Supporting Information
Electrocatalytic
Asymmetric
Nozaki
–
Hiyama
–
Kishi
Decarboxylative Coupling: Scope, Applications, and
Mechanism
Yang Gao
1
,
†
Baiyang Jiang
1
,
†
,
Nathan C. Friede
2
, Arianne C. Hunter
2
, Dylan G. Boucher
3
,
Shelley D. Minteer
3
,
Matthew Sigman
3
, Sarah E. Reisman
2
*
, and Phil S. Baran
1
*
1
Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA
92037, United States.
2
The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical
Engineering,
Division of Chemistry and Chemical Engineering, California Institute of Technology,
Pasadena, CA 91125, United States.
3
D
epartment of Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
*Correspondence to:
reisman@caltech.edu
,
pbaran@scripps.edu
†
These authors
contributed equally to this work.
2
Table of Contents
General Experimental
................................
................................
................................
.............
3
Preparation of NHPI Redox
-
Active Esters (General Procedure A)
................................
....
4
Table S1
–
Known NHPI Redox Active Esters
................................
................................
......
5
General Procedure B
................................
................................
................................
...............
6
General Procedure
C
................................
................................
................................
...............
8
Graphical Guide
................................
................................
................................
.....................
10
Troubleshooting: Frequently Asked Questions
................................
................................
..
14
Experimental Procedures and Characterization Data
................................
.......................
16
Synthetic Applications
................................
................................
................................
...........
70
Preparation of Chiral Ligands
................................
................................
..............................
96
Electrochemical Experimental Details
................................
................................
..............
110
Finite Element Simulations
................................
................................
................................
.
116
NMR Spectra:
................................
................................
................................
.....................
132
6
3
General Experimental
Tetrahydrofuran (THF), dichloromethane (CH
2
Cl
2
) and acetonitrile (CH
3
CN) were obtained
by passing the previously degassed solvents through an activated
alumina column. All the other
reagents were purchased at the highest commercial quality and used without further
purification, unless otherwise stated. Anhydrous CrCl
2
was purchased from Strem. 1,8
-
Bis(dimethylamino)naphthalene (Proton Sponge) and tetrakis
(dimethylamino)ethylene
(TDAE) were purchased from Sigma
-
Aldrich. Triethylsilyl chloride (TESCl) and
tetrabutylammonium perchlorate (TBAClO
4
) were purchased from Oakwood. Yields refer to
chromatographically and spectroscopically (
1
H NMR) homogeneous materi
al. TLC was
performed on 0.25 mm E. Merck silica plates (60F
-
254), using short
-
wave UV light as the
visualizing agent, and cerium ammonium molybdate (CAM) or KMnO
4
and heat as developing
agents. NMR spectra were recorded on Bruker DRX
-
600, DRX
-
500,
AMX
-
400
,
and
NEO
-
400
instruments and are calibrated using residual undeuterated solvent (CDCl
3
at 7.26 ppm
1
H
NMR, 77.16 ppm
13
C NMR; CD
3
OD at
1
H NMR δ = 3.31 ppm,
13
C NMR δ = 49.00 ppm).
The following abbreviations were used to explain multiplicities: s = single
t, d = doublet, t =
triplet, q = quartet,
sep = septet,
m = multiplet, br = broad. Column chromatography was
performed using E. Merck silica gel (60, particle size 0.043
–
0.063 mm). High
-
resolution mass
spectra (HRMS) were recorded on Waters LC with
G2
-
XS TOF mass spectrometer by
electrospray ionization time
-
of
-
flight reflectron experiments
or Field Desorption Ionization
mass spectrometry (FD
-
MS) using an JMS
-
T2000 AccuTOF GC
-
Alpha (JEOL, Inc).
GCMS
(EI) were recorded on Agilent 7820A GC systems
with
FID detection
and 5975 Series MSD
or 5975C series VL MSD with triple
-
axis detector.
Melting points were recorded on a Fisher
-
Johns 12
-
144 melting point apparatus and are uncorrected.
4
Preparation of
NHPI Redox
-
Active Esters
(
General Procedure A)
A roun
d
-
bottom flask or culture tube was charged with carboxylic acid (1.0 equiv),
N
-
hydroxyphthalimide (1.0
–
1.1 equiv), and DMAP (0.1 equiv). DCM was added (0.1
–
0.2 M),
and the mixture was stirred vigorously. DIC (1.1 equiv) was then added dropwise via syri
nge,
and the reaction mixture was allowed to stir until the acid was consumed (determined by TLC).
Typical reaction times were between 0.5 and 2 hours. Upon completion, the mixture was
concentrated and was directly purified via silica gel column chromatogr
aphy to afford the
activated ester. If necessary, the NHPI redox
-
active ester could be further recrystallized from
DCM/MeOH.
Redox
-
active esters shown below
S1
,
1
S2
,
2
S3
,
3
S4
,
4
S5
,
5
S6
,
6
S7
,
7
S8
,
8
S9
,
1
S10
,
9
S11
,
10
S12
,
11
S13
,
1
2
and
S14
1
3
have
previously been reported in the literature. Please see these references for
characterization.
For newly reported redox active esters, HRMS failed to detect the target mass
due to instability of the NHPI ester motif.
OH
O
R
1
R
3
R
2
NHPI
(1.0
equiv)
DIC
(1.1
equiv)
DMAP
(0.1
equiv)
DCM,
rt
O
O
R
1
R
3
R
2
N
O
O
5
Table S1
–
Known NHPI Redox
Active Esters
O
O
N
O
O
Ph
O
O
N
O
O
O
O
N
O
O
N
O
O
Me
O
O
N
O
O
S1
S2
S3
S4
S5
S6
S7
S8
S9
S10
S11
S13
S12
S14
Me
O
N
O
O
O
Me
O
N
O
O
O
O
N
O
O
O
Me
Me
O
N
O
O
O
O
N
O
O
O
MeO
O
O
N
O
O
O
Cl
O
N
O
O
O
BocHN
O
O
O
N
O
O
PinB
N
Cl
Cl
O
O
N
O
O
Me
O
O
N
O
O