Synthesis and characterization of novel chiral [(NHC)Au(I)Cl] complexes: Featuring ortho-biphenyl substituents

Article abstract of DOI:10.1016/j.jorganchem.2015.02.034

A series of new chiral [(NHC)Au(I)Cl] are synthesized. The chiral NHC ligands feature pairs of ortho-biphenyl groups. The distal phenyl groups of the biphenyl substituents are varied from simple phenyl, 3,5-dimethylphenyl, to 3,5-di-t-butylphenyl. X-Ray structure analysis were performed for two such [(NHC)Au(I)Cl] complexes. High percent buried volumes were calculated for two novel chiral [(NHC)Au(I)Cl]complexes whose structure were solved by an X-ray analysis. The rotational motion in the biphenyl group is slow on the NMR time scale. Rotational barriers were determined using WINDNMR for two of the chiral gold complexes.

Full text of DOI:10.1016/j.jorganchem.2015.02.034

Accepted Manuscript
Synthesis and characterization of novel chiral [(NHC)Au(I)CL] complexes: Featuring
Ortho-Biphssenyl substituents
Michael R. Holmes, John F. Manganaro, Charles L. Barnes, Benjamin W. Gung
PII:
S0022-328X(15)00112-6
10.1016/j.jorganchem.2015.02.034
JOM 18935
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 31 December 2014
Revised Date: 20 February 2015
Accepted Date: 21 February 2015
Please cite this article as: M.R. Holmes, J.F. Manganaro, C.L. Barnes, B.W. Gung, Synthesis and
characterization of novel chiral [(NHC)Au(I)CL] complexes: Featuring Ortho-Biphssenyl substituents,
Journal of Organometallic Chemistry (2015), doi: 10.1016/j.jorganchem.2015.02.034.
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Graphical Abstract
Nine novel chiral [(NHC)Au(I)Cl] complexes are synthesized and
characterized. The new chiral [(NHC)Au(I)Cl] complexes feature pairs of o-
biphenyl substituents. The rotational barriers determined for the biphenyl C-
C bond rotation in these complexes are greater than usual.

ACCEPTED MANUSCRIPT
Synthesis and Characterization of Novel Chiral [(NHC)Au(I)Cl]
Complexes: Featuring ortho-Biphenyl Substituents
Michael R. Holmesa, John F. Manganaroa, Charles L. Barnesb, Benjamin W. Gunga*
aDepartment of Chemistry & Biochemistry, Miami University, Oxford, Ohio 45056
bElmer O. Schlemper X-Ray Diffraction Center, University of Missouri-Columbia, Columbia, MO 65211 United States.
Received: The date will be inserted once the manuscript is accepted.
Abstract: A series of new chiral [(NHC)Au(I)Cl] are synthesized. The chiral NHC ligands feature pairs of ortho-biphenyl groups.
The distal phenyl groups of the biphenyl substituents are varied from simple phenyl, 3,5-dimethylphenyl, to 3,5-di-t-butylphenyl.
X-Ray structure analysis were performed for two such [(NHC)Au(I)Cl] complexes. High percent buried volumes were calculated
for two novel chiral [(NHC)Au(I)Cl]complexes whose structure were solved by an X-ray analysis. The rotational motion in the
biphenyl group is slow on the NMR time scale. Rotational barriers were determined using WINDNMR for two of the chiral gold
complexes.
Key words: NHC ligands, gold (I) complexes, ligand dynamics, percent buried volumes, rotational barrier.
Introduction
The field of the N-heterocyclic (NHC) ligands in homogeneous catalysis has significantly
expanded in the last two decades due to many advantages in their stability and structural variability.[1-3]
Chiral NHC ligands are being developed to replace chiral phosphines for several transition metal
complexes.[4-7] As shown in Figure 1, NHC ligands 1-3 with saturated imidazole ring allow for two
chiral centers in the ring, and the "gearing" effect transmits the asymmetry to the coordination site.[4-7]
Ph
Ph
R1
N
N
R1
Ph
Ph
t-Bu t-Bu
Ar
N
N
Ar
R2
R2
N
N
4
Ar
N
N
R
Ar
Ar
Ar
Ar
a: R1 = Naph, R2 = Me
b
: R1 = Mes, R2 = Et
c: R = Ar, R = Pr, Bu
1 Ar=substituted
2
3
phenyl
i
t
1
2
Figure 1. Representative chiral N-heterocyclic carbenes previously reported.
One of the earliest reported chiral NHCs has a core structure of imidazole (4) with varying
substituents of R1 and R2. Herrmann and coworkers prepared the chiral NHC 4a for a Rhodium
complex.[8] Later Alexakis and coworkers were able to extend the usage to Cu-catalyzed conjugate
additions with similar chiral NHCs.[9] Saito reported a three component Ni-catalyzed reaction with chiral
NHC ligand 4b.[10] At the same time, Kundig found that 4c with a t-butyl group as the substituent R2 and
variations at the aryl substituent R1 provided an effective chiral NHC ligand for a Pd-catalyzed C-H
activation reaction.[11]
* Corresponding author.
E-mail addresses: gungbw@miamioh.edu (B. W. Gung).

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During our study of intramolecular [4+3] cycloadditions, we discovered that gold complexes with
NHC ligands are most suitable for such transformations.[12] Gold complexes with chiral NHC ligands are
relatively new and have only begun to appear recently. The tendency of gold(I) to form linear two-
coordinate complexes makes the design of new chiral NHC ligands limited to mono dentate NHCs. The
two coordination sites allow one mono dentate ligand and one coordination site for substrate. This
limitation increases the challenge for the development of enantioselective catalysts. Our initial attempt in
2010 at the preparation of chiral NHC ligands for Au(I) complexes (Figure 2, 5 and 6) revealed the
importance of the ligand structure on gold complex stability.[13] Complexes 5 and 6 were activated for
the cyclopropanation reactions of propargyl esters upon treatment with a silver salt. However, their
thermal stability is much less robust compared to Nolan's achiral complex Au(IPr)Cl.[14] The lesson we
learned was that the design of chiral NHC ligands for preparing gold catalysts must take into account the
steric bulk of the ligand to protect the gold atom. Some of the more successful chiral
[(NHC)Au(I)Cl]complexes are from the groups of Tomioka and Kundig, independently.[15, 16]
N
N
N
N
Au
Cl
Ph
Ph
Au
Cl
5
6
Figure 2. Thermally labile chiral [(NHC)Au(I)Cl] complexes previously reported by us.[13]
Our continued interest in improving NHC ligands so that it will be suitable for Au(I) catalysis
with cycloaddition reactions led us to choose the unsaturated NHC as the core structure (4). We surmised
that the substituents on nitrogen atoms can be further improved so that a strong steric bias would occur
when coordinated to Au(I). Thus far the groups of Alexakis,[17] Saito,[10] and Kundig[18] have
modified NHC 4 by changing the alkyl and aryl groups with varying degree of success. The alkyl group
variations include methyl, ethyl, isopropyl, and t-butyl, while the aryl groups employed so far were
phenyl, naphthyl, mesityl, and 2-methylphenyl and 2-methoxyphenyl groups.[19] Kundig's group did
most work in this area including a chiral ligand with a p-biphenyl substituent.[16] The difference between
the chiral NHC reported in this study and the one example from Kundig's group is the position where the
biphenyl attaches to the chiral center. We have ortho-biphenyl substitution while one example of a para-
biphenyl was reported previously.
Results and discussion
In our design, both stability and steric bias are aimed for the NHC ligand. Thus both steric and
electronic effects need to be considered. The important key element in the new design is a bulky o-
biphenyl group as the aryl substituent. Buchwald and co-workers were the first to use a biphenyl o-(di-
tert-butylphosphino) palladium complex in the catalysis of Suzuki coupling reactions.[20, 21] The same
biphenyl phosphino ligand was then used for Au catalysts by Echavarren.[22] Favorable metal-pi
interactions have been reported in transition metal complexes.[23, 24] The ligand containing the o-
biphenyl moiety appears to provide a favorable scaffold for such stabilizing interactions. To the best of
our knowledge, none of the effective N-heterocyclic carbene ligands reported so far has incorporated the
o-biphenyl group.[7, 25] As depicted in Scheme 1, the ortho aryl groups in two ligand series are further

