Subscribe to RSS
DOI: 10.1055/a-2106-5108
Synthesis of Carbamoyl Azides from Redox-Active Esters and TMSN3
This work was supported by the National Natural Science Foundation of China (NSFC; Grant No. 22001251, 21871258, 21922112, and 22225107), the National Key Research and Development Program of China (Grant No. 2017YFA0700103), and the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB20000000).
Abstract
An efficient method for construction of C–N bonds is reported here. The iron-catalyzed azidation of N-hydroxy phthalimide (NHP) esters provides a convenient approach for the synthesis of carbamoyl azides with good substrate scope and functional group tolerance. Both aryl carbon C(sp2) and alkyl carbon C(sp3) sources can be used deliver the carbamoyl azides. Mechanistic studies were conducted and a two-stage process was identified.
#
Highly efficient construction of C–N bonds is of particular importance because such methods can provide strategic approaches for the synthesis of amines that are ubiquitously involved in modern organic synthesis and bioactive lead discovery.[1] Currently, there are several classical strategies for the construction of C(sp2)–N bonds, including Ullmann-type aminations,[2] Chan–Lam aminations,[3] and Buchwald–Hartwig aminations.[4] However, due to the feasibility of β-hydrogen elimination from the alkyl-metal intermediate, it is difficult to achieve C(sp3)–N bond formation under the classical transition-metal-catalyzed reaction conditions.[1d] [1g]
N-Hydroxy phthalimide esters (NHP esters), as a typical kind of redox-active esters,[5] can be easily generated from a broad class of readily available carboxylic acids. In recent years, NHP esters have been widely applied as alkyl precursors for the construction of C(sp3)–C and C(sp3)–heteroatom bonds through radical coupling reactions.[6] Among them, the formation of C(sp3)–N bonds with NHP esters as the C(sp3) carbon source is a very useful and practical method for the synthesis of amines.[1d] [1g] For example, Fu and co-workers discovered that the NHP esters can undergo single-electron transfer (SET) process to afford alkylamines via photoinduced, copper-catalyzed intramolecular decarboxylation (Scheme [1a]),[7] while Hu’s work allowed the construction of the C(sp3)–N bond through a two-component reaction between the NHP esters and extra amine sources (Scheme [1b]).[8] Very recently, Lopchuk and co-workers reported a method for decarboxylative construction of the C(sp3)–N bond with diazirines as single electrophilic nitrogen transfer reagents when NHP esters were exposed to a reductive iron catalysis (Scheme [1c]).[9] However, although progress has been achieved, methods for the formation of C–N bonds with NHP esters are still limited and almost all of them proceed through a SET process.
Herein, we report an alternative method for the construction of the C–N bond with NHP esters via a nucleophilic substitution process. This iron-catalyzed reaction[10] is thought to proceed through a two-stage process, with the intermediate azido ketones generated from the nucleophilic substitution of trimethylsilylazide (TMSN3) with NHP esters. Both aryl carbon C(sp2) sources and alkyl carbon C(sp3) sources can be used to deliver carbamoyl azides[11] in good to excellent yields.
Initial studies used NHP ester 1a and TMSN3 as model reaction substrates to optimize the reaction conditions (Table [1]). The optimization studies showed that the reaction was best carried out with ferric acetate (Fe(OH)(OAc)2, 10 mol%) in THF (0.1 M) at 70 °C for 24 h under an atmosphere of nitrogen (entry 1).[12] Other selected results of the optimization led to the conditions provided. For example, when the reaction was run with other iron metal catalyst, such as Fe(OTf)3, Fe(OTf)2, Fe(acac)3, Fe(acac)2, FeCl3, or FeCl2, 0–29% yields of the desired product 2a were obtained (entries 2–7). A range of solvents were also tested. While toluene and DCM did not afford 2a, other solvents such as acetonitrile and 1,4-dioxane, showed a lower reaction efficiency (entries 8–12). Unexpectedly, instead of forming the carbamoyl azide 2a, benzoyl azide turned out to be the major product when acetone was utilized as the solvent (entry 13).[13] Notably, when the reaction was run at a lower temperature, almost no 2a formed, presumably because of the blocked transformation of benzoyl azide into 2a. In addition, a high reaction temperature resulted in a messy reaction (entries 14–16). Finally, when the reaction was run in the absence of an iron catalyst it was found that the desired product 2a was not formed at 70 °C and most of the starting substrate 1a was recovered (entry 17).
