germylation )–h bonds facile synthesis of β-germyl-α-amino · 2018-11-20 · 1. general...
TRANSCRIPT
Supporting Information
Facile synthesis of β-germyl-α-amino amides via Pd(II)-
catalyzed primary and secondary C(sp3)–H bonds
germylation
Zheng-Xin Zhou,† Wei-Hao Rao,‡ Ming-Hua Zeng,† and Yue-Jin Liu*,†
†Hubei Collaborative Innovation Center for Advanced Chemical Materials, Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, and College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China‡ College of Chemistry and Chemical Engineering, Xinyang Normal University, Xinyang, 464000, China§
Table of Contents:
1. General information S2
2. Experimental Section S3
2.1 Optimization for C(sp3)-H Germylation S3
2.2 General Procedure for C(sp3)-H Germylation S3
2.3 Scale-up Reaction for C(sp3)-H Germylation S4
2.4 Removal of directing group S15
2.5 Mechanistic Investigation S15
3. References S16
4. Spectra S17
S1
Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2018
1. General Information
Toluene was dried by Sodium, distilled under reduced pressure and stored under
nitrogen. Pd(OAc)2 (Stream), Ag2CO3 (Adamas), BINA-PO2H (Adamas) were
purchased from above mentioned company and used without additional purification.
Other chemical reagents were commercially available and directly used without any
further purification. NMR spectra were recorded on a Bruke Avance operating for 1H
NMR at 400 MHz, 13C NMR at 100 MHz, and 19F NMR at 376 MHz, using TMS as
internal standard. The peaks were internally referenced to TMS (0.00 ppm) or residual
undeuterated solvent signal (7.26 ppm for 1H NMR and 77.16 ppm for 13C NMR).
The following abbreviations (or combinations thereof) were used to explain
multiplicities: s = singlet, d = doublet, t = triplet, m = multiplet, b = broad. High
resolution mass spectroscopy (HRMS) analyses were performed at a Thermo
Scientific Exactive Plus. Inc mass instrument (ESI).
.
S2
2. Experimental Section
2.1 Optimization for C(sp3)-H Germylation
a The reactions were carried out 1a (0.10 mmol), 2 (0.50 mmol), Pd(OAc)2 (0.010 mmol), ligand(0.03 mmol), Ag2CO3 (0.20 mmol), NaHCO3 (0.20 mmol), LiOAc (0.05 mmol), toluene (1.0 mL),air, 125 C, 12 h. Yield of 1H NMR. b Isolated yield.
Pd(OAc)2 (10 mol%)
Ag2CO3, NaHCO3LiOAc, toluene,125 C
ligand (30 mol%)[GeMe3]2
1a 3a2
Entrya Yield of 3a
4
5
6
7
8 BINA-PO2H
55%
58%
45%
71%b
38%
Ligand
N-Boc-Val-OH
N-Boc-lle-OH
N-Boc-Ala-OH
BINA-PO2H
1
2
3
37%
42%
46%
AdCOOH
PivOH
MesCO2H
3.0 eq.
[GeMe3]2
5.0 eq.
5.0 eq.
5.0 eq.
5.0 eq.
5.0 eq.
5.0 eq.
5.0 eq.
NHQ
O
NPhthNHQ
O
NPhthH Me3Ge
9 BINA-PO2H 20%1.5 eq.
+
2.2 General Procedure for C(sp3)-H Germylation
Pd(OAc)2 10 mol%
Ag2CO3, NaHCO3LiOAc, toluene, 125 oC
BINA-PO2H 30 mol%
[Me3Ge]2 2
CONHQ
R,R
H
CONHQ
R,R
GeMe3
To an oven-dried 50 mL screw-capped vial was added substrate amides (0.15 mmol),
hexamethylgermane (0.75 mmol), Pd(OAc)2 (3.5 mg, 0.015 mmol), BINA-PO2H
(15.2 mg, 0.045 mmol), Ag2CO3 (82.8 mg, 0.3 mmol), NaHCO3 (25.2 mg, 0.3 mmol),
LiOAc (4.7 mg, 0.075 mmol), toluene (1.0 mL). The mixture was stirred for 10 h at
125 °C under air followed by cooling. The resulting mixture was filtered through a
S3
celite pad and concentrated in vacuo. The residue was purified by preparative TLC
using hexane/EtOAc as the eluent to afford the product.
2.3 Scale-up Reaction for C(sp3)-H Germylation
Pd(OAc)2 10 mol%
Ag2CO3, NaHCO3LiOAc, toluene, 125 oC
BINA-PO2H 30 mol%
[Me3Ge]2 2
PhthN CONHQ PhthN CONHQ
GeMe3H1a 3a
To an oven-dried 50 mL screw-capped vial was added substrate amides (1.0 mmol),
hexamethylgermane (5.0 mmol), Pd(OAc)2 (23 mg, 0.1 mmol), BINA-PO2H (0.3
mmol), Ag2CO3 (2.0 mmol), NaHCO3 (2.0 mmol), LiOAc (1.0 mmol), toluene (5.0
mL). The mixture was stirred for 24 h at 125 °C under air followed by cooling. The
resulting mixture was filtered through a celite pad and concentrated in vacuo. The
residue was purified by flash column chromatography using hexane/EtOAc as the
eluent to afford the product 3a in 65% yield.
NHO
N
N
O
O
GeMe3
(R)-2-(1,3-dioxoisoindolin-2-yl)-N-(quinolin-8-yl)-3-
(trimethylgermyl)propanamide 3a
1H NMR (400 MHz, CDCl3) δ = 10.47 (br, 1H), 8.75 (dd, J=4.4, 1.6, 1H), 8.72 (t,
J=4.4, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.89 (dd, J=5.6, 3.1, 2H), 7.74 (dd, J=5.6, 3.1,
2H), 7.50 (d, J=4.4, 2H), 7.43 (dd, J=8.4, 4.4, 1H), 5.23 (dd, J=12.0, 5.6, 1H), 2.20
(dd, J=13.6, 12.0, 1H), 1.80 (dd, J=13.6, 5.6, 1H), 0.18 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ = 168.37, 168.19, 148.51, 138.75, 136.41, 134.34, 134.20, 132.11, 128.03,
127.45, 123.71, 122.00, 121.74, 116.79, 53.25, 17.21, -1.80; HRMS (EI-TOF) calcd
for C23H23N3O3GeNa (M+Na)+: 486.0843, found: 486.0833.
S4
NHO
N
N
O
O
GeMe3
Ph
(2R,3S)-2-(1,3-dioxoisoindolin-2-yl)-3-phenyl-N-(quinolin-8-yl)-3-
(trimethylgermyl)propanamide 3b1H NMR (400 MHz, CDCl3) δ = 10.85 (s, 1H), 8.90 (dd, J=4.4, 1.6, 1H), 8.80 (dd,
J=5.6, 3.2, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.71-7.68 (m, 2H), 7.59-7.53-7.50 (m, 2H),
7.53-7.50 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 7.14-7.08 (m, 4H), 6.97-6.93 (m, 1H),
5.64 (d, J=13.6, 1H), 4.00 (d, J=13.6, 1H), 0.13 (s, 9H); 13C NMR (100 MHz, CDCl3)
δ = 168.24, 167.14, 148.78, 140.29, 138.93, 136.28, 134.56, 134.06, 131.44, 128.43,
128.06, 127.38, 125.41, 123.45, 122.23, 121.77, 117.39, 59.42, 36.62, -2.19; HRMS
(EI-TOF) calcd for C29H27N3O3Ge Na (M+Na)+: 562.1162, found: 562.1147.
NHO
N
N
O
O
GeMe3
OMe
(2R,3S)-2-(1,3-dioxoisoindolin-2-yl)-3-(4-methoxyphenyl)-N-(quinolin-8-yl)-3-
(trimethylgermyl)propanamide 3c
dr~15:1 estimated by 1H NMR. 1H NMR (400 MHz, CDCl3)δ = 10.86 (br, 1H), 8.90
(dd, J=4.4, 1.6, 1H), 8.79 (dd, J=5.6, 3.2, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.71 (dd,
J=5.6, 3.0, 2H), 7.58 (dd, J=5.6, 3.0, 2H), 7.52-7.50 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H),
5.57 (d, J=13.6, 1H), 3.93 (d, J=13.6, 1H), 3.66 (s, 3H), 0.12 (s, 9H); 13C NMR (100
MHz, CDCl3) δ = 168.26, 167.22, 157.33, 148.76, 138.93, 136.26, 134.58, 134.07,
132.19, 131.47, 128.06, 127.38, 123.47, 122.21, 121.75, 117.39, 113.89, 59.71, 55.18,
35.54, -2.21; HRMS (EI-TOF) calcd for C30H29N3O4GeNa (M+Na)+: 592.1268,
found: 592.1254.
S5
NHO
N
N
O
O
GeMe3
Et
(2R,3S)-2-(1,3-dioxoisoindolin-2-yl)-3-(4-ethylphenyl)-N-(quinolin-8-yl)-3-
(trimethylgermyl)propanamide 3d1H NMR (400 MHz, CDCl3) δ = 10.86 (br, 1H), 8.90 (dd, J=4.4, 1.6, 1H), 8.80 (dd,
J=5.6, 3.2, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.70 (dd, J=5.6, 3.2, 2H), 7.57 (dd, J=5.6,
3.2, 2H), 7.53-7.51 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 6.99 (d, J=8.4, 2H), 6.93 (d,
J=8.0, 2H), 5.61 (d, J=13.6, 1H), 3.95 (d, J=13.6, 1H), 2.44 (d, J=7.6, 2H), 1.04 (t,
J=7.6, 3H), 0.13 (s, 9H); 13C NMR (100 MHz, CDCl3) δ = 168.30, 167.28, 148.77,
141.18, 138.95, 137.15, 136.26, 134.61, 133.98, 131.53, 128.06, 127.83, 127.38,
123.42, 122.20, 121.75, 117.40, 59.69, 36.15, 28.33, 15.44, -2.17; HRMS (EI-TOF)
calcd for C31H31N3O3Ge Na (M+Na)+: 590.1475, found: 590.1460.