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adorned with 3,5-dialkyl (methyl or t-butyl) group. The alkyl groups (R) at the stereocenter vary in size
from a methyl group to an isopropyl group. Using this modular approach, a total of nine chiral amines
(11a-12c, and 15a-c) with unique structures are prepared. We employed the known chiral amines 7 and 8
as the starting materials for the desired amines 11a-12c, Scheme 1.[26, 27] The protection of the amino
function in 7 and 8 using t-butoxycarbonyl (t-BOC) enabled Suzuki coupling with three different aryl
boronic acids. After Suzuki coupling, the removal of the t-BOC with CF3CO2H produced chiral amines
11a-12c.
O
ArB(OH)2
Ar NH2
R
Br NH2
R
Br HN
O Bu
t
Boc2O
1. Pd(PPh3)4, Cs2CO3
R
CHCl3
99%
2. CF3CO2H, CH2Cl2
7
9
11a-c
R = Me ( )
= Pr (12a-c)
R = Me ( )
R = Me ( )
= Pr (8)
= Pr (10)
Ar = Ph (11a, 12a, 15a)
Bu Bu
t
t
Me
Me
Ar =
Ar =
11b, 12b, 15b
11c, 12c, 15c
( )
(
)
O
S
O
S
BF3-OEt2
RI, nBu3SnH
BEt3, O2
ArB(OH)2
Ar NH2
Pr
Br
N
tBu
Br HN
tBu
1. Pd(PPh3)4, Cs2CO3
2. MeOH-HCl
i
H
Pr
i
DCM, -78oC
13
14
15a-c
Scheme 1 Synthesis of chiral amines 11a-12c and 15a-c with ortho-biphenyl groups via Suzuki coupling
reactions.
Chiral amines 15a-c were prepared efficiently through intermolecular alkyl radical addition
starting from the known sulfonamide 13, Scheme 1.[28, 29] We were pleased to observe smooth Suzuki
coupling reactions of the sulfonamide 14 with different ArB(OH)2, which eliminated the need of using an
amino protecting group. The sulfinyl group of 14 was removed with acidic methanol after Suzuki
coupling to afford chiral amines 15a-c.
The chiral Au(I) complexes 19a-21c are prepared as shown in Scheme 2 following the improved
procedure by Nolan and co-workers.[30] Briefly the chiral amines (11, 12, or 15) are converted to diimine
intermediates by treating with glyoxal and formic acid. The resulting diimines were immediately allowed
to react with chloromethyl ethyl ether to produce the imidazolium chlorides (16a-18c). The chiral NHC-
gold(I) complexes (19a-21c) were obtained by stirring the imidazolium chloride with Au[S(Me)2]Cl in
acetone in the presence of K2CO3. The gold(I) complexes of 19a-21c are stable and can be purified by
column chromatograph. All of their structures are carefully studied by 1H and 13C NMR spectroscopy.

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1. glyoxal, CH2Cl2
Na2SO4, HCO2H
K2CO3
Au[S(Me)2]Cl
N+
N
11, 12
, or
15
Ar
Ar
Cl-
R
R
2. THF
Acetone
~70%
16a-18c
O
Cl
~72%
R'
R'
Ar =
N
N
Ar
Ar
19a b c 20a b c 21a b c
R Me Me Me Pr Pr Pr Pr Pr Pr
R
R
Au
Cl
n
n
n
i
i
i
19a-21c
R' H Me tBu H Me Bu H Me Bu
t
t
Scheme 2 Synthesis of Au(I) complexes 19a-21c with variations at the alkyl (R) and the aryl (Ar) groups.
For comparison purpose, we prepared the [(ADC)Au(I)Cl] complex (23) from the known
isonitrile 22[31] as shown in eq. 1.[32] An X-ray structure analysis of 23 is shown in Figure 3. The key
structural data for the [(ADC)Au(I)Cl] complex (23) are compiled in Table 1 along with the NHC-AuCl
complexes.
Cl
Ph
Au
H
N
N
Ph
Ph
N
Ph
H
(1)
N
Ph Au
0.5 M CH2Cl2
reflux, 44 h
82%
Cl
23
Ph
22
X-Ray quality crystals were also obtained for two of the NHC complexes (19a and 21b) when the
purified [NHCAu(I)Cl] complexes were dissolved in a minimal amount of dichloromethane in a long test
tube and hexanes were carefully layered on top of the solution. ORTEP representations of [NHC][AuCl]
(19a and 21b) and [ADC][AuCl] (23) are presented in Figure 3.
19a
21b
23
Figure 3. ORTEP representation of [NHC][AuCl] (19a and 21b) and [ADC][AuCl] (23).

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We are pleased to find that the new chiral gold(I) complexes (19a-21c) can produce catalysts that
are much more stable than those we have previously reported, i.e., catalysts prepared from complexes 5
and 6 or 23. To avoid unpredictable effects of the silver salt, we usually try to minimize the presence of
the silver salt by protecting Au(I) with benzonitrile after abstraction of the chloride with AgSbF6 and
filtering off the resulting AgCl, eq. 2.[12, 33]
CN
[NHC][Au(I)PhCN]+
(2)
+ AgCl
SbF6
[NHC][Au(I)Cl]
AgSbF6, CH2Cl2
88%
Upon the chloride abstraction by using AgSbF6, the cationic Au(I) complexes are active catalysts
and are susceptible to disproportionation reaction leading to "gold mirroring".[13] However the
complexes prepared in this study (Scheme 2) appear to be stable for days after the chloride abstraction
treatment as shown in eq. 2. In order to compare their thermal stability, variable temperature NMR
-
experiments were performed on the two different Au(I) complexes, the [NHC][Au(I)PhCN]+SbF6
complex prepared from 21b, and the [ADC][Au(I)PhCN]+SbF6 complex prepared from 23. Each gold
-
complex was treated with an equal molar amount of AgSbF6 and PhCN in CDCl3 and stirred at room
temperature for 15 min, eq. (2).
Catalyst stability study
110
100
90
80
70
60
50
40
30
20
20
25
30
35
40
45
50
55
Temperature (oC)
Figure 4. Catalyst stability study: (♦) catalyst prepared from 21b, (■) catalyst prepared from 23.
The resulting suspension was filtered and the filtrate was loaded into an NMR tube and the 1H
NMR spectra were recorded at 30 min interval from room temperature to 50 ºC. The 1H NMR spectra of
the cationic Au(I) complexes were recorded from rt to 50 ºC during a five hour time period. The CDCl3

