Synlett 2020; 31(07): 708-712
DOI: 10.1055/s-0039-1691596
letter
© Georg Thieme Verlag Stuttgart · New York

Facile Synthesis of Oxime Amino Ethers via Lewis Acid Catalyzed SN2-Type Ring Opening of Activated Aziridines with Aryl Aldehyde Oximes

,
Subhomoy Das
,
Navya Chauhan
,
Pronay K. Biswas
,
M.K.G. is thankful to the Department of Science and Technology (DST), India for financial support. A.B. thanks the Council of Scientific and Industrial Research (CSIR), New Delhi, India for a research fellowship. S.D. and N.C. thank University Grants Commission (UGC), New Delhi, India for Senior Research Fellowships.
Further Information

Publication History

Received: 20 December 2019

Accepted after revision: 21 January 2020

Publication Date:
02 March 2020 (online)

 


Abstract

A simple strategy to access a wide range of substituted oxime amino ethers in good to high yields via Lewis acid catalyzed SN2-type ring opening of activated aziridines with aryl aldehyde oximes is reported.


#

Oxime ethers have been used as valuable synthons for the preparation of a wide spectrum of biologically significant molecular moieties such as chiral α-, β-, and γ-amino acid derivatives,[1] γ-butyrolactones,[2] primary amines,[3] benzofurans,[4] pyrrolidines and piperidines,[5] C-glycosylthreonine and allothreonine,[6] chiral ligands,[7] and α-amino esters.[8] In addition, oxime ethers have also been used as a suitable class of radical acceptors under various photochemical[9] and nonphotochemical conditions,[1b] [c] as auxiliary linkers,[10] as directing group for C–H functionalization,[11] and as coupling partners in annulation reactions with olefins.[12] The available reports for the synthesis of oxime ethers mainly involve etherification of oximes[13] – another valuable functional group in organic synthesis.[14] Dehydrogenative cross-coupling reaction between allylic sp3 C–H bonds with oximes[15] have also been performed to access oxime ethers. In this context, we realized that regio- and stereospecific synthetic routes to functionalized and structurally diverse oxime amino ethers are scarce in the literature which could nonetheless emerge as potential synthons for valuable biologically active compounds.

In recent years, the small-ring aza-heterocycles have emerged as one of the most advantageous building blocks in organic synthesis.[16] We have been working on Lewis acid catalyzed SN2-type ring-opening transformations of activated aziridines and azetidines to access various value-added aza-heterocyclic compounds either by ring-opening cyclization (ROC)[17] or by domino ring-opening cyclization (DROC)[18] strategies. Notably, aziridin-1-yl oximes have drawn attention from the synthetic chemists owing to their cytotoxic activity that make them potential anticancer agents.[19] Its prevalent chemistry involves the intramolecular ring-opening reactions of the aziridine functionality with the hydroxylamine group under suitable reaction conditions.[19] [20] A very few literature reports describe intermolecular ring opening of aziridines with hydroxylamine anions in the presence of a strong base,[21] or with the nitrogen center of the oximes[22] or with α-carbanion of the oxime functionalities.[23] Ring opening of aziridines with nitrones is also documented.[18c] We anticipated that a wide variety of oxime amino ethers could easily be obtained via Lewis acid catalyzed intermolecular SN2-type ring opening of activated aziridines with aryl aldehyde oximes. Herein, we wish to report our preliminary results as a letter.

To test the viability of our approach, we performed a preliminary experiment with the reaction of racemic 2-phenyl-N-tosylaziridine (1a) with 1.5 equivalents of 4-methoxybenzaldehyde oxime (2a) in the presence of 40 mol % Cu(OTf)2 as the Lewis acid in dichloromethane at room temperature. To our delight, the ring opening of the aziridine 1a occurred at the benzylic position, and the corresponding 2-phenyl substituted oxime amino ether derivative 3a was formed in 60% yield as a single regioisomer (Scheme [1]). The molecular structure of 3a was characterized by its spectral and analytical data.[24]

Zoom Image
Scheme 1 Lewis acid catalyzed ring opening of 2-phenyl-N-tosylaziridine (1a) with 4-methoxybenzaldehyde oxime (2a)

Next to optimize the reaction conditions for achieving better yields of the product, several other non-nucleophilic metal salts as the Lewis acids and solvents, such as 1,2-­dichloroethane and tetrahydrofuran, were screened.

