CC BY-ND-NC 4.0 · SynOpen 2019; 03(04): 91-95
DOI: 10.1055/s-0037-1611922
letter
Copyright with the author(s) (2019) The author(s)

Copper-Catalyzed Amination of Vinyl Azides to α-Ketoamides

Yu Wang
a  School of Chemistry and Environmental Engineering, Yancheng Teachers University, Yancheng224007, P. R. of China   Email: fangzhongxue120@163.com
,
Dongling Zhang
a  School of Chemistry and Environmental Engineering, Yancheng Teachers University, Yancheng224007, P. R. of China   Email: fangzhongxue120@163.com
,
Kaining Zhang
b  College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, P. R. of China   Email: liuzhenhua2012@163.com
,
Zhenhua Liu
b  College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, P. R. of China   Email: liuzhenhua2012@163.com
,
Jing Lin
a  School of Chemistry and Environmental Engineering, Yancheng Teachers University, Yancheng224007, P. R. of China   Email: fangzhongxue120@163.com
,
Wei Cao
a  School of Chemistry and Environmental Engineering, Yancheng Teachers University, Yancheng224007, P. R. of China   Email: fangzhongxue120@163.com
,
a  School of Chemistry and Environmental Engineering, Yancheng Teachers University, Yancheng224007, P. R. of China   Email: fangzhongxue120@163.com
› Author Affiliations
The authors wish to thank the National Natural Science Foundation of China (21605097), the Natural Science Foundation of Shandong Province of China (ZR2016BQ01), the China Postdoctoral Science Foundation (2017M610442), and The Natural Science Foundation of the Jiangsu Higher Education Institutions of China (18KJB610021).
Further Information

Publication History

Received: 01 July 2019

Accepted after revision: 19 August 2019

Publication Date:
02 October 2019 (online)

 

Abstract

An efficient approach for the amination of vinyl azides with N,N-dialkylacylamides has been developed. By using this protocol, structurally important α-ketoamides can be easily synthesized. The key to success is not only the introduction of a Cu(I)/oxygen catalytic system but also the utilization of t-BuOCl and benzoic acid as additives. The reaction is operationally simple, scalable, and displays broad scope and functional group tolerance. A possible mechanism involving copper-catalyzed oxidative generation of peroxide radicals is proposed.


#

Vinyl azides are a class of unique functionalized alkenes with high intrinsic reactivity.[1] The numerous transformations of vinyl azides provide reliable synthetic approaches to diverse, structurally distinct molecular frameworks, including hetero/carbocycles,[2] amides,[3] ketones,[4] and 2H-azirines.[5] Recently, Wu and Liu[6] described an efficient and mild method for the synthesis of various α-fluoroketones from the corresponding vinyl azides by using Selectfluor® as the fluorine source (Scheme [1a]). Additionally Chiba[7] and Liu,[4a] respectively, disclosed radical trifluoromethylation of vinyl azides with Me3SiCF3, to allow construction of α-trifluoromethyl azines, which could be further converted into α-trifluoromethyl ketones (Scheme [1b]). Bi and co-workers presented a radical-induced enamination of vinyl azides that proceeded with electron-withdrawing substrates, and a variety of β-functionalized primary enamines, including β-nitro, acyl, and sulfonyl derivatives, could be prepared, which were successfully transformed into a series of α-functionalized ketones (Scheme [1c]).[8] However, with respect to the construction of α-functionalized ketones, these methods usually suffer from disadvantages such as tedious multistep operations or harsh conditions. In a continuation of our efforts on the construction of C–N bond reactions,[9] we herein report a novel radical amination of vinyl azides using a copper catalyst, to afford a series of α-ketoamides (Scheme [1]). To our knowledge, this is the first example of the conversion of vinyl azides into α-ketoamides, which are important units in biologically active molecules, synthetic drugs, and drug candidates.[10]

