of 97
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
1
Supporting Information for
Formation of All
-
Carbon Quaternary Centers via Enantioselective Pd
-
catalyzed α
-
Vinylation of γ
-
Lactams.
Farbod A. Moghadam
,
Jay P. Barbor
,
Melinda Chan
,
Carina Jette, Shunya Sakurai,
Brian M.
Stoltz*
Warren
and Katharine Schlinger Laboratory of Chemistry and Chemical Engineering, Division
of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena,
California 91125
, United States
.
*
stoltz@caltech.edu
Table of Contents:
Materials and Methods
................................
................................
................................
................................
.................
S
2
List of Abbreviations
................................
................................
................................
................................
....................
S
3
Additional Optimization Data
................................
................................
................................
................................
......
S3
Pd
-
catalyzed Vinylation Reactions
: General Procedure A
................................
................................
..........................
S
4
Preparation of
Vinyl Chloride Substrates
: General Procedure B
................................
................................
...............
S
1
7
Derivatization of
Vinylation Products
................................
................................
................................
.....................
S
20
Crystal Structure Analysis of (S)
-
1
-
(4
-
methoxyphenyl)
-
3
-
methyl
-
3
-
(2
-
methylprop
-
1
-
en
-
1
-
yl)pyrrolidin
-
2
-
one (3a)
(sample No.: V24190)
................................
................................
................................
................................
................
S27
References
................................
................................
................................
................................
................................
.
S
36
NMR and IR
Spectra
of New Compounds
................................
................................
................................
................
S
37
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
2
Materials and Methods
Unless otherwise stated, reactions were performed in flame
-
dried glassware under an argon
or nitrogen atmosphere using dry,
deoxygenated solvents. Solvents were dried by passage through
an activated alumina column under argon.
1
Reaction progress was monitored by thin
-
layer
chromatography (TLC) or
Agilent 1290 UHPLC
-
MS
.
TLC was performed using E. Merck silica
gel 60 F254 precoated glass plates (0.25 mm) and visualized by UV fluorescence quenching,
p
-
anisaldehyde, or KMnO
4
staining. Silicycle Silia
Flash
® P60 Academic Silica gel (particle size
40
63
μm
)
and Teledyne Isco CombiFlash Rf+ UV with Luknova s
tandard silica (avg
particle size
50μm) flash columns
were
used for flash chromatography.
1
H NMR spectra were recorded on
Varian Inova 500 MHz and Bruker 400 MHz spectrometers and are reported relative to residual
CHCl
3
(
δ
7.26 ppm).
13
C NMR spectra were recorded on a Varian Inova 500 MHz spectrometer
(125 MHz) and Bruker 400 MHz spectrometers (100 MHz) and are reported relative to CHCl
3
(
δ
77.16 ppm). Data for
1
H NMR are reported as follows: chemical shift (
δ
ppm) (multiplicity,
coupling constant (Hz), integration). Multip
licities are reported as follows: s = singlet, d = doublet,
t = triplet, q = quartet, p = pentet, sept = septuplet, m = multiplet, br s = broad singlet, br d
= broad
doublet
. Data for
13
C NMR are reported in terms of chemical shifts (
δ
ppm). IR spectra were
obtained by use of a
Perkin Elmer Spectrum BXII
spectrometer using thin films deposited on NaCl
plates and reported in frequency of absorption (cm
1
). Optical rotations were measured with a
Jasco P
-
2000 polarimeter operating on the sodium D
-
line (589
nm), using a 100 mm path
-
length
cell
.
Analytical SFC was performed with a Mettler SFC supercritical CO
2
analytical
chromatography system utilizing Chiralpak (
AD
-
3
, AS
-
H or IC) or Chiralcel (OD
-
H, OJ
-
H, or
OB
-
H) columns (4.6 mm x 25 cm)
obtained from
Daicel Chemical Industries, Ltd
.