Table 1 Optimization Studies for the Lewis Acid Catalyzed Ring Opening of 2-Phenyl-N-tosylaziridine (1a) with 4-Methoxybenzaldehyde Oxime (2a)

Entry

Lewis acid (mol%)

Solvent

Temp

Time

Yield (%)a

1

Cu(OTf)2 (40)

CH2Cl2

rt

10 min

60

2

Cu(OTf)2 (40)

THF

rt

3 h

43

3

Cu(OTf)2 (40)

(CH2)2Cl2

rt

30 min

55

4

Sc(OTf)3 (40)

CH2Cl2

rt

1 h

53

5

Zn(OTf)2 (40)

CH2Cl2

rt

1.5 h

68

6

Yb(OTf)3 (40)

CH2Cl2

rt

2 h

41

7

Mg(OTf)2 (40)

CH2Cl2

rt

24 h

nr

8

BF3⋅OEt2 (40)

CH2Cl2

rt

1 h

76

9

BF3⋅OEt2 (20)

CH2Cl2

0 °C to rt

2 h

83

a Yields of isolated products after column chromatographic purification.

All the results are shown in Table [1]. The use of Cu(OTf)2 furnished the product in short time with moderate yield (entry 1). Changing the solvents from CH2Cl2 to either THF (entry 2) or 1,2-DCE (entry 3) led to the formation of the product 3a with reduced yields. The yield of the reaction further decreased with Sc(OTf)3 (53%, entry 4). Encouraging result was obtained with Zn(OTf)2, and the desired product could be obtained in 68% yield in 1.5 h (entry 5). The use of water-resistant Lewis acid Yb(OTf)3 afforded 3a in poor yield (41%, entry 6). No reaction was observed when a milder Lewis acid such as Mg(OTf)2 was used (entry 7). Notable increase in the yield was observed when 40 mol% BF3·OEt2 was used, and 3a was obtained in 76% yield (entry 8). The best result was obtained with 20 mol % BF3·OEt2 as the Lewis acid at 0 °C to room temperature, and 3a was obtained in 83% yield (entry 9). When the amount of Lewis acid was further decreased, the reaction was found to be sluggish.

Zoom Image
Scheme 2 Ring opening of 2-aryl-N-tosylaziridines 1ai with 4-methoxybenzaldehyde oxime (2a)

To generalize the strategy a wide range of 2-aryl-N-tosylaziridines bearing variety of substitution patterns on the aryl groups under the optimized reaction condition were studied. All the results are tabulated in Scheme [2]. When the aziridine 1b with a strong electron-donating tert-butyl group at the 4-position of the 2-phenyl group was used, the corresponding ring-opened product 3b was formed as a single regioisomer in good yield (64%). Interestingly, when aziridines 1ce bearing halogen groups (F, Cl, and Br) at the 4-position of the 2-phenyl group were reacted, the respective oxime amino ethers 3ce were obtained in high yields. With relatively more sterically constrained aziridines with halogen groups at the 2-position of the 2-phenyl groups 1f (Cl) and 1g (F), the respective oxime amino ethers 3f and 3g were obtained in 67% and 76% yields.

A marginal reduction in yield was observed with 2-(3- halophenyl)-substituted aziridines 1h (Cl) and 1i (F), and the corresponding ring-opened products 3h and 3i were furnished in 71% and 68% yields, respectively.

To study the electronic effect of the N-arylsulfonyl groups, a variety of N-arylsulfonylaziridines 1jm with varying electron-withdrawing ability on the nitrogen were reacted with 4-methoxybenzaldehyde oxime (2a) under the optimized reaction conditions, and the results are shown in Scheme [3].

Zoom Image
Scheme 3 Ring opening of various 2-phenyl-N-arylsulfonylaziridines 1jm with 4-methoxybenzaldehyde oxime (2a)

The N-benzenesulfonyl aziridine 1j reacted smoothly with 2a and furnished the corresponding product 3j in 74% yield. On the other hand, with strong electron-donating groups such as 2,4,6-Me3 (mesityl; 1k), OMe (1l), or t-Bu (1m) attached with the phenylsulfonyl group of the aziridine, the respective oxime amino ethers 3km were formed as single regioisomers in excellent yield (up to 82%).