NHO
N
N
O
O
GeMe3
Me
(2R,3S)-2-(1,3-dioxoisoindolin-2-yl)-N-(quinolin-8-yl)-3-(p-tolyl)-3-
(trimethylgermyl)propanamide 3e
dr ~ 12.5:1 estimated by 1H NMR. 1H NMR (400 MHz, CDCl3)δ = 10.86 (br, 1H),
8.90 (dd, J=4.4, 1.6, 1H), 8.79 (dd, J=5.6, 3.2, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.70 (td,
J=5.6, 2.4, 2H), 7.58 (dd, J=5.6, 3.2, 2H), 7.53-7.50 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H),
6.98 (d, J=8.0, 2H), 6.92 (d, J=8.0, 2H), 5.61 (d, J=13.6, 1H), 3.96 (d, J=13.6, 1H),
2.15 (s, 3H), 0.12 (s, 9H); 13C NMR (100 MHz, CDCl3) δ = 168.25, 167.24, 148.77,
138.95, 136.93, 136.26, 134.74, 134.60, 134.01, 131.52, 129.14, 128.06, 127.38,
123.47, 122.20, 121.75, 117.39, 59.61, 36.08, 21.02, -2.21; HRMS (EI-TOF) calcd
for C30H29N3O3Ge Na (M+Na)+: 576.1318, found: 576.1302.
S6
NHO
N
N
O
O
GeMe3
Br
(2R,3S)-3-(4-bromophenyl)-2-(1,3-dioxoisoindolin-2-yl)-N-(quinolin-8-yl)-3-
(trimethylgermyl)propanamide 3f
dr ~ 4:1 estimated by 1H NMR. 1H NMR of main product (400 MHz, CDCl3) δ =
10.78 (br, 1H), 8.88 (dd, J=4.4, 1.6, 1H), 8.79-8.76 (m, 1H), 8.14 (dd, J=8.4, 1.6, 1H),
7.73 (dd, J=5.6, 3.2, 2H), 7.62 (dd, J=5.6, 3.2, 2H), 7.52 (d, J=4.0, 2H), 7.45 (dd,
J=8.4, 4.4, 1H), 7.27-7.25 (m, 2H), 6.98 (d, J=8.4, 2H), 5.58 (d, J=13.6, 1H), 4.00 (d,
J=13.6, 1H), 0.13 (s, 9H); 13C NMR (100 MHz, CDCl3) δ = 168.19, 166.76, 148.79,
139.63, 138.89, 136.31, 134.44, 134.27, 134.07, 131.59, 131.36, 128.44, 128.07,
127.39, 123.63, 123.47, 122.33, 121.81, 119.03, 117.39, 58.95, 36.12, -2.19, -2.22;
HRMS (EI-TOF) calcd for C29H26BrN3O3Ge Na (M+Na)+: 640.0267, found:
640.0248.
NHO
N
N
O
O
GeMe3
F
(2R,3S)-2-(1,3-dioxoisoindolin-2-yl)-3-(4-fluorophenyl)-N-(quinolin-8-yl)-3-
(trimethylgermyl)propanamide 3g1H NMR (400 MHz, CDCl3) δ 10.82 (s, 1H), 8.88 (dd, J = 4.0, 1.6 Hz, 1H), 8.79 (dd,
J = 5.2, 3.6 Hz, 1H), 8.14 (dd, J = 8.4, 1.6 Hz, 1H), 7.72 (dd, J = 5.6, 3.2 Hz, 2H),
7.61 (dd, J = 5.6, 3.2 Hz, 2H), 7.45 (dd, J = 8.4, 4.2 Hz, 1H), 7.05 (dd, J = 8.8, 5.2 Hz,
2H), 6.83 (t, J = 8.8 Hz, 2H), 5.58 (d, J = 13.6 Hz, 1H), 3.98 (d, J = 13.6 Hz, 1H),
0.14 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 168.20, 166.90, 160.85, 148.78, 138.91,
136.30, 136.12(d, J = 3.1 Hz),134.49, 134.22, 131.36, 128.94, 128.06, 127.39, 123.54,
122.04 (d, J = 50.1 Hz), 117.38, 115.33(d, J = 21.1 Hz), 59.39, 35.76, -2.21; 19F NMR
(376 MHz, CDCl3) δ -117.79; HRMS (EI-TOF) calcd for C29H26FN3O3GeNa
(M+Na)+: 580.1068, found: 580.1057.
S7
NHO
N
N
O
O
GeMe3OMe
(2R,3S)-2-(1,3-dioxoisoindolin-2-yl)-3-(3-methoxyphenyl)-N-(quinolin-8-yl)-3-
(trimethylgermyl)propanamide 3h
D.r. = 15:1 estimated by 1H NMR. 1H NMR (400 MHz, CDCl3) δ = 10.86 (br, 1H),
8.89 (dd, J=4.4, 1.6, 1H), 8.80 (dd, J=5.6, 3.2, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.71 (dd,
J=5.6, 3.2, 2H), 7.58 (dd, J=5.6, 3.2, 2H), 7.53-7.51 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H),
5.73 (d, J=13.2, 0H), 5.63 (d, J=13.6, 1H), 3.98 (d, J=13.6, 1H), 3.71 (s, 3H), 0.15 (s,
9H); 13C NMR (100 MHz, CDCl3) δ = 168.23, 167.08, 159.56, 148.77, 141.90,
138.93, 136.27, 134.56, 134.08, 131.48, 129.38, 128.06, 127.37, 123.48, 122.23,
121.76, 117.40, 111.65, 59.37, 55.24, 36.75, -2.13; HRMS (EI-TOF) calcd for
C30H29N3O4Ge Na (M+Na)+: 592.1268, found: 592.1254.
NHO
N
N
O
O
GeMe3F
(2R,3S)-2-(1,3-dioxoisoindolin-2-yl)-3-(3-fluorophenyl)-N-(quinolin-8-yl)-3-
(trimethylgermyl)propanamide 3i
dr~14:1 estimated by 1H NMR. 1H NMR (400 MHz, CDCl3) δ = 10.80 (br, 1H), 8.88
(dd, J=4.4, 1.6, 1H), 8.78 (dd, J=5.2, 4.0, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.73 (dd,
J=5.6, 3.1, 2H), 7.60 (dd, J=5.6, 3.2, 2H), 7.53-7.51 (m, 2H), 7.44 (dd, J=8.4, 4.2, 1H),
7.10 (td, J=8.0, 6.4, 1H), 6.88 (d, J=8.0, 1H), 6.82 (dt, J=10.0, 2.0, 1H), 6.67 (td,
J=8.4, 2.0, 1H), 5.60 (d, J=13.5, 1H), 4.03 (d, J=13.6, 1H), 0.15 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ = 168.13, 166.75, 162.81 (d, J=244.2), 148.78, 143.27 (d, J=7.3),
138.87, 136.29, 134.43, 134.19, 131.36, 129.89, 128.04 (s, 3H), 127.36, 123.56,
122.31, 121.79, 117.36, 112.45 (d, J=21.1), 59.02, 36.59, -2.17; 19F NMR (376 MHz,
CDCl3) δ -112.97; HRMS (EI-TOF) calcd for C29H26N3O3Ge Na (M+Na)+: 580.1068,
found: 580.1051.
S8
NHO
N
N
O
O
GeMe3S
(2R,3R)-2-(1,3-dioxoisoindolin-2-yl)-N-(quinolin-8-yl)-3-(thiophen-2-yl)-3-
(trimethylgermyl)propanamide 3j
dr ~ 4:1 estimated by 1H NMR. 1H NMR of the main product (400 MHz, CDCl3) δ =
10.84 (s, 1H), 8.90 (dd, J=4.4, 1.6, 1H), 8.78 (t, J=4.4, 1H), 8.14 (dd, J=8.4, 1.6, 1H),
8.07 (dd, J=8.4, 1.6, 0H), 7.77-7.74 (m, 2H), 7.62 (dd, J=5.6, 3.2, 2H), 7.52 (d, J=4.4,
2H), 7.45 (dd, J=8.4, 4.4, 1H), 6.88 (d, J=5.2, 1H), 6.76-6.72 (m, 2H), 5.48 (d, J=13.2,
1H), 4.34 (d, J=13.2, 1H), 0.20 (s, 9H); 13C NMR (100 MHz, CDCl3) δ = 168.20,
166.67, 148.81, 143.39, 138.93, 136.28, 134.50, 134.15, 131.52, 128.06, 127.36,
126.82, 124.13, 123.92, 123.56, 122.34, 122.31, 121.78, 117.45, 60.76, 31.29, -2.20;
HRMS (EI-TOF) calcd for C27H25SN3O3GeNa (M+Na)+: 568.0726, found: 568.0707.
NAc
GeMe3O
HN
N
(2R,3S)-1-acetyl-N-(quinolin-8-yl)-3-(trimethylgermyl)pyrrolidine-2-
carboxamide 3k1H NMR (400 MHz, CDCl3) δ 9.93 (br, 1H), 8.55 (dd, J = 4.0, 1.6 Hz, 1H), 8.31 (d, J
= 8.4 Hz, 1H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.78 (dd, J =
12.4, 7.6 Hz, 2H), 7.59-7.37 (m, 5H), 7.29 (dd, J = 8.0, 4.0 Hz, 1H), 4.64 (t, J = 7.6
Hz, 1H), 1.82 (dd, J = 14.8, 7.2 Hz, 1H), 1.52 (dd, J = 14.8, 8.4 Hz, 1H), -0.06 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 173.29, 148.13, 138.54, 137.63, 136.16, 134.77,
134.40, 131.69, 129.19, 128.14, 127.89, 127.41, 126.61, 125.81, 125.77, 123.60,
121.50, 121.34, 116.17, 46.81, 20.75, -1.03; HRMS (EI-TOF) calcd for
C19H25N3O2Ge Na (M+Na)+: 424.1056, found: 424.1037.