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we used was purchased and used as received. The one equivalent of PhCN serves to stabilize the cationic
gold complex in solution. The cationic catalyst prepared from 21b showed no signs of change from room
temperature to 50 ºC and from the first to the last spectrum taken during the 5 hours of time, Figure 4.
For catalyst prepared from 23, it was convenient to monitor the ortho protons on one of the
phenyl groups during the NMR study because of their up-field chemical shifts. A steady decrease of the
peak at 6.6 ppm was observed as the temperature rises. At the conclusion of the experiments for catalyst
23, a gold mirror was deposited onto the bottom of the NMR tube. Thus the variable temperature NMR
experiments carried out with the two gold complexes support the hypothesis that the o-biphenyl
-
substituent protect the cationic Au(I) catalyst in the [NHC][Au(I)PhCN]+SbF6 complex prepared from
21b.
It is interesting and informative to compare their properties with what we have reported
previously in order to understand the important elements in [(NHC)Au(I)Cl] structures. Both steric and
electronic effects of the ligands in metal complexes play a role in the property of the complex. In gold(I)
complexes, steric effects appear to be extremely important. One likely reason is that the steric bulk of the
ligands can protect the Au atom from disproportionation reaction, hence leading to improved thermal
stability. The evaluation of ligand steric effects has been developed for both phosphines and NHCs.
Tertiary phosphine ligands are commonly classified using the Tolman cone model for steric effects
around metal center.[34] Nolan and Cavallo proposed an alternate model, initially intended to measure the
NHC steric bulk.[35, 36] The "percent buried volume", %VBur gives a measure of the space occupied by
an organometallic ligand in the first coordination sphere of the metal center. The sphere has a defined
radius and has the metal center at the core. %VBur is calculated using crystallographic data. A website
named SambVca has been set up for the calculations of the percent buried volume.[37] By definition the
bulkier a specific ligand is, the larger the amount of the sphere that will be occupied by the ligand, i.e.
greater %VBur. The relative significance of %Vbur was found to be more important in gold and silver
complexes than in [PdCl(NHC)(allyl)] complexes.[38] The linear geometry of the silver and gold
complexes was suggested to be at the origin of these differences.
Table 1. Comparison of Au-C bond length, C-Au-Cl bond angle and %VBur for [LAu(I)Cl] complexes.
a
Complex
Au-C1 (Å)
C(Ar)--Au (Å)
Close contact
%VBur
C-Au-Cl (°)
Bond angle
177.0(4)
CCCC (°)
Bond length
Aryl-aryl torsion
IPrAuClb
1.942(3)
1.998(3)
na
na
na
na
44.5
36.4
5c
6c
178.1(4)
179.5(4)
na
na
2.003(3)
29.4
23d
19a
21b
2.004(3)
1.979(3)
1.989(3)
177.9(4)
180.0(4)
179.1(4)
3.73
4.00
3.36
na
36.7
44.6
53.8
65.7
66.8
a Parameters used for SambVca calculations: sphere radius, 3.50 A; Au-C1, 2.00 Å; mesh spacing, 0.10;
Bondi radius, 1.17. H atoms are excluded.
b Taken from Ref. [36]. c Work reported in Ref. [13]. d Taken from Ref.[32]

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The values of %VBur were calculated for Au(I) complexes 5, 6, 19a, 21b and 23 and comparison
is made to the steric demanding complex IPrAuCl.[39] The exact values of the %VBur also depend on the
choice of several parameters: the sphere radius defined for the metal complex, the metal ligand bond
distance, and a scale constant (bondi radius). In order to obtain consistent results, one should be careful to
keep the same set of variables for all calculations. We employed the standard constant set reported by
Nolan and the resulting percent buried volumes calculated are shown in Table 1, which include all gold(I)
complexes that we have crystallographic data.
Figure 5. Left: temperature-dependent NMR signals (300 MHz in CDCl3) of the 3,5-dimethyl protons
on the distal phenyl group of compound 21b. Right: computer simulations using a line shape analysis
program (WINDNMR)[40] with the rate constants reported.
There is a remarkable correlation between the calculated %VBur and the Au(I) catalyst stability.
Nolan's IPrAu(I)Cl complex has a value of 44.5 and is known to generate an extraordinarily stable
catalyst. Our previously reported complex 6 has the smallest %VBur value of 29.4 in Table 1 and it was the
least stable catalyst. Once the chloride is removed, complex 6 immediately decomposed about 50% when
the NMR sample was run.[13] Complex 5 has a percent buried volume of 36.4 and it showed more
stability than 6, but it also decomposed within a few hours after activating with AgSbF6.[13] The ADC
complex 23 has a similar %VBur to 5 and it showed very similar stability as a catalyst.[32]

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Figure 6. Left: temperature-dependent NMR signals (300 MHz in CDCl3) of the 3,5-di-t-butyl protons on
the distal phenyl group of compound 21c. Right: computer simulations using a line shape analysis
program (WINDNMR)[40] with the rate constants reported.
We are pleased to see the percent buried volumes calculated for the new complexes 19a and 21b
are substantially larger. The gold(I) complex 19a have a calculated %VBur of 44.6, almost identical to that
of IPrAu(I)Cl. The complex 21b has a %Vbur of 53.8, which is greater than the very bulky [IPr*Au(I)Cl]
complex (%Vbur = 50.4) reported by Nolan.[41] We proceeded to remove the chloride from complexes
19a and 21b according to eq. 1 and observed no significant change in their 1H NMR spectra after several
days .

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The large percent buried volumes for the new gold complexes may be attributed to the o-biphenyl
group. The biphenyl substituents through their ortho attachment to the stereogenic carbons place the distal
phenyl group inside or near the first coordination sphere centered by the gold atom. Crystal packing
forces also contribute to the solid state conformations. The rotational flexibility of the biphenyl axis
allows the distal phenyl group to wrap around the Au atom. This analysis is supported by the X-ray
structure (although the solution structure may differ from the solid state structure) and by the observation
that the rotation around the biphenyl axis is slowed to such a degree that coalescence was observed for
complexes 21b and 21c at room temperature, rather than at much lower temperatures. Usually mono-
substituted biphenyls have free rotation at room temperature on the NMR time scale.[42] However in
these complexes the hindrance to free rotation may arise from steric interactions involving the 3,5-dialkyl
substituents and the Au-Cl moiety of the complex. The distal phenyl groups are right next to the gold
atom and any substituents on the phenyl group could cause steric interactions when rotating around the
biphenyl axis.
Table 2. Rate constants for Compounds 21b and 21c at Different Temperatures obtained using
WINDNMR.[40]
T(K)a
323
318
313
308
303
297
293
288
283
278
273
268
263
258
253
kr (21b)
3.37x105
1.71x105
7.11x104
5303
1392
440
kr (21c)
2606
1678
900
493
263
122
69
236
93
32
40
16
26
7.5
6.3
4.0
2.8
2.0
1.8
0.95
0.41
0.35
a Temperature was not calibrated and was recorded as shown on the instrument dial.
In order to understand the o-biphenyl ligand center C-C bond rotational dynamics in the gold
complexes, we performed NMR spectroscopic study for complexes 21b and 21c at different temperatures,
Figure 4. Variable temperature NMR experiments were performed from –20 to 50 °C with deuterated

