enantioselective synthesis of 3-fluoro-3-allyl-oxindoles via phos … · 2015. 5. 14. · 3 bn(6c)...
TRANSCRIPT
SUPPORTING INFORMATION
Enantioselective Synthesis of 3-Fluoro-3-allyl-oxindoles via Phos-phine-Catalyzed Asymmetric -addition of 3-Fluoro-Oxindoles to
2,3-Butadienoates
Tianli Wang, Ding Long Hoon, and Yixin Lu*
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543
E-mail: [email protected]
1. General Information -------------------------------------------------------------------------------------------1
2. Optimization of Reaction Conditions ------------------------------------------------------------------------3
3. Proposed Reaction Cycle -------------------------------------------------------------------------------------6
4. Preparation of 3-Fluoro-substituted Oxindoles ---------------------------------------------------------8
5. Representative Procedure for -Addition of 3-Fluorinated Oxindoles ----------------------------------9
6. Asymmetric Synthesis of Chiral 3-Fluoro-3-allyl Oxindole Derivatives -----------------------------23
7. References-------------------------------------------------------------------------------------------------------24
8. NMR Spectra of the Products---------------------------------------------------------------------------------25
Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2015
1. General Information
All the starting materials were obtained from commercial sources and used without further
purification unless otherwise noted. 1H and 13C NMR spectra were recorded at ambient temperature in
CDCl3 or D2O on a Bruker ACF300 or AMX500 (500 MHz) spectrometer. The chemical shifts are
reported in parts permillion (ppm) relative to CDC3 (δ = 7.26) for 1H-NMR and relative to the central
resonances of CDCl3 (δ = 77.0) for 13C-NMR. Multiplicity was indicated as follows: s (singlet), d
(doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of doublet), br s (broad singlet). Coupling
constants (J) were reported in Hertz (Hz). Low resolution mass spectra were obtained on a
Finnigan/MAT LCQ pectrometer in ESI mode, and a Finnigan/MAT 95–T mass spectrometer in FAB
mode. All high resolution mass spectra were obtained on a Finnigan/MAT 95XL–T spectrometer. For
thin layer chromatography (TLC), Merck pre-coated TLC plates (Merck 60 F254) were used, and
compounds were visualized with a UV light at 254 nm. Further visualization was achieved by staining
with iodine, or ceric ammonium molybdate followed by heating on a hot plate. Flash chromatographic
separations were performed on 200-300 mesh silica gel. Enantiomeric excess was determined by HPLC
analysis using chiral column described below in detail. Optical rotations were measured with
polarimeter.
All the chiral phosphine catalysts were prepared by following our previously reported procedures.[1]
All the 3-fluoro-substituted oxindoles were synthesized based on known methods reported in
literature.[2]
The absolute configuration of 7a1 was assigned by comparing optical rotation of the corresponding
derivative 9 (Scheme S3) with the value reported in the literature,[3] and the configuration of other
-addition products were assigned by analogy.
2. Optimization of Reaction Conditions
R
NH
PPh2
NH
PPh2
OTBDPS
O
NHBoc
HN
PPh2
HN
S
F1d
O
F3C CF3
2a: R = Me2b: R = i-Pr2c: R = t-Bu
NH
PPh2
O
F3C CF3
2d
OH
3
NH
PPh2
OTBDPS
O
NHBoc
NHR
PPh2
1a: R = Boc1b: R = Ts
NH
PPh2
1c
O
4
NH
PPh2
O
F3C CF3
2e: R = TMS, 2f: R = TBS2g: R = TBDPS
OR
Scheme S1: Chiral phosphine catalysts used in this study. (TBDPS = tert-butyldiphenylsilyl, TBS = tert-butyldimethylsilyl, TMS = trimethylsilyl, Ts = 4-toluenesulfonyl)
A. Optimization of conditions for ‐Addition of 3‐fluoro‐oxindoles
Table S1: Asymmetric -addition of 3-fluoro-oxindole 5a with allenoate 6c catalyzed by different
chiral phosphines in toluene [a]
Entry Cat. R(5a) t [h] Yield [%][b] ee [%][c]
1 1a Boc(5a1) 1 88 32
2 1b Boc(5a1) 0.5 95 55
3 1c Boc(5a1) 1 88 41
4 1d Boc(5a1) 0.5 98 77
5 2a Boc(5a1) 1 95 90
6 2b Boc(5a1) 1 93 90
7 2c Boc(5a1) 2 88 88
8 2d Boc(5a1) 2 89 64
9 2e Boc(5a1) 2 93 93
10 2f Boc(5a1) 2 92 92
11 2g Boc(5a1) 2 95 93
12 3 Boc(5a1) 2 90 6
13 4 Boc(5a1) 2 90 -9
14 2g Cbz(5a2) 2 86 93
15 2g Ac(5a3) 4 82 83
16 2g Me(5a4) 4 <5 --
[a] Reactions were performed with 5a (0.05 mmol), 6c (0.06 mmol) and catalyst (0.005 mmol) in toluene (0.5 mL) at
room temperature. [b] Yields of isolated products. [c] Determined by HPLC analysis on a chiral stationary phase.
Table S2: Asymmetric -addition of 3-fluoro-oxindole (5a1) with different allenoates (6) catalyzed by
phosphine catalyst 2g in toluene [a]
Entry R (6) 7 Yield [%][b] ee [%][c]
1 Me(6a) 7a1-1 92 91
2 t-Bu(6b) 7a1-2 90 91
3 Bn(6c) 7a1-3 95 93
4 6d 7a1-4 91 93
5 6e 7a1-5 92 93
6 6f 7a1-6 89 92
7 6g 7a1-7 85 86
8 Ph(6h) 7a1-8 88 77
[a] Reaction conditions: 5a1 (0.05 mmol), 6 (0.06 mmol), and the catalyst 2g (0.005 mmol) in toluene (0.5 mL). [b]
Yields of isolated products. [c] Determined by HPLC analysis on a chiral stationary phase.
Table S3: Asymmetric -addition oxindole 5a1 with allenoate 6c catalyzed by 2g: optimizing the
solvents and other reaction conditions [a]
Entry Solvent T [oC] t [h] Yield [%][b] ee [%][c]
1 toluene RT 2 95 93
2 xylene RT 2 95 90
3 Et2O RT 2 88 73
4 CHCl3 RT 4 90 88
5 CH2Cl2 RT 4 92 92
6 EA RT 6 81 45
7 toluene 0 12 83 69
[a] Reaction conditions: 5a1 (0.05 mmol), 6c (0.06 mmol), and the catalyst 2g (0.005 mmol) in solvent (0.5 mL). [b]
Yields of isolated products. [c] Determined by HPLC analysis on a chiral stationary phase.
Scheme S2: Reactions of -substituted and -substituted allenoates (6i and 6j) with
N-Boc-3-fluoro-oxindole (5a1) by catalyst 2g.
3. Proposed Reaction Cycle
= PR3•
CO2Bn
PR3
CO2Bn
H-shiftPR3
CO2Bn
NO
Boc
F
NO
Boc
F
NO
Boc
CO2Bn
PR3
F
NO
Boc
CO2Bn
PR3
F
NO
Boc
CO2Bn
F NH
PPh2
O
F3C CF3
OTBDPS
Figure S1: Proposed catalytic cycle.
Figure S2. Proposed transition-state model.