S9
ON
HN
GeMe3
2-phenyl-N-(quinolin-8-yl)-3-(trimethylgermyl)propanamide 5a
1H NMR (400 MHz, CDCl3) δ 9.93 (br, 1H),8.76- 8.74 (m, 2H), 8.10 (dd, J = 8.0, 1.6
Hz, 1H), 7.51-7.24 (m, 8H), 3.85 (dd, J = 9.2, 7.2 Hz, 1H), 1.75 (dd, J = 13.6, 6.8 Hz,
1H), 1.51 (dd, J = 13.6, 9.2 Hz, 1H), 0.05 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
173.18, 148.26, 141.57, 138.64, 136.36, 134.76, 128.97, 128.09, 128.01, 127.51,
127.45, 121.62, 121.46, 116.40, 51.81, 21.39, -1.73; HRMS (EI-TOF) calcd for
C21H24N2OGeNa (M+Na)+: 417.0998, found: 417.0980.
ON
HN
GeMe3
Me
N-(quinolin-8-yl)-2-(o-tolyl)-3-(trimethylgermyl)propanamide 5b1H NMR (400 MHz, CDCl3) δ 9.87 (br, 1H), 8.74 (d, J = 7.4 Hz, 1H), 8.68 (d, J = 2.8
Hz, 1H), 8.09 (d, J = 7.2 Hz, 1H), 7.55-7.43 (m, 3H), 7.37 (dd, J = 8.0, 4.0 Hz, 1H),
7.25-7.17 (m, 3H), 4.11 (dd, J = 8.4, 7.6 Hz, 1H), 2.52 (s, 3H), 1.79 (dd, J = 13.6, 7.2
Hz, 1H), 1.50 (dd, J = 13.6, 9.2 Hz, 1H), 0.07 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
173.32, 148.24, 139.57, 138.62, 136.31, 135.91, 134.81, 130.95, 127.98, 127.54,
127.50, 127.24, 126.80, 121.58, 121.38, 116.31, 47.30, 20.73, 20.17, -1.59; HRMS
(EI-TOF) calcd for C22H26N2OGe Na (M+Na)+: 431.1155, found: 431.1139.
ON
HN
GeMe3
Cl
2-(2-chlorophenyl)-N-(quinolin-8-yl)-3-(trimethylgermyl)propanamide 5c
S10
1H NMR (400 MHz, CDCl3) δ 9.85 (br, 1H), 8.83-8.79 (m, 2H), 8.16 (dd, J = 8.0, 1.2
Hz, 1H), 7.56-7.44 (m, 3H), 2.58-2.51 (m, 1H), 1.87-1.78 (m, 1H), 1.60-1.53 (m, 1H),
1.40-1.25 (m, 8H), 1.13 (dd, J = 14.8, 8.8 Hz, 1H), 0.91-0.82 (m, 4H), 0.03 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 175.71, 148.30, 138.63, 136.45, 134.75, 128.09,
127.63, 121.67, 121.36, 116.59, 45.31, 36.74, 31.85, 29.49, 27.69, 22.74, 21.11, 14.19,
-0.94; HRMS (EI-TOF) calcd for C21H23ClN2OGeNa (M+Na)+: 451.0608, found:
451.0588.
ON
HN
GeMe3
F
2-(2-fluorophenyl)-N-(quinolin-8-yl)-3-(trimethylgermyl)propanamide 5d1H NMR (400 MHz, CDCl3) δ10.04 (br, 1H), 8.78-8.74 (m, 2H), 8.11 (d, J = 8.0 Hz,
1H), 7.58 (t, J = 6.8 Hz, 1H), 7.52-7.45 (m, 2H), 7.41 (dd, J = 8.0, 4.0 Hz, 1H), 7.24-
7.21 (m, 1H), 7.16 (t, J = 7.2 Hz, 1H), 7.07 (t, J = 7.2 Hz, 1H), 4.27 (dd, J = 8.4, 7.6
Hz, 1H), 1.75 (dd, J = 13.6, 7.2 Hz, 1H), 1.51 (dd, J = 13.6, 8.8 Hz, 1H), 0.08 (s, 9H);
13C NMR (100 MHz, CDCl3) 172.28, 161.41 (d, J = 243.2 Hz), 148.38, 138.65,
136.32, 134.74, 129.36 (d, J = 3.8 Hz), 128.84 (d, J = 8.3 Hz), 128.52 (d, J = 14.6
Hz),128.01, 127.46, 124.74 (d, J = 3.5 Hz), 121.63 (d, J = 8.3 Hz), 116.52, 115.73,
115.50, 43.03 (d, J = 2.6 Hz), 20.17, -1.81; 19F NMR (376 MHz, CDCl3) δ -118.12;
HRMS (EI-TOF) calcd for C21H23FN2OGe Na (M+Na)+: 435.0904, found: 435.0888.
ON
HN
GeMe3Cl
2-(3-chlorophenyl)-N-(quinolin-8-yl)-3-(trimethylgermyl)propanamide 5e1H NMR (400 MHz, CDCl3) δ 9.96 (br, 1H), 8.77 (dd, J = 4.0, 1.6 Hz, 1H), 8.73 (dd,
J = 7.2, 1.6 Hz, 1H), 8.12 (dd, J = 8.4, 1.6 Hz, 1H), 7.52-7.38 (m, 5H), 7.30-7.23 (m,
2H), 3.83 (t, J = 8.0 Hz, 1H), 1.73 (dd, J = 13.6, 7.2 Hz, 1H), 1.46 (dd, J = 13.6, 8.8
Hz, 1H), 0.08 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 172.35, 148.32, 143.72, 138.54,
136.52, 134.74, 134.49, 130.15, 128.19, 128.04, 127.62, 127.52, 126.27, 121.72,
S11
116.62, 51.47, 21.52, -1.70; HRMS (EI-TOF) calcd for C21H23ClN2OGeNa (M+Na)+:
451.0608, found: 451.0588.
ON
HN
GeMe3F
2-(3-fluorophenyl)-N-(quinolin-8-yl)-3-(trimethylgermyl)propanamide 5f
1H NMR (400 MHz, CDCl3) δ = 9.95 (br, 1H), 8.77 (dd, J=4.4, 1.6, 1H), 8.73 (dd,
J=7.2, 1.6, 1H), 8.12 (dd, J=8.4, 1.6, 1H), 7.52-7.46 (m, 2H), 7.42 (dd, J=8.4, 4.4, 1H),
7.34-7.22 (m, 3H), 6.98-6.93 (m, 1H), 3.84 (dd, J=8.4, 7.6, 1H), 1.73 (dd, J=13.6, 7.2,
1H), 1.47 (dd, J=13.7, 8.8, 1H), 0.07 (s, 9H); 13C NMR (100 MHz, CDCl3) δ =
172.45, 164.44, 161.99, 148.36, 144.21, 144.14, 138.61, 136.43, 134.56, 130.41,
130.33, 128.03, 127.50, 123.81, 123.78, 121.71, 121.67, 116.50, 115.09, 114.87,
114.48, 114.27, 51.53, 51.51, 21.44, -1.72; 19F NMR (376 MHz, CDCl3) δ = -
112.59.;HRMS (EI-TOF) calcd for C21H23FN2OGeNa (M+Na)+: 435.0904, found:
435.0886.
ON
HN
GeMe3
F
2-(4-fluorophenyl)-N-(quinolin-8-yl)-3-(trimethylgermyl)propanamide 5g1H NMR (400 MHz, CDCl3) δ 9.93 (br, 1H), 8.76 (dd, J=4.4, 1.6, 1H), 8.73 (dd,
J=7.2, 1.6, 1H), 8.12 (dd, J=8.4, 1.6, 1H), 7.52-7.41 (m, 5H), 7.07-7.02 (m, 2H), 3.84
(dd, J=9.2, 6.8, 1H), 1.72 (dd, J=13.6, 6.8, 1H), 1.48 (dd, J=13.6, 9.2, 1H), 0.06 (s,
9H); 13C NMR (100 MHz, CDCl3) δ 173.03, 163.49, 161.05, 148.33, 138.61, 137.36,
137.32, 136.44, 134.60, 129.63, 129.55, 128.03, 127.50, 121.69, 121.63, 116.46,
115.86, 115.65, 51.00, 21.61, -1.71; 19F NMR (376 MHz, CDCl3) δ -115.46; HRMS
(EI-TOF) calcd for C21H23FN2OGeNa (M+Na)+: 435.0904, found: 435.0856.
S12
ON
HN
GeMe3
F3C
N-(quinolin-8-yl)-2-(4-(trifluoromethyl)phenyl)-3-(trimethylgermyl)propanamide
5h
1H NMR (400 MHz, CDCl3) δ10.47 (br, 1H), 8.75 (dd, J=4.4, 1.6, 1H), 8.72 (t, J=4.4,
1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.89 (dd, J=5.2, 3.2, 2H), 7.74 (dd, J=5.2, 3.2, 2H),
7.50 (d, J=4.4, 2H), 7.43 (dd, J=8.4, 4.4, 1H), 5.23 (dd, J=12.0, 5.6, 1H), 2.20 (dd,
J=13.6, 12.0, 1H), 1.80 (dd, J=13.6, 5.6, 1H), 0.18 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ172.22, 148.37, 142.66, 138.60, 136.45, 134.44, 131.54,131.22 (q, J=32.0),
129.39, 128.03, 127.48, 124.87 (q, J=3.8), 124.32 (q, J=3.8), 124.25 (q, J=270.8),
121.78 (d, J=1.8), 116.55, 51.63, 21.67, -1.73; 19F NMR (376 MHz, CDCl3) δ -62.52;
HRMS (EI-TOF) calcd for C22H23F3N2OGeNa (M+Na)+: 485.0872, found: 485.0856.