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chloroform as solvent. At around 5 °C, the rotation around the biphenyl axis becomes slow enough that
the signals for the two methyl groups decoalesce, with one at ~2.15 ppm and the other at ~2.4 ppm,
Figure 4. At around 30 °C, the rotation around the biphenyl axis becomes fast enough that the signals for
the two methyl groups become a single peak centered at ~2.28 ppm, Figure 4.
According to the thermodynamic equation ∆G‡= ∆H‡ - T∆S‡ and transition state theory,[43]
enthalpies, entropies and free energies of activation are related to rate constants by the following
equations:
S‡/R
kr = kBT/h e∆G‡/RT = (kBT/h) e-∆H‡/RT e∆
(3)
(4)
∆G‡= -RTln(krh/kBT) = 1.987 cal mol-1 T (23.76+ln(T/kr))
where kr = rate constant, kB = Boltzman constant 1.380x10-23, T = Temperature in K, h = Planck’s
constant 6.626x10-34, R = gas constant 1.987 cal deg-1 mol-1, ln(h/kB) = 23.76.
The free energies of activation (∆G‡) are calculated from the rate constants (eq. 4 and Table 2),
which are obtained from the simulations performed using WINDNMR (see Figure 5 and 6). Plotting the
calculated ∆G‡ vs. T, enthalpy and entropy of activation can be estimated, Figure 7 and Table 3.
16
15.5
y = -0.0244x + 21.85
15
R² = 0.9795
14.5
21b
21c
14
13.5
13
y = -0.043x + 26.55
R² = 0.9681
250
260
270
280
290
300
310
T (K)
Figure 7. The plot of ∆Gǂ vs. T for center C-C bond rotation of the biphenyl substituent of complexes 21b
and 21c.
The observed biphenyl center C-C bond rotational barriers for the complexes 21b and 21c are
14.7 and 13.8 kcal/mol, respectively and the rotational barrier has a significant entropy term. The fact that
both complexes have a positive and substantial rotational entropy of activation indicate the biphenyl
group experiences more than a simple rotational barrier because simple rotations have small and negative
entropy of activation.[44] Our current interpretation for the positive entropy of activation is that the

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substituents on the distal phenyl group have restricted movements in the ground state due to steric
interactions with the Au-Cl moiety.
Table 3. Activation parameters for center C-C bond rotation of the biphenyl substituent of complexes 21b
and 21c in CDCl3
Complexa
Coalescence
Temp (K)
∆Gǂ(rotation)
(kcal/mol)
∆Hǂ(rotation)
(kcal/mol)
∆Sǂ(rotation)
(cal/mol K)
14.0(1)
14.6(1)
26.6(0.8)
21.9(0.4)
43.0(3)
24.4(2)
293
297
21b
21c
a The standard errors for the intercept and slope are analyzed with the Excel’s LINEST function, which
calculates the statistics of the line with least square fit.
In the rotational transition state of the biphenyl group, the substituents on the distal phenyl group
may actually have more freedom of movements due to moving away from the Au-Cl. In other words, the
methyl (21b) and t-butyl groups (21c) on the distal phenyl may rotate more freely when the biphenyl unit
has a twist angle of near zero degree. This explanation is somewhat speculative; however there are
literature precedents where external interactions cause the activation entropy to be positive. One literature
example similar to this bond rotation dynamics is the report by Bergman and Raymond.[45] They
examined the rotational dynamics of encapsulated guest molecules to probe the steric consequences of
encapsulation within a host. Encapsulation was found to increase the Ph-CH2 bond rotational barrier for
ortho-substituted benzyl phosphonium guest molecules by 3 to 6 kcal/mol, and also change the entropy of
activation from negative to positive. Very similar parallel observations are documented here for the o-
biphenyl substituents in the gold(I) complexes. The precursors to gold complexes (imidazoliums 18b and
18c) showed no sign of 1H NMR peak broadening at room temperature, which indicates a lower rotational
barrier. However once coordinated to Au(I), the rotational barriers are raised so that coalescence is
observed for the biphenyl center C-C bond rotation. Therefore the study of the biphenyl rotational barriers
support the notion that steric interactions are present between the substituents and the Au-Cl moiety,
which in turn, explains the high percent buried volumes calculated for gold complexes 21b and 21c.
Conclusion
We have prepared new chiral [(NHC)Au(I)Cl] complexes featuring pairs of o-biphenyl
substituents. X-Ray structure analysis was performed for two of the nine gold complexes. Large percent
buried volumes are calculated for the two complexes. This indicates the proximity of the ligand
substituents to the Au atom. The proximity is further corroborated by a variable temperature NMR study,
which showed a free energy activation ~14 kcal/mol for the biphenyl rotational barriers. Normally mono-
substituted biphenyls have rotational barriers around 3-10 kcal/mol. The rotational barriers determined for
these complexes are greater than usual, which indicates additional steric interactions between substituents
and the Au-Cl moiety in addition to the usual biphenyl ortho substituent interactions. Our current efforts
include (1) to more precisely substantiate the correlation between steric bulk of the NHC and catalyst

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stability by estimating the half-life time of the cationic complexes under given conditions; and (2) to
employ the gold complexes as enantioselective catalysts in cycloaddition reactions.
Acknowledgements
Financial support from the NSF (TUES program) and Miami University for the NMR Facility are
acknowledged. We are grateful to Professor Hans Reich for assistance with the WINDNMR program. We
thank Dr. Ryan Conyers for preparing the [(ADC)Au(I)Cl] complex 23 and Caleb Jones for preparing
complex 21a.
Appendix A. Supporting material
CCDC 1049077-1049078 contain the supplementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Appendix B. Supplementary data
Supplementary material featuring experimental details and NMR spectra related to this article can be
found at http://dx.doi.org/.
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16264.

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High Lights:
• Nine novel chiral [(NHC)Au(I)Cl] complexes are synthesized and
characterized.
• X-Ray structure analysis was performed for two of the nine gold complexes.
Large percent buried volumes are calculated for the two complexes.
• The new chiral [(NHC)Au(I)Cl] complexes feature pairs of o-biphenyl
substituents. The rotational barriers determined for the biphenyl C-C bond
rotation in these complexes are greater than usual.

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Supporting Information for:
Synthesis and Characterization of Novel Chiral [(NHC)Au(I)Cl]
Complexes: Featuring ortho-Biphenyl Substituents
Michael R. Holmesa, John F. Manganaroa, Charles L. Barnesb, Benjamin W. Gunga*
aDepartment of Chemistry & Biochemistry, Miami University, Oxford, Ohio 45056
bElmer O. Schlemper X-Ray Diffraction Center, University of Missouri-Columbia, Columbia, MO 65211 United States.
Experimental procedures…………………………………………………………………………………2
NMR Spectra……………………………………………………………………………………………..17
Crystallographic data for 19a………………………………………………………………………...…26
Crystallographic data for 21b………………………………………………………………………...…27
Literature Cited…………………………………………………………………………………………..28
1