Zoom Image
Scheme 1 Transformations of vinyl azides

For the optimization of the reaction conditions, we carried out the reaction of vinyl azide 1a and N,N-dimethylformamide (DMF; 2a), as model substrates for the amination reaction, to screen different catalysts, solvents and additives (Table [1]). Firstly, when CuI was used as the catalyst in DMF as the solvent at 100 °C for 5 h under an oxygen atmosphere, the corresponding α-ketoamide 3a was obtained in 67% yield (entry 1). Using CuBr as the catalyst also gave a comparable yield under similar conditions (entry 2). Other metal catalysts, such as CuCl2, NiCl2, or Ag2CO3, gave either low yields or trace amounts of the desired product 3a (entries 3–5). Subsequent solvent screening demonstrated that DMF was the best choice; solvents, such as toluene, ethylene glycol, and nitromethane resulted in no desired product (entries 6–8). The use of additives, such as m-CPBA, TBHP or BPO, did not improve the efficiency of the reaction (entries 9–11). However, the addition of acids (HBF4 or benzoic acid) did improve the efficiency of the reaction, affording 3a in 70% and 88% yields, respectively (entries 12 and 13). The reaction failed to occur in the absence of either the catalyst or additive (entries 14 and 15).

Table 1 Optimization of the Reaction Conditionsa

Entry

Catalyst

Solvent

Additive

Yield (%)b

1

CuI

DMF

t-BuOCl

67

2

CuBr

DMF

t-BuOCl

56

3

CuCl2

DMF

t-BuOCl

trace

4

NiCl2

DMF

t-BuOCl

19

5

Ag2CO3

DMF

t-BuOCl

20

6

CuI

toluene

t-BuOCl

0

7

CuI

EG

t-BuOCl

0

8

CuI

MeNO2

t-BuOCl

0

9

CuI

DMF

m-CPBA

26

10

CuI

DMF

TBHP

53

11

CuI

DMF

BPO

38

12

CuI

DMF

t-BuOCl + HBF4 c

70

13

CuI

DMF

t-BuOCl + PhCO2Hc

88

14

DMF

t-BuOCl + PhCO2Hc

0

15

CuI

DMF

0

a Reaction conditions: 1a (0.5 mmol), 2a (0.75 mmol), catalyst (0.15 mmol), solvent (1.0 mL), additive (1.0 mmol), O2 atmosphere, 100 °C, 5 h.

b Isolated yield.

c Acid (1.0 mmol).

With the optimized reaction conditions in hand (Table [1], entry 13), the generality of this α-ketoamide synthesis was examined by using a series of vinyl azides to react with DMF (Scheme [2]). α-Aryl-substituted vinyl azides were readily transformed into the corresponding α-ketoamides 3an in moderate to excellent yields. Electron-donating groups in the para-position of the aromatic ring were well tolerated, leading to the corresponding products 3ae in good to excellent yields. Likewise, vinyl azides possessing aryl substituents bearing electron-withdrawing groups, such as -F, -Cl, -Br, -CHO, and -CO2Me, afforded the desired α-ketoamides 3fj in 79–90% yield. Note that vinyl azides bearing heteroaromatic substituents such as thienyl could be smoothly incorporated onto α-ketoamide 3k in 88% yield. Moreover, vinyl azide derivatives bearing a variety of substitutions in the meta-position of the aryl ring, including both electron-donating and electron-withdrawing groups, were well tolerated; thereby affording the functionalized α-ketoamides 3ln in 69−87% yields.

Zoom Image
Scheme 2 Substrate scope for the reaction of vinyl azides with DMF (used as both solvent and reactant)

To investigate the applicability of this protocol further, N,N-diethyl-α-ketoamide products 4af were prepared using vinyl azides 1 and N,N-diethylformamide (2b) as the substrates under the optimized conditions (Scheme [3]). Vinyl­ azides 1af with aromatic substituents, including aryl and heteroaryl groups, underwent the reaction smoothly to give the desired products 4af in 77−93% yield.

Zoom Image
Scheme 3 Substrate scope for the reaction of vinyl azides with N,N-diethylformamide. Reaction conditions: 1 (0.5 mmol), 2 (1.0 mL), CuI (0.15 mmol), PhCO2H (1.0 mmol), t-BuOCl (1.0 mmol), O2 atmosphere, 100 °C, 5 h.