To further investigate the substrate tolerance, a wide range of aryl aldehyde oximes 2bg were employed as the nucleophiles. Accordingly, when p-halo-substituted benzaldehyde oxime derivatives 2b (F) and 2c (Br) reacted with 1a, the corresponding oxime amino ethers 3n and 3o were obtained in 82% and 76% yields, respectively. The 3-Br variant 2d was also reacted efficiently, and 3p was formed in good yield (73%). When 2e with a nitro group at the 2-position of the aryl group was reacted with 1a, the corresponding product 3q was obtained in 70% yield. Interestingly, when sterically congested 1-naphthaldehyde oxime (2f) and 2-naphthaldehyde oxime (2g) were employed as the nucleophiles, the reactions proceeded well, and the products 3r and 3s were obtained in 72% and 78% yields, respectively, in short time. All the results are summarized in Scheme [4].

Zoom Image
Scheme 4 Ring opening of 2-phenyl-N-tosylaziridine (1a) with various aryl aldehyde oximes 2bg

Additional significance of our protocol was validated in the synthesis of nonracemic oxime amino ether derivative (R)-3a from (S)-1a. As we demonstrated in our earlier reports that the tetraalkylammonium salts could effectively control the racemization process of the enantiopure aziridines during the reaction,[25] we used a number of such salts in stoichiometric amount to enhance the stereospecificity of the product. After several screenings when (S)-1a was treated with 10.0 equivalents of 2a at –40 °C in the presence of 5 mol% Cu(OTf)2 as the Lewis acid and 3.0 equivalents of tetrabutylammonium tetrafluoroborate (TBABF4) as the additive using 1,2-dichloroethane as the solvent, the desired product 3a was obtained in good yield with up to 72% enantiomeric excess (Scheme [5]).

Zoom Image
Scheme 5 Stereospecific synthesis of nonracemic oxime amino ether (R)-3a from (S)-1a

A plausible mechanistic pathway is shown in Scheme [6]. Based on the experimental observations, we propose that the Lewis acid catalyzed ring opening of the activated aziridines with aryl aldehyde oximes proceeds via an SN2-type pathway as demonstrated by us earlier.[17] [18] At first, the Lewis acid gets coordinated with the nitrogen of the aziridine ring (or with the sulfonyl oxygen) and thereby further activates the aziridine towards nucleophilic attack. Then, the oxygen of the oxime functionality attacks at the benzylic position of the aziridine and after protonation/deprotonation produces the corresponding ring-opened product with high stereospecificity.

Zoom Image
Scheme 6 Plausible mechanistic pathway for the formation of oxime amino ethers from activated aziridines and aryl aldehyde oximes

In conclusion, we have developed an operationally simple synthetic route to a wide variety of substituted racemic and nonracemic oxime amino ethers in good to high yields via Lewis acid catalyzed SN2-type ring opening of activated aziridines with aryl aldehyde oximes.[26] We believe that the developed methodology will be useful to the organic and medicinal chemists.