Analytical
chiral
HPLC
was performed with a
n Agilent 1100 Series
HPLC
utilizing Chiralpak (
I
H) or
Chiralcel (OD
-
H) columns (4.6 mm x 25 cm)
both
obtained from
Daicel Chemical Industries, Ltd
.
High resolution mass spectra (HRMS) were obtained from
the Caltech Mass Spectral Facility using
a JEOL JMS
-
600H High Resolution Mass Spectrometer in field ionization (FI+) or field desorption
(FD+) mode, or an Agilent 6200 Series TOF with an Agilent G1978A Multimode source in
electrospr
ay ionization (ESI+), atmospheric pressure chemical ionization (APCI), or mixed
ionization mode (MM: ESI
-
APCI+)
.
Reagents were purchased from
commercial sources
and used
as received unless otherwise stated.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
3
Low
-
temperature diffraction data (
-
and
-
scans) were collected on a Bruker AXS D8
VENTURE KAPPA diffractometer coupled to a PHOTON II CPAD detector with
K
radiation (
= 1.54178 Å) from an I
μ
S
micro
-
source for the structure of compound V24190. The structure was
solved by direct methods using SHELXS
2
and refined against
F
2
on all data by full
-
matrix least
squares with SHELXL
-
2019
3
using established refinement techniques.
4
All non
-
hydrogen atoms
were refined anisotropically. All hydrogen atoms were included into the model at geometrically
calculated positions and refined using a riding model. The isotropic displacement parameters of
all hydrogen atoms were fixed to 1.2 time
s the
U
value of the atoms they are linked to (1.5 times
for methyl groups).
Compound V24190 crystallizes in the orthorhombic space group
P
2
1
2
1
2
1
with one
molecule in the asymmetric unit.
List of Abbreviations
:
ee
enantiomeric excess
, SFC
supercritical fluid
chromatography
,
HPLC
high
-
performance
liquid chromatography,
TLC
th
in
-
layer chromatography
,
Dr
dram
Additional Optimization Data
Table S1.
Ligand evaluation.
a
a
Yields determined by
1
H NMR analysis of crude reaction mixture using
1,3,5
-
trimethoxybenzene as a standard.
Enantiomeric excess (ee) was determined by chiral SFC analysis of the isolated product.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
4
Table S2.
Nucleophile substitution.
a
Yields determined by
1
H NMR with CH
2
Br
2
internal standard.
Table S3.
Survey of vinyl halides.
a
Yields determined by
1
H NMR with CH
2
Br
2
internal standard.
R
eaction performed with 1.5 eq of vinyl
halide/pseudohalide, 1 equiv lactam, 1 equiv LiHMDS
Pd
-
catalyzed Vinylation Reactions: General Procedure
A
In a
nitrogen
-
filled glovebox, a catalyst solution of Pd(dba)
2
(
9.6
mg/mL) and
(S,S)
-
Me
-
Ferr
ocelane
(10.4 mg/mL) in
1,4
-
dioxane was stirred for 20 min at 40 °C. In a vial, the lactam
was dissolved in
1,4
-
dioxane (1.5 equiv, 0.09 M), and subsequently LHMDS (2 equiv) was added.
A 2 Dr vial was charged with neat vinyl chloride (0.1 mmol, 1 equiv) and a magnetic stir bar. After
the catalyst pre
-
stir was complete, 0.4 mL of the catalyst solution was added to th
e vinyl chloride,
followed by 1.6 mL of the nucleophile/base mixture. The vial was sealed with a Teflon
-
lined cap,
removed from the glovebox, and stirred at 80 °C in a meta
l heating block for 24 h unless noted
otherwise. After 24 h, 3 mL 0.5 M HCl
or sat. NH
4
Cl
was added to the crude reaction mixture,
which was then extracted three times with ethyl acetate, dried over Na
2
SO
4
, concentrated, and
purified by silica gel flash chromatography to provide the desired vinylation product.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
5
(S)
-
1
-
(4
-
methoxyphenyl)
-
3
-
methyl
-
3
-
(2
-
methylprop
-
1
-
en
-
1
-
yl)pyrrolidin
-
2
-
one
(
3a
)
Prepared
according to
general procedure
A
using
vinyl chloride
2a
(
0.1 mmol
)
and
lactam
1
.