Encouraged by these results, we next turned our attention to other representative nitrogen sources (Table [2]). Indeed, not only DMF (2a) and N,N-diethylformamide (2b) but also N,N-dimethylacetamide (DMA) and N,N-dimethylpropylamide (DMP) were tolerated under the standard conditions, with the resultant α-ketoamide products being obtained in slightly lower yields (entries 1–4). In addition, the long chain N,N-dimethylbutylamide (DMB) was also examined, although no desired product was detected (entry 5).

Table 2 Substrate Scope for the Reaction of Vinyl Azides with N,N-Dimethyl Substratesa

Entry

Substrate

Product

Yield (%)b

1

3a

51

2

3b

44

3

3g

55

4

DMPA

3a

20

5

DMB

3a

0

a Reaction conditions: 1 (0.5 mmol), 2 (1.0 mL), CuI (0.15 mmol), PhCO2H (1.0 mmol), t-BuOCl (1.0 mmol), O2 atmosphere, 100 °C, 5 h.

b Isolated yield.

To elucidate a plausible reaction mechanism for this transformation, some potential intermediates were prepared and tested under the standard conditions (Table [1], entry 13). Vinyl azide 1a′ did not afford benzamide 3a under the standard conditions (Scheme [4a]), although 3-phenyl-2H-azirine (1b′), N-(1-phenylvinyl)acetamide (1c′), and 2-chloro-1-phenylethan-1-one (1d′) all afforded 3a in good yields (Scheme [4b–d]). 2-(Diethylamino)-1-phenylethan-1-one (1e′) did not react under the standard conditions (Scheme [4e]),[11] nor did dimethylamine (2a′; Scheme [4f]). Interestingly, the addition of the radical scavengers 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or 2,6-di-tert-butyl-p-cresol (BHT) suppressed the reaction, which indicates that free radical intermediates could be involved in this transformation (Scheme [4g]). Notably, only 20% yield of 3a was observed under an argon atmosphere, suggesting that oxygen is required to oxidize the catalyst in preparation for another cycle (Scheme [4g]). These control experiments indicate that the vinyl azide substrate possibly reacts with the t-BuOCl as the electrophile and then undergoes oxidation catalyzed by the Cu/O2 system.

Zoom Image
Scheme 4 Control experiments

According to previous reports and considering the above results,[2e] [12] a possible mechanism for this amination reaction is proposed in Scheme [5]. Initially, the vinyl azide 1a undergoes thermal decomposition into a highly strained three-membered cyclic imine (2H-azirine A) that reacts with the Cu(I) catalyst and t-BuOCl to form Cu(II) imine B, which is then converted into Cu(II) imine C.[2e] [13] Radical intermediate E would be formed via Cu(III) peroxide radical D, which could be generated by a combination of molecular oxygen with Cu(II) imine C. Subsequent reductive elimination of radical intermediate E gives intermediate F and regenerates the active Cu(I) species. Finally, α-ketoamide 3a is obtained through acid hydrolysis of intermediate F.

Zoom Image
Scheme 5 Proposed mechanism

The potential synthetic applicability of this method was investigated on a gram scale by using the model reaction. As shown in Scheme [6, 1].54 g of α-ketoamide 3a was isolated in 87% yield without any significant loss of efficiency, demonstrating the potential of this methodology for large-scale synthesis of α-ketoamide derivatives.

Zoom Image
Scheme 6 Gram-scale experiment

In conclusion, we have developed a general and efficient method for the synthesis of α-ketoamides from vinyl azides with N,N-dialkylacylamide as the nitrogen source.[14] The key to success is not only the introduction of a Cu/O2 catalytic system but also the use of t-BuOCl and benzoic acid as additives. This method features readily accessible substrates, commercially available and inexpensive reagents, and mild conditions. This mild catalytic reaction demonstrates a broad substrate scope and high functional group tolerance. A possible mechanism involving copper-catalyzed oxidative generation of peroxide radicals is proposed. The reaction can be effectively scaled up and the product conveniently obtained in a one-pot process. Efforts to further clarify the mechanism and to expand the application of vinyl azides are under way in our laboratory.