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Experimental Procedures and Analytical Data
General
Unless otherwise stated, all reactions were carried out under an inert nitrogen atmosphere with anhydrous
solvents. Dichloromethane (CH2Cl2) was distilled over calcium hydride. Reagents were purchased and used without
further purification unless otherwise stated. Yields refer to chromatographically and spectroscopically (1H NMR)
homogeneous materials, unless otherwise stated. Reactions were monitored by thin-layer chromatography (TLC)
carried out on Merck silica gel plates (60F-254; 0.25 mm) by using UV light as the visualizing agent and an acidic
mixture of anisaldehyde, phosphomolybdic acid, ceric ammonium molybdate, or basic aqueous potassium
permanganate (KMnO4) and heat as developing agents. Merck silica gel (60, particle size 0.043–0.063 mm) was
used for flash column chromatography. NMR spectra were recorded on Bruker Av-500 and Av-300 instruments and
calibrated by using residual undeuterated solvent as an internal reference (CHCl3 : δ=7.26 (1H), 77.0 ppm (13C)). The
following abbreviations (or combinations thereof) were used to explain the multiplicities: s=singlet, d=doublet,
t=triplet, q=quartet, m=multiplet, br=broad.
(R)-1-(2-bromophenyl)ethanamine (7).
Using the procedure reported by Klingensmith et. al.a The desired amine 7 was produced as a light yellow
oil (53%). [α] = −35.3 (0.2, CHCl3) 1H NMR (500 MHz, CDCl3): 1.37-1.38 (d, 1H), 1.57 (bs, 2H), 4.48-
4.52 (q, 1H), 7.06-7.1 (t, 1H), 7.26-7.52 (m, 2H), 7.53-7.54 (m, 1H).
9 (R)-1-(2-Bromo-phenyl)-ethylamine-N-t-Boc.
To a solution of the amine (7) (926 mg, 4.65 mmol) in CHCl3 (9 mL) was added Boc anhydride (1.2 mL,
5.12 mmol). The reaction mixture was allowed to stir overnight, concentrated, and purified by column
(20% EtOAc/Hex) to yield a white solid (Quant.). [α] = +11.3 (0.02, CHCl3), 1H NMR (500 MHz,
CDCl3): 1.26-1.27 (d, 3H), 1.42 (s, 9H), 4.97 (bs, 1H), 5.08 (bs, 1H), 7.08-7.11 (t, 1H), 7.26-7.32 (m,
2H), 7.52-7.53 (d, 1H). 13C NMR (125 MHz, CDCl3): 21.7, 28.3, 50.2, 19.6, 107.6, 110.5, 112.4, 126.4,
127.7, 128.4. LCMS m/z calcd for C13H18BrNO2 299.0 found 299.2 (M+).
2

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(R) – (+) - 2’- (biphenyl)- α-phenylethyl-N-tert-butylcarbonylamine
A dry, 200 mL RB flask with magnetic stir bar was charged with (R)-1-(2-Bromo-phenyl)-ethylamine-N-
t-Boc (9) (1.39 g, 4.66 mmol), DME (33 mL), phenylboronic acid (795 mg, 6.52 mmol), Na2CO3 (1.48 g,
13.98 mmol), and H2O (33 mL). The suspension was degassed under N2 (x3) and then charged with
Pd(PPh3)4 (538 mg, 0.47 mmol), fitted with a reflux condenser, and degassed and additional x2 under N2.
The solution was heated to reflux overnight, cooled to RT, diluted with EtOAc (50 mL), separated, and
the aqueous phase was extracted with EtOAc (2x50mL). Combined organics washed with brine, dried
over Na2SO4, filtered and purified by column (20% EtOAc / Hex) to yield a colorless oil. (73%) [α] = +
33.6 (0.2, CHCl3). 1H NMR (500 MHz, CDCl3): 1.25-1.26 (d, 3H), 1.39 (bs, 9H), 4.80 (bs, 1H), 4.92 (bs,
1H), 7.18-7.19 (d, 2H), 7.19-7.20 (t, 2H), 7.25-7.34 (m, 3H). 13C NMR (125 MHz, CDCl3): 28.4, 61.2,
124.7, 126.7, 127.1, 127.8, 128.2, 129.3, 130.4, 141.0, 141.9. LCMS m/z calcd for C19H23NO2 297.2
found 297.4 (M+).
11a (R) – (-) - 2’-(biphenyl)- α-phenylethylamine
To a cooled (0oC) solution of the Boc-protected amine (1.00 g, 3.37 mmol) in CHCl3 (26 mL) was added
trifluoroacetic acid (1.81 mL, 23.62 mmol) dropwise. The reaction was allowed to warm to ambient
temperature and stirred overnight. The reaction mixture is carefully basified with 10% NaOH (to pH ~
10) and then separated. The aqueous phase is extracted into EtOAc (3 x 30 mL), combined organics dried
over Na2SO4, filtered, and solvent removed under reduced pressure to provide the free amine as a light
yellow oil (92%). [α] = -23.6 (0.01, CHCl3) 1H NMR (500 MHz, CDCl3): 1.31-1.33 (d, 3H), 3.53 (bs,
2H), 4.24-4.28 (q, 1H), 7.18-7.20 (d, 1H), 7.25-7.29 (m, 2H), 7.35-7.41 (m, 3H), 7.58-7.60 (d, 1H) 13C
NMR (125 MHz, CDCl3): 25.3, 46.7, 125.2, 126.4, 126.9, 127.9, 128.1, 129.3, 130.1, 140.7, 141.4, 145.0
LCMS m/z calcd for C14H15N 197.1, found 196.1 (M+-H+).
3

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16a 1,3-bis((R)-1-([1,1'-biphenyl]-2-yl)ethyl)-1H-imidazol-3-ium chloride
In a dry RB flask under N2, A solution of 40% wt glyoxal (0.17 mL, 1.48 mmol) in DCM (3.0 mL) was
charged with oven dried Na2SO4 (839 mg, 5.91 mmol), then formic acid (0.005 mL, 0.118 mmol). To this
suspension was added a solution of the corresponding amine (588 mg, 2.95 mmol) in DCM (3.0 mL),
allowed to stir for 30 minutes, then another portion of Na2SO4 (839 mg, 5.91 mmol) was added, and
allowed to stir for 3 hours. The solution was filtered, solvent removed, and used in the next step without
further purification. In a dry RB flask under N2, to a solution of chlormethyl ethyl ether (0.14 mL, 1.48
mmol) in THF (1.0 mL) is added 1 drop of water (approx. 0.01 mL), then a solution of the diimine (615
mg, 1.48 mmol) in THF (2.0 mL). The mixture is fitted with a reflux condenser and stirred at RT for 24 h,
then heated to 45o C for 16h. The reaction mixture was cooled to RT, quenched with H2O (10 mL),
separated, and aqueous portion extracted into DCM (3 x 10 mL). Combined organics dried over Na2SO4,
filtered solvent removed and purified by column (5% MeOH/DCM) to yield a brown solid. (63%) [α] =
+61.6 (0.01, CHCl3) 1H NMR (500 MHz, CDCl3): 1.91-1.93 (d, 6H), 5.82-5.83 (q 2H), 6.57 (s, 2H), 7.14-
7.49 (m, 14H), 9.71 (s, 1H) 13C NMR (125 MHz, CDCl3): 21.1, 50.8, 56.7, 120.2, 126.4, 128.0, 128.5,
128.7, 128.9, 129.2, 130.8, 135.1, 136.5, 139.4, 142.0. LCMS m/z calcd for C31H29N2Cl 464.2 found
428.6 (M+-Cl-)
19a (1,3-bis((R)-1-([1,1'-biphenyl]-2-yl)ethyl)-2,3-dihydro-1H-imidazol-2-yl)gold(I) chloride
In a dry 10 mL RB flask under N2, the imidazolium chloride (16a) (90 mg, 0.19 mmol), Au[S(Me)2]Cl
(57.1 mg, 0.19 mmol), and K2CO3 (27 mg, 0.19 mmol) were suspended in acetone (1.0 mL). The flask
was fitted with a reflux condenser, and the reaction was heated to reflux for 3h. The reaction was cooled,
solvent removed under reduced pressure, residue re-suspended in DCM then filtered through a pad of
celite and silica. Compound purified by column chromatography (50% EtOAc/Hex) to yield a white solid
4