ON
HN
GeMe3
ClCl
2-(3,4-dichlorophenyl)-N-(quinolin-8-yl)-3-(trimethylgermyl)propanamide 5i1H NMR (400 MHz, CDCl3) δ9.95 (br, 1H), 8.79 (dd, J=4.4, 1.6, 1H), 8.71 (dd, J=6.8,
2.4, 1H), 8.14 (dd, J=8.0, 1.6, 1H), 7.62 (d, J=2.0, 1H), 7.53-7.34 (m, 5H), 3.80 (t,
J=8.0, 1H), 1.73 (dd, J=13.6, 8.0, 1H), 1.42 (dd, J=13.6, 8.4, 1H), 0.10 (s, 9H).; 13C
NMR (100 MHz, CDCl3) δ171.92, 148.44, 142.05, 138.57, 136.51, 134.38, 132.89,
131.45, 130.78, 129.97, 128.05, 127.50, 127.40, 121.86, 121.79, 116.60, 50.99, 21.60,
-1.64; HRMS (EI-TOF) calcd for C21H22Cl2N2OGeNa (M+Na)+: 485.2019, found:
485.0196.
S13
ON
HN
GeMe3
2-(naphthalen-2-yl)-N-(quinolin-8-yl)-3-(trimethylgermyl)propanamide 5j1H NMR (400 MHz, CDCl3) δ 10.95 (s, 1H), 8.86-8.84 (m, 2H), 8.15 (dd, J=8.4, 1.6,
1H), 7.58-7.53 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 7.15-7.05 (m, 3H), 6.91 (td, J=7.6,
0.8, 1H), 5.53 (d, J=9.2, 1H), 3.36 (d, J=9.2, 1H), 0.15 (s, 9H).; 13C NMR (100 MHz,
CDCl3) δ 173.04, 148.24, 139.15, 138.60, 136.32, 134.70, 133.76, 132.89, 128.75,
127.97, 127.95, 127.79, 127.47, 126.79, 126.26, 126.10, 125.88, 121.59, 121.49,
116.40, 51.93, 21.35, -1.62; HRMS (EI-TOF) calcd for C25H26N2OGeNa (M+Na)+:
476.1155, found: 476.1140.
ON
HN
GeMe3O
N-(quinolin-8-yl)-3-(trimethylgermyl)-2,3-dihydrobenzofuran-2-carboxamide 5k1H NMR (400 MHz, CDCl3) δ 10.95 (s, 1H), 8.86-8.84 (m, 2H), 8.15 (dd, J=8.4, 1.6,
1H), 7.58-7.53 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 7.15-7.05 (m, 3H), 6.91 (td, J=7.6,
0.8, 1H), 5.53 (d, J=9.2, 1H), 3.36 (d, J=9.2, 1H), 0.15 (s, 9H).; 13C NMR (100 MHz,
CDCl3) δ168.52, 157.73, 148.80, 138.95, 136.27, 133.90, 130.96, 128.15, 127.38,
126.95, 123.60, 122.33, 121.84, 121.73, 116.91, 110.05, 86.08, 36.63, -1.75; HRMS
(EI-TOF) calcd for C21H22N2O2Na (M+Na)+: 431.0791, found: 431.0773.
ON
HN
GeMe3O
N-(quinolin-8-yl)-3-(trimethylgermyl)tetrahydrofuran-2-carboxamide 5l1H NMR (400 MHz, CDCl3) δ 10.82 (br, 1H), 8.85 (dd, J=4.4, 1.6, 1H), 8.77 (dd,
J=6.4, 2.8, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.55-7.49 (m, 2H), 7.44 (dd, J=8.4, 4.4, 1H),
S14
4.74-4.72 (m, 1H), 4.47-4.43 (m, 1H), 3.90-3.84 (m, 1H), 2.12-2.04 (m, 1H), 1.91-
1.82 (m, 2H), 0.23 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 171.65, 148.74, 139.04,
136.26, 134.17, 128.16, 127.42, 121.88, 121.70, 116.47, 82.21, 69.57, 32.62, 28.53, -
1.78; HRMS (EI-TOF) calcd for C17H22N2O2GeNa (M+Na)+: 383.0791, found:
383.0777.
2.4 Removal of Directing Group
BF3.Et2ONHQ
NPhth
O
3ab, 82%MeOH, 80 C
Me3Ge OMeNPhth
O
Me3Ge
3a
To an oven-dried 50 mL round-bottomed flask was added substrate 3a (0.1 mmol),
BF3·Et2O (1.0 mmol) in MeOH (1 mL). The flask was stirred for 12 h at 80 °C. The
crude product was purified by prepared column chromatography(Rf = 0.7, EtOAc/PE
= 1/5) to afford 3ab (31.0 mg, 85%). 1H NMR (400 MHz, CDCl3) δ 7.90 – 7.84 (m,
2H), 7.77 – 7.71 (m, 2H), 4.97 (dd, J = 11.1, 5.7 Hz, 1H), 3.72 (s, 3H), 1.80 (dd, J =
14.1, 11.1 Hz, 1H), 1.69 (dd, J = 14.1, 5.7 Hz, 1H), 0.10 (s, 9H). 13C NMR (101 MHz,
CDCl3) δ = 170.87, 167.42, 134.02, 131.71, 123.34, 52.65, 49.85, 16.98, -2.23.
HRMS (EI-TOF) calcd for C15H19GeNNaO4 (M+Na)+: 374.0424, found: 374.0415.
2.5 Mechanistic Investigation
Synthesis of Palladacycle Int-A
NH
Me
NPhth
O
Int-A1a
Pd(OAc)2 NPd
PhthNN
NCMe
N
O
DCM-MeCN
To an oven-dried 50 mL round-bottomed flask was added substrate 1a (1.0 mmol),
Pd(OAc)2 (1.0 mmol) in DCM (10 mL) and MeCN (5 mL). The flask was stirred for
12 h at 60 °C followed by cooling. The purified product was collected by filtration,
washed with MeCN, diethyl ether and dried under vacuum to afford Int-A (392 mg,
S15
80%) as yellow power.1 1H NMR (501 MHz, CDCl3) δ 8.93 (d, J = 7.5 Hz, 1H), 8.18
(s, 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.83 (s, 2H), 7.68 (s, 2H), 7.40 (t, J = 8.0 Hz, 1H),
7.19 (d, J = 7.5 Hz, 1H), 7.15 (dd, J = 7.5, 4.5 Hz, 1H), 5.32 (t, J = 10.0 Hz, 1H), 2.40
(t, J = 9.0 Hz, 1H), 2.32 (s, 3H),1.95 (t, J = 8.0 Hz, 1H).
Stoichiometric Reaction of Int-A
Int-A
NHQNPhth
O
3a, 46%
(GeMe3)2 Me3Gestandard conditions
NPd
O
PhthNN
NCMe
To an oven-dried 50 mL screw-capped vial was added Int-A (0.1 mmol), 2 (0.5
mmol), BINA-PO2H (0.03 mmol), Ag2CO3 (0.2 mmol), NaHCO3 (0.2 mmol), LiOAc
(0.05 mmol), toluene (1.0 mL). The mixture was stirred for 10 h at 125 °C under air
followed by cooling. The resulting mixture was filtered through a celite pad and
concentrated in vacuo. The product 3a was obtained in 52% yield (determined by 1H
NMR).
Catalytic Reaction of Int-A
NHQMe
NPhth
O
1a
(GeMe3)2
standard conditions
cat. Int-A NHQNPhth
O
3a, 53%
Me3Ge
To an oven-dried 50 mL screw-capped vial was added 1a (0.1 mmol),2 (0.5 mmol),
Int-A (0.01 mmol), BINA-PO2H (0.03 mmol), Ag2CO3 (0.2 mmol), NaHCO3 (0.2
mmol), LiOAc (0.05 mmol), toluene (1.0 mL). The mixture was stirred for 10 h at 125
°C under air followed by cooling. The resulting mixture was filtered through a celite
pad and concentrated in vacuo. The product 3a was obtained in 28% yield
(determined by 1H NMR yield).
3. References:
S16
1. Liu, Y.-J.; Liu, Y.-H.; Zhang, Z.-Z.; Chen, K.; Shi, B.-F., Angew. Chem. Int. Ed.
2016, 55, 13859.
4. NMR Spectra
-2-1012345678910111213f1 (ppm)
8.92
1.00
1.03
1.00
1.03
2.00
1.99
1.96
0.99
1.00
1.00
0.96
0.17
7
1.77
81.
792
1.81
2
2.17
12.
200
2.20
42.
234
5.20
95.
222
5.23
95.
252
7.41
27.
444
7.73
37.
754
7.89
7
8.70
48.
727
8.74
9
10.4
75
1H NMR (400 MHz, CDCl3) δ = 10.47 (br, 1H), 8.75 (dd, J=4.4, 1.6, 1H), 8.72 (t, J=4.4, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.89 (dd, J=5.6, 3.1, 2H), 7.74 (dd, J=5.6, 3.1, 2H), 7.50 (d, J=4.4, 2H), 7.43 (dd, J=8.4, 4.4, 1H), 5.23 (dd, J=12.0, 5.6, 1H), 2.20 (dd, J=13.6, 12.0, 1H), 1.80 (dd, J=13.6, 5.6, 1H), 0.18 (s, 9H).
S17
NHO
N
N
O
O
GeMe3
3a
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-1.7
96
17.2
06
53.2
48
116.7
9312
1.74
512
3.71
012
8.02
813
4.19
713
6.41
3
148.
510
168.
188
168.
371
13C NMR (101 MHz, CDCl3) δ = 168.37, 168.19, 148.51, 138.75, 136.41, 134.34, 134.20, 132.11, 128.03, 127.45, 123.71, 122.00, 121.74, 116.79, 53.25, 17.21, -1.80.
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
9.03
0.98
1.00
1.02
3.97
1.03
1.92
2.03
2.00
0.98
1.00
1.00
0.95
0.13
4
3.98
04.
014
5.62
25.
656
6.93
26.
956
7.12
47.