#

Supporting Information

  • References and Notes

    • 1a Ueda M, Miyabe H, Sugino H, Miyata O, Naito T. Angew. Chem. Int. Ed. 2005; 44: 6190
    • 1b Fujino H, Nagatomo M, Paudel A, Panthee S, Hamamoto H, Sekimizu K, Inoue M. Angew. Chem. Int. Ed. 2017; 56: 11865
    • 1c Nagatomo M, Nishiyama H, Fujino H, Inoue M. Angew. Chem. Int. Ed. 2015; 54: 1537
    • 1d Miyabe H, Nishimura A, Ueda M, Naito T. Chem. Commun. 2002; 1454
    • 1e Miyabe H, Fujii K, Naito T. Org. Biomol. Chem. 2003; 1: 381
    • 1f Miyabe H, Konishi C, Naito T. Org. Lett. 2000; 2: 1443
    • 1g Miyata O, Muroya K, Kobayashi T, Yamanaka R, Kajisa S, Koide J, Naito T. Tetrahedron 2002; 58: 4459
  • 2 Miyabe H, Ueda M, Fujii K, Nishimura A, Naito T. J. Org. Chem. 2003; 68: 5618
  • 3 Huang X, Ortiz-Marciales M, Huang K, Stepanenko V, Merced FG, Ayala AM, Correa W, De Jesús M. Org. Lett. 2007; 9: 1793
  • 4 Takeda N, Miyata O, Naito T. Eur. J. Org. Chem. 2007; 1491
  • 5 Miyata O, Takahashi S, Tamura A, Ueda M, Naito T. Tetrahedron 2008; 64: 1270
  • 6 Bragnier N, Guillot R, Scherrmann M.-C. Org. Biomol. Chem. 2009; 7: 3918
  • 7 Cooper TS, Larigo AS, Laurent P, Moody CJ, Takle AK. Org. Biomol. Chem. 2005; 3: 1252
  • 8 Jeon G.-H, Yoon J.-Y, Kim S, Kim SS. Synlett 2000; 128
  • 9 Wu G, Wang J, Liu C, Sun M, Zhang L, Ma Y, Cheng R, Ye J. Org. Chem. Front. 2019; 6: 2245
  • 10 Dong Y, Liu G. J. Org. Chem. 2017; 82: 3864
  • 11 Saha R, Perveen N, Nihesh N, Sekar G. Adv. Synth. Catal. 2019; 361: 510
    • 12a Fu X, Yang J, Deng K, Shao L, Xia C, Ji Y. Org. Lett. 2019; 21: 3505
    • 12b Li Y, Chen H, Qu L.-B, Houk KN, Lan Y. ACS Catal. 2019; 9: 7154
    • 12c Behnke NE, Lovato K, Yousufuddin M, Kürti L. Angew. Chem. 2019; 131: 14357
    • 12d Huang F, Zhang S. Org. Lett. 2019; 21: 7430
    • 13a Cao Z, Liu Z, Liu Y, Du H. J. Org. Chem. 2011; 76: 6401
    • 13b Li C, Zhang H, Cui Y, Zhang S, Zhao Z, Choi MC. K, Chan AS. C. Synth. Commun. 2003; 33: 543
    • 13c Soltani RadM. N, Khalafi-Nezhad A, Karimitabar F, Behrouz S. Synthesis 2010; 1724
    • 13d Jia X, Wang X, Yang C, Da Y, Yang L, Liu Z. Tetrahedron 2009; 65: 2334
    • 13e Zeng H, Zhu C, Jiang H. Org. Lett. 2019; 21: 1130
  • 14 Abele E, Lukevics E. Synthesis of Heterocycles from Oximes. In The Chemistry of Hydroxylamines, Oximes and Hydroxamic Acids. The Chemistry of Functional Groups. Rappoport Z, Liebman JF. John Wiley & Sons; Chichester: 2008: 233
  • 15 Jin J, Li Y, Wang Z.-J, Qian W.-X, Bao W.-L. Eur. J. Org. Chem. 2010; 1235
    • 16a Ghorai MK, Bhattacharyya A, Das S, Chauhan N. Top. Heterocycl. Chem. 2016; 41: 49
    • 16b Dolfen J, De Kimpe N, D’hooghe M. Synlett 2016; 27: 1486
    • 16c Takeda Y, Kuroda A, Sameera WM. C, Morokuma K, Minakata S. Chem. Sci. 2016; 7: 6141
    • 16d Takeda Y, Ikeda Y, Kuroda A, Tanaka S, Minakata S. J. Am. Chem. Soc. 2014; 136: 8544
    • 16e Callebaut G, Meiresonne T, De Kimpe N, Mangelinckx S. Chem. Rev. 2014; 114: 7954
    • 16f Schneider C. Angew. Chem. Int. Ed. 2009; 48: 2082
    • 16g Aziridines and Epoxides in Organic Synthesis. Yudin AK. Wiley-VCH; Weinheim: 2006: 517
    • 16h Stankovic S, D'hooghe M, Catak S, Eum H, Waroquier M, Van Speybroeck V, De Kimpe N, Ha H.-J. Chem. Soc. Rev. 2012; 41: 643
    • 16i Dolfen J, Vervisch K, De Kimpe N, D’hooghe M. Chem. Eur. J. 2016; 22: 4945
    • 16j D’hooghe M, Ha H.-J, Macha L. Synthesis 2019; 51: 1491
    • 16k Remete AM, Kiss L. Eur. J. Org. Chem. 2019; 5574
    • 17a Mal A, Goswami G, Ahmad WaniI, Ghorai MK. Chem. Commun. 2017; 53: 10263
