6
Tetrahedron
mL/min, tR1 = 10.6 min, tR2 = 12.7 min], ee = 74%; [α]D
=
8.0, 1.6 Hz, 1H), 5.47–5.43 (m, 1H), 2.71–2.64 (m, 3H), 2.18–
ACCEPTED MANUSCRIPT
25
+22.25 (c 0.36, CHCl3).
2.08 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 176.1, 139.6,
133.1, 132.5, 130.8, 127.3, 124.5, 79.5, 30.8, 28.7; HPLC [Daicel
(R)-5-(3,5-Dimethylphenyl)dihydrofuran-2(3H)-one (2q)[6j]
Chiralcel AS-H, n-hexane/i-PrOH = 75/25, 210 nm, 0.8 mL/min,
tR1 = 14.1 min, tR2 = 19.6 min], ee = 74%; [α]D = +18.60 (c 0.32,
1
Colorless oil (45.6 mg, 96%); H NMR (400 MHz, CDCl3): δ
25
CHCl3).
6.94 (s, 1H), 6.92 (s, 2H), 5.44–5.39 (m, 1H), 2.63–2.56 (m, 3H),
2.30 (s, 6H), 2.19–2.11 (m, 1H); 13C NMR (100 MHz, CDCl3): δ
177.1, 139.3, 138.4, 130.0, 123.0, 81.4, 30.9, 28.9, 21.3; HPLC
[Daicel Chiralcel AS-H, n-hexane/i-PrOH = 75/25, 210 nm, 0.8
The synthesis of (R)-4-hydroxy-N-isopropyl-4-phenyl-
butyramide (3)[8]
mL/min, tR1 = 10.2 min, tR2 = 13.1 min], ee = 85%; [α]D = +18.83
A mixture of 2a (1 g, 6.2 mmol) and isopropylamine (5 mL,
58.7 mmol) was stirred at room temperature for approximately 10
hours. The additional isopropylamine was removed under
reduced pressure to give 4-hydroxy-N-isopropyl-4-phenyl-
25
(c 0.46, CHCl3).
(R)-5-(3,5-Difluorophenyl)dihydrofuran-2(3H)-one (2r)
1
1
butyramide 3 as a white solid (1.36 g, 100%). H NMR (400
Colorless oil (49.5 mg, 99%); H NMR (400 MHz, CDCl3): δ
MHz, CDCl3): δ 7.35−7.29 (m, 4H), 7.25−7.21 (m, 1H), 5.73 (d,
J = 6.0 Hz, 1H), 4.73 (q, J = 4.0 Hz, 1H), 4.09−3.98 (m, 1H),
2.26 (t, J = 6.8 Hz, 2H), 2.04−1.93 (m, 2H), 1.11 (d, J = 6.8 Hz,
6H); 13C NMR (100 MHz, CDCl3): δ 172.7, 144.6, 128.3, 127.2,
125.7, 73.5, 41.5, 34.5, 33.1, 22.6; HPLC [Daicel Chiralcel OX-
H, n-hexane/i-PrOH = 95/5, 210 nm, 0.5 mL/min, tR1 = 85.0 min,
6.87-6.81 (m, 2H), 6.77–6.70 (m, 1H), 5.46–5.43 (m, 1H), 2.72–
2.61 (m, 3H), 2.16–2.07 (m, 1H); 13C NMR (100 MHz, CDCl3): δ
176.1, 164.4 (d, J = 12.6 Hz), 161.9 (d, J = 12.6 Hz), 143.5 (t, J =
8.9 Hz), 108.1 (d, J = 26.4 Hz), 108.1 (d, J = 11.6 Hz), 103.7 (t, J
= 25.1 Hz), 79.5, 30.6, 28.5; IR (KBr) cm-1: 2959, 2830, 2716,
1787, 1631, 1366, 1119, 785, 774; HRMS (ESI): calcd for
C10H8F2O2 [M+Na]+: 221.0385, found 221.0383; HPLC [Daicel
Chiralcel AS-H, n-hexane/i-PrOH = 75/25, 210 nm, 0.8 mL/min,
tR2 = 123.6 min], ee = 86%; [α]D = +38.95 (c 0.32, CHCl3).
25
tR1 = 11.6 min, tR2 = 14.6 min], ee = 80%; [α]D = +11.06 (c 0.52,
Acknowledgments
This work was partially supported by the National Natural Science
Foundation of China (Nos. 21672142, 21620102003 and 21831005),
25
CHCl3).