433
7.56
3
8.12
88.
148
8.78
68.
794
8.80
08.
809
8.88
98.
893
10.8
53
1H NMR (400 MHz, CDCl3) δ = 10.85 (s, 1H), 8.90 (dd, J=4.4, 1.6, 1H), 8.80 (dd, J=5.6, 3.2, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.71-7.68 (m, 2H), 7.59-7.53-7.50 (m, 2H), 7.53-7.50 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 7.14-7.08 (m, 4H), 6.97-6.93 (m, 1H), 5.64 (d, J=13.6, 1H), 4.00 (d, J=13.6, 1H), 0.13 (s, 9H).
S18
NHO
N
N
O
O
GeMe3
3a
NHO
N
N
GeMe3
O
O3b
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-2.1
93
36.6
17
59.4
23
117.3
9012
1.76
512
2.23
412
3.45
512
5.41
412
7.38
512
8.06
212
8.43
313
1.43
713
4.06
3
136.
276
148.
776
167.
137
168.
235
13C NMR (101 MHz, CDCl3) δ = 168.24, 167.14, 148.78, 140.29, 138.93, 136.28, 134.56, 134.06, 131.44, 128.43, 128.06, 127.38, 125.41, 123.45, 122.23, 121.77, 117.39, 59.42, 36.62, -2.19.
-1.00.01.02.03.04.05.06.07.08.09.010.011.012.013.0f1 (ppm)
8.83
3.05
1.00
1.00
1.04
1.96
2.01
2.02
0.98
1.01
0.96
0.96
0.12
5
3.65
93.
916
3.95
0
5.55
75.
591
6.65
86.
688
7.02
47.
442
8.12
48.
145
8.78
28.
790
8.79
68.
804
8.90
2
10.8
58
d.r. = 15:1 determined by 1H NMR. 1H NMR (400 MHz, CDCl3)δ = 10.86 (br, 1H), 8.90 (dd, J=4.4, 1.6, 1H), 8.79 (dd, J=5.6, 3.2, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.71 (dd, J=5.6, 3.0, 2H), 7.58 (dd, J=5.6, 3.0, 2H), 7.52-7.50 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 5.57 (d, J=13.6, 1H), 3.93 (d, J=13.6, 1H), 3.66 (s, 3H), 0.12 (s, 9H).
S19
NHO
N
N
GeMe3
O
O3b
NHO
N
N
GeMe3
O
O
OMe
3c
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-2.2
13
35.5
36
55.1
7759
.714
113.8
8611
7.387
121.
751
122.
208
123.
470
127.
376
128.
055
131.
472
132.
188
134.
067
134.
583
136.
263
148.
763
157.
329
167.
218
168.
263
13C NMR (101 MHz, CDCl3) δ = 168.26, 167.22, 157.33, 148.76, 138.93, 136.26, 134.58, 134.07, 132.19, 131.47, 128.06, 127.38, 123.47, 122.21, 121.75, 117.39, 113.89, 59.71, 55.18, 35.54, -2.21.
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
8.86
2.98
1.00
1.00
1.94
2.01
1.02
2.00
1.98
2.00
0.98
1.04
0.97
0.97
0.12
1
2.15
0
3.94
53.
979
5.59
35.
627
6.91
36.
933
6.97
0
7.51
1
8.12
58.
146
8.78
38.
792
8.79
78.
806
8.90
0
10.8
57
d.r. = 12.5:1 determined by 1H NMR. 1H NMR (400 MHz, CDCl3)δ = 10.86 (br, 1H), 8.90 (dd, J=4.4, 1.6, 1H), 8.79 (dd, J=5.6, 3.2, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.70 (td, J=5.6, 2.4, 2H), 7.58 (dd, J=5.6, 3.2, 2H), 7.53-7.50 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 6.98 (d, J=8.0, 2H), 6.92 (d, J=8.0, 2H), 5.61 (d, J=13.6, 1H), 3.96 (d, J=13.6, 1H), 2.15 (s, 3H), 0.12 (s, 9H).
S20
NHO
N
N
GeMe3
O
O
OMe
3c
NHO
N
N
GeMe3
O
O
Me
3d
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-2.2
09
21.0
16
36.0
77
59.6
14
117.3
9412
1.75
412
2.20
212
3.47
212
7.38
312
8.06
112
9.14
013
1.52
213
4.00
613
4.59
813
4.73
913
6.26
114
8.76
9
167.
242
168.
253
13C NMR (101 MHz, CDCl3) δ = 168.25, 167.24, 148.77, 138.95, 136.93, 136.26, 134.74, 134.60, 134.01, 131.52, 129.14, 128.06, 127.38, 123.47, 122.20, 121.75, 117.39, 59.61, 36.08, 21.02, -2.21.
-2-1012345678910111213f1 (ppm)
9.04
3.12
2.05
1.03
1.02
2.00
2.04
1.03
2.02
2.03
2.01
1.00
1.03
1.00
0.97
0.12
6
1.01
91.
038
1.05
7
2.43
32.
452
3.93
33.
966
5.59
15.
625
6.92
06.
981
7.43
1
8.12
4
8.78
78.
801
8.89
48.
904
10.8
62
1H NMR (400 MHz, CDCl3) δ = 10.86 (br, 1H), 8.90 (dd, J=4.4, 1.6, 1H), 8.80 (dd, J=5.6, 3.2, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.70 (dd, J=5.6, 3.2, 2H), 7.57 (dd, J=5.6, 3.2, 2H), 7.53-7.51 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 6.99 (d, J=8.4, 2H), 6.93 (d, J=8.0, 2H), 5.61 (d, J=13.6, 1H), 3.95 (d, J=13.6, 1H), 2.44 (d, J=7.6, 2H), 1.04 (t, J=7.6, 3H), 0.13 (s, 9H).
S21
NHO
N
N
GeMe3
O
O
Me
3d
NHO
N
N
GeMe3
O
O
Et
3e
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-2.1
74
15.4
37
28.3
35
36.1
46
59.6
91
117.3
9612
1.74
912
2.19
912
3.42
112
7.38
412
7.83
012
8.06
313
1.52
613
3.97
513
4.60
913
6.26
4
148.
771
167.
283
168.
301
13C NMR (101 MHz, CDCl3) δ = 168.30, 167.28, 148.77, 141.18, 138.95, 137.15, 136.26, 134.61, 133.98, 131.53, 128.06, 127.83, 127.38, 123.42, 122.20, 121.75, 117.40, 59.69, 36.15, 28.33, 15.44, -2.17.
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
9.86
1.23
1.00
2.04
3.10
1.05
2.08
1.91
2.06
1.05
1.00
1.02
0.91
3.98
34.
017
5.56
65.
599
6.96
97.
255
7.27
17.
457
7.51
7
7.72
18.
132
8.15
38.
762
8.77
48.
785
8.87
4
8.88
9
10.7
84
d.r. = 4:1 determined by 1H NMR. 1H NMR of main product (400 MHz, CDCl3) δ = 10.78 (br, 1H), 8.88 (dd, J=4.4, 1.6, 1H), 8.79-8.76 (m, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.73 (dd, J=5.6, 3.2, 2H), 7.62 (dd, J=5.6, 3.2, 2H), 7.52 (d, J=4.0, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 7.27-7.25 (m, 2H), 6.98 (d, J=8.4, 2H), 5.58 (d, J=13.6, 1H), 4.00 (d, J=13.6, 1H), 0.13 (s, 9H).
S22
NHO
N
N
GeMe3
O
O
Et
3e
NHO
N
N
GeMe3
O
O
Br
3f
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-2.2
15-2
.186
36.1
19
58.9
45
117.3
9311
9.034
121.
810
122.
330
123.
467
123.
634
127.
388
128.
065
128.
440
131.
359
131.
586
148.
792
166.
759
168.
186
13C NMR (101 MHz, CDCl3) δ = 168.19, 166.76, 148.79, 139.63, 138.89, 136.31, 134.44, 134.27, 134.07, 131.59, 131.36, 128.44, 128.07, 127.39, 123.63, 123.47, 122.33, 121.81, 119.03, 117.39, 58.95, 36.12, -2.19, -2.22.
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
9.01
1.02
1.05
2.01
2.02
1.02
2.03
2.00
1.01
1.04
1.00
0.99
0.13
7
3.96
74.
000
5.55
95.
593
6.80
76.
850
7.05
1
7.43
57.
597
8.13
18.
152
8.77
58.
784
8.78
88.
797
8.88
1
10.8
17
1H NMR (400 MHz, CDCl3) δ 10.82 (s, 1H), 8.88 (dd, J = 4.0, 1.6 Hz, 1H), 8.79 (dd, J = 5.2, 3.6 Hz, 1H), 8.14 (dd, J = 8.4, 1.6 Hz, 1H), 7.72 (dd, J = 5.6, 3.2 Hz, 2H), 7.61 (dd, J = 5.6, 3.2 Hz, 2H), 7.45
S23
NHO
N
N
GeMe3
O
O
Br
3f
NHO
N
N
GeMe3
O
O
F
3g
(dd, J = 8.4, 4.2 Hz, 1H), 7.05 (dd, J = 8.8, 5.2 Hz, 2H), 6.83 (t, J = 8.8 Hz, 2H), 5.58 (d, J = 13.6 Hz, 1H), 3.98 (d, J = 13.6 Hz, 1H), 0.14 (s, 9H).
-100102030405060708090100110120130140150160170180190200210
f1 (ppm)
-2.2
12
35.7
65
59.3
95
115.2
3311
5.444
117.3
8412
1.78
612
2.28
712
3.53
612
7.38
712
8.06
412
8.94
013
1.35
913
4.21
6
136.
299
148.
777
159.
638
162.
057
166.
900
168.
203
13C NMR (101 MHz, CDCl3) δ 168.20, 166.90, 160.85, 148.78, 138.91, 136.30, 136.12(d, J = 3.1 Hz),134.49, 134.22, 131.36, 128.94, 128.06, 127.39, 123.54, 122.04 (d, J = 50.1 Hz), 117.38, 115.33(d, J = 21.1 Hz), 59.39, 35.76, -2.21.