Table S4. Asymmetric -addition promoted by different phosphine catalysts: investigating the H-bonding effect.[a]
cat. (10 mol%)
toluene, RTNO
NO
6c
7a1: R = Boc7a': R = H
•CO2Bn
+
5a1: R = Boc; 5a': R = H
CO2Bn
RR
FF
N
PPh2
O
F3C CF3
2g: R = H2g': R = Me
R
OTBDPS
Entry Sub. Cat. t [h] 7/Yield [%][b] ee [%][c]
1 5a1 2g 2 7a/95 93
2 5a1 2g’ 4 7a/85 37
3 5a’ 2g 2 7a’/81 43
[a] Reaction conditions: substrate (0.05 mmol), 6c (0.06 mmol), and catalyst (0.005 mmol) in toluene (0.5 mL) at room terature. [b] Isolated yield. [c] Determined by HPLC analysis on a chiral stationary phase.
4. Preparation of the 3-fluoro-substituted oxindoles
General procedure for preparing 3-fluoro-substituted oxindoles 5:[2]
All 3-fluoro-substituted oxindoles 5 were prepared from compounds 5-1 via known fluorination
using NFSI as F-source following literature procedure (16-48% yields).[2] Substrates 5a-c and 5f-h are
known compounds, and their characterization data were in agreement with those reported in the
literature.[2] Unknown compounds 5d, 5e and 5a’ were fully characterized.
tert-Butyl 6-bromo-3-fluoro-2-oxoindoline-1-carboxylate (5d)
A white sold; 1H NMR (500 MHz, CDCl3) δ 8.13 (s, 1H), 7.40-7.35 (m, 2H), 5.70 (d, J = 51.1 Hz, 1H),
1.64 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 168.34 (d, J = 18.2 Hz), 148.40, 141.89 (d, J = 4.6 Hz),
128.14 (d, J = 2.7 Hz), 127.08, 125.81 (d, J = 3.6 Hz), 119.23, 85.62, 85.23 (d, J = 189.5 Hz), 27.99; 19F
NMR (282.38 MHz, CDCl3) δ -187.10 (d, J = 51.5 Hz); HRMS (ESI) m/z calcd C13H13BrFNNaO3
[M+Na]+ = 351.9955, found = 351.9950.
tert-Butyl 3-fluoro-2-oxo-5-(trifluoromethyl)indoline-1-carboxylate (5e)
A white sold; 1H NMR (500 MHz, CDCl3) δ 7.95 (d, J = 8.8 Hz, 1H), 7.39 (s, 1H), 7.31 (d, J = 8.9 Hz,
1H), 5.71 (d, J = 50.4 Hz, 1H), 1.63 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 168.17 (d, J = 17.3 Hz)
148.45, 146.10, 139.35 (d, J = 4.6 Hz), 124.61, 123.15 (d, J = 17.3 Hz), 121.43, 119.24 (d, J = 32.8 Hz),
116.99, 85.54, 85.19 (d, J = 190.4 Hz), 27.98; 19F NMR (282.38 MHz, CDCl3) δ -58.28, -188.44 (d, J =
50.5 Hz); HRMS (ESI) m/z calcd C14H13F4NNaO3 [M+Na]+ = 342.0729, found = 342.0720.
3-Fluoroindolin-2-one (5a’)
NH
O
F
5a'
A white sold; 1H NMR (500 MHz, CDCl3) δ 9.07 (s, 1H), 7.45 (d, J = 7.6 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H),
7.09 (t, J = 7.6 Hz, 1H), 6.94 (d, J = 8.2 Hz, 1H), 5.74 (d, J = 51.1 Hz, 1H); 13C NMR (125 MHz, CDCl3)
δ 173.87 (d, J = 18.2 Hz), 141.96 (d, J = 5.5 Hz), 131.51 (d, J = 2.7 Hz), 126.27, 123.32 (d, J = 2.7 Hz),
123.26 (d, J = 16.4 Hz), 110.90, 86.67 (d, J = 188.6 Hz); 19F NMR (282.38 MHz, CDCl3) δ -193.68 (d, J
= 50.5 Hz); HRMS (ESI) m/z calcd C8H6FNNaO [M+H]+ = 174.0331, found = 174.0229.
5. Representative Procedure for -Addition of 3-Fluorinated Oxindoles
To dried schlenk tube equipped with a stirrer bar were added 3-fluoro-oxindole 5a1 (12.5 mg, 0.05 mmol)
and catalyst 2g (3.8 mg, 0.005 mmol), followed by the addition of dry toluene (0.5 mL). Allenoate 6c
(10.5 mg, 0.06 mmol) was slowly added via syringe, and the reaction mixture was stirred at room
temperature for 2 h. Then, the solvent of toluene was removed under reduced pressure, and the residue
was purified by column chromatography on silica gel (hexane/ethyl acetate = 15:1) to afford 7a1 (20.3
mg, 95% yield) as a white foam.
(R,E)-tert-Butyl 3-(4-(benzyloxy)-4-oxobut-2-enyl)-3-fluoro-2-oxoindoline-1-carboxylate (7a1)
NBoc
O
F
COOBn
7a1
A white foam; []25D = +25.5 (c 0.40, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.91 (d, J = 8.2 Hz, 1H),
7.47-7.41 (m, 2H), 7.38-7.31 (m, 5H), 7.22 (d, J = 7.6 Hz, 1H), 6.90-6.83 (m, 1H), 5.97 (d, J = 15.8 Hz,
1H), 5.17 (s, 2H), 3.15-3.09 (m, 1H), 2.97-2.88 (m, 1H), 1.63 (s, 9H); 13C NMR (125 MHz, CDCl3) δ
170.01 (d, J = 21.0 Hz), 165.25, 148.51, 140.11 (d, J = 4.6 Hz), 138.78 (d, J = 7.3 Hz), 135.74, 131.83
(d, J = 3.6 Hz), 128.53, 128.23, 128.12, 126.71, 125.09 (d, J = 2.7 Hz), 124.86, 123.92 (d, J = 19.1 Hz),
115.72, 91.69 (d, J = 189.5 Hz), 85.19, 66.31, 38.34 (d, J = 30.1 Hz), 27.98; 19F NMR (282.38 MHz,
CDCl3) δ -149.02 (dd, J1,2 = 12.4 Hz, J1,3 = 18.6 Hz); HRMS (ESI) m/z calcd for C24H24FNNaO5
[M+Na]+ = 448.1531, found = 448.1543; The ee value was 93%, tR (major) = 25.3 min, tR (minor) = 22.4
min (Chiralcel IE, λ = 254 nm, 5% i-PrOH/hexanes, flow rate = 1.0 mL/min).
Racemic 7a
Enantiomerically enriched 7a
(R,E)-tert-Butyl 3-(4-(benzyloxy)-4-oxobut-2-enyl)-5-chloro-3-fluoro-2-oxoindoline-
1-carboxylate (7b)
NBoc
O
F
COOBnCl
7b
A white foam; []25D = +29.8 (c 0.64, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.88 (d, J = 8.8 Hz, 1H),
7.43 (dt, J1,2 = 1.9 Hz, J1,3 = 8.9 Hz, 1H), 7.40-7.37 (m, 1H), 7.35-7.31 (m, 5H), 6.84-6.78 (m, 1H),
5.98 (d, J = 15.8 Hz, 1H), 5.17 (s, 2H), 3.12-3.05 (m, 1H), 2.98-2.90 (m, 1H), 1.62 (s, 9H); 13C NMR
(125 MHz, CDCl3) δ 169.33 (d, J = 21.0 Hz), 165.12, 148.34, 138.63 (d, J = 5.5 Hz), 138.00 (d, J = 7.4
Hz), 135.70, 131.87 (d, J = 2.7 Hz), 130.73 (d, J = 2.7 Hz), 128.58, 128.28, 128.15, 127.13, 125.54 (d,
J = 19.1 Hz), 125.01, 117.15, 91.34 (d, J = 191.3 Hz), 85.60, 66.42, 38.23 (d, J = 29.2 Hz), 27.97; 19F
NMR (282.38 MHz, CDCl3) δ -149.61 (t, J = 14.4 Hz); HRMS (ESI) m/z calcd for C24H23FClNNaO5
[M+Na]+ = 482.1141, found = 482.1150; The ee value was 83%, tR (major) = 16.9 min, tR (minor) = 14.6
min (Chiralcel IE, λ = 254 nm, 5% i-PrOH/hexanes, flow rate = 1.0 mL/min).
