squaramide‐catalyzed asymmetric mannich reactions …and broad (br). high-resolution mass spectra...
TRANSCRIPT
Squaramide‐Catalyzed Asymmetric Mannich Reactions Between
3‐Fluorooxindoles and Pyrazolinone Ketimines
Qing-Da Zhang, Bo-Liang Zhao, Bing-Yu Li and Da-Ming Du*
School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, People’s Republic of China
Supporting Information
Contents
1. General information and starting materials..........................................………..…………S1 2. General procedure for the synthesis of compound 3……………………………………..S2 3. Copies of 1H, 13C and 19F NMR spectra of new products................................…………...S3 4. Copies of HPLC chromatograms of products..........................……………...…………..S82
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2019
S1
1. General information and starting materials
General information. All solvents commercially and available chemicals were used without
further purification. The column chromatography was performed with silica gel (200−300
mesh) using mixtures of petroleum ether and ethyl acetate. Melting points were determined
with a XT-4 melting-point apparatus without corrected. 1H NMR spectra were measured with
Bruker Ascend 400 MHz spectrometer, and chemical shifts were reported in δ (ppm) units
relative to tetramethylsilane (TMS) as the internal standard. 13C NMR spectra were measured
at 101 MHz with Bruker Ascend 400 MHz spectrometer or 176 MHz with Bruker Avance III
HD 700 MHz spectrometer, and chemical shifts are reported in δ (ppm) units relative to
tetramethylsilane and referenced to the solvent peak (CDCl3, δ(C) = 77.00 ppm). 19F NMR
spectra were measured at 376 MHz with Bruker Ascend 400 MHz spectrometer. Proton
coupling patterns are described as singlet (s), doublet (d), triplet (t), quartet (q), multiplet (m),
and broad (br). High-resolution mass spectra were obtained with an Agilent 6520
Accurate-Mass-Q-TOF MS system equipped with an electrospray ionization (ESI) source.
The enantiomeric excesses were determined by chiral HPLC analysis using an Agilent 1200
LC instrument with Daicel Chiralpak IA, IB, IC or AD-H columns. Optical rotations were
measured with Krüss P8000 polarimeter at the indicated concentration with the units of grams
per 100 mL at 20 C using sodium D light.
Starting materials. 1a−1p were prepared according to the literature.[1]
S2
2a−2h were prepared according to the literature.[2]
The squaramide organocatalysts C1-C8 were prepared by the reported procedures.[3]
2. General procedure for the synthesis of compound 3
To a dried small bottle were added pyrazolone imine 1 (0.22mmol), 3-fluorooxindole 2 (0.2
mmol), and squaramide catalyst C5 (5 mol%) in MeCN (2.0 mL) at room temperature. The
reaction mixture was stirred for 36 h and the progress of the reaction was monitored by TLC
analysis (Petroleum ether/ ethyl acetate = 2:1). After the completion of the reaction, the crude
product mixture was purified by flash column chromatography on silica (petroleum
ether/ethyl acetate = 5:1) to afford the pure product 3. The racemic standard of 3 was prepared
using achiral catalyst C9.[4]
References
[1] P. Chauhan, S. Mahajan, U. Kaya, A Peuronen and K. Rissanen, J. Org. Chem. 2017, 82,
7050.
[2] Q. Yang, G. -L. Dai, Y.-M. Yang, Z.-Z. Luo and Z.-Y. Tang, J. Org. Chem. 2018, 83, 6762.
[3] (a) Y. Zhu, J. P. Malerich and V. -H. Rawal, Angew. Chem., Int. Ed. 2010, 49, 153; (b) W.
Yang and D.-M. Du, Org. Lett. 2010, 12, 5450; (c) C. Cassani, R.-M. Rapún, E. Arceo1, F.
Bravo and P. Melchiorre, Nat. Protoc. 2013, 8, 325; (d) E. Massolo, M. Benaglia, A.
Genoni, R. Annunziata, G. Celentanob and N. Gaggero, Org. Biomol. Chem. 2015, 13,
5591.
[4] S. Sopeña, E. Martin, E. -C. Escuder and A. -W. Kleij, ACS Catal. 2017, 7, 3532.