With the optimal reaction conditions in hand, the generality of this iron-catalyzed protocol with respect to a wide range of NHP esters was investigated. As summarized in Scheme [2], both aryl and alkyl functionalities can be incorporated in the NHP esters, making this protocol a convenient method for the synthesis of amines starting from readily available carboxylic acids. For example, aryl carboxylic acids with various functional groups, such as methyl, methoxyl, fluoride, bromide, and phenyl group can be smoothly converted into the corresponding carbamoyl azides 2b–f in up to 96% yield. Substrates with an electron-deficient group, such as carbonyl and nitro group reacted with less efficiency (2g–i). Substitution at the meta- or ortho-position of the aryl group was tolerated, and the reactions provided the desired products 2j–l in good yields. Notably, other aromatic carboxylic acids such as 1-naphthoic acid, and 2-thenoic acid were transformed into the corresponding NHP esters, and the subsequent azidation reactions delivered the carbamoyl azides 2m and 2n in good yields. Both aryl carboxylic acids and alkyl carboxylic acids could be used as precursors; for example, carbamoyl azides 2o–q, with an alkyl chain, were obtained.
To further showcase the generality of this iron-catalyzed azidation of NHP esters, derivatives from bioactive dehydrocholic acid, isoxepac, and testosterone 17β-carboxylic acid were subjected into this procedure and the reactions afforded the corresponding carbamoyl azides 2r, 2s, and 2t in good to high yields (Scheme [3]). This result indicates that the method can be used for the late-stage decoration of natural products and other bioactive carboxylic acids.
a Standard reaction conditions: 1a (0.2 mmol), TMSN3 (3 equiv), iron catalyst (10 mol%) in solvent at the stated temperature under a nitrogen atmosphere for 24 h.
b Benzoyl azide was the major product.
To gain more insights into the mechanistic process, control experiments were conducted (Scheme [4]). First, the reaction was run with the addition of one equivalent of TEMPO and the result indicated that radical species might not be involved in the reaction (Scheme [4a]); the reactions with 1u and 1v further support this hypothesis. Moreover, while the reaction with NaN3 afforded the desired product 2b in 81% yield, a non-redox active ester 1b′ also afforded 2b in 72% yield (Scheme [4b]). In addition, this reaction was not catalyzed by either Fe(OH)3 or the FeCl3/NaOH system (Scheme [4c]). These results suggest that an ionic pathway might be involved and therefore the basicity of Fe(OH)(OAc)2 might play a role in promoting the reaction. As discussed in the optimization of reaction conditions, when the reaction was carried out at low temperature, only a trace amount of the desired carbamoyl azide was detected. Therefore, a control reaction with the addition of one equivalent of TMSN3 was carried out. As expected, the reaction stopped at the first stage to only produce the carbonyl azide 3b in 78% yield at 45 °C (Scheme [4d]). Furthermore, at higher temperature (70 °C), the carbonyl azide 3b react directly with TMSN3 to undergo Curtius rearrangement and afford the corresponding carbamoyl azide 2b in quantitative yield in the absence of any iron metal (Scheme [4e]).[14] These mechanistic reactions suggest that the iron catalyst promotes the reaction of NHP ester with TMSN3 in the first stage to afford the carbonyl azide intermediate, and conversion of the intermediate into the final product only needs elevated temperature.
Based on the results of these mechanistic experiments, a possible reaction mechanism was proposed (Scheme [5]). First, ferric acetate (A), acting as a Lewis acid, coordinates with the NHP ester to form iron species B, which facilitates the nucleophilic attack of the ester by an azido anion. Then, a new iron species C is generated, together with the formation of carbonyl azide. Dissociation of NHPI regenerates species A and the isocyanate intermediate is transformed by Curtius rearrangement. Finally, the carbamoyl azide is produced via a second nucleophilic attack of the carbamoyl azide by TMSN3.