Racemic 7b
Enantiomerically enriched 7b
(R,E)-tert-Butyl 3-(4-(benzyloxy)-4-oxobut-2-enyl)-6-chloro-3-fluoro-2-oxoindoline-
1-carboxylate (7c)
NBoc
O
F
COOBn
7c
Cl
A white foam; []25D = +43.4 (c 0.47, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.99 (s, 1H), 7.38-7.32 (m,
6H), 7.21 (dd, J1,2 = 1.3 Hz, J1,3 = 8.2 Hz, 1H), 6.86-6.80 (m, 1H), 5.98 (d, J = 15.1 Hz, 1H), 5.17 (s,
2H), 3.14-3.07 (m, 1H), 2.94-2.85 (m, 1H), 1.63 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 169.57 (d, J =
21.0 Hz), 165.17, 148.27, 141.06 (d, J = 5.5 Hz), 138.23 (d, J = 7.3 Hz), 137.87 (d, J = 3.7 Hz), 135.67,
128.58, 128.31, 128.19, 127.02, 125.82, 125.28 (d, J = 2.8 Hz), 122.08, 116.60, 91.27 (d, J = 190.5
Hz), 85.78, 66.43, 38.21 (d, J = 29.2 Hz), 27.95; 19F NMR (282.38 MHz, CDCl3) δ -148.82 (dd, J1,2 =
12.4 Hz, J1,3 = 19.6 Hz); HRMS (ESI) m/z calcd for C24H23FClNNaO5 [M+Na]+ = 482.1141, found =
482.1147; The ee value was 94%, tR (major) = 15.3 min, tR (minor) = 13.7 min (Chiralcel IE, λ = 254 nm,
5% i-PrOH/hexanes, flow rate = 1.0 mL/min).
Racemic 7c
Enantiomerically enriched 7c
(R,E)-tert-Butyl 3-(4-(benzyloxy)-4-oxobut-2-enyl)-6-bromo-3-fluoro-2-oxoindoline-
1-carboxylate (7d)
NBoc
O
F
COOBn
Br
7d
A white foam; []25D = +34.6 (c 0.77, CHCl3);
1H NMR (500 MHz, CDCl3) δ 8.16 (s, 1H), 7.39-7.33 (m,
7H), 6.85-6.79 (m, 1H), 5.98 (d, J = 15.8 Hz, 1H), 5.17 (s, 2H), 3.13-3.06 (m, 1H), 2.93-2.85 (m, 1H),
1.63 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 169.50 (d, J = 21.0 Hz), 165.17, 148.29, 141.09 (d, J = 4.6
Hz), 138.27 (d, J = 7.3 Hz), 135.69, 128.60 (d, J = 12.8 Hz), 128.33, 128.20, 128.02, 127.85, 127.07,
126.06, 122.75 (d, J = 19.1 Hz), 119.39, 91.33 (d, J = 190.4 Hz), 85.80, 66.44, 38.18 (d, J = 29.2 Hz),
27.97; 19F NMR (282.38 MHz, CDCl3) δ -149.24 (dd, J1,2 = 12.4 Hz, J1,3 = 19.6 Hz); HRMS (ESI) m/z
calcd for C24H23BrFNNaO5 [M+Na]+ = 526.0636, found = 526.0645; The ee value was 94%, tR (major) =
15.8 min, tR (minor) = 14.1 min (Chiralcel IE, λ = 254 nm, 5% i-PrOH/hexanes, flow rate = 1.0 mL/min).
Racemic 7d
Enantiomerically enriched 7d
(R,E)-tert-Butyl 3-(4-(benzyloxy)-4-oxobut-2-enyl)-3-fluoro-2-oxo-5-(trifluoromethyl)indoline-
1-carboxylate (7e)
NBoc
O
F
COOBnF3C
7e
A white foam; []25D = +26.7 (c 0.27, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.8 Hz, 1H),
7.37-7.31 (m, 6H), 7.27 (d, J = 8.2 Hz, 1H), 6.87-6.81 (m, 1H), 5.99 (d, J = 15.8 Hz, 1H), 5.17 (s, 2H),
3.15-3.08 (m, 1H), 2.95-2.86 (m, 1H), 1.63 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 169.44 (d, J = 21.0
Hz), 165.06, 148.34, 146.07, 138.55 (d, J = 5.5 Hz), 137.87 (d, J = 6.4 Hz), 135.69, 128.57, 128.29 (d,
J = 16.2 Hz), 127.32, 125.45 (d, J = 19.1 Hz), 124.68, 121.40, 119.35, 118.16, 117.18, 91.30 (d, J =
192.2 Hz), 85.73, 66.45, 38.32 (d, J = 29.2 Hz), 27.97; 19F NMR (282.38 MHz, CDCl3) δ -58.28,
-150.80 (dd, J1,2 = 13.4 Hz, J1,3 = 20.6 Hz); HRMS (ESI) m/z calcd for C25H23F4NKO5 [M+K]+ =
532.1149, found = 532.1143; The ee value was 92%, tR (major) = 8.8 min, tR (minor) = 8.2 min
(Chiralcel IE, λ = 254 nm, 5% i-PrOH/hexanes, flow rate = 1.0 mL/min).
Racemic 7e
Enantiomerically enriched 7e
(R,E)-tert-Butyl 3-(4-(benzyloxy)-4-oxobut-2-enyl)-3-fluoro-5-methyl-2-oxoindoline-
1-carboxylate (7f)
NBoc
O
F
COOBnMe
7f
A white foam; []25D = +17.1 (c 0.88, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.76 (d, J = 8.2 Hz, 1H),
7.38-7.31 (m, 5H), 7.25-7.21 (m, 2H), 6.86-6.80 (m, 1H), 5.99 (d, J = 15.5 Hz, 1H), 5.17 (s, 2H),
3.12-3.05 (m, 1H), 2.97-2.91 (m, 1H), 2.35 (s, 3H), 1.62 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 170.26
(d, J = 21.0 Hz), 165.31, 148.59, 138.91 (d, J = 7.3 Hz), 137.76 (d, J = 5.5 Hz), 135.79, 134.97 (d, J =
2.7 Hz), 132.35 (d, J = 2.7 Hz), 128.56, 128.26, 128.13, 126.63, 125.27, 123.86 (d, J = 18.2 Hz),
115.55, 91.86 (d, J = 189.5 Hz), 85.02, 66.31, 38.36 (d, J = 30.1 Hz), 28.02, 20.98; 19F NMR (282.38
MHz, CDCl3) δ -148.47 (dd, J1,2 = 13.4 Hz, J1,3 = 18.6 Hz); HRMS (ESI) m/z calcd for C25H26FNNaO5
[M+Na]+ = 462.1687, found = 462.1701; The ee value was 90%, tR (major) = 27.9 min, tR (minor) = 23.3
min (Chiralcel IE, λ = 254 nm, 5% i-PrOH/hexanes, flow rate = 1.0 mL/min).