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(28%). [α] = -34.3 (0.01, CHCl3). 1H NMR (500 MHz, CDCl3): 1.62-1.64 (d, 6H), 5.95-5.99 (q, 2H), 6.34
(s, 2H), 7.01-7.02 (d, 3H), 7.01-7.02 (d, 2H), 7.29-7.46 (m, 9H) 13C NMR (125 MHz, CDCl3): 21.6, 56.9,
117.3, 125.9, 127.6, 127.7, 128.3, 128.5, 128.9, 130.9, 136.2, 139.7, 143.1, 171.6.
tert-butyl (1-(3',5'-dimethyl-[1,1'-biphenyl]-2-yl)ethyl)carbamate:
Using the same general procedure as reported for (R) – (-) - 2’- (biphenyl)-α-phenylethyl-N-tert-
1
butylcarbonylamine, the carbamate was obtained as a white foam, (92%). [α] =+16.7 H NMR (500
MHz, CDCl3): 1.28 (s, 3H), 1.42 (s, 9H), 2.37 (s, 6H), 4.78 (bs, 1H), 4.92 (bs, 1H), 6.98-7.00 (d, 3H),
7.19-7.21 (d, 1H), 7.26-7.29 (t, 1H), 7.33-7.36 (t, 1H), 7.41-7.42 (d, 1H) 13C NMR(125 MHz, CDCl3):
21.4, 28.4, 47.4, 79.0, 124.9, 126.8, 127.1, 127.6, 128.7,130.5, 137.6, 140.8, 141.2, 141.5, 154.5. LCMS
m/z calcd for C21H27NO2 325.4 found 348.2 (M+Na)
11b (R)-1-(3',5'-dimethyl-[1,1'-biphenyl]-2-yl)ethanamine
Same procedure as reported for 11a, obtained as a yellow oil (Quant.) [α] = -19.5 (0.1, CHCl3) 1H NMR
(500 MHz, CDCl3): 1.29-1.31 (d, 3H), 1.47 (bs, 2H), 2.36 (s, 6H), 4.22-4.26 (q, 1H), 6.91 (s, 2H), 7.00 (s,
1H), 7.16-7.17 (d, 1H), 7.23-7.26 (t, 1H), 7.36-7.39 (t, 1H), 7.58-7.59 (d, 1H) 13C NMR (125 MHz,
CDCl3): 21.4, 25.3, 46.7, 125.0, 126.2, 127.1, 127.8, 128.6, 129.9, 137.6, 140.9, 141.3, 145.1. LCMS m/z
calcd for C16H19N 225.3 found 224.3 (M-H+)
5

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16b 3-((R)-1-(3',5'-dimethyl-[1,1'-biphenyl]-2-yl)ethyl)-1-((S)-1-(3',5'-dimethyl-[1,1'-biphenyl]-2-
yl)ethyl)-1H-imidazol-3-ium chloride
Following the same general procedure for 16a, 16b was produced as a brown solid (17%) [α] = +89.4
(0.02, CHCl3) 1H NMR (500 MHz, CDCl3): 2.11-2.12 (d, 2H), 2.34 (s, 12H), 5.75-5.78 (q, 2H), 6.57 (s,
2H), 6.78 (bs, 5H), 7.00 (s, 2H), 7.23-7.24 (d,3H), 7.36-7.44 (m, 4H), 7.54-7.55 (d, 2H), 10.45 (s, 1H) 13C
NMR (125 MHz, CDCl3):: 21.4, 21.7, 23.5, 57.1, 120.5, 136.5, 136.6, 128.7, 128.9, 129.6, 130.6, 135.5,
136.5, 138.5, 139.5, 141.9. LCMS m/z calcd for C35H37N2Cl 520.3 found 485.7 (M-Cl-)
19b (1,3-bis((R)-1-(3',5'-dimethyl-[1,1'-biphenyl]-2-yl)ethyl)-2,3-dihydro-1H-imidazol-2-yl)gold(I)
chloride:
Following the same general procedure for 19a, 19 b was obtained as a light yellow solid (41%) [α] =
+15.4 (0.05, CHCl3). 1H NMR(500 MHz, CDCl3): 1.60-1.61 (d, 6H), 2.34 (s, 12H), 6.06-6.10 (q, 2H),
6.30 (s, 2H), 6.63 (bs, 4H), 6.94 (s, 2H), 7.19-7.20 (d, 2H), 7.37-7.42 (m, 8H). 13C NMR (125 MHz,
CDCl3): 21.5, 21.6, 56.8, 117.1, 125.9, 126.2, 127.5, 128.5, 129.3, 130.9, 135.9, 138.1, 139.6, 143.5,
171.6.
11c (R)-tert-butyl (1-(3',5'-di-tert-butyl-[1,1'-biphenyl]-2-yl)ethyl)carbamate:
Following the same general procedure for 11a, 11c was obtained as a yellow oil (Quant.). [α] = +30.2
(0.1, CHCl3) 1H NMR (500 MHz, CDCl3): 1.35 (s, 21H), 1.52 (bs, 2H), 4.19-4.23 (q, 1H), 7.14 (s, 2H),
7.24-7.29 (m, 2H), 7.38-7.41 (t, 2H), 7.60-7.62 (d, 1H). 13C NMR (125 MHz, CDCl3): 25.5, 31.5, 34.9,
46.8, 120.7, 123.6, 125.2, 126.3, 127.7, 130.1, 140.4, 141.7, 145.4, 150.3. LCMS m/z calcd for
C27H39NO2 409.3 found 409.1 (M+)
6