P
urification by
silica gel chromatography
(
0
-
3
0
%
EtOAc
/He
xanes)
provided
1
5
mg (5
8
%
, 94%
ee
) of a
yellow
oil
.
The reaction was
also performed using 3 mmol vinyl chloride to obtain
456 mg
(59%)
of
a
tan
solid
;
[
]
D
25
79.9 (
c
1.0, CHCl
3
);
1
H NMR (400
MHz, CDCl
3
) δ 7.54 (d,
J
= 9.2
Hz,
2
H), 6.90 (d,
J
= 9.1 Hz,
2
H), 5.46 (t,
J
= 1.4 Hz, 1H), 3.79 (s,
3
H), 3.78
3.63 (m, 2H), 2.32
2.12 (m, 2H), 1.74 (d,
J
= 1.5 Hz,
3
H), 1.69 (d,
J
= 1.4 Hz,
3
H), 1.36 (s,
3
H
);
13
C NMR (101
MHz, CDCl
3
) δ 177.
8
,
156.5, 134.
6
, 133.
3
, 128.5, 121.
6
, 114.1, 55.6, 46
.
3, 45.7, 34.
3
, 27.
1
, 24.
4
,
19.
2
;
IR (Neat Film, NaCl)
2965
,
1694
,
1513
,
1400
,
1297
,
1250, 1170, 1089, 1063, 1033, 828
cm
1
;
HRMS (MM:ESI
-
APCI+) m/z calc’d C
16
H
2
2
NO
2
[M+H]
+
: 260.1645, found 260.1649.
SFC
conditions:
30% IPA, 2.5 mL/min, Chiralcel
AD
-
3
column,
λ = 254 nm, tR (min): minor = 3.
37
,
major =
5.18
.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
6
(S)
-
3
-
(cyclopentylidenemethyl)
-
1
-
(4
-
methoxyphenyl)
-
3
-
methylpyrrolidin
-
2
-
one
(
3b
)
Prepared according to general procedure
A
using
2b
. Purification by column chromatography (0
25 % EtOAc
/He
xanes) yielded
3b
as a white solid
(15.6 mg, 55% yield); 90%
ee
; [α]
D
25
56.8 (c
0.75, CHCl
3
);
1
H NMR (400 MHz, CDCl
3
) δ 7.55 (d,
J
= 9.1 Hz, 2H), 6.90 (d,
J
= 9.1 Hz, 2H),
5.53 (p,
J
= 2.3 Hz, 1H), 3.79 (s, 3H), 3.75
3.51 (m, 2H), 2.26 (m, 5H), 2.15
1.87 (m, 1H), 1.88
1.60 (m, 2H), 1.60
1.42 (m, 2H), 1.35 (s, 3H);
13
C NMR (101 MHz, CDCl
3
) δ 177.4, 156.5,
145.1, 133.3, 123.7, 121.5, 114.1, 55.6, 47.1, 45.8, 35.5, 34.0, 28.9, 27.3, 25.8, 23.9; IR (neat film,
NaCl) 3835, 3732, 2951, 2866, 2360, 1693, 1511, 1455, 1395, 1298, 1248, 1181,
1084, 1035, 833,
662 cm
1
; HRMS (MM:ESI
-
APCI+) m/z calc’d for C
18
H
24
NO
2
[M+H]
+
: 286.1802, found
286.1815;
SFC conditions: 30% IPA, 2.5 mL/min, Chiralcel
AD
-
3
column, λ = 254 nm, tR (min):
minor =
4.69
, major =
7.78
.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
7
(S)
-
3
-
(cyclohexylidenemethyl)
-
1
-
(4
-
methoxyphenyl)
-
3
-
methylpyrrolidin
-
2
-
one
(
3c
)
Prepared according to general procedure
A
using
2c
. Purification by column chromatography (0
25 % EtOAc
/He
xanes) yielded
3c
as a white solid (15.3 mg, 51% yield); 84%
ee
;
[α]
D
25
64.5 (c