Racemic 7f
Enantiomerically enriched 7f
(R,E)-tert-Butyl 3-(4-(benzyloxy)-4-oxobut-2-enyl)-3-fluoro-5-methoxy-2-oxoindoline-1-
carboxylate (7g)
NBoc
O
F
COOBnMeO
7g
A white foam; []25D = +15.6 (c 0.40, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.82 (d, J = 8.8 Hz, 1H),
7.38-7.31 (m, 5H), 6.98-6.94 (m, 2H), 6.88-6.82 (m, 1H), 5.99 (d, J = 15.8 Hz, 1H), 5.16 (s, 2H), 3.77
(s, 3H), 3.13-3.06 (m, 1H), 2.95-2.86 (m, 1H), 1.62 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 170.19 (d, J
= 21.0 Hz), 165.25, 157.15 (d, J = 2.7 Hz), 148.61, 138.75 (d, J = 7.3 Hz), 135.76, 133.24 (d, J = 5.5
Hz), 128.56, 128.27 (d, J = 10.9 Hz), 126.79, 124.97 (d, J = 18.2 Hz), 117.02, 117.00, 116.88, 110.46,
91.92 (d, J = 190.5 Hz), 84.99, 66.34, 55.67, 38.42 (d, J = 29.2 Hz), 28.03; 19F NMR (282.38 MHz,
CDCl3) δ -149.56 (dd, J1,2 = 14.4 Hz, J1,3 = 19.6 Hz); HRMS (ESI) m/z calcd for C25H26FNNaO6
[M+Na]+ = 478.1636, found = 478.1647; The ee value was 94%, tR (major) = 33.0 min, tR (minor) = 31.7
min (Chiralcel IE, λ = 254 nm, 5% i-PrOH/hexanes, flow rate = 1.0 mL/min).
Racemic 7g
Enantiomerically enriched 7g
(R,E)-tert-Butyl
3-(4-(benzyloxy)-4-oxobut-2-enyl)-3-fluoro-5,7-dimethyl-2-oxoindoline-1-carboxylate (7h)
NBoc
O
F
COOBnMe
Me
7h
A white foam; []25D = +12.4 (c 0.36, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.37-7.32 (m, 5H), 7.05 (s,
2H), 6.85-6.79 (m, 1H), 5.97 (d, J = 15.8 Hz, 1H), 5.16 (s, 2H), 3.08-3.01 (m, 1H), 2.97-2.88 (m, 1H),
2.31 (s, 1H), 2.19 (s, 1H), 1.60 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 171.25 (d, J = 21.0 Hz), 165.29,
148.41, 139.05 (d, J = 7.3 Hz), 136.14 (d, J = 5.5 Hz), 135.86, 135.28 (d, J = 3.7 Hz), 134.96 (d, J =
2.7 Hz), 128.54, 128.21, 128.11, 126.50, 125.26 (d, J = 18.2 Hz), 124.55, 122.79, 92.61 (d, J = 190.4
Hz), 85.28, 66.26, 38.57 (d, J = 30.1 Hz), 27.76, 20.85, 19.48; 19F NMR (282.38 MHz, CDCl3) δ
-149.29 (t, J = 12.4 Hz); HRMS (ESI) m/z calcd for C26H28FNNaO5 [M+Na]+ = 476.1844, found =
476.1858; The ee value was 90%, tR (major) = 22.2 min, tR (minor) = 19.1 min (Chiralcel IE, λ = 254 nm,
5% i-PrOH/hexanes, flow rate = 1.0 mL/min).
Racemic 7h
Enantiomerically enriched 7h
(R,E)- Benzyl 4-(3-fluoro-2-oxoindolin-3-yl)but-2-enoate (7a’)
NH
O
F
COOBn
7a'
A white foam; []25D = +5.6 (c 0.22, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.50 (d, J = 7.0 Hz, 1H),
7.38-7.32 (m, 5H), 7.13 (t, J = 7.6 Hz, 1H), 6.97 (dt, J1,2 = 4.4 Hz, J1,3 = 15.8 Hz, 1H), 6.75 (d, J = 8.2
Hz, 1H), 5.97 (dt, J1,2 = 1.9 Hz, J1,3 = 15.8 Hz, 1H), 5.78 (d, J = 51.1 Hz, 1H), 5.16 (s, 2H), 4.55-4.50
(m, 1H), 4.42-4.37 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 170.85 (d, J = 18.2 Hz), 165.17, 143.26 (d,
J = 4.6 Hz), 140.53, 135.53, 131.58 (d, J = 2.7 Hz), 128.60, 128.40 (d, J = 2.7 Hz), 126.40, 123.67 (d,
J = 2.7 Hz), 123.10, 122.75 (d, J = 16.4 Hz), 109.28, 85.97 (d, J = 188.6 Hz), 66.63, 40.62; 19F NMR
(282.38 MHz, CDCl3) δ -192.47 (d, J = 50.5 Hz); HRMS (ESI) m/z calcd for C19H16FNNaO3 [M+Na]+
= 348.1012, found = 348.1017; The ee value was 43%, tR (major) = 32.5 min, tR (minor) = 24.5 min
(Chiralcel IE, λ = 254 nm, 40% i-PrOH/hexanes, flow rate = 1.0 mL/min).
Racemic 7a’
Enantiomerically enriched 7a’
6. Asymmetric Synthesis of Chiral 3-Fluoro-3-allyl Oxindole Derivatives
i) O3, DCM, - 78 oC
ii) Me3P=CH2, THF, 0 - RTNBoc
O
F CO2Bn
7a1
NBoc
O
F
8
Pd/C, H2
EA, 0 oC, 10 min
(76 % for two steps) (91%)NBoc
O
F
9
Found: []D25 = +15.5 (c 0.46 CHCl3)
Reported [3]: (R)-9 with 91% ee
[]D20 = +12.9 (c 1.09 CHCl3)
Scheme S3: Syntheis chiral 3-fluoro-3-allyl oxindole and its derivatives.
(R)-tert-Butyl 3-allyl-3-fluoro-2-oxoindoline-1-carboxylate (8)
NBoc
O
F
8
To a solution of 7a1 (85 mg, 0.20 mmol) in CH2Cl2 (3.0 mL) at -78 oC, O3 was bubbled until the
reaction was complete (monitored by TLC). Ph3P was added to quench the reaction at -78 oC, and then
kept stirring for another 10 min. The reaction mixture was warmed to room temperature and passed
through a short pad of silica gel, and eluted with EtOAc. The filtrate was concentrated and the residue
was purified by flash column chromatography on silical gel (hexane/ethyl acetate = 5:1) to afford the
corresponding aldehyde as a white foam, which was used directly in the next step.
To a solution of methyltrimethylphosphonium iodide (54 mg, 0.30 mmol) in dry THF (3.0 mL) at -78 oC, n-BuLi (133 µL, 2.0 M in hexane, 0.30 mmol) was slowly added and the mixture was kept stirring
at -78 oC for 1 h. Then, the mixture was warmed to 0 oC and stirred for another 1 h. The above crude
aldehyde in dry THF (2.0 mL) was introduced dropwise, and the resulting mixture was stirred at 0 oC
until the reaction was completed (monitored by TLC). The reaction mixture was filtrated by a short
pad of silica gel, and eluted with CH2Cl2. The filtrate was concentrated and the residue was purified by
flash column chromatography (hexane/ethyl acetate = 20:1) to afford pure compound 8 as a white
foam-oil (44.1 mg, 76% total yield). []25D = +13.5 (c 0.22, CHCl3);
1H NMR (500 MHz, CDCl3) δ
7.89 (d, J = 8.2 Hz, 1H), 7.47-7.41 (m, 2H), 7.22 (t, J = 7.6 Hz, 1H), 5.60-5.53 (m, 1H), 5.16 (d, J =
6.3 Hz, 1H), 5.13 (s, 1H), 3.01-2.94 (m, 1H), 2.88-2.80 (m, 1H), 1.64 (s, 9H); 13C NMR (125 MHz,
CDCl3) δ 170.78 (d, J = 21.0 Hz), 148.71, 140.21 (d, J = 4.6 Hz), 131.40 (d, J = 2.7 Hz), 128.44 (d, J =
8.2 Hz), 124.84, 124.68, 124.52, 121.50, 115.47, 92.50 (d, J = 188.6 Hz), 84.93, 40.06 (d, J = 28.2 Hz),
28.04; 19F NMR (282.38 MHz, CDCl3) δ -149.45 (dd, J1,2 = 11.4 Hz, J1,3 = 16.5 Hz); HRMS (ESI) m/z
calcd for C16H18FNNaO3 [M+Na]+ = 314.1170, found = 314.1168.