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16c 1,3-bis((R)-1-(3',5'-di-tert-butyl-[1,1'-biphenyl]-2-yl)ethyl)-1H-imidazol-3-ium chloride:
Following the general procedure for 16a, 16c was obtained as a brown solid (42%). [α] = +54.1 (0.1,
CHCl3). 1H NMR (500 MHz, CDCl3): 1.31 (s 36H), 2.32-2.34 (d, 6H), 5.46-5.50 (q, 2H), 6.40 (s, 2H),
7.01 (s, 4H), 7.27-7.29 (d, 2H), 7.35-7.38 (t, 2H), 7.42-7.45 (t, 2H), 7.74-7.76 (d, 2H), 11.19 (s, 1H). 13C
NMR (125 MHz, CDCl3): 31.5, 31.6, 34.9, 57.9, 120.9, 121.8, 123.1, 127.1, 128.7, 129.0, 130.2, 136.2,
138.9, 142.4, 151.3. LCMS m/z calcd for C47H61N2Cl 688.4 found 654.0 (M+-Cl-)
19c (1,3-bis((R)-1-(3',5'-di-tert-butyl-[1,1'-biphenyl]-2-yl)ethyl)-2,3-dihydro-1H-imidazol-2-
yl)gold(I) chloride:
Same procedure as reported for 19a, white solid (72%) [α] = +49.0 (0.02, CHCl3) 1H NMR (500 MHz,
CDCl3): 1.31 (s, 36H), 1.70-1.71 (d, 6H), 5.86-5.91 (q, 2H), 6.64 (s, 2H), 6.99 (s, 4H), 7.18-7.25 (m, 2H),
7.27-7.29 (m, 2H), 7.36-7.39 (m, 6H). 13C NMR (125 MHz, CDCl3): 22.4, 31.6, 34.9, 57.6, 117.8, 121.6,
122.9, 126.0, 127.6, 128.3, 1313.2, 136.9, 139.1, 143.5, 150.8, 172.0.
8 (R)-1-(2-bromophenyl)butan-1-amine:
Using the procedure reported by Dalmolen et. al.b, the starting amine was produced as a light yellow oil.
(65%) [α] = +17.6 (0.1, CHCl3). 1H NMR (500 MHz, CDCl3): 0.87-0.93 (t, 3H), 1.29-1.31 (m, 1H), 1.41-
4.43 (m, 1H), 1.84-7.89 (m, 2H), 4.60-4.63 (t, 1H), 7.12-7.14 (t, 1H), 7.42-7.44 (d, 1H), 7.54-7.56 (d,
1H), 7.61-7.62 (d, 1H).
7