1.0, CHCl
3
);
1
H NMR (400 MHz, CDCl
3
) δ 7.44 (d,
J
= 9.1 Hz, 2H), 6.80 (d,
J
= 9.1 Hz, 2H), 5.36
5.31 (m, 1H), 3.69 (s, 3H), 3.67
3.34 (m, 2H), 2.12 (m, 2H), 2.08
1.94 (m, 4H), 1.55
1.32
(m, 6H), 1.25 (s, 3H);
13
C NMR (101 MHz, CDCl
3
) δ 177.9, 156.4, 142.7, 133.2, 125.4, 121.5,
114.0, 55.5, 45.9, 45.6, 37.7, 34.6, 30.2, 28.7, 27.6, 26.5, 24.7; IR (neat film, NaCl) 3835, 3745,
2925, 2851, 2359, 1693, 1513, 1443, 1396, 1298, 1248, 1179, 1088, 1035, 828 cm
1
; HRMS
(MM:ESI
-
APCI+) m/z calc
’d for C
19
H
26
NO
2
[M+H]
+
: 300.1958, found 300.1972;
SFC conditions:
30% IPA, 2.5 mL/min, Chiralcel
AD
-
3
column, λ = 254 nm, tR (min): minor =
5.21
, major =
9.35
.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
8
(S)
-
3
-
(cycloheptylidenemethyl)
-
1
-
(4
-
methoxyphenyl)
-
3
-
methylpyrrolidin
-
2
-
one
(
3d
)
Prepared according to general procedure
A
using
2d
. Purification by column chromatography (0
25 % EtOAc
/Hexanes
) yielded
3d
as a white solid (4.7 mg, 15% yield); 86%
ee
; [α]
D
25
39.4 (c
0.5, CHCl
3
);
1
H NMR (400 MHz, CDCl
3
) δ 7.54 (d,
J
= 9.2 Hz, 2H), 6.90 (d,
J
= 9.1 Hz, 2H),
5.52 (p,
J
= 1.4 Hz, 1H), 3.80 (s, 3H), 3.77
3.32 (m, 2H), 2.86
1.98 (m, 6H), 1.84
1.40 (m,
8H), 1.36 (s, 3H);
13
C NMR (101 MHz, CDCl
3
) δ 177.9, 156.5, 144.2, 133.3, 128.8, 121.6, 121.6,
114.2, 55.6, 46.3, 45.8, 38.5, 34.1, 31.
0, 29.9, 29.7, 29.3, 27.0, 24.4; IR (neat film, NaCl) 3834,
3732, 2923, 2849, 2341, 1693, 1511, 1395, 1298, 1247, 1087, 1035, 827 cm
1
; HRMS (MM:ESI
-
APCI+) m/z calc’d for C
20
H
28
NO
2
[M+H]
+
: 314.2115, found 314.2029;
SFC conditions: 30% IPA,
2.5 mL/min, Chiralcel
AD
-
3
column, λ = 254 nm, tR (min): minor =
5.32
, major =
9.13
.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
9
(S)
-
3
-
(
tetrahydropyran
lidenemethyl)
-
1
-
(4
-
methoxyphenyl)
-
3
-
methylpyrrolidin
-
2
-
one
(
3e
)
Prepared according to general procedure
A
using
2e
. Purification by column chromatography (0
30
% EtOAc
/Hexanes
) yielded
3e
as a
colorless oil
(13.2 mg, 4
3
%)
;
8
6
%
ee
; [α]
D
25
41.4 (c 1.0,
CHCl
3
);
1
H NMR (400 MHz, CDCl
3
) δ 7.52 (d,
J
= 9.0 Hz, 2H), 6.90 (d,
J
= 9.1 Hz, 2H), 5.54 (d,
J
= 1.3 Hz, 1H), 3.79 (s, 3H), 3.78
3.57 (m, 6H), 2.34 (tt,
J
= 5.8, 1.2 Hz, 2H), 2.29
2.17 (m,
4H), 1.37 (s, 3H)
;
13
C NMR (101 MHz, CDCl
3
) δ 177.4, 156.6, 137.5, 133.