(R)-tert-Butyl 3-fluoro-2-oxo-3-propylindoline-1-carboxylate (9)
To a mixture of compound 8 (29 mg, 0.10 mmol) and 10% Pd/C (3 mg) in EtOAc (1.0 mL) at 0 oC, H2
was bubbled about 5 min, and the TLC shows that the reaction is completed. The catalyst Pd/C was
removed by filtration. The filtrate was concentrated and further purified by flash column
chromatography (hexane/ethyl acetate = 20:1) to give the known compound 9 as a white foam-solid
(26.5 mg, 91% yield). []25D = +15.5 (c 0.46, CHCl3);
1H NMR (500 MHz, CDCl3) δ 7.90 (d, J = 8.8
Hz, 1H), 7.44-7.41 (m, 2H), 7.23 (t, J = 7.6 Hz, 1H), 2.23-2.07 (m, 2H), 1.64 (s, 9H), 1.33-1.25 (m,
1H), 1.21-1.13 (m, 1H), 0.90 (t, J = 7.6 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 171.41 (d, J = 21.9
Hz), 148.81, 140.29 (d, J = 5.5 Hz), 131.27 (d, J = 2.7 Hz), 125.28 (d, J = 19.1 Hz), 124.95 (d, J = 2.7
Hz), 124.42, 115.50, 93.57 (d, J = 184.9 Hz), 84.90, 37.80 (d, J = 27.3 Hz), 28.05, 16.15 (d, J = 6.4
Hz), 13.95; 19F NMR (282.38 MHz, CDCl3) δ -148.30 (t, J = 13.4 Hz).
(R)-9 was reported in literature[3]: 91% ee, []20D = +12.9 (c 1.09, CHCl3). The above obtained
compound 9 was found to have an []25D = +15.5 (c 0.46, CHCl3). Therefore, the absolute
configuration of oxindole 7a1 was deduced to be R.
7. References
[1] (a) X. Han, Y. Wang, F. Zhong, Y. Lu, J. Am. Chem. Soc. 2011, 133, 1726; (b) X. Han, F. Zhong, Y. Wang, Y. Lu, Angew. Chem. Int. Ed. 2012, 51, 767; (c) F. Zhong, X. Han, Y. Wang, Y. Lu, Chem. Sci. 2012, 3, 1231; (d) F. Zhong, X. Han, Y. Wang, Y. Lu, Angew. Chem. Int. Ed. 2011, 50, 7837; (e) F. Zhong, J. Luo, G.-Y. Chen, X. Dou, Y. Lu, J. Am. Chem. Soc. 2012, 134, 10222; (f) F. Zhong, X. Dou, X. Han, W. Yao, Q, Zhu, Y. Meng, Y. Lu, Angew. Chem. Int. Ed. 2013, 52, 943; (g) T. Wang, W. Yao, F. Zhong, G. H. Pang, Y. Lu, Angew. Chem. Int. Ed. 2014, 53, 2964.
[2] X. Dou, Y. Lu, Org. Biomol. Chem., 2013, 11, 5217.
[3] X. Gu, Y. Zhang, Z.-J. Xu, C.-M. Che, Chem. Commun., 2014, 50, 7870.
8. NMR Spectra of the Products
0.90
97
1.97
54
1.00
00
9.16
32
Inte
gral
8.13
18
7.40
06
7.38
42
7.38
17
7.37
03
7.35
27
7.26
06
5.70
36
5.60
15
1.63
53
(ppm)
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0
*** Current Data Parameters ***
NAME : wtl-1114
EXPNO : 3
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 37
NUCLEUS : off
O1 : 3088.51 Hz
PULPROG : zg30
SFO1 : 500.1330885 MHz
SOLVENT : CDCl3
SW : 20.6557 ppm
TD : 32768
TE : 297.9 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 500.1300134 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
1H AMX500
HDL-75
168.
3434
168.
1977
148.
3979
141.
8757
141.
8392
128.
1463
128.
1244
127.
0750
125.
8143
125.
7852
120.
5893
120.
4581
119.
2338
85.6
172
85.2
309
83.7
152
77.2
585
77.0
035
76.7
557
27.9
886
(ppm)
102030405060708090100110120130140150160170180190
*** Current Data Parameters ***
NAME : wtl-1114
EXPNO : 2
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 415
NUCLEUS : off
O1 : 13204.57 Hz
PULPROG : zgpg30
SFO1 : 125.7709936 MHz
SOLVENT : CDCl3
SW : 238.7675 ppm
TD : 65536
TE : 298.5 K
*** Processing Parameters ***
LB : 1.00 Hz
SF : 125.7577906 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
13C AMX500
HDL-75
-187
.103
5-1
87.2
860
(ppm)
-215-210-205-200-195-190-185-180-175-170-165-160-155
*** Current Data Parameters ***
NAME : nov14-~1
EXPNO : 4
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 43
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : DMSO
SW : 239.2822 ppm
TD : 131072
TE : 296.3 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
HDL-75
-187
.103
5
-187
.286
0
(ppm)
-188.0-187.0-186.0
0.99
21
0.96
50
1.02
89
1.00
00
9.15
85
Inte
gral
7.96
407.
9464
7.38
667.
3236
7.30
597.
2606
5.76
785.
6670
1.63
27
(ppm)
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5
*** Current Data Parameters ***
NAME : wtl-1108
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 34
NUCLEUS : off
O1 : 3088.51 Hz
PULPROG : zg30
SFO1 : 500.1330885 MHz
SOLVENT : CDCl3
SW : 20.6557 ppm
TD : 32768
TE : 300.0 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 500.1300134 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
1H AMX500
hdl-70(5-CF3 sub)
0.99
21
0.96
50
1.02
89
Inte
gral
7.96
407.
9464
7.38
66
7.32
367.
3059
7.26
06(ppm)
7.37.47.57.67.77.87.98.08.1
168.
2419
168.
1034
148.
4494
146.
0956
139.
3693
139.
3329
124.
6051
123.
2205
123.
0820
121.
4278
119.
3728
119.
1104
116.
9898
85.5
448
85.1
877
83.6
647
77.2
518
76.9
967
76.7
489
27.9
818
(ppm)
102030405060708090100110120130140150160170180190
*** Current Data Parameters ***
NAME : wtl-1108
EXPNO : 2
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 743
NUCLEUS : off
O1 : 13204.57 Hz
PULPROG : zgpg30
SFO1 : 125.7709936 MHz
SOLVENT : CDCl3
SW : 238.7675 ppm
TD : 65536
TE : 300.2 K
*** Processing Parameters ***
LB : 1.00 Hz
SF : 125.7577906 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
13C AMX500
hdl-70(5-CF3 sub)
-58.
