Direct Amination of Benzylic Pinacol Boronates by an Aminoazanium

Abstract

A practical stereospecific direct amination of benzylic pinacol boronates was achieved by using 4-amino-4-methylmorpholinium iodide as a new amination reagent and cesium carbonate as the base. After amination, an in situ reductive N-alkylation with an aldehyde proceeded well to produce secondary amines.

Key words

benzylic pinacol boronates - amination - asymmetric synthesis - secondary amines - aminomethylmorpholinium iodide

Publication History

Received: 19 December 2022

Accepted after revision: 03 February 2023

Accepted Manuscript online:
03 February 2023

Article published online:
28 February 2023

• References and Notes

• 1 Sandford C, Aggarwal VK. Chem. Commun. 2017; 53: 5481
• 2 Roscales S, Csáky AG. Chem. Soc. Rev. 2020; 49: 5159
• 3 Yang R.-Y, Dai L.-X. Synthesis 1993; 481
• 4a Brown HC, Heydkamp WR, Breuer E, Murphy WS. J. Am. Chem. Soc. 1964; 86: 3565
• 4b Davies AG, Hook SC. W, Roberts BP. J. Organomet. Chem. 1970; 23: C11
• 4c Zhou Z, Kweon J, Jung H, Kim D, Seo S, Chang S. J. Am. Chem. Soc. 2022; 144: 9161
• 5a Bagutski V, Elford TG, Aggarwal VK. Angew. Chem. Int. Ed. 2011; 50: 1080
• 5b Brown HC, Midland MM, Levy AB. J. Am. Chem. Soc. 1973; 95: 2394
• 5c Brown HC, Salunkhe AM, Singaram B. J. Org. Chem. 1991; 56: 1170
• 5d Brown HC, Suzui A, Sonao S, Itoh M, Midland MM. J. Am. Chem. Soc. 1971; 93: 4329
• 5e Kabalka GW, Henderson DA, Varma RS. Organometallics 1987; 6: 1369
• 6a Phanstiel OI, Wang QX, Powell DH, Ospina MP, Leeson BA. J. Org. Chem. 1999; 64: 803
• 6b Tamura Y, Minamikawa J, Fujii S, Ikeda M. Synthesis 1974; 196
• 6c Xiao Q, Tian L, Tan R, Xia Y, Qiu D, Zhang Y, Wang J. Org. Lett. 2012; 14: 4230
• 6d Zhu C, Li G, Ess DH, Falck JR, Kürti L. J. Am. Chem. Soc. 2012; 134: 18253
• 6e Kumar P, Verma S, Rathi K, Chandra D, Prakash Verma V, Jat JL. Eur. J. Org. Chem. 2022; e202200508
• 7a Lennox AJ, Lloyd-Jones GC. Chem. Soc. Rev. 2014; 43: 412
• 7b Synthesis and Application of Organoboron Compounds . Fernandez E, Whiting A. Springer; Cham: 2015
• 8 Brown HC, Kim KW, Cole TE, Singaram B. J. Am. Chem. Soc. 1986; 108: 6761
• 9a Fernandez E, Hooper MW, Knight FI, Brown JM. Chem. Commun. 1997; 173
• 9b Fernandez E, Maeda K, Hooper MW, Brown JM. Chem. Eur. J. 2000; 6: 1840
• 10a Matteson DS, Kim GY. Org. Lett. 2002; 4: 2153
• 10b Kim BJ, Matteson DS. Angew. Chem. Int. Ed. 2004; 43: 3056
• 11 Mlynarski SN, Karns AS, Morken JP. J. Am. Chem. Soc. 2012; 134: 16449
• 12 Edelstein EK, Grote AC, Palkowitz MD, Morken JP. Synlett 2018; 29: 1749
• 13a He Z, Zhu Q, Hu X, Wang L, Xia C, Liu C. Org. Chem. Front. 2019; 6: 900
• 13b He Z, Fan M, Xu J, Hu Y, Wang L, Wu X, Xia C, Liu C. Youji Huaxue 2019; 39: 3438
• 13c Hu Y, Sun W, Zhang T, Xu N, Xu J, Lan Y, Liu C. Angew. Chem. Int. Ed. 2019; 58: 15813
• 13d Zhu Q, Xia C, Liu C. Youji Huaxue 2021; 41: 661
• 13e Wang L, Zhang T, Sun W, He Z, Xia C, Lan Y, Liu C. J. Am. Chem. Soc. 2017; 139: 5257