#
  • References and Notes


    • For recent progress in the synthesis of vinyl azides, see:
    • 1a Liu Z, Liu J, Zhang L, Liao P, Song J, Bi X. Angew. Chem. Int. Ed. 2014; 53: 5305
    • 1b Liu Z, Liao P, Bi X. Org. Lett. 2014; 16: 3668
    • 2a Lopez E, Lopez L. Angew. Chem. Int. Ed. 2017; 56: 5121
    • 2b Shu W, Lorente A, Gómez-Bengoa E, Nevado C. Nat. Commun. 2017; 8: 13832
    • 2c Wang Y.-F, Toh KK, Ng EP. J, Chiba S. J. Am. Chem. Soc. 2011; 133: 6411
    • 2d Wang Y.-F, Chiba S. J. Am. Chem. Soc. 2009; 131: 12570
    • 2e Wang Y.-F, Toh KK, Lee J.-Y, Chiba S. Angew. Chem. Int. Ed. 2011; 50: 5927
    • 3a Lin C, Shen Y, Huang B, Liu Y, Cui S. J. Org. Chem. 2017; 82: 3950
    • 3b Zhang Z, Kumar RK, Li G, Wu D, Bi X. Org. Lett. 2015; 17: 6190
    • 3c Zhang F.-L, Wang Y.-F, Lonca GH, Zhu X, Chiba S. Angew. Chem. Int. Ed. 2014; 53: 4390
    • 3d Qin C, Feng P, Ou Y, Shen T, Wang T, Jiao N. Angew. Chem. Int. Ed. 2013; 52: 7850
    • 4a Qin H.-T, Wu S.-W, Liu J.-L, Liu F. Chem. Commun. 2017; 53: 1696
    • 4b Chen W, Liu X, Chen E, Chen B, Shao J, Yu Y. Org. Chem. Front. 2017; 4: 1162
    • 5a Xu H.-D, Zhou H, Pan Y.-P, Ren X.-T, Wu H, Han M, Han R.-Z, Shen M.-H. Angew. Chem. Int. Ed. 2016; 55: 2540
    • 5b Farney EP, Yoon TP. Angew. Chem. Int. Ed. 2014; 53: 793
  • 6 Wu S.-W, Liu F. Org. Lett. 2016; 18: 3642
  • 7 Wang Y.-F, Lonca GH, Chiba S. Angew. Chem. Int. Ed. 2014; 53: 1067
  • 8 Ning Y, Zhao X.-F, Wu Y.-B, Bi X. Org. Lett. 2017; 19: 6240
    • 9a Wang Y, Wei C, Tang R, Zhan H, Lin J, Liu Z, Tao W, Fang Z. Org. Biomol. Chem. 2018; 16: 6191
    • 9b Fang Z, Feng Y, Dong H, Li D, Tang T. Chem. Commun. 2016; 52: 11120
    • 9c Liu J, Fang Z, Zhang Q, Liu Q, Bi X. Angew. Chem. Int. Ed. 2013; 125: 7091
    • 9d Fang Z, Yuan H, Liu Y, Tong Z, Li H, Yang J, Barry B.-D, Liu J, Liao P, Zhang J, Liu Q, Bi X. Chem. Commun. 2012; 48: 8802
    • 9e Wang K, Bi X, Xing S, Liao P, Fang Z, Meng X, Zhang Q, Liu Q, Ji Y. Green Chem. 2011; 13: 562
    • 10a Blackburn EA, Walkinshaw MD. Curr. Opin. Pharmacol. 2011; 11: 365
    • 10b Álvarez S, Álvarez R, Khanwalkar H, Germain P, Lemaire G, Rodríguez-Barrios F, Gronemeyer H, de Lera AR. Bioorg. Med. Chem. 2009; 17: 4345
    • 10c Avolio S, Robertson K, Hernando JI. M, DiMuzio J, Summa V. Bioorg. Med. Chem. Lett. 2009; 19: 2295
    • 10d Knust H, Nettekoven M, Pinard E, Roche O, Rogers-Evans M. PCT Int. Appl. WO 2009016087, 2009
    • 10e Njoroge F, Chen KX, Shih N.-Y, Piwinski JJ. Acc. Chem. Res. 2008; 41: 50