2780
-188
.443
3-1
88.6
222
(ppm)
-200-180-160-140-120-100-80-60-40-200
*** Current Data Parameters ***
NAME : nov08-~1
EXPNO : 8
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 14
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 298.5 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
hdl-70(5-CF3 sub)
-188
.443
3-1
88.6
222
(ppm)
-190-188-186
-193
.678
5-1
93.8
574
(ppm)
-210-200-190-180-170-160-150-140-130-120-110
*** Current Data Parameters ***
NAME : nov20-~1
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 17
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 299.1 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1051
-193
.678
5
-193
.857
4
(ppm)
-194.4-194.0-193.6-193.2-192.8-192.4
1.04
90
2.06
54
5.02
76
1.06
60
1.02
58
1.00
00
2.14
43
1.14
50
1.06
84
9.18
70
Inte
gral
7.42
20
7.40
69
7.38
04
7.37
54
7.36
65
7.36
27
7.35
14
7.34
76
7.33
75
7.33
38
7.33
00
7.32
37
7.31
48
7.31
11
7.26
06
7.23
92
7.22
41
7.20
89
6.89
50
6.88
24
6.87
86
6.86
48
6.85
09
6.84
71
6.83
45
5.99
61
5.96
46
5.16
53
3.15
19
3.14
81
3.13
80
3.13
55
3.12
29
3.11
28
3.10
90
3.10
65
3.09
77
3.09
39
3.08
38
3.08
13
2.96
53
2.94
89
2.94
64
2.93
51
2.92
62
2.92
37
2.91
99
2.91
74
2.90
73
2.89
72
2.87
83
1.63
27
(ppm)
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5
*** Current Data Parameters ***
NAME : wtl-1101
EXPNO : 3
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 30
NUCLEUS : off
O1 : 3088.51 Hz
PULPROG : zg30
SFO1 : 500.1330885 MHz
SOLVENT : CDCl3
SW : 20.6557 ppm
TD : 32768
TE : 297.8 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 500.1300134 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
1H AMX500
wtl-1038
1.04
90
2.06
54
5.02
76
1.06
60
Inte
gral
7.91
75
7.90
11
7.46
61
7.44
97
7.43
71
7.43
46
7.43
08
7.42
20
7.40
69
7.38
04
7.37
54
7.36
65
7.36
27
7.35
14
7.34
76
7.33
75
7.33
38
7.33
00
7.32
37
7.31
48
7.31
11
7.26
06
7.23
92
7.22
41
7.20
89
(ppm)
7.37.47.57.67.77.87.98.0
-148
.981
9-1
49.0
257
-149
.047
6-1
49.0
951
(ppm)
-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-100
*** Current Data Parameters ***
NAME : nov08-~1
EXPNO : 4
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 6
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 298.5 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1038
-148
.981
9-1
49.0
257
-149
.047
6-1
49.0
951
(ppm)
-149.6-149.2-148.8-148.4
NBoc
O
FCOOBn
7b
Cl
NBoc
O
FCOOBn
7b
Cl
-149
.562
4-1
49.6
135
-149
.671
9
(ppm)
-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-100
*** Current Data Parameters ***
NAME : nov08-~1
EXPNO : 2
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 35
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 298.6 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1040
-149
.562
4-1
49.6
135
-149
.671
9
(ppm)
-150.8-150.4-150.0-149.6-149.2
NBoc
O
FCOOBn
7b
Cl
-148
.751
9-1
48.7
957
-148
.821
3-1
48.8
651
(ppm)
-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-100
*** Current Data Parameters ***
NAME : nov08-~1
EXPNO : 3
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 37
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 298.5 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1039
-148
.751
9-1
48.7
957
-148
.821
3-1
48.8
651
(ppm)
-149.6-149.2-148.8-148.4
0.8
61
3
7.0
35
4
1.0
01
7
1.0
00
0
2.2
34
8
1.1
07
4
1.0
92
9
8.9
78
0
Inte
gra
l
8.1
58
37
.38
54
7.3
67
87
.35
77
7.3
50
17
.34
51
7.3
36
37
.32
87
7.2
60
66
.85
47
6.8
40
86
.83
83
6.8
24
46
.81
05
6.8
06
86
.79
29
5.9
89
85
.95
83
5.1
69
1
3.1
31
73
.12
92
3.1
17
93
.11
53
3.1
04
03
.09
01
3.0
77
53
.07
50
3.0
64
93
.06
24
2.9
32
52
.91
49
2.9
03
52
.89
22
2.8
87
12
.87
58
2.8
63
22
.84
68
1.6
27
7
︵ppm ︶
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
*** Current Data Parameters ***
NAME : wtl-1115
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
DS : 0
INSTRUM : spect
LOCNUC : 2H
NS : 30
NUCLEUS : off
O1 : 3088.51 Hz
PULPROG : zg30
SFO1 : 500.1330885 MHz
SOLVENT : CDCl3
SW : 20.6557 ppm
TD : 32768
TE : 297.8 K
*** Processing Parameters ***
LB : 0.30 Hz
OFFSET : 16.477 ppm
SI : 16384
*** 1D NMR Plot Parameters ***
NUCLEUS : off
1H AMX500
wtl-1054
16
9.4
95
01
69
.32
74
16
5.1
73
6
14
8.2
88
81
41
.08
88
14
1.0
52
41
38
.26
86
13
8.2
10
31
35
.68
89
12
8.5
98
31
28
.49
63
12
8.3
28
71
28
.20
48
12
8.0
15
31
27
.84
77
12
7.0
67
91
26
.06
23
12
2.7
53
81
22
.60
08
11
9.3
94
3
91
.33
07
89
.80
76
85
.79
95
77
.25
87
77
.00
37
76
.74
86
66
.44
43
38
.18
39
37
.95
07
27
.96
70
︵ppm ︶
102030405060708090100110120130140150160170180190
*** Current Data Parameters ***
NAME : wtl-1115
EXPNO : 2
PROCNO : 1
*** Acquisition Parameters ***
DS : 0
INSTRUM : spect
LOCNUC : 2H
NS : 3577
NUCLEUS : off
O1 : 13204.57 Hz
PULPROG : zgpg30
SFO1 : 125.7709936 MHz
SOLVENT : CDCl3
SW : 238.7675 ppm
TD : 65536
TE : 298.1 K
*** Processing Parameters ***
LB : 1.00 Hz
OFFSET : 224.383 ppm
SI : 32768
*** 1D NMR Plot Parameters ***
NUCLEUS : off
13C AMX500
wtl-1054
-149
.171
7-1
49.2
155
-149
.241
1-1
49.2
849
(ppm)
-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-100
*** Current Data Parameters ***
NAME : nov17-~1
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 93
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 299.2 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1054
-149
.171
7-1
49.2
155
-149
.241
1-1
49.2
849
(ppm)
-149.6-149.2-148.8-148.4
1.01
72
6.13
01
1.11
00
1.00
29
1.00
00
2.19
98
1.07
54
1.03
71
9.40
70
Inte
gral
7.98
93
7.97
17
7.36
52
7.36
15
7.35
01
7.34
51
7.34
00
7.33
12
7.32
36
7.30
60
7.27
83
7.26
06
6.86
73
6.85
46
6.85
09
6.83
70
6.82
31
6.81
93
6.80
55
5.99
36
5.96
20
5.17
28
3.14
56
3.14
18
3.13
17
3.12
92
3.11
66
3.10
27
3.09
01
3.08
76
3.07
75
2.95
02
2.93
25
2.92
12
2.90
73
2.90
48
2.89
22
2.88
08
2.86
19
1.62
64
(ppm)
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
*** Current Data Parameters ***
NAME : wtl-1110
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 34
NUCLEUS : off
O1 : 3088.51 Hz
PULPROG : zg30
SFO1 : 500.1330885 MHz
SOLVENT : CDCl3
SW : 20.6557 ppm
TD : 32768
TE : 299.9 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 500.1300134 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
1H AMX500
wtl-1045
NBoc
O
FCOOBn
7e
F3C
16
9.4
36
21
69
.26
86
16
5.0
63
8
14
8.3
39
31
46
.07
29
13
8.5
59
61
38
.51
59
13
7.8
74
61
37
.82
36
13
5.6
88
41
28
.56
86
12
8.2
99
01
28
.16
05
12
7.3
22
51
25
.45
69
12
5.3
03
91
24
.67
72
12
1.3
97
91
19
.35
01
11
8.1
62
31
17
.17
85
91
.30
10
89
.76
34
85
.73
35
77
.25
82
77
.00
32
76
.74
81
66
.45
11
38
.32
18
38
.08
86
27
.97
37
︵ppm ︶
102030405060708090100110120130140150160170180190
*** Current Data Parameters ***
NAME : wtl-1110
EXPNO : 2
PROCNO : 1
*** Acquisition Parameters ***
DS : 0
INSTRUM : spect
LOCNUC : 2H
NS : 12547
NUCLEUS : off
O1 : 13204.57 Hz
PULPROG : zgpg30
SFO1 : 125.7709936 MHz
SOLVENT : CDCl3
SW : 238.7675 ppm
TD : 65536
TE : 300.2 K
*** Processing Parameters ***
LB : 1.00 Hz
OFFSET : 224.383 ppm
SI : 32768
*** 1D NMR Plot Parameters ***
NUCLEUS : off
13C AMX500
wtl-1045
13
8.5
59
61
38
.51
59
13
7.8
74
61
37
.82
36
13
5.6
88
4
12
8.5
68
61
28
.29
90
12
8.1
60
51
27
.32
25
12
5.4
56
91
25
.30
39
12
4.6
77
2
︵ppm ︶
128132136
NBoc
O
FCOOBn
7e
F3C
-58.
