
N
N SbF H 6 X Ir(III) Me Me
Ph N H 7b, conv. 69%
developed D conditions
OMe + N N N N 1:1 ratio 1i same vessel
Chart 3. Possible Four Mechanistic Pathways N
N
developed conditions N N N N H N N 11 12, 0%, no reaction D) effects of substituents at C3 and C4 position of arene: OMe OMe
Ph
Next, we studied the mechanism and the product formation might be explained by the following four mechanisms, which are depicted in Chart 3, such as: i) C–H activation15 via TS-I, ii) C–H insertion via TS-II, iii) electrophilic aromatic substitution (EAS) via TS-III and iv) electrocyclization via TS-IV.17
N SbF 6
N
Me D/ H N N N N N N N N KH/KD = 1.034 KH/KD = 1.01 D/ H D/ H N N N N 1b/1b-d2 2b/2b-d2 1b–d 2b–d C) control reaction with non-conjugated 1,2,3,4-tetrazole:
N H 7f: 96%
a Reactions were conducted with 0.5 mmol scale; isolated yields were reported after purification.
H
H
developed conditions
OMe N
developed conditions
developed Ph conditions N N N H N N 9, 0%, no reaction 10, Z-isomer B) measurement of KIE value (intermolecular & intramolecular): Me D/H H Me D/H N N N N 8
N
N
N H 7a: 86%
with substrate 11 and observed no reaction, which clearly indicates that conjugation is essential for the reaction.
N H product
N
N SbF 6
X
Me
Ir(III) Me
Me
Me
X
Me Me
Me
N
H Ir(III) SbF6 Me
N
(E) X
TS-IV: Electrocyclization
Me
1,5 H-shift
Me N
N
X Me
H Ir(III)
Me Me
4-electron 5-atom electrocyclization
SbF6 Me Me
(D)
N3
N
N 1a N N N N N N2
X
Me
Thus, to shed light on the mechanistic aspects of the proposed pathways, we executed several control experiments (Chart 4). According to the literature report, since the [Cp*IrCl2]2 is known15 to catalyze the reaction via direct C-H activation mechanism, we thus decided to verify whether our transannulation/C(sp2)–H amination would follow the same C-H activation or π-electron participation. For that reason, we conducted a control experiment with substrate 8, where conjugation was disturbed by one methylene group. We observed that substrate 8 does not give even a trace amount of the desired product, which indicates that the present transannulation/amination strategy might not follow neither C–H activation mechanism (TS-I) nor C–H insertion mechanism (TS-II). For further studies, we performed another control experiment with substrate 10 (Z-isomer),18 where C-H bond is away from the reaction center. We anticipated that due to the geometric constrain, transannulation should not occur with the Z-isomer (10). But, to our surprise, substrate 10 smoothly underwent the transannulation affording 69% product conversion, which also oppose the C-H activation and C–H insertion mechanism (TS-I & TSII). Finally, determining the KIE value (intermolecular and intramolecular), we observed a secondary kinetic isotope effect (~1.0), which is again ruling out the possibility of TS-I and TS-II. Next, we hypothesized that if the reaction goes via electrophilic aromatic substitution (EAS, TS-III), then substrate 11 should furnish the corresponding transannulation product 12, because continuous conjugation is not essential for the EAS process. Following this hypothesis, reaction was performed
Ph
Me X = SbF6 AC-1
Me Me
Ph
SbF6 Ir(III) Me
N SbF 6 Ir(III)
Ir(III)
Me
Me SbF 6
Me
Me Me (A)
Me
N2
Me
N
Me TS-IV N
N SbF H 6 X Ir(III) Me Me Me
SbF6
N (B)
Me
X Me
Ir(v)
Me SbF6
Me
N N X Ir(v) Me Me