    • 10f De Clercq E. Nat. Rev. Drug Discovery 2007; 6: 1001
  • 11 Liang S, Zeng C.-C, Tian H.-Y, Sun B.-G, Luo X.-G, Ren F.-Z. J. Org. Chem. 2016; 81: 11565
    • 12a Hayashi H, Kaga A, Chiba S. J. Org. Chem. 2017; 82: 11981
    • 12b Liu H, Feng M, Jiang X. Chem. Asian J. 2014; 9: 3360
    • 12c Ding S, Jiao N. Angew. Chem. Int. Ed. 2012; 51: 9226
    • 12d Liu Z.-Q, Zhao L, Shang X, Cui Z. Org. Lett. 2012; 14: 3218
    • 12e Rolff M, Schottenheim J, Decker H, Tuczek F. Chem. Soc. Rev. 2011; 40: 4077
    • 12f Too PC, Chua SH, Wong SH, Chiba S. J. Org. Chem. 2011; 76: 6159
    • 12g Chiba S, Zhang L, Ang GY, Hui BW.-Q. Org. Lett. 2010; 12: 2052
    • 12h Que LJ, Tolman WB. Nature 2008; 455: 333
    • 12i Cramer CJ, Tolman WB. Acc. Chem. Res. 2007; 40: 601
    • 12j Arends I, Gamez P, Sheldon RA. Adv. Inorg. Chem. 2006; 58: 235
    • 12k Mirica LM, Vance M, Rudd DJ, Hedman B, Hodgson KO, Solomon EI, Stack TD. P. Science 2005; 308: 1890
    • 12l Prigge ST, Eipper BA, Mains RE, Amzel LM. Science 2004; 304: 864
    • 12m Wang Y, DuBios JL, Hedman B, Hodgson KO, Stack TD. P. Science 1998; 279: 537
    • 12n Manis PA, Rathke MW. J. Org. Chem. 1980; 45: 4952
  • 13 Fu J, Zanoni G, Anderson EA, Bi X. Chem. Soc. Rev. 2017; 46: 7208
  • 14 Synthesis of 4a; Typical Procedure: To a solution of α-azido styrene (1a; 72.5 mg, 0.5 mmol), tert-butyl hypochlorite (113.1 μL, 1.0 mmol), and benzoic acid (122.1 mg, 1.0 mmol) in N,N-diethylformamide (2b; 1 mL) at room temperature, CuI (28.6 mg, 0.15 mmol) was added. The reaction mixture was heated at 100 °C and stirred for 5 h under an oxygen atmosphere, when TLC analysis confirmed that substrate 1a had been consumed. The resulting reaction mixture was cooled to room temperature and K2CO3 was added. The mixture was extracted with dichloromethane (3 × 15 mL), and the combined organic extracts were washed with brine (3 × 40 mL), dried over MgSO4, filtered and concentrated. Purification of the crude product by flash column chromatography (silica gel; petroleum ether) afforded 4a (77% yield) as a yellow oil. N,N-Diethyl-2-oxo-2-phenylacetamide (4a): 1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 7.1 Hz, 2 H), 7.64 (t, J = 7.4 Hz, 1 H), 7.51 (t, J = 7.7 Hz, 2 H), 3.61–3.53 (m, 2 H), 3.29–3.20 (m, 2 H), 1.29 (t, J = 7.2 Hz, 3 H), 1.16 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 191.5, 166.7, 134.5, 133.2, 129.6, 128.9, 42.0, 38.7, 14.0, 12.8. HRMS (ESI): m/z [M + H]+ calcd for C12H15NO2: 206.1181; found: 206.1142.