19F NMR (376 MHz, CDCl3) δ = -117.79.
S24
NHO
N
N
GeMe3
O
O
F
3g
NHO
N
N
GeMe3
O
O
F
3g
-2-1012345678910111213f1 (ppm)
9.00
3.04
1.01
1.00
0.07
1.03
2.07
2.01
2.06
1.00
1.03
0.98
1.00
0.14
8
3.71
33.
962
3.99
6
5.61
15.
645
6.49
86.
634
6.69
9
7.43
0
8.12
5
8.78
48.
798
8.88
78.
898
10.8
56
d.r. = 15:1 determined by 1H NMR. 1H NMR (400 MHz, CDCl3) δ = 10.86 (br, 1H), 8.89 (dd, J=4.4, 1.6, 1H), 8.80 (dd, J=5.6, 3.2, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.71 (dd, J=5.6, 3.2, 2H), 7.58 (dd, J=5.6, 3.2, 2H), 7.53-7.51 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 5.73 (d, J=13.2, 0H), 5.63 (d, J=13.6, 1H), 3.98 (d, J=13.6, 1H), 3.71 (s, 3H), 0.15 (s, 9H).
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-2.1
27
36.7
55
55.2
4459
.368
111.6
5511
7.397
122.
234
127.
373
129.
378
134.
083
136.
271
148.
773
159.
556
167.
082
168.
225
13C NMR (101 MHz, CDCl3) δ = 168.23, 167.08, 159.56, 148.77, 141.90, 138.93, 136.27, 134.56, 134.08, 131.48, 129.38, 128.06, 127.37, 123.48, 122.23, 121.76, 117.40, 111.65, 59.37, 55.24, 36.75, -2.13.
S25
NHO
N
N
GeMe3
O
O
OMe
3h
NHO
N
N
GeMe3
O
O
OMe
3h
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
9.01
1.00
1.00
1.00
1.01
1.03
1.00
1.03
2.00
2.05
2.03
1.01
1.02
1.04
1.01
0.15
2
4.01
34.
046
5.58
75.
621
6.64
56.
687
6.82
66.
893
7.42
9
7.73
68.
124
8.14
48.
771
8.78
18.
784
8.79
4
8.88
2
10.8
01
d.r. = 14:1 determined by 1H NMR. 1H NMR (400 MHz, CDCl3) δ = 10.80 (br, 1H), 8.88 (dd, J=4.4, 1.6, 1H), 8.78 (dd, J=5.2, 4.0, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.73 (dd, J=5.6, 3.1, 2H), 7.60 (dd, J=5.6, 3.2, 2H), 7.53-7.51 (m, 2H), 7.44 (dd, J=8.4, 4.2, 1H), 7.10 (td, J=8.0, 6.4, 1H), 6.88 (d, J=8.0, 1H), 6.82 (dt, J=10.0, 2.0, 1H), 6.67 (td, J=8.4, 2.0, 1H), 5.60 (d, J=13.5, 1H), 4.03 (d, J=13.6, 1H), 0.15 (s, 9H).
-100102030405060708090100110120130140150160170180190200210
f1 (ppm)
-2.1
67
36.5
92
59.0
24
112.2
6011
2.469
117.3
5912
2.30
712
7.35
612
9.85
213
1.35
513
4.43
2
148.
778
161.
591
164.
033
166.
754
168.
129
13C NMR (101 MHz, CDCl3) δ = 168.13, 166.75, 162.81 (d, J=244.2), 148.78, 143.27 (d, J=7.3), 138.87, 136.29, 134.43, 134.19, 131.36, 129.89, 128.04 (s, 3H), 127.36, 123.56, 122.31, 121.79, 117.36, 112.45 (d, J=21.1), 59.02, 36.59, -2.17
S26
NHO
N
N
GeMe3
O
O
F
3i
NHO
N
N
GeMe3
O
O
F
3i
19F NMR (376 MHz, CDCl3) δ = -112.97.
-1.00.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
8.67
1.01
0.99
1.95
0.98
1.00
2.03
2.02
2.13
0.25
1.00
0.94
0.96
0.91
0.19
9
4.32
04.
353
5.46
35.
496
6.71
86.
737
6.88
87.
437
7.61
88.
130
8.15
18.
771
8.78
28.
794
8.89
7
8.90
8
10.8
42
d.r. = 4:1 determined by 1H NMR. 1H NMR (400 MHz, CDCl3) δ = 10.84 (s, 1H), 8.90 (dd, J=4.4, 1.6, 1H), 8.78 (t, J=4.4, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 8.07 (dd, J=8.4, 1.6, 0H), 7.77-7.74 (m, 2H), 7.62 (dd, J=5.6, 3.2, 2H), 7.52 (d, J=4.4, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 6.88 (d, J=5.2, 1H), 6.76-6.72 (m, 2H), 5.48 (d, J=13.2, 1H), 4.34 (d, J=13.2, 1H), 0.20 (s, 9H).
S27
NHO
N
N
GeMe3
O
O
S
3j
NHO
N
N
GeMe3
O
O
F
3i
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-2.1
98
31.2
94
60.7
57
117.4
4612
1.78
512
2.30
912
2.34
112
3.56
412
3.91
912
4.13
212
6.81
612
7.36
412
8.06
513
1.52
213
4.15
414
8.80
7
166.
670
168.
201
13C NMR (101 MHz, CDCl3) δ = 168.20, 166.67, 148.81, 143.39, 138.93, 136.28, 134.50, 134.15, 131.52, 128.06, 127.36, 126.82, 124.13, 123.92, 123.56, 122.34, 122.31, 121.78, 117.45, 60.76, 31.29, -2.20.
-1.00.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.5f1 (ppm)
9.01
1.17
1.27
2.20
0.76
1.03
0.65
1.08
1.05
0.70
0.21
3.00
1.00
0.98
0.99
0.96
0.18
3
1.65
01.
685
1.87
11.
905
2.08
72.
159
2.32
53.
465
3.51
43.
581
3.85
04.
061
4.52
94.
870
4.89
0
5.83
9
7.26
07.
421
7.44
37.
471
8.10
5
8.67
78.
708
8.80
1
10.2
6010
.333
d.r. = 2.4:1 determined by 1H NMR.1H NMR(400 MHz, CDCl3) δ = 10.27 (s, 1H), 8.81-8.79 (m, 1H), 8.72-8.68 (m, 1H), 8.12 (dd, J=8.4, 1.6, 1H), 7.54-7.40 (m, 3H), 5.84 (s, 0.21 H), 4.88 (d, J=8.4, 1H), 4.12-3.85 (m, 1H), 3.80 (s, 0.65 H), 3.61-3.47 (m, 1H), 2.38-2.27 (m, 0.76 H), 2.16 (s, 2H), 2.09 (s, 1H), 1.93-1.63 (m, 1H), 0.18 (s, 9H).
S28
NHO
GeMe3
N
NAc
3k
NHO
N
N
GeMe3
O
O
S
3j
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-2.6
47-2
.402
22.6
2622
.868
26.0
0427
.933
31.9
2734
.020
47.4
38
56.5
84
64.0
1966
.580
107.
519
116.5
7412
1.66
512
7.31
013
3.62
313
6.27
713
8.59
614
8.46
714
8.97
2
157.
416
169.
874
169.
903
170.
321
186.
952
13C NMR (101 MHz, CDCl3) δ = 186.95, 170.32, 169.90, 169.87, 157.42, 148.97, 148.47, 138.69, 138.60, 136.38, 136.28, 134.43, 133.62, 128.03, 127.38, 127.31, 122.36, 121.95, 121.70, 121.67, 116.61, 116.57, 107.52, 66.58, 64.02, 56.58, 48.73, 47.44, 34.02, 31.93, 27.93, 26.00, 22.87, 22.63, -2.40, -2.65.
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.5f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
120009.
00
1.02
1.00
1.00
8.29
0.98
1.93
0.97
0.05
0
1.48
21.
505
1.51
71.
540
1.72
31.
740
1.75
71.
774
3.82
83.
846
3.85
13.
869
7.24
07.
255
7.27
67.
332
7.35
27.
370
7.38
27.
393
7.49
08.
089
8.09
28.
109
8.73
68.
741
8.74
68.
755
9.93
4
1H NMR (400 MHz, CDCl3) δ 9.93 (br, 1H),8.76- 8.74 (m, 2H), 8.10 (dd, J = 8.0, 1.6 Hz, 1H), 7.51-7.24 (m, 8H), 3.85 (dd, J = 9.2, 7.2 Hz, 1H), 1.75 (dd, J = 13.6, 6.8 Hz, 1H), 1.51 (dd, J = 13.6, 9.2 Hz, 1H), 0.05 (s, 9H).
S29
NHO
GeMe3
N
NAc
3k
ON
HN
GeMe3
5a
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
-1.7
29
21.3
90
51.8
12
116.
401
121.
461
127.
446
134.
760
138.
642
148.
263
173.
181
13C NMR (101 MHz, CDCl3) δ 173.18, 148.26, 141.57, 138.64, 136.36, 134.76, 128.97, 128.09, 128.01, 127.51, 127.45, 121.62, 121.46, 116.40, 51.81, 21.39, -1.73
-10123456789101112f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
9.07
1.01
1.00
3.04
0.99
3.15
0.99
3.04
1.00
0.96
0.98
0.98
0.07
3
1.47
51.
497
1.50
91.
532
1.76
21.
780
2.51
5
4.09
04.
111
4.13
0
7.17
07.
233
7.35
97.
379
7.42
57.
470
7.54
5
8.07
78.
095
8.67
88.
685
8.74
59.
