Synlett, Table of Contents Synlett 2022; 33(20): 2019-2025DOI: 10.1055/a-1955-2016 letter Enantioselective Synthesis of α-Hydroxyamino Ketones by a Chiral Phosphine–Silver Complex Catalyzed N-Nitroso Aldol Reaction Akira Yanagisawa∗ , Shiho Kasahara , Akihiro Takeishi , Tomoki Marui Recommend Article Abstract Buy Article All articles of this category Abstract A catalytic asymmetric N-nitroso aldol reaction of alkenyl trifluoroacetates with nitrosoarenes was achieved using a DTBM-SEGPHOS·AgOTf complex as the chiral precatalyst and KHMDS as the base precatalyst in the presence of methanol. Optically active α-hydroxyamino ketones with up to 89% ee were regioselectively obtained in moderate to high yields not only from acyclic alkenyl esters but also from cyclic ones through the in situ generated chiral silver enolates. Key words Key wordsasymmetric catalysis - alkenyl ester - nitroso aldol reaction - nitrosoarene - silver Full Text References References and Notes For representative examples, see: 1a Myers MC, Wang J, Iera JA, Bang J.-K, Hara T, Saito S, Zambetti GP, Appella DH. J. Am. Chem. Soc. 2005; 127: 6152 1b Meltzer PC, Butler D, Deschamps JR, Madras BK. J. Med. Chem. 2006; 49: 1420 1c Nchinda AT, Chibale K, Redelinghuys P, Sturrock ED. Bioorg. Med. Chem. Lett. 2006; 16: 4612 1d Carroll FI, Blough BE, Abraham P, Mills AC, Holleman JA, Wolckenhauer SA, Decker AM, Landavazo A, McElroy KT, Navarro HA, Gatch MB, Forster MJ. J. Med. Chem. 2009; 52: 6768 2 Evans RW, Zbieg JR, Zhu S, Li W, MacMillan DW. C. J. Am. Chem. Soc. 2013; 135: 16074 3 Várdi A, Palmer TC, Haselton N, Afonin D, Subrath JJ, Rouzic VL, Hunkele A, Pasternak GW, Marrone GF, Borics A, Majumdar S. ACS Chem. Neurosci. 2015; 6: 1570 4a Ramakrishna I, Bhajammanavar V, Mallik S, Baidya M. Org. Lett. 2017; 19: 516 For reviews on N-nitroso aldol reactions see: 4b Yamamoto H, Momiyama N. Chem. Commun. 2005; 3514 4c Merino P, Tejero T, Delso I, Matute R. Synthesis 2016; 48: 653 4d Dana S, Ramakrishna I, Baidya M. Synthesis 2017; 49: 3281 For notable examples of N-nitroso aldol reactions promoted by organocatalysts, see: 5a Momiyama N, Yamamoto H. J. Am. Chem. Soc. 2005; 127: 1080 5b Kano T, Ueda M, Takai J, Maruoka K. J. Am. Chem. Soc. 2006; 128: 6046 5c Palomo C, Vera S, Velilla I, Mielgo A, Gómez-Bengoa E. Angew. Chem. Int. Ed. 2007; 46: 8054 5d Zhang T, Cheng L, Liu L, Wang D, Chen Y.-J. Tetrahedron: Asymmetry 2010; 21: 2800 5e Yang H.-J, Dai L, Yang S.-Q, Chen F.-E. Synlett 2012; 23: 948 5f Kano T, Shirozu F, Maruoka K. J. Am. Chem. Soc. 2013; 135: 18036 5g Maji B, Yamamoto H. Angew. Chem. Int. Ed. 2014; 53: 8714 5h Kano T, Shirozu F, Maruoka K. Org. Lett. 2014; 16: 1530 5i Xu C, Zhang L, Luo S. Angew. Chem. Int. Ed. 2014; 53: 4149 5j Xu C, Zhang L, Luo S. Org. Lett. 2015; 17: 4392 5k Macharia J, Wambua V, Hong Y, Harris L, Hirschi JS, Evans GB, Vetticatt MJ. Angew. Chem. Int. Ed. 2017; 56: 8756 5l Chen W, Wang Y, Mi X, Luo S. Org. Lett. 2019; 21: 8178 For examples of N-nitroso aldol reactions catalyzed by chiral Lewis acids (Ag, Sc, Sn, Cu, Mg, and Ra), see: 6a Momiyama N, Yamamoto H. J. Am. Chem. Soc. 2004; 126: 5360 6b Yamamoto Y, Momiyama N, Yamamoto H. J. Am. Chem. Soc. 2004; 126: 5962 6c Shen K, Liu X, Wang G, Lin L, Feng X. Angew. Chem. Int. Ed. 2011; 50: 4684 6d Yanagisawa A, Fujinami T, Oyokawa Y, Sugita T, Yoshida K. Org. Lett. 2012; 14: 2434 6e Maji B, Baidya M, Yamamoto H. Chem. Sci. 2014; 5: 3941 6f Zhang J, Fu K, Lin L, Lu Y, Liu X, Feng X. Chem. Eur. J. 2018; 24: 4289 7 Yanagisawa A, Lin Y, Takeishi A, Yoshida K. Eur. J. Org. Chem. 2016; 5355 8a Gil J, Medio-Simon M, Mancha G, Asensio G. Eur. J. Org. Chem. 2005; 1561 8b Claraz A, Leroy J, Oudeyer S, Levacher V. J. Org. Chem. 2011; 76: 6457 9a In our previous study on the chiral silver(I)-catalyzed asymmetric allylation of aldehydes, we showed that a considerable amount