(R)-5-(3,5-Dichlorophenyl)dihydrofuran-2(3H)-one (2s)
Shanghai
Municipal
Education
Commission
(No.
1
Colorless oil (57.3 mg, 99%); H NMR (400 MHz, CDCl3): δ
201701070002E00030). We also thank the Instrumental Analysis
Center of Shanghai Jiao Tong University.
7.32–7.30 (m, 1H), 7.23–7.21 (m, 2H), 5.45–5.41 (m, 1H), 2.72–
2.63 (m, 3H), 2.17–2.10 (m, 1H); 13C NMR (100 MHz, CDCl3): δ
176.1, 142.9, 135.5, 128.5, 123.7, 79.4, 30.8, 28.6; IR (KBr) cm-1:
3078, 2926, 2854, 1782, 1570, 1436, 1179, 799, 691; HRMS
(ESI): calcd for C10H8Cl2O2 [M+H]+: 230.9974, found 230.9981;
HPLC [Daicel Chiralcel AS-H, n-hexane/i-PrOH = 85/15, 210
References and notes
1. Selected reviews, see: (a) Takaya, H.; Ohta, T.; Noyori, R. In Catalytic
Asymmetric Synthesis; Ojima, I., Ed.; Wiley-VCH: New York, 1993; p 1;
(b) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley: New
York, 1994; Chapter 2; (c) Ohkuma, T.; Noyori, R. In Transition Metals
for Organic Synthesis: Building Blocks and Fine Chemicals; Beller, M.,
Bolm, C., Eds.; Wiley-VCH: Weinheim, 1998; Vol. 2, p 25; (d)
nm, 0.8 mL/min, tR1 = 17.9 min, tR2 = 37.8 min], ee = 75%; [α]D
25
= +14.70 (c 0.50, CHCl3).
(R)-5-(3-Chloro-5-fluorophenyl)dihydrofuran-2(3H)-one (2t)
Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: Berlin, 1999; (e) Knowles, W. S. Angew.
Chem., Int. Ed. 2002, 41, 1998; (f) Noyori, R. Angew. Chem., Int. Ed. 2002,
41, 2008; (g) Tang, W.; Zhang, X. Chem. Soc. Rev. 2012, 41, 4126; (h)
Chen, Q.; Ye, Z.; Duan, Y.; Zhou, Y. Chem. Soc. Rev. 2013, 42, 497; (i)
Zhang, Z.; Butt, N. A.; Zhang, W. Chem. Rev. 2016, 116, 14769; For
selected papers, see: (j) Llorente, N.; Fernández-Pérez, H.; Núñez-Rico, J.
L.; Carreras, L.; Martínez-Carrión, A.; Iniesta, E.; Romero-Navarro, A.;
Martínez-Bascuñana, A.; Vidal-Ferran, A. Pure Appl. Chem. 2019, 91, 3;
(k) Mazuela, J.; Antonsson, T.; Knerr, L.; Marsden, S. P.; Munday, R. H.;
Johansson, M. J. Adv. Synth. Catal. 2019, 361, 578; (l) Seo, C. S. G.;
Morris, R. H. Organometallics, 2019, 38, 47; (m) Yan, Q.; Xiao, G.; Wang,
Y.; Zi, G.; Zhang, Z.; Hou, G. J. Am. Chem. Soc., 2019, 141, 1749.
2. (a) Takaya, H.; Ohta, T.; Sayo, N.; Kumobayashi, H.; Akutagawa, S.;
Inoue, S.-I.; Kasahara, I.; Noyori, R. J. Am. Chem. Soc. 1987, 109, 1596; (b)
Murahashi, E. I.; Nakota, T.; Kuwabara, T.; Saito, T.; Kumobayashi, H.;
Akutagawa, S. J. Am. Chem. Soc. 1990, 112, 7820; (c) Kitamura, M.;
Tokunaga, M.; Noyori, R. J. Am. Chem. Soc. 1993, 115, 144; (d) Dobbs, D.
A.; Vanhessche, K. P. M.; Brazi, E.; Rautenstrauch, V.; Lenoir, J. Y.;
Genet, J. P.; Wiles, J.; Bergens, S. H. Angew. Chem. Int. Ed. 2000, 39,
1992; (e) Bulliard, M.; Laboue, B.; Lastanet, J.; Roussiasse, S. Org.
Process Res. Dev. 2001, 438; (f) Genet, J. P. Acc. Chem. Res. 2003, 36,
908; (g) Wu, J.; Chen, H.; Yeung, C. H.; Chan, A. S. C. Tetrahedron Lett.