874
1H NMR (400 MHz, CDCl3) δ 9.87 (br, 1H), 8.74 (d, J = 7.4 Hz, 1H), 8.68 (d, J = 2.8 Hz, 1H), 8.09 (d, J = 7.2 Hz, 1H), 7.55-7.43 (m, 3H), 7.37 (dd, J = 8.0, 4.0 Hz, 1H), 7.25-7.17 (m, 3H), 4.11 (dd, J = 8.4, 7.6 Hz, 1H), 2.52 (s, 3H), 1.79 (dd, J = 13.6, 7.2 Hz, 1H), 1.50 (dd, J = 13.6, 9.2 Hz, 1H), 0.07 (s, 9H).
S30
ON
HN
GeMe3
5a
ON
HN
GeMe3
Me 5b
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
-1.5
89
20.1
6820
.727
47.2
97
116.
311
121.
383
126.
803
127.
540
139.
570
148.
240
173.
322
13C NMR (101 MHz, CDCl3) δ 173.32, 148.24, 139.57, 138.62, 136.31, 135.91, 134.81, 130.95, 127.98, 127.54, 127.50, 127.24, 126.80, 121.58, 121.38, 116.31, 47.30, 20.73, 20.17, -1.59
-2-1012345678910111213f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
17000
9.03
1.04
1.04
1.01
1.02
1.08
4.05
1.03
1.00
0.96
0.94
0.92
0.08
9
1.47
11.
492
1.50
51.
526
1.58
41.
716
1.73
51.
750
1.76
9
4.47
24.
492
4.51
2
7.16
57.
259
7.38
27.
419
7.46
87.
495
8.10
18.
121
8.72
98.
747
8.76
88.
778
10.0
70
1H NMR (400 MHz, CDCl3) δ 10.07 (br, 1H), 8.77 (dd, J = 4.0, 1.6 Hz, 1H), 8.74 (dd, J = 7.2, 1.6 Hz, 1H), 8.11 (dd, J = 8.0, 1.2 Hz, 1H), 7.63 (d, J = 7.6 Hz, 1H), 752-7.38 (m, 4H), 7.29 (d, J = 7.6 Hz, 1H),
S31
ON
HN
GeMe3
Me 5b
ON
HN
GeMe3
Cl 5c
7.18 (t, J = 7.6 Hz, 1H), 4.49 (t, J = 8.0 Hz, 1H), 1.74 (dd, J = 13.6, 7.6 Hz, 1H), 1.50 (dd, J = 13.6, 8.4 Hz, 1H), 0.09 (s, 9H).
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
-1.6
75
20.6
27
46.6
70
116.
510
121.
585
127.
457
128.
005
129.
191
136.
296
148.
393
172.
190
13C NMR (101 MHz, CDCl3) δ 172.19, 148.39, 139.16, 138.64, 136.30, 134.82, 133.60, 129.72, 129.19, 128.47, 128.01, 127.55, 127.46, 121.68, 121.59, 116.51, 46.67, 20.63, -1.68
-2-10123456789101112f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
9.07
1.03
1.03
0.96
0.97
1.03
0.92
1.01
2.08
1.05
1.00
2.07
0.99
0.07
9
1.47
91.
501
1.51
31.
535
1.72
61.
744
1.76
01.
778
4.24
94.
270
4.28
9
7.04
97.
141
7.21
27.
260
7.41
97.
469
7.49
8
8.10
58.
125
8.74
18.
759
8.77
2
10.0
44
1H NMR (400 MHz, CDCl3) δ 10.04 (br, 1H), 8.78-8.74 (m, 2H), 8.11 (d, J = 8.0 Hz, 1H), 7.58 (t, J = 6.8 Hz, 1H), 7.52-7.45 (m, 2H), 7.41 (dd, J = 8.0, 4.0 Hz, 1H), 7.24-7.21 (m, 1H), 7.16 (t, J = 7.2 Hz,
S32
ON
HN
GeMe3
Cl 5c
ON
HN
GeMe3
F 5d
1H), 7.07 (t, J = 7.2 Hz, 1H), 4.27 (dd, J = 8.4, 7.6 Hz, 1H), 1.75 (dd, J = 13.6, 7.2 Hz, 1H), 1.51 (dd, J = 13.6, 8.8 Hz, 1H), 0.08 (s, 9H).
-100102030405060708090100110120130140150160170180190200210
f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
6500
7000-1.8
05
20.1
67
43.0
1343
.039
115.
502
115.
728
116.
519
121.
587
128.
453
134.
743
136.
321
148.
379
159.
195
161.
627
172.
282
13C NMR (101 MHz, CDCl3) δ 172.28, 161.41 (d, J = 243.2 Hz), 148.38, 138.65, 136.32, 134.74, 129.36 (d, J = 3.8 Hz), 128.84 (d, J = 8.3 Hz), 128.52 (d, J = 14.6 Hz),128.01, 127.46, 124.74 (d, J = 3.5 Hz), 121.63 (d, J = 8.3 Hz), 116.52, 115.73, 115.50, 43.03 (d, J = 2.6 Hz), 20.17, -1.81.
19F NMR (376 MHz, CDCl3) δ = -118.12.
S33
ON
HN
GeMe3
F 5d
ON
HN
GeMe3
F 5d
-1.00.01.02.03.04.05.06.07.08.09.010.011.012.0f1 (ppm)
-2000
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
22000
24000
26000
9.00
1.00
1.04
1.00
2.16
5.05
1.00
1.02
0.97
0.97
0.07
8
1.43
01.
452
1.46
51.
486
1.70
81.
727
1.74
31.
761
3.80
63.
826
3.84
6
7.22
67.
242
7.25
17.
276
7.38
17.
406
7.42
77.
454
7.51
78.
110
8.11
48.
131
8.71
78.
735
8.76
68.
776
9.95
5
1H NMR (400 MHz, CDCl3) δ 9.96 (br, 1H), 8.77 (dd, J = 4.0, 1.6 Hz, 1H), 8.73 (dd, J = 7.2, 1.6 Hz, 1H), 8.12 (dd, J = 8.4, 1.6 Hz, 1H), 7.52-7.38 (m, 5H), 7.30-7.23 (m, 2H), 3.83 (t, J = 8.0 Hz, 1H), 1.73 (dd, J = 13.6, 7.2 Hz, 1H), 1.46 (dd, J = 13.6, 8.8 Hz, 1H), 0.08 (s, 9H).
-100102030405060708090100110120130140150160170180190200210
f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500-1
.697
21.5
24
51.4
73
116.
624
121.
716
126.
273
128.
037
134.
491
143.
723
148.
323
172.
354
13C NMR (101 MHz, CDCl3) δ 172.35, 148.32, 143.72, 138.54, 136.52, 134.74, 134.49, 130.15,
128.19, 128.04, 127.62, 127.52, 126.27, 121.72, 116.62, 51.47, 21.52, -1.70.
S34
ON
HN
GeMe3Cl
5e
ON
HN
GeMe3Cl
5e
-1.5-0.50.51.52.53.54.55.56.57.58.59.510.511.512.5f1 (ppm)
8.99
1.06
1.04
1.02
1.00
3.47
1.02
2.05
1.00
1.00
0.99
0.95
0.07
4
1.44
31.
465
1.47
71.
499
1.70
71.
725
1.74
1
3.82
53.
844
3.86
5
6.93
26.
961
6.98
27.
258
7.30
17.
340
7.48
58.
111
8.72
38.
741
8.76
99.
948
1H NMR (400 MHz, CDCl3) δ = 9.95 (br, 1H), 8.77 (dd, J=4.4, 1.6, 1H), 8.73 (dd, J=7.2, 1.6, 1H), 8.12
(dd, J=8.4, 1.6, 1H), 7.52-7.46 (m, 2H), 7.42 (dd, J=8.4, 4.4, 1H), 7.34-7.22 (m, 3H), 6.98-6.93 (m,
1H), 3.84 (dd, J=8.4, 7.6, 1H), 1.73 (dd, J=13.6, 7.2, 1H), 1.47 (dd, J=13.7, 8.8, 1H), 0.07 (s, 9H).
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-1.7
23
21.4
39
51.5
1251
.527
114.2
7011
4.479
114.8
7411
5.090
116.5
0012
1.67
312
3.78
112
7.50
1
136.
430
144.
136
144.
206
148.
358
161.
992
172.
455
13C NMR (101 MHz, CDCl3) δ = 172.45, 164.44, 161.99, 148.36, 144.21, 144.14, 138.61, 136.43,
S35
ON
HN
GeMe3F
5f
ON
HN
GeMe3F
5f
134.56, 130.41, 130.33, 128.03, 127.50, 123.81, 123.78, 121.71, 121.67, 116.50, 115.09, 114.87,
114.48, 114.27, 51.53, 51.51, 21.44, -1.72.
19F NMR (376 MHz, CDCl3) δ = -112.59.
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.5f1 (ppm)
9.01
1.05
1.05
1.02
1.97
5.00
1.00
1.00
0.97
0.98
0.05
9
1.45
01.
473
1.48
41.
507
1.69
91.
716
1.73
31.
750
3.81
83.
835
3.84
13.
859
7.01
57.
023
7.02
87.
040
7.04
5
7.06
77.
405
7.46
48.
110
8.11
48.
130
8.72
38.
741
8.75
28.
763
9.92
6
S36
ON
HN
GeMe3
F 5g
ON
HN
GeMe3F
5f
1H NMR (400 MHz, CDCl3) δ = 9.93 (br, 1H), 8.76 (dd, J=4.4, 1.6, 1H), 8.73 (dd, J=7.2, 1.6, 1H), 8.12 (dd, J=8.4, 1.6, 1H), 7.52-7.41 (m, 5H), 7.07-7.02 (m, 2H), 3.84 (dd, J=9.2, 6.8, 1H), 1.72 (dd, J=13.6, 6.8, 1H), 1.48 (dd, J=13.6, 9.2, 1H), 0.06 (s, 9H).
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-1.7
14
21.6
05
51.0
05
115.6
5211
5.864
116.4
6312
1.62
612
7.50
4
134.
600
148.
329
161.
045
163.
486
173.