  • References and Notes


    • For recent progress in the synthesis of vinyl azides, see:
    • 1a Liu Z, Liu J, Zhang L, Liao P, Song J, Bi X. Angew. Chem. Int. Ed. 2014; 53: 5305
    • 1b Liu Z, Liao P, Bi X. Org. Lett. 2014; 16: 3668
    • 2a Lopez E, Lopez L. Angew. Chem. Int. Ed. 2017; 56: 5121
    • 2b Shu W, Lorente A, Gómez-Bengoa E, Nevado C. Nat. Commun. 2017; 8: 13832
    • 2c Wang Y.-F, Toh KK, Ng EP. J, Chiba S. J. Am. Chem. Soc. 2011; 133: 6411
    • 2d Wang Y.-F, Chiba S. J. Am. Chem. Soc. 2009; 131: 12570
    • 2e Wang Y.-F, Toh KK, Lee J.-Y, Chiba S. Angew. Chem. Int. Ed. 2011; 50: 5927
    • 3a Lin C, Shen Y, Huang B, Liu Y, Cui S. J. Org. Chem. 2017; 82: 3950
    • 3b Zhang Z, Kumar RK, Li G, Wu D, Bi X. Org. Lett. 2015; 17: 6190
    • 3c Zhang F.-L, Wang Y.-F, Lonca GH, Zhu X, Chiba S. Angew. Chem. Int. Ed. 2014; 53: 4390
    • 3d Qin C, Feng P, Ou Y, Shen T, Wang T, Jiao N. Angew. Chem. Int. Ed. 2013; 52: 7850
    • 4a Qin H.-T, Wu S.-W, Liu J.-L, Liu F. Chem. Commun. 2017; 53: 1696
    • 4b Chen W, Liu X, Chen E, Chen B, Shao J, Yu Y. Org. Chem. Front. 2017; 4: 1162
    • 5a Xu H.-D, Zhou H, Pan Y.-P, Ren X.-T, Wu H, Han M, Han R.-Z, Shen M.-H. Angew. Chem. Int. Ed. 2016; 55: 2540
    • 5b Farney EP, Yoon TP. Angew. Chem. Int. Ed. 2014; 53: 793
  • 6 Wu S.-W, Liu F. Org. Lett. 2016; 18: 3642
  • 7 Wang Y.-F, Lonca GH, Chiba S. Angew. Chem. Int. Ed. 2014; 53: 1067
  • 8 Ning Y, Zhao X.-F, Wu Y.-B, Bi X. Org. Lett. 2017; 19: 6240
    • 9a Wang Y, Wei C, Tang R, Zhan H, Lin J, Liu Z, Tao W, Fang Z. Org. Biomol. Chem. 2018; 16: 6191
    • 9b Fang Z, Feng Y, Dong H, Li D, Tang T. Chem. Commun. 2016; 52: 11120
    • 9c Liu J, Fang Z, Zhang Q, Liu Q, Bi X. Angew. Chem. Int. Ed. 2013; 125: 7091
    • 9d Fang Z, Yuan H, Liu Y, Tong Z, Li H, Yang J, Barry B.-D, Liu J, Liao P, Zhang J, Liu Q, Bi X. Chem. Commun. 2012; 48: 8802
    • 9e Wang K, Bi X, Xing S, Liao P, Fang Z, Meng X, Zhang Q, Liu Q, Ji Y. Green Chem. 2011; 13: 562
    • 10a Blackburn EA, Walkinshaw MD. Curr. Opin. Pharmacol. 2011; 11: 365
    • 10b Álvarez S, Álvarez R, Khanwalkar H, Germain P, Lemaire G, Rodríguez-Barrios F, Gronemeyer H, de Lera AR. Bioorg. Med. Chem. 2009; 17: 4345
    • 10c Avolio S, Robertson K, Hernando JI. M, DiMuzio J, Summa V. Bioorg. Med. Chem. Lett. 2009; 19: 2295
    • 10d Knust H, Nettekoven M, Pinard E, Roche O, Rogers-Evans M. PCT Int. Appl. WO 2009016087, 2009
    • 10e Njoroge F, Chen KX, Shih N.-Y, Piwinski JJ. Acc. Chem. Res. 2008; 41: 50
    • 10f De Clercq E. Nat. Rev. Drug Discovery 2007; 6: 1001
  • 11 Liang S, Zeng C.-C, Tian H.-Y, Sun B.-G, Luo X.-G, Ren F.-Z. J. Org. Chem. 2016; 81: 11565
    • 12a Hayashi H, Kaga A, Chiba S. J. Org. Chem. 2017; 82: 11981
    • 12b Liu H, Feng M, Jiang X. Chem. Asian J. 2014; 9: 3360