2002, 43, 1539; (h) Utsumi, N.; Arai, N.; Kawaguchi, K.; Katayama, T.;
Yasuda, T.; Murata, K.; Ohkuma, T. ChemCatChem 2018, 10, 3955.
3. (a) Gunasekera, S. P.; Isbrucker, R. A.; Longley, R. E.; Wright, A. E.;
Pomponi, S. A.; Reed, J. K.; J. Nat. Prod. 2004, 67, 110; (b) Bandichhor,
R.; Nosse, B.; Reiser, O. Top. Curr. Chem. 2005, 243, 43; (c) Kitson, R. R.
A.; Millemaggi, A.; Taylor, R. J. K. Angew. Chem. Int. Ed. 2009, 48, 9426;
(d) Xia, S.; Chen, Y.; Zhuo, J.; Xu, H. Biocatal. Biotransfor. 2013, 31, 66.
4. (a) Ohkuma, T.; Kitamura, M.; Noyori, R. Tetrahedron Lett. 1990, 31,
5509; (b) Benincori, T.; Rizzo, S.; Pilati, T.; Ponti, A.; Sada, M.;
1
Colorless oil (53.5 mg, 99%); H NMR (400 MHz, CDCl3): δ
7.14–7.11 (m, 1H), 7.08–7.04 (m, 1H), 6.98-6.93 (m, 1H), 5.47–
5.43 (m, 1H), 2.73–2.63 (m, 3H), 2.18–2.09 (m, 1H); 13C NMR
(100 MHz, CDCl3): δ 175.9, 162.8 (d, J = 249.6 Hz), 143.3 (d, J
= 8.1 Hz), 135.7 (d, J = 10.3 Hz), 121.2 (d, J = 3.2 Hz), 116.1 (d,
J = 24.5 Hz), 110.8 (d, J = 22.7 Hz), 79.4, 30.7, 28.5; IR (KBr)
cm-1: 2830, 1787, 1657, 1366, 1119, 786, 774; HRMS (ESI):
calcd for C10H8ClFO2 [M+Na]+: 237.0089, found 237.0095;
HPLC [Daicel Chiralcel AS-H, n-hexane/i-PrOH = 75/25, 210
nm, 0.8 mL/min, tR1 = 10.1 min, tR2 = 12.6 min], ee = 81%; [α]D
25
= +18.36 (c 0.32, CHCl3).
(R)-5-(3,4-Difluorophenyl)dihydrofuran-2(3H)-one (2u)
1
Colorless oil (49.5 mg, 99%); H NMR (400 MHz, CDCl3): δ
7.21–7.12 (m, 2H), 7.08–7.04 (m, 1H), 5.47–5.41 (m, 1H), 2.71–
2.62 (m, 3H), 2.20–2.09 (m, 1H); 13C NMR (100 MHz, CDCl3): δ
176.3, 151.5 (dd, J = 29.5, 13.0 Hz), 149.1 (dd, J = 29.0, 12.6 Hz),
136.4 (dd, J = 5.4, 3.6 Hz), 121.4 (dd, J = 6.5, 2.7 Hz), 117.7 (d,
J = 17.5 Hz), 114.6 (d, J = 18.3 Hz), 79.8, 30.9, 28.8; IR (KBr)
cm-1: 2925, 2830, 2716, 1765, 1631, 1366, 1068, 785, 774;
HRMS (ESI): calcd for C10H8F2O2 [M+Na]+: 221.0385, found
221.0387; HPLC [Daicel Chiralcel AS-H, n-hexane/i-PrOH =
75/25, 210 nm, 0.8 mL/min, tR1 = 11.6 min, tR2 = 13.5 min], ee =
74%; [α]D = +9.42 (c 0.44, CHCl3).
(R)-5-(3,4-Dichlorophenyl)dihydrofuran-2(3H)-one (2v)[9a]
25
1
Colorless oil (57.4 mg, 99%); H NMR (400 MHz, CDCl3): δ
Pagliarini, E. Tetrahedron: Asymmetry 2004, 15, 2289; (c) Starodubtseva,
E. V.; Turova, O. V.; Vinogradov, M. G.; Gorshkova, L. S.; Ferapontov, V.
A.; Struchkova, M. I. Tetrahedron 2008, 64, 11713; (d) Arai, N.; Namba,
7.47 (d, J = 14.8 Hz, 1H), 7.43 (d, J = 2.0 Hz, 1H), 7.17 (dd, J =