    • 17b Pradhan S, Shahi CK, Bhattacharyya A, Chauhan N, Ghorai MK. Org. Lett. 2017; 19: 3438
    • 17c Shahi CK, Bhattacharyya A, Nanaji Y, Ghorai MK. J. Org. Chem. 2017; 82: 37
    • 17d Pradhan S, Shahi CK, Bhattacharyya A, Ghorai MK. Chem. Commun. 2018; 54: 8583
    • 17e Chauhan N, Pradhan S, Ghorai MK. J. Org. Chem. 2019; 84: 1757
    • 18a Bhattacharyya A, Kavitha CV, Ghorai MK. J. Org. Chem. 2016; 81: 6433
    • 18b Ghorai MK, Tiwari DP. J. Org. Chem. 2013; 78: 2617
    • 18c Wani IA, Sayyad M, Ghorai MK. Chem. Commun. 2017; 53: 4386
    • 18d Mal A, Sayyad M, Wani IA, Ghorai MK. J. Org. Chem. 2017; 82: 4
    • 18e Lin T.-Y, Wu H.-H, Feng J.-J, Zhang J. Org. Lett. 2017; 19: 6526
    • 18f Bhattacharyya A, Shahi CK, Pradhan S, Ghorai MK. Org. Lett. 2018; 20: 2925
    • 19a Nikitjuka A, Jirgensons A. Chem. Heterocycl. Compd. 2014; 49: 1544
    • 19b Nikitjuka A, Shestakova I, Romanchikova N, Jirgensons A. Chem. Heterocycl. Compd. 2015; 51: 647
  • 20 Abele E. Heterocycl. Lett. 2013; 3: 229
  • 21 Tabarki MA, Besbes R. Tetrahedron 2014; 70: 1060
  • 22 Dondas HA, Cummins JE, Grigg R, Thornton-Pett M. Tetrahedron 2001; 57: 7951
  • 23 Chen D.-D, Ding C.-H, Hou X.-L, Dai L.-X. Chem. J. Chin. Univ. 2011; 32: 694
  • 24 See the Supporting Information for details.
  • 25 Ghorai MK, Shukla D, Bhattacharyya A. J. Org. Chem. 2012; 77: 3740
  • 26 Representative Experimental Procedure for the BF3·OEt2-Catalyzed Ring Opening of Aziridines with Aldehyde Oximes (Scheme 2) To a solution of the aziridine 1ai (50 mg, 1.0 equiv) and 4-methoxybenzaldehyde oxime (2a, 1.5 equiv) in 2.0 mL dry dichloromethane was added anhydrous BF3·OEt2 (0.2 equiv) with a microsyringe at 0 °C under an argon atmosphere. The reaction mixture was stirred for an appropriate time (Scheme 2) at an appropriate temperature while the progress of the reaction was monitored by TLC. Upon completion the reaction was quenched with saturated aqueous NaHCO3 solution. The aqueous layer was extracted with CH2Cl2 (3 × 5.0 mL) and it was washed with brine solution. The combined organic layers were dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The crude concentrate was purified by flash column chromatography on silica gel (230–400 mesh) using 10% ethyl acetate in petroleum ether to provide the pure products 3ai.(E)-N-(2-{[(4-methoxybenzylidene)amino]oxy}-2-phenylethyl)-4-methylbenzenesulfonamide (3a)The general method described above was followed when the aziridine 1a (50.0 mg, 0.1829 mmol, 1.0 equiv) was reacted with the 4-methoxybenzaldehyde oxime (2a, 41.5 mg, 0.274 mmol, 1.5 equiv) in the presence of BF3·OEt2 (4.6 μL, 0.037 mmol, 20 mol %) in dichloromethane (2.0 mL) at 0  °C to rt for 2 h to afford the product 3a (64.5 mg, 0.1518 mmol) as a white solid in 83 % yield ; mp 98–100  °C. Rf = 0.30 (EtOAc/petroleum ether, 3:7). IR (KBr): 3283, 2955, 2925, 2854, 1606, 1572, 1513, 1495, 1454, 1419, 1329, 1306, 1252, 1161, 1092, 1063, 1029, 955, 832, 814, 756, 701, 664, 602, 550 cm– 1. 1H NMR (500 MHz, CDCl3): δ = 8.00 (s, 1 H), 7.71 (d, 2 H, J = 8.3 Hz), 7.42 (d, 2 H, J = 8.6 Hz), 7.33–7.23 (m, 7 H), 6.86 (d, 2 H, J = 8.6 Hz), 5.18 (dd, 1 H, J = 8.3, 3.9 Hz), 5.01–4.99 (m, 1 H), 3.82 (s, 3 H), 3.46–3.41 (m, 1 H), 3.37–3.32 (m, 1 H), 2.39 (s, 3 H). 13 C{1 H} NMR (125 MHz, CDCl3): δ = 161.3, 149.7, 143.5, 138.3, 137.0, 129.8, 128.7, 128.6, 128.3, 127.2, 126.7, 124.3, 114.2, 82.9, 55.4, 48.1, 29.8, 21.6. HRMS (ESI-TOF): m/z calcd for C23H25N2O4S [ M + H ]+: 425.1535; found: 425.1529