Me Me Me
Me Me (B’) disfavored
steric between lp of N & Me grs of Cp*
(C) Me
To gain more insight, we conducted another competitive experiment using a 1/1 mixture of 3-OMe and 4-OMesubstituted substrates (1i/1c), hypothesizing that the EAS (TSIII) and electrocyclization process (TS-IV) would be more favored with 1i and 1c respectively, producing more product conversion due to the electronic effects (Chart 4, D).19 However, we virtually observed that whereas, substrate 1i gave only 6% conversion, substrate 1c afforded 38% conversion, which is evidencing the proof-of-concept for the electrocyclization process (TS-IV). Thus, based on the experimental evidences, we proposed the following electrocyclization mechanism (Chart 5). Treating with AgSbF6, dimeric [Cp*IrCl2]2 generates the active catalytic species (AC-1),15a,20 which coordinates with the N1 atom of the tetrazole (1a) to form the species (A). Then, the species (A), might produce the sterically favored (B)21 by the loss of dinitrogen. Next, the metal-nitrene (B) upon rearrangement of its π-electron generates the TS-IV, which undergoes 4electron-5-atom electrocyclization to form the C–N bond in species (C). Subsequently, by a routine 1,5-H shift from the
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Wentrup, C. J. Am. Chem. Soc. 2011, 133, 5413 (l) Messmer, A.; Hajos, G.; Juhasz-Riedl, Z.; Sohar, P. J. Org. Chem. 1988, 53, 973. (m) For click reaction, see: Chattopadhyay, B.; Rivera Vera, C. I.; Chuprakov, S.; Gevorgyan, V. Org. Lett. 2010, 12, 2166. (6) For representative examples, see: (a) Boyer, J. H.; Miller, E. J. J. Am. Chem. Soc. 1959, 81, 4671. (b) Lowe-Ma, Ch. K.; Nissan, R. A.; Wilson, W. S. J. Org. Chem. 1990, 55, 3755. (c) Evans, R. A.; Wentrup, C. J. Chem. Soc., Chem. Commun. 1992, 1062. (d) Sasaki, T.; Kanematsu, K.; Murata, M. J. Org. Chem. 1971, 36, 446. (e) Pochinok, V. V.; Avramenko, L. F.; Grigorenko, P. S.; Skopenko, V. N. Russ. Chem. Rev. 1975, 44, 481. (7) Sun, K.; Sachwani, R.; Richert, K. J.; Driver, T. G. Org. Lett. 2009, 11, 3598. (8) For a leading review of C–H aminations by metal-nitrene formation, see: Davies, H. M. L.; Manning, J. R. Nature 2008, 451, 417. (9) For selected examples, see: (a) Helbecque, N.; Moquin, C.; Bernier, J. L.; Morel, E.; Guyot, M.; Henichart, J. P. Cancer Biochem. Biophys. 1987, 9, 271. (b) Yeung, B. K. S.; Nakao, Y.; Kinnel, R. B.; Carney, J. R.; Yoshida, W. Y.; Scheuer, P. J. J. Org. Chem. 1996, 61, 7168. (c) Aza, H.; King, R. S.; Squires, R. B.; Guengerich, F. P.; Miller, D. W.; Freeman, J. P.; Lang, N. P.; Kadlubar, F. F. Drug Metab. Dispos. 1996, 24, 395. (10) For selected examples, see: (a) He, L.; Allwein, S. P.; Dugan, B.; Knouse, K. W.; Ott, G. R.; Zificsak, C. A. Org. Synth. 2016, 93, 271. (b) Wadsworth, A. D.; Naysmith, B. J.; Brimble, M. A. Eur. J. Med. Chem. 2015, 97, 816. (11) This is the first report for the intramolecular denitrogenative transannulation/C(sp2)–H amination of fused 1,2,3,4-tetrazoles via metal-nitrene. Attempted transannulation of 1,2,3,4-tetrazoles with alkynes and nitriles failed under the developed reaction conditions. (12) Extensive screenings were carried out by the different combinations of solvents, catalysts and additives, for details, see: SI. (13) Based on the NMR studies at room temperature, we observed that 