031
13C NMR (101 MHz, CDCl3) δ = 173.03, 163.49, 161.05, 148.33, 138.61, 137.36, 137.32, 136.44, 134.60, 129.63, 129.55, 128.03, 127.50, 121.69, 121.63, 116.46, 115.86, 115.65, 51.00, 21.61, -1.71.
19F 19F NMR (376 MHz, CDCl3) δ = -115.46.
S37
ON
HN
GeMe3
F 5g
ON
HN
GeMe3
F 5g
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.5f1 (ppm)
8.93
1.00
1.03
1.01
1.01
1.98
1.99
1.95
1.00
0.90
0.97
0.95
0.17
7
1.77
81.
792
1.81
21.
826
2.17
12.
200
2.20
42.
234
5.20
95.
222
5.23
95.
252
7.41
27.
433
7.49
37.
733
7.74
67.
883
7.89
78.
704
8.71
68.
727
8.74
58.
749
10.4
75
1H NMR (400 MHz, CDCl3) δ = 10.47 (br, 1H), 8.75 (dd, J=4.4, 1.6, 1H), 8.72 (t, J=4.4, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.89 (dd, J=5.2, 3.2, 2H), 7.74 (dd, J=5.2, 3.2, 2H), 7.50 (d, J=4.4, 2H), 7.43 (dd, J=8.4, 4.4, 1H), 5.23 (dd, J=12.0, 5.6, 1H), 2.20 (dd, J=13.6, 12.0, 1H), 1.80 (dd, J=13.6, 5.6, 1H), 0.18 (s, 9H).
13C -100102030405060708090100110120130140150160170180190200210
f1 (ppm)
-1.7
32
21.6
71
51.6
26
116.5
4912
1.76
612
2.89
812
4.30
112
4.37
612
4.84
812
4.92
312
7.48
012
8.31
413
0.74
013
1.37
913
1.69
913
6.45
114
8.37
4
172.
217
NMR (101 MHz, CDCl3) δ = 172.22, 148.37, 142.66, 138.60, 136.45, 134.44, 131.54,131.22 (q, J=32.0), 129.39, 128.03, 127.48, 124.87 (q, J=3.8), 124.32 (q, J=3.8), 124.25 (q, J=270.8), 121.78 (d, J=1.8), 116.55, 51.63, 21.67, -1.73.
S38
ON
HN
GeMe3
F3C 5h
ON
HN
GeMe3
F3C 5h
19F NMR (376 MHz, CDCl3) δ = -62.52.
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.5f1 (ppm)
9.01
1.02
1.05
1.00
5.03
0.98
1.00
1.02
0.99
0.96
0.09
7
1.39
11.
412
1.42
51.
446
1.70
11.
721
1.73
61.
755
3.78
13.
801
3.82
1
7.33
97.
360
7.40
77.
441
7.46
27.
496
7.51
37.
618
8.13
28.
152
8.70
18.
718
8.78
68.
797
9.95
3
1H NMR (400 MHz, CDCl3) δ = 9.95 (br, 1H), 8.79 (dd, J=4.4, 1.6, 1H), 8.71 (dd, J=6.8, 2.4, 1H), 8.14 (dd, J=8.0, 1.6, 1H), 7.62 (d, J=2.0, 1H), 7.53-7.34 (m, 5H), 3.80 (t, J=8.0, 1H), 1.73 (dd, J=13.6, 8.0, 1H), 1.42 (dd, J=13.6, 8.4, 1H), 0.10 (s, 9H).
S39
ON
HN
GeMe3Cl
Cl 5i
ON
HN
GeMe3
F3C 5h
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-1.6
42
21.6
03
50.9
87
116.6
0212
1.79
512
7.39
812
8.05
013
0.78
4
136.
512
148.
438
171.
925
13C NMR (101 MHz, CDCl3) δ = 171.92, 148.44, 142.05, 138.57, 136.51, 134.38, 132.89, 131.45, 130.78, 129.97, 128.05, 127.50, 127.40, 121.86, 121.79, 116.60, 50.99, 21.60, -1.64.
-2-10123456789101112f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
9.05
1.02
1.01
1.00
1.00
4.05
1.04
3.03
1.05
1.00
1.00
1.05
1.00
0.08
3
1.59
01.
612
1.62
41.
647
1.83
81.
856
1.87
21.
890
4.03
14.
051
4.07
1
7.26
07.
357
7.37
87.
442
7.46
57.
480
7.51
27.
661
7.82
27.
856
8.66
08.
670
8.75
48.
773
10.0
15
1H NMR (400 MHz, CDCl3) δ 10.01 (br, 1H), 8.76 (d, J = 7.6 Hz, 1H), 8.67 (d, J = 4.0 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.96 (s, 1H), 7.88-7.80 (m, 3H), 7.65 (d, J = 8.4 Hz, 1H), 7.51-7.42 (m, 4H), 7.36 (dd, J = 8.0, 4.0 Hz, 1H), 4.05 (t, J = 8.0 Hz, 1H), 1.86 (dd, J = 13.6, 7.2 Hz, 1H), 1.62 (dd, J = 13.6, 8.8 Hz, 1H), 0.08 (s, 9H).
S40
ON
HN
GeMe3
5j
ON
HN
GeMe3Cl
Cl 5i
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
-1.6
22
21.3
47
51.9
29
116.
399
121.
491
126.
095
127.
470
127.
972
139.
150
148.
242
173.
037
13C NMR (101 MHz, CDCl3) δ 173.04, 148.24, 139.15, 138.60, 136.32, 134.70, 133.76, 132.89, 128.75, 127.97, 127.95, 127.79, 127.47, 126.79, 126.26, 126.10, 125.88, 121.59, 121.49, 116.40, 51.93, 21.35, -1.62
-2-101234567891011121314f1 (ppm)
9.07
1.02
1.01
1.03
3.01
1.02
2.02
1.00
1.99
0.96
0.15
5
3.35
03.
373
5.51
55.
538
6.89
56.
934
7.13
27.
465
8.13
9
8.83
78.
844
8.84
8
8.85
9
10.9
53
1H NMR (400 MHz, CDCl3) δ = 10.95 (s, 1H), 8.86-8.84 (m, 2H), 8.15 (dd, J=8.4, 1.6, 1H), 7.58-7.53 (m, 2H), 7.45 (dd, J=8.4, 4.4, 1H), 7.15-7.05 (m, 3H), 6.91 (td, J=7.6, 0.8, 1H), 5.53 (d, J=9.2, 1H), 3.36 (d, J=9.2, 1H), 0.15 (s, 9H).
S41
ON
HN
GeMe3
5j
NH
O
GeMe3
N
O
5k
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-1.7
51
36.6
34
86.0
80
110.0
4811
6.910
121.
843
123.
598
127.
383
130.
963
136.
266
148.
801
157.
728
168.
518
13C NMR (101 MHz, CDCl3) δ = 168.52, 157.73, 148.80, 138.95, 136.27, 133.90, 130.96, 128.15, 127.38, 126.95, 123.60, 122.33, 121.84, 121.73, 116.91, 110.05, 86.08, 36.63, -1.75.
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
9.01
2.05
1.04
1.02
1.00
0.97
1.03
2.03
1.00
0.99
1.01
0.93
0.23
5
1.82
01.
844
1.85
91.
866
1.88
62.
043
2.10
03.
842
3.85
83.
867
3.88
7
4.42
94.
438
4.45
34.
464
4.47
34.
730
7.42
77.
437
7.44
77.
458
7.49
0
7.51
18.
132
8.15
38.
755
8.76
28.
771
8.77
8
8.85
4
10.8
16
1H NMR (400 MHz, CDCl3) δ = 10.82 (br, 1H), 8.85 (dd, J=4.4, 1.6, 1H), 8.77 (dd, J=6.4, 2.8, 1H), 8.14 (dd, J=8.4, 1.6, 1H), 7.55-7.49 (m, 2H), 7.44 (dd, J=8.4, 4.4, 1H), 4.74-4.72 (m, 1H), 4.47-4.43 (m, 1H), 3.90-3.84 (m, 1H), 2.12-2.04 (m, 1H), 1.91-1.82 (m, 2H), 0.23 (s, 9H).
S42
NH
O
GeMe3
N
O
5k
NH
O
GeMe3
N
O
5l
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-1.7
76
28.5
3432
.620
69.5
69
82.2
06
116.4
6812
1.69
712
7.41
513
4.17
313
6.26
3
148.
744
171.
649
13C NMR (101 MHz, CDCl3) δ = 171.65, 148.74, 139.04, 136.26, 134.17, 128.16, 127.42, 121.88, 121.70, 116.47, 82.21, 69.57, 32.62, 28.53, -1.78.
1H NMR (400 MHz, CDCl3) δ 7.90 – 7.84 (m, 2H), 7.77 – 7.71 (m, 2H), 4.97 (dd, J = 11.1, 5.7 Hz,
1H), 3.72 (s, 3H), 1.80 (dd, J = 14.1, 11.1 Hz, 1H), 1.69 (dd, J = 14.1, 5.7 Hz, 1H), 0.10 (s, 9H).
S43
NH
O
GeMe3
N
O
5l
OMeN
O
Me3Ge
O O
3ab
13C NMR (101 MHz, CDCl3) δ = 170.87, 167.42, 134.02, 131.71, 123.34, 52.65, 49.85, 16.98, -2.23.
1H NMR (501 MHz, CDCl3) δ 8.93 (d, J = 7.5 Hz, 1H), 8.18 (s, 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.83 (s, 2H), 7.68 (s, 2H), 7.40 (t, J = 8.0 Hz, 1H), 7.19 (d, J = 7.5 Hz, 1H), 7.15 (dd, J = 7.5, 4.5 Hz, 1H), 5.32 (t, J = 10.0 Hz, 1H), 2.40(t, J = 9.0 Hz, 1H)2.32 (s, 3H),1.95(t, J = 8.0 Hz, 1H).
S44
OMeN
O
Me3Ge
O O
3ab