  • References and Notes

    • 1a Ueda M, Miyabe H, Sugino H, Miyata O, Naito T. Angew. Chem. Int. Ed. 2005; 44: 6190
    • 1b Fujino H, Nagatomo M, Paudel A, Panthee S, Hamamoto H, Sekimizu K, Inoue M. Angew. Chem. Int. Ed. 2017; 56: 11865
    • 1c Nagatomo M, Nishiyama H, Fujino H, Inoue M. Angew. Chem. Int. Ed. 2015; 54: 1537
    • 1d Miyabe H, Nishimura A, Ueda M, Naito T. Chem. Commun. 2002; 1454
    • 1e Miyabe H, Fujii K, Naito T. Org. Biomol. Chem. 2003; 1: 381
    • 1f Miyabe H, Konishi C, Naito T. Org. Lett. 2000; 2: 1443
    • 1g Miyata O, Muroya K, Kobayashi T, Yamanaka R, Kajisa S, Koide J, Naito T. Tetrahedron 2002; 58: 4459
  • 2 Miyabe H, Ueda M, Fujii K, Nishimura A, Naito T. J. Org. Chem. 2003; 68: 5618
  • 3 Huang X, Ortiz-Marciales M, Huang K, Stepanenko V, Merced FG, Ayala AM, Correa W, De Jesús M. Org. Lett. 2007; 9: 1793
  • 4 Takeda N, Miyata O, Naito T. Eur. J. Org. Chem. 2007; 1491
  • 5 Miyata O, Takahashi S, Tamura A, Ueda M, Naito T. Tetrahedron 2008; 64: 1270
  • 6 Bragnier N, Guillot R, Scherrmann M.-C. Org. Biomol. Chem. 2009; 7: 3918
  • 7 Cooper TS, Larigo AS, Laurent P, Moody CJ, Takle AK. Org. Biomol. Chem. 2005; 3: 1252
  • 8 Jeon G.-H, Yoon J.-Y, Kim S, Kim SS. Synlett 2000; 128
  • 9 Wu G, Wang J, Liu C, Sun M, Zhang L, Ma Y, Cheng R, Ye J. Org. Chem. Front. 2019; 6: 2245
  • 10 Dong Y, Liu G. J. Org. Chem. 2017; 82: 3864
  • 11 Saha R, Perveen N, Nihesh N, Sekar G. Adv. Synth. Catal. 2019; 361: 510
    • 12a Fu X, Yang J, Deng K, Shao L, Xia C, Ji Y. Org. Lett. 2019; 21: 3505
    • 12b Li Y, Chen H, Qu L.-B, Houk KN, Lan Y. ACS Catal. 2019; 9: 7154
    • 12c Behnke NE, Lovato K, Yousufuddin M, Kürti L. Angew. Chem. 2019; 131: 14357
    • 12d Huang F, Zhang S. Org. Lett. 2019; 21: 7430
    • 13a Cao Z, Liu Z, Liu Y, Du H. J. Org. Chem. 2011; 76: 6401
    • 13b Li C, Zhang H, Cui Y, Zhang S, Zhao Z, Choi MC. K, Chan AS. C. Synth. Commun. 2003; 33: 543
    • 13c Soltani RadM. N, Khalafi-Nezhad A, Karimitabar F, Behrouz S. Synthesis 2010; 1724
    • 13d Jia X, Wang X, Yang C, Da Y, Yang L, Liu Z. Tetrahedron 2009; 65: 2334
    • 13e Zeng H, Zhu C, Jiang H. Org. Lett. 2019; 21: 1130
  • 14 Abele E, Lukevics E. Synthesis of Heterocycles from Oximes. In The Chemistry of Hydroxylamines, Oximes and Hydroxamic Acids. The Chemistry of Functional Groups. Rappoport Z, Liebman JF. John Wiley & Sons; Chichester: 2008: 233
  • 15 Jin J, Li Y, Wang Z.-J, Qian W.-X, Bao W.-L. Eur. J. Org. Chem. 2010; 1235
    • 16a Ghorai MK, Bhattacharyya A, Das S, Chauhan N. Top. Heterocycl. Chem. 2016; 41: 49
    • 16b Dolfen J, De Kimpe N, D’hooghe M. Synlett 2016; 27: 1486