1,2,3,4-tetrazole always exits in closed form, there is no effect of substituent at C8 position. However, halogen substituent at C5 position gives appreciable amount of open form. For details, see ref. 6. (14) For lower reactivity of 2-pyridyl diazo-compounds in Rhcatalyzed reactions, see: Davies, H. M. L.; Townsend, R. J. J. Org. Chem. 2001, 66, 6595. (15) For selected examples, see: (a) Ryu, J.; Kwak, J.; Shin, K.; Lee, D.; Chang, S. J. Am. Chem. Soc. 2013, 135, 12861. (b) Park, Y.; Heo, J.; Baik, M.-H.; Chang, S. J. Am. Chem. Soc. 2016, 138, 14020. (c) Hong, S. Y.; Park, Y.; Hwang, Y.; Kim, Y. B.; Baik, M.-H.; Chang, S. Science 2018, 359, 1016. (d) Shin, K.; Park, Y.; Baik, M. H.; Chang, S. Nat. Chem. 2018, 10, 218. (e) Park, Y.; Kim, Y.; Chang, S. Chem. Rev. 2017, 117, 9247. (16) Notably, for C5-substituted pyridine, reaction completed within short period of time, which might be due to more open azide form of the tetrazole. (17) Selected examples of electrocyclization of other types of azides: (a) Shen, M.; Leslie, B. E.; Driver, T. G. Angew. Chem. Int. Ed. 2008, 47, 5056. (b) Stokes, B. J.; Jovanovic, B.; Dong, H.; Richert, K. J.; Riell, R. D.; Driver, T. G. J. Org. Chem. 2009, 74, 3225. (c) Stokes, B. J.; Richert, K. J.; Driver, T. G. J. Org. Chem. 2009, 74, 6442. (d) Driver, T. G. Org. Biomol. Chem. 2010, 8, 3831. (e) Pumphrey, A. L.; Dong, H.; Driver, T. G. Angew. Chem. Int. Ed. 2012, 51, 5920. (f) Nguyen, Q.; Nguyen, T.; Driver, T. G. J. Am. Chem. Soc. 2013, 135, 620. (g) Harrison, J. G.; Gutierrez, O.; Jana, N.; Driver, T. G.; Tantillo, D. J. Am. Chem. Soc. 2016, 138, 487. (h) Mazumdar, W.; Jana, N.; Thurman, B. T.; Wink, D. J.; Driver, T. G. J. Am. Chem. Soc. 2017, 139, 5031. (i) Alford, J. S.; Spangler, J. E.; Davies, H. M. L. J. Am. Chem. Soc. 2013, 135, 11712. (18) To verify the isomerization during the reaction, Z-isomer (10) was heated at 130 oC for several hours and found no interconversion. (19) For detailed mechanistic studies via electrocyclization pathway of nonpyridyl azide substrates, see: ref. 17c. (20) Wang, L.; Yang, Z.; Yang, M.; Zhang, R.; Kuaia, C.; Cui, X. Org. Biomol. Chem. 2017, 15, 8302. (21) (a) Figg, T. M.; Park, S.; Park, J.; Chang, S.; Musaev, D. G. Organometallics 2014, 33, 4076. (b) Liu, J.-B.; Sheng, X.-H.; Sun, C.-Z.; Huang, F.; Chen, D.-Z. ACS Catal. 2016, 6, 2452.
resonating structure (D) of (C) led to the product formation with the regeneration of the active catalytic species (AC-1). In conclusion, we have developed an efficient intramolecular denitrogenative transannulation/C(sp2)–H amination method for the synthesis of a wide number of carbolines and 7azaindoles by Ir(III)-catalyzed electrocyclization process. The essential requirement of this approach is the employment of [Cp*IrCl2]2 and AgSbF6 to generate the active catalytic species that help to form the metal-nitrene intermediate for the transannulation/amination. This is the first report for the denitrogenative transannulation/amination via metal-nitrene formation, which undergoes via an unprecedented electrocyclization process. The developed method shows very broad substrate scope and functional group tolerance. The synthetic benefits of the developed approach are showcased with a short synthesis of important bioactive molecules. More efforts are underway in our laboratory.