1
, 127.5, 121.6, 114.
2
,
69.8, 68.4, 55.6, 46.0, 45.
7
, 37.5, 34.
9
, 31.3, 24.
8
.
IR (neat film, NaCl)
2958, 2839, 1691, 1511,
1462, 1396, 1286, 1269, 1246, 1087, 1032, 831
cm
1
;
HRMS (MM:ESI
-
APCI+) m/z calc’d for
C
18
H
2
4
NO
3
[M+H]
+
:
302.1751, found 302.1750
; SFC
conditions:
2
0% IPA, 2.5 mL/min, Chiralcel
AD
-
3
column, λ = 254 nm, tR (min): minor =
8.03
, major =
11.15
.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
10
(S)
-
3
-
(
tetrahydro
-
thiopyran
lidenemethyl)
-
1
-
(4
-
methoxyphenyl)
-
3
-
methylpyrrolidin
-
2
-
one
(
3f
)
Prepared according to general procedure
A
using
2f
. Purification by column chromatography (0
25 % EtOAc
/Hexanes
) yielded
3f
as a
colorless oil
(
13.5 mg, 4
4
%
); 8
8
%
ee
; [α]
D
25
58.3 (c 1.0,
CHCl
3
);
1
H NMR (400 MHz, CDCl
3
) δ 7.52 (d,
J
= 9.1 Hz, 1H), 6.90 (d,
J
= 9.1 Hz, 1H), 5.55 (t,
J
= 1.0 Hz, 1H), 3.80 (s, 2H), 3.78
3.68 (m, 1H), 2.76
2.48 (m, 4H), 2.44 (td,
J
= 5.4, 2.5 Hz,
1H), 2.24
2.17 (m, 1H), 1.36 (s, 2H)
;
13
C NMR (101 MHz, CDCl
3
) δ 177.4, 156.6, 139.6, 133.05,
12
9.0
, 121.6, 114.
2
, 55.6, 45.9, 45.
7
, 39.
4
, 34.
8
, 32.
2
, 31.2, 29.
9
, 24.
8
.
IR (neat film, NaCl)
2953,
1689, 1511, 1428, 1398, 1297, 1247, 1180, 1087, 1034, 821
cm
1
; HRMS (MM:ESI
-
APCI+) m/z
calc’d for C
18
H
2
4
NO
2
S
[M+H]
+
:
318.1522, found 318.1
520
; SFC conditions:
2
0% IPA, 2.5
mL/min, Chiralcel
OJ
-
3
column, λ = 254 nm, tR (min): minor =
7.45
, major =
6.32
.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
11
(
S
)
-
3
-
((1,4
-
dioxaspiro[
4.5]decan
-
8
-
ylidene)methyl)
-
1
-
(4
-
methoxyphenyl)
-
3
-
methylpyrrolidin
-
2
-
one
(3g)
Prepared according to general procedure
A
using
2
g
.
The crude product was purified by
silica gel
chromatography (30% EtOAc/Hexanes) to afford vinylated lactam
3
g
(48% yield,
74
% ee) as a
colorless oil;
[a]
D
25
+ 4.
5
° (
c
0.52, CHCl
3
)
;
1
H NMR (400 MHz, CDCl
3
) δ 7.53 (d,
J
= 9.1 Hz,
2H), 6.90 (d,
J
= 9.1 Hz, 2H), 5.54 (d,
J
= 1.7 Hz, 1H), 3.95 (s, 3H), 3.80 (s, 3H), 3.76
3.60 (m,
2H), 2.40
2.29 (m, 2H), 2.31
2.16 (m, 4H), 1.71 (td,
J
= 6.7, 3.9 Hz, 3H), 1.68
1.62 (m, 1H),
1.60 (s, 1H), 1.37 (s, 3H);
13
C NMR (101 MHz, CDCl
3
) δ 177.7, 156.