    • 16c Takeda Y, Kuroda A, Sameera WM. C, Morokuma K, Minakata S. Chem. Sci. 2016; 7: 6141
    • 16d Takeda Y, Ikeda Y, Kuroda A, Tanaka S, Minakata S. J. Am. Chem. Soc. 2014; 136: 8544
    • 16e Callebaut G, Meiresonne T, De Kimpe N, Mangelinckx S. Chem. Rev. 2014; 114: 7954
    • 16f Schneider C. Angew. Chem. Int. Ed. 2009; 48: 2082
    • 16g Aziridines and Epoxides in Organic Synthesis. Yudin AK. Wiley-VCH; Weinheim: 2006: 517
    • 16h Stankovic S, D'hooghe M, Catak S, Eum H, Waroquier M, Van Speybroeck V, De Kimpe N, Ha H.-J. Chem. Soc. Rev. 2012; 41: 643
    • 16i Dolfen J, Vervisch K, De Kimpe N, D’hooghe M. Chem. Eur. J. 2016; 22: 4945
    • 16j D’hooghe M, Ha H.-J, Macha L. Synthesis 2019; 51: 1491
    • 16k Remete AM, Kiss L. Eur. J. Org. Chem. 2019; 5574
    • 17a Mal A, Goswami G, Ahmad WaniI, Ghorai MK. Chem. Commun. 2017; 53: 10263
    • 17b Pradhan S, Shahi CK, Bhattacharyya A, Chauhan N, Ghorai MK. Org. Lett. 2017; 19: 3438
    • 17c Shahi CK, Bhattacharyya A, Nanaji Y, Ghorai MK. J. Org. Chem. 2017; 82: 37
    • 17d Pradhan S, Shahi CK, Bhattacharyya A, Ghorai MK. Chem. Commun. 2018; 54: 8583
    • 17e Chauhan N, Pradhan S, Ghorai MK. J. Org. Chem. 2019; 84: 1757
    • 18a Bhattacharyya A, Kavitha CV, Ghorai MK. J. Org. Chem. 2016; 81: 6433
    • 18b Ghorai MK, Tiwari DP. J. Org. Chem. 2013; 78: 2617
    • 18c Wani IA, Sayyad M, Ghorai MK. Chem. Commun. 2017; 53: 4386
    • 18d Mal A, Sayyad M, Wani IA, Ghorai MK. J. Org. Chem. 2017; 82: 4
    • 18e Lin T.-Y, Wu H.-H, Feng J.-J, Zhang J. Org. Lett. 2017; 19: 6526
    • 18f Bhattacharyya A, Shahi CK, Pradhan S, Ghorai MK. Org. Lett. 2018; 20: 2925
    • 19a Nikitjuka A, Jirgensons A. Chem. Heterocycl. Compd. 2014; 49: 1544
    • 19b Nikitjuka A, Shestakova I, Romanchikova N, Jirgensons A. Chem. Heterocycl. Compd. 2015; 51: 647
  • 20 Abele E. Heterocycl. Lett. 2013; 3: 229
  • 21 Tabarki MA, Besbes R. Tetrahedron 2014; 70: 1060
  • 22 Dondas HA, Cummins JE, Grigg R, Thornton-Pett M. Tetrahedron 2001; 57: 7951
  • 23 Chen D.-D, Ding C.-H, Hou X.-L, Dai L.-X. Chem. J. Chin. Univ. 2011; 32: 694
  • 24 See the Supporting Information for details.
  • 25 Ghorai MK, Shukla D, Bhattacharyya A. J. Org. Chem. 2012; 77: 3740
  • 26 Representative Experimental Procedure for the BF3·OEt2-Catalyzed Ring Opening of Aziridines with Aldehyde Oximes (Scheme 2) To a solution of the aziridine 1ai (50 mg, 1.0 equiv) and 4-methoxybenzaldehyde oxime (2a, 1.5 equiv) in 2.0 mL dry dichloromethane was added anhydrous BF3·OEt2 (0.2 equiv) with a microsyringe at 0 °C under an argon atmosphere. The reaction mixture was stirred for an appropriate time (Scheme 2) at an