In summary, we have developed an efficient method for iron-catalyzed synthesis of carbamoyl azides directly from NHP esters and TMSN3 under mild reaction conditions. Many functional groups are tolerated and the substrate scope is broad. Mechanistic studies reveal that this reaction involves a two-stage process, and the iron catalyst presumably promotes the conversion of the NHP esters into the carbonyl azide intermediate.[15]
#
Conflict of Interest
The authors declare no conflict of interest.
Supporting Information
- Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-2106-5108.
- Supporting Information
-
References and Notes
- 1a Yin XT, Li WJ, Zhao BL, Cheng K. Chin. J. Org. Chem. 2018; 38: 2879
- 1b Arshadi S, Ebrahimiasl S, Hosseinian A, Monfared A, Vessally E. RSC Adv. 2019; 9: 8964
- 1c Singh S, Roy VJ, Dagar N, Sen PP, Roy SR. Adv. Synth. Catal. 2020; 363: 937
- 1d Wang Y, Tian L, Zheng Y, Shao X, Ramadoss V. Synthesis 2020; 52: 1357
- 1e Yu W.-Y, Chan C.-M, Chow Y.-C. Synthesis 2020; 52: 2899
- 1f Zeng Z, Feceu A, Sivendran N, Gooßen LJ. Adv. Synth. Catal. 2021; 363: 2678
- 1g Rivas M, Palchykov V, Jia X, Gevorgyan V. Nat. Rev. Chem. 2022; 6: 544
- 2a Ullmann F. Ber. Dtsch. Chem. Ges. 1903; 36: 2382
- 2b Monnier F, Taillefer M. Angew. Chem. Int. Ed. 2009; 48: 6954
- 3a Chan DM. T, Monaco KL, Wang R.-P, Winters MP. Tetrahedron Lett. 1998; 39: 2933
- 3b Lam PY. S, Clark CG, Saubern S, Adams J, Winters MP, Chan DM. T, Combs A. Tetrahedron Lett. 1998; 39: 2941
- 4a Guram AS, Rennels RA, Buchwald SL. Angew. Chem., Int. Ed. Engl. 1995; 34: 1348
- 4b Louie J, Hartwig JF. Tetrahedron Lett. 1995; 36: 3609
- 5a Cornella J, Edwards JT, Qin T, Kawamura S, Wang J, Pan CM, Gianatassio R, Schmidt M, Eastgate MD, Baran PS. J. Am. Chem. Soc. 2016; 138: 2174
- 5b Liu H.-Y, Lu Y, Li Y, Li J.-H. Org. Lett. 2020; 22: 8819
- 5c Liu X.-J, Zhou S.-Y, Xiao Y, Sun Q, Lu X, Li Y, Li J.-H. Org. Lett. 2021; 23: 7839
- 6a Goossen LJ, Rodriguez N, Goossen K. Angew. Chem. Int. Ed. 2008; 47: 3100
- 6b Rodriguez N, Goossen LJ. Chem. Soc. Rev. 2011; 40: 5030
- 6c Weaver JD, Recio A III, Grenning AJ, Tunge JA. Chem. Rev. 2011; 111: 1846
- 6d Dzik WI, Lange PP, Goossen LJ. Chem. Sci. 2012; 3: 2671
- 6e Larrosa I, Cornella J. Synthesis 2012; 44: 653
- 6f Park K, Lee S. RSC Adv. 2013; 3: 14165
- 6g Shen C, Zhang P, Sun Q, Bai S, Hor TS, Liu X. Chem. Soc. Rev. 2015; 44: 291
- 7 Zhao W, Wurz RP, Peters JC, Fu GC. J. Am. Chem. Soc. 2017; 139: 12153
- 8 Mao R, Frey A, Balon J, Hu X. Nat. Catal. 2018; 1: 120
- 9 Chandrachud PP, Wojtas L, Lopchuk JM. J. Am. Chem. Soc. 2020; 142: 21743
- 10 Bauer I, Knolker HJ. Chem. Rev. 2015; 115: 3170
- 11a Feng P, Sun X, Su Y, Li X, Zhang LH, Shi X, Jiao N. Org. Lett. 2014; 16: 3388
- 11b Li X.-Q, Wang W.-K, Han Y.-X, Zhang C. Adv. Synth. Catal. 2010; 352: 2588