of an inert 2:1 complex of BINAP/silver(I) salt was formed accompanied by a reactive 1:1 complex when BINAP was added to an equimolar amount of the silver salt in MeOH. In the reaction, a 0.6:1 mixture of BINAP/silver(I) salt was found to produce the desired 1:1 complex without the formation of the 2:1 complex: 9b Yanagisawa A, Kageyama H, Nakatsuka Y, Asakawa K, Matsumoto Y, Yamamoto H. Angew. Chem. Int. Ed. 1999; 38: 3701 9c Yanagisawa A, Nakatsuka Y, Asakawa K, Kageyama H, Yamamoto H. Synlett 2001; 69 9d Yanagisawa A, Nakatsuka Y, Asakawa K, Wadamoto M, Kageyama H, Yamamoto H. Bull. Chem. Soc. Jpn. 2001; 74: 1477 10 Typical Experimental Procedure for the Asymmetric N-Nitroso Aldol Reaction Catalyzed by (R)-DTBM-SEGPHOS·(AgOTf)2 and KHMDS: Synthesis of 2-[Hydroxy(2-isopropylphenyl)amino]-1-phenylpentan-1-one (3eg, Entry 2 in Table 3 Entry 7 in Table 4, and Entry 4 in Table 5) AgOTf (51.3 mg, 0.20 mmol) was dissolved in dry THF (2 mL) under an argon atmosphere and with direct light excluded at room temperature. To the solution was added a 0.5 mol/L solution of KHMDS in toluene (200 μL, 0.1 mmol) at –40 °C and stirred for 30 min at this temperature. Subsequently, a solution of (R)-DTBM-SEGPHOS (23.6 mg, 0.02 mmol) in dry THF (1 mL) was added and stirred at –40 °C for 30 min. Then a solution of 1-isopropyl-2-nitrosobenzene (2g, 74.6 mg, 0.50 mmol) in dry MeOH (2 mL) and alkenyl trifluoroacetate 1e (230 μL, 1.0 mmol) were successively added to the resulting solution at this temperature. After stirring at –40 °C for 2 h, the mixture was treated with MeOH (3 mL) and stirred at this temperature for 20 min. Then, the mixture was filtered with a glass filter funnel filled with Celite® and washed with Et2O, and the combined filtrate and washes were concentrated in vacuo. The residual crude product was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane as the eluant to give corresponding α-hydroxyamino ketone 3eg (146.4 mg, 94% yield). The enantiomeric ratio of the N-adduct was determined to be 89% ee by HPLC analysis using a chiral column (Daicel Chiralpak AS-H, hexane–i-PrOH (80:1), flow rate = 1.0 mL/min) t 1 = 15.6 min (minor), t 2 = 32.4 min (major). Spectral Data of the Product 1H NMR (396 MHz, CDCl3): δ = 7.98 (d, J = 7.1 Hz, 2 H), 7.58 (m, 1 H), 7.40–7.51 (m, 3 H), 7.27–7.35 (m, 1 H), 7.13–7.19 (m, 2 H), 6.57 (s, 1 H), 4.76 (t, J = 6.7 Hz, 1 H), 3.67 (sept, J = 7.0 Hz, 1 H), 1.76–1.85 (m, 2 H), 1.30–1.43 (m, 2 H), 1.26 (dd, J = 15.2, 7.0 Hz, 6 H), 0.83 (t, J = 7.5 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 202.7, 147.2, 143.9, 136.5, 133.4, 128.6 (2 C), 128.4 (2 C), 126.4, 126.2, 126.1, 121.6, 70.7, 32.1, 26.6, 24.6, 23.5, 19.5, 14.0. IR (neat): 3409, 2961, 2871, 1682, 1597, 1486, 1447, 1383, 1232, 1086, 1032, 1002, 968, 908, 756, 731 cm–1. MS (ESI): m/z calcd for [C20H25O2NNa]+ [M + Na]+: 334.1778; found: 334.1773; [α]D 14.2 +16.0 (c 1.0, CHCl3, 89% ee). 11 Bannykh AV, Bakulina OY, Dar’in DV, Krasavin M. Mendeleev Commun. 2019; 29: 337 12 Guo W, Luo Y, Sung HH.-Y, Williams ID, Li P, Sun J. J. Am. Chem. Soc. 2020; 142: 14384 13 The absolute stereochemistry of cyclic α-hydroxyamino ketones has not yet been determined. Two examples of the synthesis of achiral silver alkoxides have been reported: 14a Edworthy IS, Rodden M, Mungur SA, Davis KM, Blake AJ, Wilson C, Schröder M, Arnold PL. J. Organomet. Chem. 2005; 690: 5710 14b Reisinger A, Himmel D, Krossing I. Angew. Chem. Int. Ed. 2006; 45: 6997 15 Although it is difficult to refer to the origin of N/O selectivity in the present nitroso aldol reaction at this stage, acyclic alkenyl esters with Z configuration exhibit higher N-selectivity compared to cyclic alkenyl esters.7 In addition, chiral phosphines have been found to affect N/O selectivity to some extent.7 Supplementary Material Supplementary Material Supporting Information