    • 12c Ding S, Jiao N. Angew. Chem. Int. Ed. 2012; 51: 9226
    • 12d Liu Z.-Q, Zhao L, Shang X, Cui Z. Org. Lett. 2012; 14: 3218
    • 12e Rolff M, Schottenheim J, Decker H, Tuczek F. Chem. Soc. Rev. 2011; 40: 4077
    • 12f Too PC, Chua SH, Wong SH, Chiba S. J. Org. Chem. 2011; 76: 6159
    • 12g Chiba S, Zhang L, Ang GY, Hui BW.-Q. Org. Lett. 2010; 12: 2052
    • 12h Que LJ, Tolman WB. Nature 2008; 455: 333
    • 12i Cramer CJ, Tolman WB. Acc. Chem. Res. 2007; 40: 601
    • 12j Arends I, Gamez P, Sheldon RA. Adv. Inorg. Chem. 2006; 58: 235
    • 12k Mirica LM, Vance M, Rudd DJ, Hedman B, Hodgson KO, Solomon EI, Stack TD. P. Science 2005; 308: 1890
    • 12l Prigge ST, Eipper BA, Mains RE, Amzel LM. Science 2004; 304: 864
    • 12m Wang Y, DuBios JL, Hedman B, Hodgson KO, Stack TD. P. Science 1998; 279: 537
    • 12n Manis PA, Rathke MW. J. Org. Chem. 1980; 45: 4952
  • 13 Fu J, Zanoni G, Anderson EA, Bi X. Chem. Soc. Rev. 2017; 46: 7208
  • 14 Synthesis of 4a; Typical Procedure: To a solution of α-azido styrene (1a; 72.5 mg, 0.5 mmol), tert-butyl hypochlorite (113.1 μL, 1.0 mmol), and benzoic acid (122.1 mg, 1.0 mmol) in N,N-diethylformamide (2b; 1 mL) at room temperature, CuI (28.6 mg, 0.15 mmol) was added. The reaction mixture was heated at 100 °C and stirred for 5 h under an oxygen atmosphere, when TLC analysis confirmed that substrate 1a had been consumed. The resulting reaction mixture was cooled to room temperature and K2CO3 was added. The mixture was extracted with dichloromethane (3 × 15 mL), and the combined organic extracts were washed with brine (3 × 40 mL), dried over MgSO4, filtered and concentrated. Purification of the crude product by flash column chromatography (silica gel; petroleum ether) afforded 4a (77% yield) as a yellow oil. N,N-Diethyl-2-oxo-2-phenylacetamide (4a): 1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 7.1 Hz, 2 H), 7.64 (t, J = 7.4 Hz, 1 H), 7.51 (t, J = 7.7 Hz, 2 H), 3.61–3.53 (m, 2 H), 3.29–3.20 (m, 2 H), 1.29 (t, J = 7.2 Hz, 3 H), 1.16 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 191.5, 166.7, 134.5, 133.2, 129.6, 128.9, 42.0, 38.7, 14.0, 12.8. HRMS (ESI): m/z [M + H]+ calcd for C12H15NO2: 206.1181; found: 206.1142.

Zoom Image
Scheme 1 Transformations of vinyl azides
Zoom Image
Scheme 2 Substrate scope for the reaction of vinyl azides with DMF (used as both solvent and reactant)
Zoom Image
Scheme 3 Substrate scope for the reaction of vinyl azides with N,N-diethylformamide. Reaction conditions: 1 (0.5 mmol), 2 (1.0 mL), CuI (0.15 mmol), PhCO2H (1.0 mmol), t-BuOCl (1.0 mmol), O2 atmosphere, 100 °C, 5 h.
Zoom Image
Scheme 4 Control experiments
Zoom Image
Scheme 5 Proposed mechanism
Zoom Image
Scheme 6 Gram-scale experiment