• 13f Xu N, Xu J, Zhu Q, Liu C. Adv. Synth. Catal. 2021; 363: 2403
• 13g Zhu Q, He Z, Wang L, Hu Y, Xia C, Liu C. Chem. Commun. 2019; 55: 11884
• 14a Shi D, Xia C, Liu C. CCS Chem. 2021; 3: 1718
• 14b Sun W, Wang L, Hu Y, Wu X, Xia C, Liu C. Nat. Commun. 2020; 11: 3113
• 14c Sun W, Wang L, Xia C, Liu C. Angew. Chem. Int. Ed. 2018; 57: 5501
• 14d Zou L.-H, Fan M, Wang L, Liu C. Chin. Chem. Lett. 2020; 31: 1911
• 15a Liu X, Zhu Q, Chen D, Wang L, Jin L, Liu C. Angew. Chem. Int. Ed. 2020; 59: 2745
• 15b Li H, Yin G. Youji Huaxue 2020; 40: 547
• 16a Asai K, Miura M, Hirano K. J. Org. Chem. 2022; 87: 7436
• 16b Li Y, Li Y, Shi H, Wei H, Li H, Funes-Ardoiz I, Yin G. Science 2022; 376: 749
• 16c Dong W, Ye Z, Zhao W. Angew. Chem. Int. Ed. 2022; 61: e202117413
• 16d Kojima Y, Nishii Y, Hirano K. Org. Lett. 2022; 24: 7450
• 16e Zhao P, Huang J, Li J, Zhang K, Yang W, Zhao W. Chem. Commun. 2021; 58: 302
• 16f Du R, Liu L, Xu S. Angew. Chem. Int. Ed. 2021; 60: 5843
• 16g Wang B, Peng P, Ma W, Liu Z, Huang C, Cao Y, Hu P, Qi X, Lu Q. J. Am. Chem. Soc. 2021; 143: 12985
• 16h Kim M, Park B, Shin M, Kim S, Kim J, Baik M.-H, Cho SH. J. Am. Chem. Soc. 2021; 143: 1069
• 17a Yu F, Tao R, Su Y, Liu G, Huang Z. Org. Lett. 2022; 24: 4563
• 17b Li H, Wang L, Zhang Y, Wang J. Angew. Chem. Int. Ed. 2012; 51: 2943
• 17c Bose SK, Brand S, Omoregie HO, Haehnel M, Maier J, Bringmann G, Marder TB. ACS Catal. 2016; 6: 8332
• 17d Wang W, Ding C, Yin G. Nat. Catal. 2020; 3: 951
• 17e Shi D, Wang L, Xia C, Liu C. Angew. Chem. Int. Ed. 2018; 57: 10318
• 17f Noh D, Chea H, Ju J, Yun J. Angew. Chem. Int. Ed. 2009; 48: 6062
• 17g Fan W, Li L, Zhang G. J. Org. Chem. 2019; 84: 5987
• 17h Sun C, Potter B, Morken JP. J. Am. Chem. Soc. 2014; 136: 6534
• 17i Wang L, Sun W, Liu C. Chin. J. Catal. 2018; 39: 1725
• 17j Wang Q.-D, Yang J.-M, Fang D, Ren J, Dong B, Zhou B, Zeng B.-B. Tetrahedron Lett. 2016; 57: 2587
• 18 Chiral Amine Synthesis: Methods, Developments and Applications. Nugent TC. Wiley-VCH; Weinheim: 2010
• 19a Xu J, Chen D, Liu C. Org. Biomol. Chem. 2022; 20: 8353
• 19b Armstrong A, Carbery DR, Lamont SG, Pape AR, Wincewicz R. Synlett 2006; 2504
• 20 Compounds 2a–ab; General Procedure An oven-dried Schlenk tube was charged with the appropriate boronate (0.2 mmol), H₂N-NMM (68.3 mg, 1.4 equiv), and Cs₂CO₃ (91.2 mg, 1.4 equiv), then purged with N₂. Anhyd toluene (2 mL) was added and the mixture was stirred at 100 °C for 10 h. A 1 M solution of Boc₂O in THF (2.0 equiv) was added and the mixture was heated at 80 °C for 1 h. The reaction was quenched with EtOAc, and the mixture was concentrated under a vacuum. The residue was purified by flash column chromatography [silica gel, PE–EtOAc (10:1)]. Visualization was performed by using ninhydrin. tert-Butyl (1-phenylethyl)carbamate (2a) White solid; yield: 36.2 mg (82%). ¹H NMR (400 MHz, CDCl₃): δ = 7.36–7.22 (m, 5 H), 4.79 (br s, 2 H), 1.53–1.21 (m, 12 H). ¹³C NMR (101 MHz, CDCl₃): δ = 155.2, 144.1, 128.7, 127.2, 126.0, 79.5, 50.3, 28.5, 22.8.