2816
-150
.727
0-1
50.7
744
-150
.800
0-1
50.8
438
(ppm)
-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010
*** Current Data Parameters ***
NAME : nov10-~1
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 40
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 298.8 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1045
-150
.727
0-1
50.7
744
-150
.800
0-1
50.8
438
(ppm)
-151.6-151.2-150.8-150.4
NBoc
O
FCOOBn
7e
F3C
170.
2600
170.
0924
165.
3119
148.
5873
138.
9170
138.
8587
137.
7583
137.
7146
135.
7907
134.
9745
134.
9527
132.
3511
132.
3292
128.
5616
128.
2556
128.
1317
126.
6305
125.
2678
123.
8613
123.
7155
115.
5537
91.8
624
90.3
467
85.0
196
77.2
585
77.0
035
76.7
484
66.3
129
38.3
586
38.1
181
28.0
178
20.9
782
(ppm)
102030405060708090100110120130140150160170180190
*** Current Data Parameters ***
NAME : wtl-1101
EXPNO : 2
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 6825
NUCLEUS : off
O1 : 13204.57 Hz
PULPROG : zgpg30
SFO1 : 125.7709936 MHz
SOLVENT : CDCl3
SW : 238.7675 ppm
TD : 65536
TE : 298.1 K
*** Processing Parameters ***
LB : 1.00 Hz
SF : 125.7577916 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
13C AMX500
wtl-1037
-148
.405
1-1
48.4
525
-148
.470
8-1
48.5
182
(ppm)
-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-100
*** Current Data Parameters ***
NAME : nov08-~1
EXPNO : 6
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 30
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 298.5 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1037
-148
.405
1-1
48.4
525
-148
.470
8
-148
.518
2
(ppm)
-149.2-148.8-148.4-148.0
-149
.485
7-1
49.5
368
-149
.555
1-1
49.6
062
(ppm)
-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-100
*** Current Data Parameters ***
NAME : nov08-~1
EXPNO : 7
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 75
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 298.5 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1036
-149
.485
7-1
49.5
368
-149
.555
1-1
49.6
062
(ppm)
-150.0-149.6-149.2-148.8
5.04
32
1.99
11
0.98
27
1.00
00
1.97
75
1.01
97
1.02
91
3.02
24
3.04
51
9.06
13
Inte
gral
7.37
297.
3602
7.35
657.
3464
7.34
267.
3338
7.33
137.
3249
7.31
747.
2606
7.05
016.
8484
6.83
586.
8320
6.81
816.
8043
6.80
056.
7879
5.97
475.
9432
5.16
03
3.08
133.
0776
3.06
753.
0649
3.05
233.
0385
3.02
593.
0233
3.01
333.
0095
2.96
532.
9628
2.94
642.
9363
2.92
882.
9200
2.91
742.
9124
2.90
992.
9010
2.89
852.
8834
2.31
232.
1925
1.59
87
(ppm)
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
*** Current Data Parameters ***
NAME : wtl-1105
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 38
NUCLEUS : off
O1 : 3088.51 Hz
PULPROG : zg30
SFO1 : 500.1330885 MHz
SOLVENT : CDCl3
SW : 20.6557 ppm
TD : 32768
TE : 300.1 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 500.1300134 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
1H AMX500
wtl-1041
171.
2510
171.
0834
165.
2899
148.
4051
139.
0481
138.
9898
136.
1404
136.
0967
135.
8562
135.
2805
135.
2513
134.
9599
134.
9380
128.
5397
128.
2117
128.
1097
126.
4992
125.
2604
125.
1146
124.
5462
122.
7899
92.6
056
91.0
826
85.2
818
77.2
584
77.0
034
76.7
483
66.2
618
38.5
698
38.3
293
27.7
553
20.8
542
19.4
842
(ppm)
102030405060708090100110120130140150160170180190
*** Current Data Parameters ***
NAME : wtl-1108
EXPNO : 3
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 3932
NUCLEUS : off
O1 : 13204.57 Hz
PULPROG : zgpg30
SFO1 : 125.7709936 MHz
SOLVENT : CDCl3
SW : 238.7675 ppm
TD : 65536
TE : 300.1 K
*** Processing Parameters ***
LB : 1.00 Hz
SF : 125.7577906 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
13C AMX500
wtl-1041
-149
.252
1-1
49.2
959
-149
.354
3
(ppm)
-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-100
*** Current Data Parameters ***
NAME : nov08-~1
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 68
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 298.6 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1041
-149
.252
1-1
49.2
959
-149
.354
3
(ppm)
-149.6-149.2-148.8-148.4
0.97
27
5.06
07
0.96
84
0.96
10
0.98
59
0.92
58
1.00
00
2.03
04
1.05
87
1.06
62
Inte
gral
7.50
277.
4888
7.38
427.
3691
7.36
277.
3577
7.34
767.
3388
7.32
877.
3224
7.26
067.
1497
7.13
467.
1194
6.98
586.
9757
6.96
696.
9543
6.94
426.
9354
6.75
386.
7374
5.96
965.
9659
5.96
215.
9381
5.93
435.
9306
5.78
055.
6784
5.15
77
4.55
134.
5475
4.54
124.
5375
4.51
484.
5110
4.50
594.
5022
4.41
644.
4126
4.40
634.
4026
4.37
994.
3761
4.36
984.
3660
(ppm)
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5
*** Current Data Parameters ***
NAME : wtl-1125
EXPNO : 3
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 26
NUCLEUS : off
O1 : 3088.51 Hz
PULPROG : zg30
SFO1 : 500.1330885 MHz
SOLVENT : CDCl3
SW : 20.6557 ppm
TD : 32768
TE : 299.3 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 500.1300134 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
1H AMX500
wtl-1056
0.97
27
5.06
07
0.96
84
0.96
10
7.50
277.