6
, 140.0, 133.2, 127.
2
,
121.6,
114.
2
, 114.1, 108.7, 77.
5
, 77.
4
, 77.
2
, 76.8, 64.
5
, 64.
5
, 55.6, 46.1, 45.7, 36.
4
, 35.3, 34.
7
, 34.
5
, 26.
7
,
24.7
; IR (thin film, NaCl)
3465, 2950, 2886, 2320, 2009, 1902, 1693, 1681, 1513, 1433, 1401,
1298, 1276, 1248, 1226, 1181, 1171, 1120, 1082, 1032, 944, 906, 826, 738, 728
cm
1
;
HRMS
(ESI) m/z calc’d C
21
H
27
NO
4
Na
[M+Na]
+
: 380.1832, found: 380.1843
; SFC conditions: 30% IPA,
2.5 mL/min, Chiralcel
AD
-
3
column, λ = 254 nm, tR (min): minor =
3.53
, major =
5.02
.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
12
(
S
)
-
1
-
(4
-
methoxyphenyl)
-
3
-
methyl
-
3
-
(2
-
propylpent
-
1
-
en
-
1
-
yl)pyrrolidin
-
2
-
one
(
3
h
)
Prepared according to general procedure
A
using
2
h
.
The crude product was purified by
silica gel
chromatography (30% EtOAc
/Hexanes) to afford vinylated lactam
3
h
(58% yield, 9
2
% ee) as a
colorless oil;
[a]
D
25
2.
5
° (
c
0.35, CHCl
3
)
;
1
H NMR (400 MHz, CDCl
3
) δ 7.54 (d,
J
= 9.1 Hz,
2H), 6.90 (d,
J
= 9.1 Hz, 2H), 5.50 (t,
J
= 1.0 Hz, 1H), 3.80 (d,
J
= 0.7 Hz, 3H), 3.78
3.67 (m,
2H), 2.34
2.25 (m, 1H), 2.25
2.17 (m, 1H), 2.12
2.03 (m, 1H), 2.03
1.94 (m, 3H), 1.48
1.38 (m, 4H), 1.36 (s, 3H), 0.93
0.84 (m, 6H)
;
13
C NMR (101 MHz, CDCl
3
) δ 177.9, 156.
4
,
142.
4
, 133.
2
, 128.
5
, 121.4, 114.
0
,
77.
4
, 77.2, 77.0, 76.7, 55.5, 46.
2
, 45.
6
, 38.
8
, 34.
5
, 3
3.0
, 24.7,
21.3, 21.1, 14.
6
, 13.8.
IR (thin film, NaCl)
2958, 2930, 2870, 1694, 1513, 1469, 1454, 1423, 1398,
1299, 1288, 1248, 1181, 1168, 1122, 1087, 1036, 836, 823, 805, 634
cm
1
; HRMS (MM:ESI
-
APCI+) m/z calc’d C
20
H
29
NO
2
Na
[M+Na]
+
: 338.2091, found: 338.2100
; SFC conditions: 30%
IPA, 2.5 mL/min, Chiralcel
AD
-
3
column, λ = 254 nm, tR (min): minor =
2.88
, major =
3.73
.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
13
(
S
)
-
3
-
(2
-
benzyl
-
3
-
phenylprop
-
1
-
en
-
1
-
yl)
-
1
-
(4
-
methoxyphenyl)
-
3
-
methylpyrrolidin
-
2
-
one
(
3i
)
Prepared according to general procedure
A
using
2i
.