- 11c Li X.-Q, Wang W.-K, Zhang C. Adv. Synth. Catal. 2009; 351: 2342
- 11d Lwowski W, De Mauriac RA, Thompson M, Wilde RE, Chen S.-Y. J. Org. Chem. 1975; 40: 2608
- 11e Salama TA, Elmorsy SS, Khalil A.-GM, Ismail MA. Chem. Lett. 2011; 40: 1149
- 11f Wei R, Ge L, Bao H, Liao S, Li Y. Synthesis 2019; 51: 4645
- 11g Yadav L, Yadav V, Srivastava V. Synlett 2016; 27: 2826
- 12a Toriyama F, Cornella J, Wimmer L, Chen TG, Dixon DD, Creech G, Baran PS. J. Am. Chem. Soc. 2016; 138: 11132
- 12b Smith JM, Qin T, Merchant RR, Edwards JT, Malins LR, Liu Z, Che G, Shen Z, Shaw SA, Eastgate MD, Baran PS. Angew. Chem. Int. Ed. 2017; 56: 11906
- 13 Montesinos-Magraner M, Costantini M, Ramirez-Contreras R, Muratore ME, Johansson MJ, Mendoza A. Angew. Chem. Int. Ed. 2019; 58: 5930
- 15 Typical Procedure: A flame-dried reaction tube with a magnetic stirring bar was charged with NHP ester 1a (0.5 mmol, 133 mg), ferric acetate (10 mol%, 9.5 mg) and THF (5.0 mL) under a nitrogen atmosphere. TMSN3 (1.5 mmol, 0.2 mL) was then injected into the tube and the mixture was heated at 70 °C (oil bath) for 24 h. After reaction completion as detected by TLC, the solid was removed by filtration and the filtrate was concentrated. The residue was purified by column chromatography (silica gel, PE/EtOAc = 10:1) to afford the carbamoyl azide 2a (73.7 mg, 91% yield) as a white solid; mp 105–106 °C. 1H NMR (600 MHz, CDCl3): δ = 7.42 (d, J = 8.1 Hz, 2 H), 7.35–7.31 (m, 2 H), 7.12 (t, J = 7.4 Hz, 1 H), 6.83 (br, 1 H). 13C NMR (151 MHz, CDCl3): δ = 154.00, 136.95, 129.31, 124.75, 119.27.
Corresponding Authors
Publication History
Received: 24 February 2023
Accepted after revision: 06 June 2023
Accepted Manuscript online:
06 June 2023
Article published online:
21 July 2023
© 2023. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References and Notes
- 1a Yin XT, Li WJ, Zhao BL, Cheng K. Chin. J. Org. Chem. 2018; 38: 2879
- 1b Arshadi S, Ebrahimiasl S, Hosseinian A, Monfared A, Vessally E. RSC Adv. 2019; 9: 8964
- 1c Singh S, Roy VJ, Dagar N, Sen PP, Roy SR. Adv. Synth. Catal. 2020; 363: 937
- 1d Wang Y, Tian L, Zheng Y, Shao X, Ramadoss V. Synthesis 2020; 52: 1357
- 1e Yu W.-Y, Chan C.-M, Chow Y.-C. Synthesis 2020; 52: 2899
- 1f Zeng Z, Feceu A, Sivendran N, Gooßen LJ. Adv. Synth. Catal. 2021; 363: 2678
- 1g Rivas M, Palchykov V, Jia X, Gevorgyan V. Nat. Rev. Chem. 2022; 6: 544
- 2a Ullmann F. Ber. Dtsch. Chem. Ges. 1903; 36: 2382
- 2b Monnier F, Taillefer M. Angew. Chem. Int. Ed. 2009; 48: 6954
- 3a Chan DM. T, Monaco KL, Wang R.-P, Winters MP. Tetrahedron Lett. 1998; 39: 2933
- 3b Lam PY. S, Clark CG, Saubern S, Adams J, Winters MP, Chan DM. T, Combs A. Tetrahedron Lett. 1998; 39: 2941
- 4a Guram AS, Rennels RA, Buchwald SL. Angew. Chem., Int. Ed. Engl. 1995; 34: 1348