ASSOCIATED CONTENT Supporting Information Available: Full characterization, copies of all spectral data, experimental procedures. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION Corresponding Author
[email protected],
[email protected] Author Contributions SKD and SR contributed equally.
Notes The authors declare no competing financial interest.
ACKNOWLEDGMENT This work was supported by CSIR-EMR-II grant (Sanction No. 02(0259)/16/EMR-II), Ramanujan grant and DST-Young Scientist Grant. SKD thanks CSIR for JRF, SR and HK thanks CSIR for SRF and JRF. We thank the NMR and mass spectrometry facility at CBMR, and the Director, for the research facilities.
REFERENCES (1) For leading reviews on transannulations of 1,2,3-triazoles, see: (a) Chattopadhyay, B.; Gevorgyan, V. Angew. Chem. Int. Ed. 2012, 51, 862. (b) Gulevich, A. V.; Gevorgyan, V. Angew. Chem. Int. Ed. 2013, 52, 1371. (c) Davies, H. M. L.; Alford, J. S. Chem. Soc. Rev. 2014, 43, 5151. (2) For the first report of denitrogenative transannulation via ionic mechanism, see: (a) Chuprakov, S.; Hwang, F. W.; Gevorgyan, V. Angew. Chem. Int. Ed. 2007, 46, 4757. (b) Horneff, T.; Chuprakov, S.; Chernyak, N.; Gevorgyan, V.; Fokin, V. V. J. Am. Chem. Soc. 2008, 130, 14972. (3) For the first report of denitrogenative transannulation by radical activation mechanism, see: Roy, S.; Das, S. K.; Chattopadhyay, B. Angew. Chem. Int. Ed. 2018, 57, 2238. (4) During preparation of our manuscript, one report appeared for the denitrogenative transannulation with monocyclic 1,2,3,4tetrazoles via metal-carbene intermediate, Nakamuro, T.; Hagiwara, K.; Miura, T.; Murakami, M. Angew. Chem. Int. Ed. 2018, 57, 5497. (5) For selected pioneering examples, see: (a) Harder, R.; Wentrup, C. J. Am. Chem. Soc. 1976, 98, 1259. (b) Wentrup, C.; Winter, H.-W. J. Am. Chem. Soc. 1980, 102, 6159. (c) Evans, R. A.; Wong, M. W.; Wentrup, C. J. Am. Chem. Soc. 1996, 118, 4009. (d) Wentrup, C.; Kuzaj, M.; Lüerssen, H. Angew. Chem. Int. Ed. Engl. 1986, 25, 480. (e) Evans, R. A.; Wentrup, C. J. Chem. Soc. Chem. Commun. 1992, 1062. (f) Addicott, C.; Reisinger, A.; Wentrup, C. J. Org. Chem. 2003, 68, 1470. (g) Reisinger, A.; Koch, R.; Bernhardt, P. V.; Wentrup, C. Org. Biomol. Chem. 2004, 2, 1227. (h) Reisinger, A.; Koch, R.; Wentrup, C. J. Chem. Soc., Perkin Trans. I 1998, 2247. (i) Reisinger, A.; Wentrup, C. Chem. Commun. 1996, 813. (j) Wentrup, C. Tetrahedron 1970, 27, 367. (k) Kvaskoff, D.; Vosswinkel, M.;
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Journal of the American Chemical Society Intramolecular Transannulation/C(sp2)–H Amination of 1,2,3,4-Tetrazoles
[Cp*Ir]-cat.
[Cp*Ir]-cat. N
N H 7-azaindole derivatives 9 examples 79-96% yields
N N N N
N2
H N2
N X Me
N
N H α-carboline 36 examples 66-95% yields
N SbF 6
Ir(III)Me
Me Me X = SbF6 via Metal-Nitrene/ Electrocyclization Me
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