appropriate temperature while the progress of the reaction was monitored by TLC. Upon completion the reaction was quenched with saturated aqueous NaHCO3 solution. The aqueous layer was extracted with CH2Cl2 (3 × 5.0 mL) and it was washed with brine solution. The combined organic layers were dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The crude concentrate was purified by flash column chromatography on silica gel (230–400 mesh) using 10% ethyl acetate in petroleum ether to provide the pure products 3ai.(E)-N-(2-{[(4-methoxybenzylidene)amino]oxy}-2-phenylethyl)-4-methylbenzenesulfonamide (3a)The general method described above was followed when the aziridine 1a (50.0 mg, 0.1829 mmol, 1.0 equiv) was reacted with the 4-methoxybenzaldehyde oxime (2a, 41.5 mg, 0.274 mmol, 1.5 equiv) in the presence of BF3·OEt2 (4.6 μL, 0.037 mmol, 20 mol %) in dichloromethane (2.0 mL) at 0  °C to rt for 2 h to afford the product 3a (64.5 mg, 0.1518 mmol) as a white solid in 83 % yield ; mp 98–100  °C. Rf = 0.30 (EtOAc/petroleum ether, 3:7). IR (KBr): 3283, 2955, 2925, 2854, 1606, 1572, 1513, 1495, 1454, 1419, 1329, 1306, 1252, 1161, 1092, 1063, 1029, 955, 832, 814, 756, 701, 664, 602, 550 cm– 1. 1H NMR (500 MHz, CDCl3): δ = 8.00 (s, 1 H), 7.71 (d, 2 H, J = 8.3 Hz), 7.42 (d, 2 H, J = 8.6 Hz), 7.33–7.23 (m, 7 H), 6.86 (d, 2 H, J = 8.6 Hz), 5.18 (dd, 1 H, J = 8.3, 3.9 Hz), 5.01–4.99 (m, 1 H), 3.82 (s, 3 H), 3.46–3.41 (m, 1 H), 3.37–3.32 (m, 1 H), 2.39 (s, 3 H). 13 C{1 H} NMR (125 MHz, CDCl3): δ = 161.3, 149.7, 143.5, 138.3, 137.0, 129.8, 128.7, 128.6, 128.3, 127.2, 126.7, 124.3, 114.2, 82.9, 55.4, 48.1, 29.8, 21.6. HRMS (ESI-TOF): m/z calcd for C23H25N2O4S [ M + H ]+: 425.1535; found: 425.1529

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Scheme 1 Lewis acid catalyzed ring opening of 2-phenyl-N-tosylaziridine (1a) with 4-methoxybenzaldehyde oxime (2a)
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Scheme 2 Ring opening of 2-aryl-N-tosylaziridines 1ai with 4-methoxybenzaldehyde oxime (2a)
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Scheme 3 Ring opening of various 2-phenyl-N-arylsulfonylaziridines 1jm with 4-methoxybenzaldehyde oxime (2a)
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Scheme 4 Ring opening of 2-phenyl-N-tosylaziridine (1a) with various aryl aldehyde oximes 2bg
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Scheme 5 Stereospecific synthesis of nonracemic oxime amino ether (R)-3a from (S)-1a
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Scheme 6 Plausible mechanistic pathway for the formation of oxime amino ethers from activated aziridines and aryl aldehyde oximes