- 4b Louie J, Hartwig JF. Tetrahedron Lett. 1995; 36: 3609
- 5a Cornella J, Edwards JT, Qin T, Kawamura S, Wang J, Pan CM, Gianatassio R, Schmidt M, Eastgate MD, Baran PS. J. Am. Chem. Soc. 2016; 138: 2174
- 5b Liu H.-Y, Lu Y, Li Y, Li J.-H. Org. Lett. 2020; 22: 8819
- 5c Liu X.-J, Zhou S.-Y, Xiao Y, Sun Q, Lu X, Li Y, Li J.-H. Org. Lett. 2021; 23: 7839
- 6a Goossen LJ, Rodriguez N, Goossen K. Angew. Chem. Int. Ed. 2008; 47: 3100
- 6b Rodriguez N, Goossen LJ. Chem. Soc. Rev. 2011; 40: 5030
- 6c Weaver JD, Recio A III, Grenning AJ, Tunge JA. Chem. Rev. 2011; 111: 1846
- 6d Dzik WI, Lange PP, Goossen LJ. Chem. Sci. 2012; 3: 2671
- 6e Larrosa I, Cornella J. Synthesis 2012; 44: 653
- 6f Park K, Lee S. RSC Adv. 2013; 3: 14165
- 6g Shen C, Zhang P, Sun Q, Bai S, Hor TS, Liu X. Chem. Soc. Rev. 2015; 44: 291
- 7 Zhao W, Wurz RP, Peters JC, Fu GC. J. Am. Chem. Soc. 2017; 139: 12153
- 8 Mao R, Frey A, Balon J, Hu X. Nat. Catal. 2018; 1: 120
- 9 Chandrachud PP, Wojtas L, Lopchuk JM. J. Am. Chem. Soc. 2020; 142: 21743
- 10 Bauer I, Knolker HJ. Chem. Rev. 2015; 115: 3170
- 11a Feng P, Sun X, Su Y, Li X, Zhang LH, Shi X, Jiao N. Org. Lett. 2014; 16: 3388
- 11b Li X.-Q, Wang W.-K, Han Y.-X, Zhang C. Adv. Synth. Catal. 2010; 352: 2588
- 11c Li X.-Q, Wang W.-K, Zhang C. Adv. Synth. Catal. 2009; 351: 2342
- 11d Lwowski W, De Mauriac RA, Thompson M, Wilde RE, Chen S.-Y. J. Org. Chem. 1975; 40: 2608
- 11e Salama TA, Elmorsy SS, Khalil A.-GM, Ismail MA. Chem. Lett. 2011; 40: 1149
- 11f Wei R, Ge L, Bao H, Liao S, Li Y. Synthesis 2019; 51: 4645
- 11g Yadav L, Yadav V, Srivastava V. Synlett 2016; 27: 2826
- 12a Toriyama F, Cornella J, Wimmer L, Chen TG, Dixon DD, Creech G, Baran PS. J. Am. Chem. Soc. 2016; 138: 11132
- 12b Smith JM, Qin T, Merchant RR, Edwards JT, Malins LR, Liu Z, Che G, Shen Z, Shaw SA, Eastgate MD, Baran PS. Angew. Chem. Int. Ed. 2017; 56: 11906
- 13 Montesinos-Magraner M, Costantini M, Ramirez-Contreras R, Muratore ME, Johansson MJ, Mendoza A. Angew. Chem. Int. Ed. 2019; 58: 5930
- 15 Typical Procedure: A flame-dried reaction tube with a magnetic stirring bar was charged with NHP ester 1a (0.5 mmol, 133 mg), ferric acetate (10 mol%, 9.5 mg) and THF (5.0 mL) under a nitrogen atmosphere. TMSN3 (1.5 mmol, 0.2 mL) was then injected into the tube and the mixture was heated at 70 °C (oil bath) for 24 h. After reaction completion as detected by TLC, the solid was removed by filtration and the filtrate was concentrated. The residue was purified by column chromatography (silica gel, PE/EtOAc = 10:1) to afford the carbamoyl azide 2a (73.7 mg, 91% yield) as a white solid; mp 105–106 °C. 1H NMR (600 MHz, CDCl3): δ = 7.42 (d, J = 8.1 Hz, 2 H), 7.35–7.31 (m, 2 H), 7.12 (t, J = 7.4 Hz, 1 H), 6.83 (br, 1 H). 13C NMR (151 MHz, CDCl3): δ = 154.00, 136.95, 129.31, 124.75, 119.27.