4888
7.38
427.
3691
7.36
277.
3577
7.34
767.
3388
7.32
877.
3224
7.26
06
7.14
977.
1346
7.11
94
6.98
586.
9757
6.96
696.
9543
6.94
426.
9354
(ppm)
7.007.107.207.307.407.50
170.
8498
170.
7040
165.
1729
143.
2962
143.
2598
140.
5343
135.
5279
131.
5927
131.
5708
128.
6049
128.
4008
128.
3790
126.
3968
123.
6859
123.
6640
123.
1029
122.
7458
122.
6146
109.
2788
85.9
665
84.4
580
77.2
508
77.0
030
76.7
479
66.6
258
40.6
171
(ppm)
102030405060708090100110120130140150160170180190
*** Current Data Parameters ***
NAME : wtl-1125
EXPNO : 4
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 12100
NUCLEUS : off
O1 : 13204.57 Hz
PULPROG : zgpg30
SFO1 : 125.7709936 MHz
SOLVENT : CDCl3
SW : 238.7675 ppm
TD : 65536
TE : 299.2 K
*** Processing Parameters ***
LB : 1.00 Hz
SF : 125.7577907 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
13C AMX500
wtl-1056
131.
5927
131.
5708
128.
6049
128.
4008
128.
3790
126.
3968
123.
6859
123.
6640
123.
1029
122.
7458
122.
6146
(ppm)
123124125126127128129130131132
-192
.466
5-1
92.6
454
(ppm)
-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10
*** Current Data Parameters ***
NAME : nov24wtl
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 56
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 299.3 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1056
-192
.466
5-1
92.6
454
(ppm)
-194.0-193.0-192.0-191.0-190.0
0.96
25
2.00
33
1.00
89
1.00
00
1.10
34
0.96
23
1.10
60
1.10
26
9.33
63
Inte
gral
7.89
357.
8771
7.46
997.
4547
7.44
847.
4447
7.44
217.
4295
7.41
697.
4131
7.26
067.
2379
7.22
287.
2076
5.60
535.
6015
5.58
895.
5863
5.58
265.
5700
5.56
365.
5510
5.54
735.
5347
5.16
155.
1489
5.12
87
3.00
562.
9930
2.98
042.
9779
2.97
292.
9678
2.96
532.
9552
2.94
262.
8821
2.86
572.
8543
2.84
802.
8380
2.83
162.
8203
2.80
391.
6365
(ppm)
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
*** Current Data Parameters ***
NAME : wtl-1125
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 30
NUCLEUS : off
O1 : 3088.51 Hz
PULPROG : zg30
SFO1 : 500.1330885 MHz
SOLVENT : CDCl3
SW : 20.6557 ppm
TD : 32768
TE : 298.8 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 500.1300134 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
1H AMX500
wtl-1057-2
0.96
25
2.00
33
1.00
89
Inte
gral
7.89
357.
8771
7.46
997.
4547
7.44
847.
4447
7.44
217.
4295
7.41
697.
4131
7.26
067.
2379
7.22
287.
2076
(ppm)
7.37.47.57.67.77.87.9
170.
7848
170.
6172
148.
7113
140.
2143
140.
1778
131.
3965
131.
3747
128.
4379
128.
3723
124.
8379
124.
6776
124.
5246
121.
5003
115.
4663
92.5
038
90.9
954
84.9
250
77.2
514
76.9
963
76.7
413
40.0
639
39.8
380
28.0
397
(ppm)
102030405060708090100110120130140150160170180190
*** Current Data Parameters ***
NAME : wtl-1125
EXPNO : 2
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 766
NUCLEUS : off
O1 : 13204.57 Hz
PULPROG : zgpg30
SFO1 : 125.7709936 MHz
SOLVENT : CDCl3
SW : 238.7675 ppm
TD : 65536
TE : 299.5 K
*** Processing Parameters ***
LB : 1.00 Hz
SF : 125.7577906 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
13C AMX500
wtl-1057-2
131.
3965
131.
3747
128.
4379
128.
3723
124.
8379
124.
6776
124.
5246
(ppm)
124125126127128129130131132
-149
.394
4-1
49.4
346
-149
.452
9-1
49.4
930
(ppm)
-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10
*** Current Data Parameters ***
NAME : nov24wtl
EXPNO : 2
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 204
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 299.3 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1057-2
-149
.394
4-1
49.4
346
-149
.452
9
-149
.493
0
(ppm)
-149.8-149.6-149.4-149.2-149.0
0.91
00
1.84
82
0.94
77
2.04
69
9.00
00
1.11
75
1.14
38
3.03
72
Inte
gral
7.90
237.
8847
7.44
347.
4396
7.42
837.
4245
7.41
327.
4094
7.26
067.
2442
7.22
917.
2140
2.23
162.
2215
2.20
892.
2051
2.19
882.
1950
2.18
242.
1761
2.17
232.
1660
2.15
212.
1421
2.12
572.
1156
2.10
172.
0916
2.07
522.
0664
1.64
151.
3276
1.31
751.
3024
1.29
111.
2772
1.26
211.
2545
1.20
911.
2041
1.19
401.
1877
1.18
011.
1663
1.15
491.
1410
1.12
970.
9179
0.90
280.
8876
(ppm)
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
*** Current Data Parameters ***
NAME : wtl-1127
EXPNO : 2
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 29
NUCLEUS : off
O1 : 3088.51 Hz
PULPROG : zg30
SFO1 : 500.1330885 MHz
SOLVENT : CDCl3
SW : 20.6557 ppm
TD : 32768
TE : 298.8 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 500.1300134 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
1H AMX500
wtl-1057-3(a)
171.
4116
171.
2367
148.
8062
140.
2872
140.
2435
131.
2655
131.
2436
125.
2825
125.
1295
124.
9473
124.
9254
124.
4226
115.
4956
93.5
679
92.0
885
84.8
959
77.2
515
76.9
964
76.7
413
37.8
049
37.5
863
28.0
544
16.1
468
16.0
958
13.9
461
(ppm)
102030405060708090100110120130140150160170180190
*** Current Data Parameters ***
NAME : wtl-1129
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 3660
NUCLEUS : off
O1 : 13204.57 Hz
PULPROG : zgpg30
SFO1 : 125.7709936 MHz
SOLVENT : CDCl3
SW : 238.7675 ppm
TD : 65536
TE : 299.6 K
*** Processing Parameters ***
LB : 1.00 Hz
SF : 125.7577906 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
13C AMX500
wtl-1057-3(a)
125.
2825
125.
1295
124.
9473
124.
9254
124.
4226
(ppm)
124.0124.4124.8125.2125.6
-148
.244
4-1
48.2
956
-148
.343
0
(ppm)
-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-100
*** Current Data Parameters ***
NAME : nov27wtl
EXPNO : 1
PROCNO : 1
*** Acquisition Parameters ***
LOCNUC : 2H
NS : 93
NUCLEUS : off
O1 : -28240.22 Hz
PULPROG : zg
SFO1 : 282.3761148 MHz
SOLVENT : CDCl3
SW : 239.2822 ppm
TD : 131072
TE : 298.9 K
*** Processing Parameters ***
LB : 0.30 Hz
SF : 282.4043550 MHz
*** 1D NMR Plot Parameters ***
NUCLEUS : off
F19(no decoupled)
wtl-1057-3(a)
-148
.244
4-1
48.2
956
-148
.343
0
(ppm)
-148.8-148.4-148.0-147.6-147.2