S3
3. Copies of 1H, 13C and 19F NMR spectra of new products
1H NMR (400 MHz)
S4
13C NMR (101 MHz)
S5
19F NMR (376 MHz)
S6
1H NMR (400 MHz)
3b
N
F
O
Me
N NO
MeHN
Me
S7
13C NMR (176 MHz)
3b
N
F
O
Me
N NO
MeHN
Me
S8
19F NMR (376 MHz)
3b
N
F
O
Me
N NO
MeHN
Me
S9
1H NMR (400 MHz)
3c
N
F
O
Me
N NO
MeHN
Cl
S10
13C NMR (176 MHz)
3c
N
F
O
Me
N NO
MeHN
Cl
S11
19F NMR (376 MHz)
3c
N
F
O
Me
N NO
MeHN
Cl
S12
1H NMR (400 MHz)
S13
13C NMR (176 MHz)
S14
19F NMR (376 MHz)
S15
1H NMR (400 MHz)
S16
13C NMR (176 MHz)
S17
19F NMR (376 MHz)
S18
1H NMR (400 MHz)
S19
13C NMR (176 MHz)
S20
19F NMR (376 MHz)
S21
1H NMR (400 MHz)
S22
13C NMR (176 MHz)
S23
19F NMR (376 MHz)
S24
1H NMR (400 MHz)
S25
13C NMR (176 MHz)
S26
19F NMR (376 MHz)
S27
1H NMR (400 MHz)
S28
13C NMR (176 MHz)
S29
19F NMR (376 MHz)
S30
1H NMR (400 MHz)
S31
13C NMR (176 MHz)
S32
19F NMR (376 MHz)
S33
1H NMR (400 MHz)
S34
13C NMR (176 MHz)
S35
19F NMR (376 MHz)
S36
1H NMR (400 MHz)
S37
13C NMR (176 MHz)
S38
19F NMR (376 MHz)
S39
1H NMR (400 MHz)
S40
13C NMR (176 MHz)
S41
19F NMR (376 MHz)
S42
1H NMR (400 MHz)
S43
13C NMR (176 MHz)
S44
19F NMR (376 MHz)
S45
1H NMR (400 MHz)
S46
13C NMR (176 MHz)
S47
19F NMR (376 MHz)
S48
1H NMR (400 MHz)
S49
13C NMR (176 MHz)
S50
19F NMR (376 MHz)
S51
1H NMR (400 MHz)
S52
13C NMR (176 MHz)
S53
19F NMR (376 MHz)
S54
1H NMR (400 MHz)
S55
13C NMR (176 MHz)
S56
19F NMR (376 MHz)
S57
1H NMR (400 MHz)
S58
13C NMR (176 MHz)
S59
19F NMR (376 MHz)
S60
1H NMR (400 MHz)
N
F
O
Me
N NO
MeHN
3u
Cl
S61
13C NMR (176 MHz)
N
F
O
Me
N NO
MeHN
3u
Cl
S62
19F NMR (376 MHz)
N
F
O
Me
N NO
MeHN
3u
Cl
S63
1H NMR (400 MHz)
S64
13C NMR (176 MHz)
S65
19F NMR (376 MHz)
S66
1H NMR (400 MHz)
S67
13C NMR (176 MHz)
S68
19F NMR (376 MHz)
S69
1H NMR (400 MHz)
S70
13C NMR (176 MHz)
S71
19F NMR (376 MHz)
S72
1H NMR (400 MHz)
S73
13C NMR (100 MHz)
S74
19F NMR (376 MHz)
S75
19F NMR (376 MHz)
S76
1H NMR (400 MHz)
S77
13C NMR (176 MHz)
S78
19F NMR (376 MHz)
S79
1H NMR (400 MHz)
S80
13C NMR (176 MHz)
S81
19F NMR (376 MHz)
S82
4. Copies of HPLC chromatograms of products
S83
S84
S85
S86
S87
S88
S89
S90
S91
S92
S93
S94
S95
S96
S97
S98
S99
S100
S101
S102
NH
F
O
N NO
MeHN
racemate
NH
F
O
N NO
MeHN
3v
S103
S104
S105
S106
S107