The crude product was purified by
silica gel
chromatography
(30% EtOAc
/Hexanes) to afford vinylated lactam
3i
(22% yield, 88% ee) as a
colorless oil;
[a]
D
25
12.4 ° (
c
0.56, CHCl
3
)
;
1
H NMR (400 MHz, CDCl
3
) δ 7.58 (d,
J
= 9.1 Hz,
2
H), 7.38
7.32 (m, 2H), 7.30
7.23 (m,
3
H), 7.23
7.17 (m, 2H), 7.17
7.10 (m,
2
H), 6.95 (d,
J
= 9.1 Hz,
2
H), 6.02 (t,
J
= 1.0 Hz, 1H), 3.86 (s,
3
H), 3.84
3.74 (m,
2
H), 3.54
3.38 (m, 2H),
3.27 (t,
J
= 1.6 Hz,
2
H), 2.43 (dt,
J
= 12.5, 8.2 Hz, 1H), 2.30 (ddd,
J
= 12.5, 7.2, 3.6 Hz, 1H), 1.52
(s,
3
H).
;
13
C NMR (101 MHz, CDCl
3
) δ 177.4, 156.5, 139.8, 139.
5
, 139.0, 132
.9
, 132.
8
, 12
9.0
,
128.9, 128.
5
, 128.3, 128.
2
, 126.1, 121.6, 114.
1
, 77.
4
, 77.2, 77.0, 76.7, 55.5, 46.
4
, 45.
7
, 43.3, 35.
9
,
34.1, 24.
8
.
IR (thin film, NaCl) 3059, 3025, 2930,
2835,m 2340, 1682, 1600, 1520, 1493, 1453,
1398, 1298, 1240, 1181, 1120, 1088, 1031, 829, 734, 702 cm
1
;
HRMS (MM:ESI
-
APCI+) m/z
calc’d C
28
H
29
NO
2
Na
[M+Na]
+
: 434.2091, found: 434.2102
; SFC conditions: 30% IPA, 2.5
mL/min, Chiralcel
AD
-
3
column, λ = 254 nm, tR (min): minor =
5.63
, major =
7.11
.
Supporting Information for
Moghadam
,
Barbor
,
Chan,
Jette
,
Sakurai,
and Stoltz
S
14
(S)
-
1
-
(4
-
methoxyphenyl)
-
3
-
methyl
-
3
-
(prop
-
1
-
en
-
2
-
yl)pyrrolidin
-
2
-
one
(
3j
)
Prepared according to general procedure A using
2j
. The crude product was purified by silica gel
chromatography (0
30% EtOAc/Hexanes) to afford vinylated lactam
3j
(
8.3
mg,
34
% yield
, 92%
ee
) as a
white solid
;
[a]
D
25
125.8
° (
c
1, CHCl
3
);
1
H NMR (400
MHz, CDCl
3
) δ
7.55 (d,
J
= 9.1
Hz,
2
H), 6.90 (d,
J
= 9.1 Hz,
2
H), 4.93 (
s
, 1H), 4.89 (s, 1H), 3.80 (s,
3
H), 3.76
3.44 (m,
2
H),
2.32 (ddd,
J
= 12.7, 7.0, 4.4 Hz, 1H), 1.94 (dt,
J
= 12.7, 7.8 Hz, 1H), 1.83 (d,
J
= 1.3 Hz,
3
H), 1.39
(s,
3
H)
;
13
C NMR
(101 MHz, CDCl
3
) δ
176.3, 156.6, 145.4, 133.1, 121.7, 114.2, 114.1, 111.9,
55.6, 51.2, 45.9, 31.9, 22.5, 19.8
;
IR (thin film, NaCl)
2933, 1738, 1693, 1643,
1512, 1455, 1396,
1297, 1248, 1181, 1088, 1034, 892, 828
cm
1
; HRMS (MM:ESI
-
APCI+) m/z calc’d C
15
H
20
NO
2
[M+H]
+
:
246.1
4
9
8
, found 246.1495.
SFC conditions: 30% IPA, 2.5 mL/min, Chiralcel
AD
-
3
column, λ = 254 nm, tR (min): minor =
3.
77
, major =
4.
09
.