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10 (R)-tert-butyl (1-(2-bromophenyl)butyl)carbamate:
Following the general procedure for 9, the boc protected amine 10 was obtained in 98% yield as a white
1
foam. [α] = +0.4 (0.1, CHCl3). H NMR (500 MHz, CDCl3): 0.89-0.95 (t, 3H), 1.27-1.49 (m, 13H), 1.53
(bs, 1H), 1.75 (bs, 1H), 4.98 (bs, 2H), 7.07-7.10 (t, 1H), 7.23-7.32 (m, 2H), 7.51-7.53 (d, 1H). 13C NMR
(125 MHz, CDCl3): 13.7, 13.8, 27.4, 28.4, 38.2, 15.3, 85.2, 122.9, 126.3, 127.1, 127.6, 128.3, 128.5,
133.2, 155.1. . LCMS m/z calcd for C15H22NO2 327.1 found 327.5 (M+)
12a (R)-1-([1,1'-biphenyl]-2-yl)butan-1-amine
Using the same general procedure as reported for 11a, 12a was isolated as a yellow oil. (63%). [α](0.02
CHCl3) = +18.7. 1H NMR (500 MHz, CDCl3): 0.67-0.70 (t, 3H), 1.03-1.05 (m, 1H), 1.13-1.14 (m, 1H),
1.35 (bs, 1H), 1.49-1.55 (m, 2H), 3.93-3.96 (t, 1H), 7.11-7.13 (dd, 1H), 7.17-7.19 (m, 3H), 7.21-7.35 (m,
4H), 7.46-7.48 (dd, 1H). LCMS m/z calcd for C16H19N 225.2 found 223.9 (M+-H+)
17a 1,3-bis((R)-1-([1,1'-biphenyl]-2-yl)butyl)-1H-imidazol-3-ium chloride:
Using the general procedure for 16a, 17a was was obtained as a light brown foam (37%) [α] = +42.8. 1H
NMR (500 MHz, CDCl3): 0.88 (t, 6H), 1.16-1.30 (m, 4H), 2.44-2.49 (m, 2H), 2.56-2.60 (m, 2H), 5.45-
5.48 (t, 2H), 6.76 (s, 2H), 7.1-7.11 (d, 2H), 7.24-7.25 (dd, 3H), 7.29-7.52 (m, 8H), 7.52-7.55 (t, 2H), 7.90-
7.91 (d, 2H), 10.28 (s, 1H). 13C NMR (125 MHz, CDCl3): 13.5, 19.5, 36.3, 61.3, 120.7, 127.2, 127.3,
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127.9, 128.3, 128.4, 128.8, 128.9, 129.2, 129.5, 130.5, 134.3, 136.1, 139.8, 142.3. . LCMS m/z calcd for
C35H37N2Cl 520.3 found 485.7 (M+-Cl-).
20a (1,3-bis((R)-1-([1,1'-biphenyl]-2-yl)butyl)-2,3-dihydro-1H-imidazol-2-yl)gold(I) chloride:
Using the general procedure reported for 19a, 20a was isolated as a white solid (80%), [α]= +13.8 (0.3,
CHCl3). 1H NMR (500 MHz, CDCl3): 0.83-0.85 (t, 6H), 1.13-1.19 (m, 1.19), 1.22-1.30 (m, 2H), 1.98-
2.06 (m, 4H), 5.90-5.94 (t, 2H), 6.63 (s, 2H), 7.14-7.16 (d, 4H), 7.23-7.25 (d, 2H), 7.37-7.45 (m, 12H).
13C NMR (125 MHz, CDCl3): 13.5, 19.6, 37.3, 61.0, 118.11, 125.9, 127.7, 127.8, 128.22, 128.7, 128.9,
131.0, 135.9, 139.8, 143.2, 171.9.
12b (R)-1-(3',5'-dimethyl-[1,1'-biphenyl]-2-yl)butan-1-amine:
Using the general procedure reported for 11a, 12b was obtained as a light yellow oil (89%). [α] = +2.1
(0.3, CHCl3). 1H NMR (500 MHz, CDCl3): 0.74-0.79 (t, 3H), 1.12-1.36 (m, 1H), 1.15-1.16 (m, 1H), 1.51-
1.65 (m, 2H), 2.35 (s, 6H), 4.01-4.04 (t, 1H), 6.89 (s, 2H), 6.99 (s, 1H), 7.16-7.18 (d, 1H), 7.22-7.27 (m,
2H), 7.35-7.38 (t, 2H), 7.51-7.57 (d, 1H). 13C NMR (125 MHz, CDCl3): 13.9, 19.8, 21.4, 41.5, 50.7,
125.5, 126.2, 126.8, 127.2, 127.7, 128.3, 128.5, 128.7, 129.9, 137.5, 141.4, 141.4,144.2. . LCMS m/z
calcd for C18H23N 253.2 found 254.6 (M++H+).
17b 1,3-bis((R)-1-(3',5'-dimethyl-[1,1'-biphenyl]-2-yl)butyl)-1H-imidazol-3-ium chloride:
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Following the general procedure for 16a, 17b was obtained as a light brown solid. (42%). [α] = +61.9 1H
NMR (500 MHz, CDCl3): 0.86-0.89 (t, 6H), 1.93-1.23 (m, 4H), 2.28 (s, 12H), 5.43-5.46 (t, 2H), 6.71 (s,
4H), 6.96 (s, 3H), 7.18-7.19 (d, 2H), 7.25-7.27 (d, 2H), 7.33-7.36 (t, 2H), 7.45-7.48 (t, 2H), 7.86-7.87 (d,
2H), 10.48 (s, 1H). 13C NMR (125 MHz, CDCl3):13.5, 13.6, 19.5, 21.2, 21.4, 23.4, 53.5, 61.3, 120.7,
126.7, 127.1, 128.8, 18.9, 129.0, 129.5, 129.9, 130.4, 134.2, 135.9, 137.9, 138.3, 139.7, 142.4. . LCMS
m/z calcd for C39H45N2Cl 576.3 found 541.7(M+-Cl-).
20b (1,3-bis((R)-1-(3',5'-dimethyl-[1,1'-biphenyl]-2-yl)butyl)-2,3-dihydro-1H-imidazol-2-yl)gold(I)
chloride:
Following the same general procedure for 19a, 20b was isolated as a light yellow solid (47%). [α]= +21.6
(0.06, CHCl3). 1H NMR (500 MHz, CDCl3): 0.81-0.84 (t, 6H), 1.12-1.17 (m, 2H), 1.21-1.25 (m, 2H),
1.96-2.02 (m ,4H), 2.33 (s, 12H), 5.92-5.95 (t, 2H), 6.58 (s, 2H), 6.71 (bs, 4H), 6.98 (s, 2H), 7.21-7.22 (d,
2H), 7.33-7.36 (m, 4H). 13C NMR (125 MHz, CDCl3): 13.6, 19.7, 21.5, 37.5, 61.1, 117.8, 126.1, 126.5,
127.4, 128.2, 129.6, 131.1, 135.4, 138.2, 139.6, 143.7, 171.7.
12c (R)-1-(3',5'-di-tert-butyl-[1,1'-biphenyl]-2-yl)butan-1-amine:
Following the same general procedure as reported for 11a, 12c was obtained as an orange oil (Quant.) [α]
= -13.2 ( 0.1, CHCl3). 1H NMR (500 MHz, CDCl3): 0.74-0.77 (t, 3H), 1.12-1.14 (m, 1H), 1.15-1.35 (m,
1H), 1.46 (s, 18H), 1.48 (bs, 2H), 1.56-1.65 (m, 2H), 3.97-4.00 (t, 1H), 7.11 (s, 2H), 7.12-7.28 (m, 2H),
7.36-7.40 (m, 2H), 7.53-7.56 (d, 1H). 13C NMR (125 MHz, CDCl3): 13.9, 19.9, 31.5, 34.9, 41.6, 51.0,
120.6, 123.7, 125.5, 126.1, 127.6, 129.9, 140.5, 142.3, 144.6, 150.3. . LCMS m/z calcd for C24H35N 337.3
found 360.5 (M++Na+).
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17c 1,3-bis((R)-1-(3',5'-di-tert-butyl-[1,1'-biphenyl]-2-yl)butyl)-1H-imidazol-3-ium chloride:
Following the same general procedure as reported for 16a, 17c was obtained as a brown foam (68%). [α]
= +88.6 ( 0.03, CHCl3). 1H NMR (500 MHz, CDCl3): 0.93-0.94 (t, 6H), 1.18-1.24 (m, 4H), 1.33 (s, 36H),
2.69-2.78 (m, 2H), 2.88-2.94 (m, 2H), 5.24-5.27 (t, 2H), 6.42 (s, 2H), 6.99 (bs, 4H), 7.25-7.28 (m, 4H),
7.35-7.38 (m, 2H), 7.47 (s, 1H), 7.52-7.54 (t, 2H), 8.11-8.13 (d, 2H), 11.35 (s, 1H). 13C NMR (125 MHz,
CDCl3): 13.5, 19.7, 31.4, 31.5, 34.9, 36.0, 62.1, 120.6, 120.8, 131.6, 123.5, 127.4, 128.6, 129.4, 129.9,
135.1, 139.3, 142.9. . LCMS m/z calcd for C51H69N2Cl 709.5 found 710.1 (M+-Cl-).
20c (1,3-bis((R)-1-(3',5'-di-tert-butyl-[1,1'-biphenyl]-2-yl)butyl)-2,3-dihydro-1H-imidazol-2-
yl)gold(I) chloride:
Following the same general procedure as reported for 19a, 20c was isolated as a light yellow solid (77%).
[α] = +38.1 (0.02, CHCl3). 1H NMR (500 MHz, CDCl3): 0.72-0.75 (t, 6H), 1.05-1.16 (m, 4H), 1.32 (s,
36H), 1.99-2.09 (m, 2H), 2.22-2.29 (m, 2H), 5.78-5.81 (t, 2H), 6.57 (s, 2H), 7.01 (s, 4H), 7.25-7.31 (m,
4H), 7.35-7.36 (d, 4H), 7.43 (s, 2H). 13C NMR (125 MHz, CDCl3): 13.4, 19.6, 31.6, 31.7, 34.9, 37.6, 61.9,
118.4, 121.6, 123.1, 126.3, 127.5, 128.1, 131.0, 136.1, 139.3, 143.9, 150.9, 171.6.
O
S
Br
N
tBu
H
13 (R,E)-N-(2-bromobenzylidene)-2-methylpropane-2-sulfinamide:
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Synthesized according to the procedure reported by Fernandez-Sals et. al.c obtained as a yellow oil
(94%). 1H NMR (500 MHz, CDCl3): 1.28 (s, 9H), 7.42-7.47 (m, 2H), 7.52-7.54 (d, 1H), 8.12-8.14 (d,
1H), 8.64 (s, 1H).
O
S
O
S
BF3-OEt2
RI, nBu3SnH
BEt3, O2
Br HN
tBu
Br
N
tBu
iPr
H
DCM, -78oC
14 (R)-N-((R)-1-(2-bromophenyl)-2-methylpropyl)-2-methylpropane-2-sulfinamide:
In a dry 250 mL flask under N2, the (R)-(-) sulfonylaldimine 13 (700 mg, 2.46 mmol) was dissolved in
DCM (62 mL) and charged with BF3-OEt2 (0.6 mL, 5.17 mmol), stirred for 5 minutes, then cooled to -78o
C in an acetone /dry ice bath. The 2-iodopropane (2.5 mL, 24.64 mmol), tributyltin hydride (1.7 mL, 6.16
mmol), triethylborane (1M in hexanes) (6.2 mL, 6.16 mmol) were added in order. The volume of oxygen
(25 mL/mmol) was added via syringe, bubbling through the solution. After 1 hour, the reaction is
quenched with sat aq. NaHCO3 (50 mL). The suspension is filtered over celite, separated, and the aqueous
portion is extracted into DCM (3x50 mL). Combined organics washed with brine, dried over Na2SO4,
filtered, and solvent removed. The resulting oil was treated with petroleum ether until crystals begin to
form then cooled in an ice bath. The resulting solid was collected by filtration and rinsed thoroughly with
petroleum ether to yield white needles (52%). [α] = -57.5. (0.3, CHCl3). 1H NMR (500 MHz, CDCl3):
0.86-0.88 (d, 3H), 0.99-1.00 (d, 3H), 1.21 (s, 9H), 2.18-2.21 (m, 1H), 3.74 (bs, 1H), 4.47 (bs, 1H), 7.09-
7.12 (t, 1H), 7.26-7.32 (m, 2H), 7.53-7.54 (d, 1H). 13C NMR (125 MHz, CDCl3): 19.8, 22.6, 33.7, 56.5,
127.5, 128.8, 129.0, 133.3, 141.2. . LCMS m/z calcd for C24H22BrNOS 331.1 found 330.3 (M+-H+).
General procedure Suzuki Coupling sulfonamide of 14:
N-(1-([1,1'-biphenyl]-2-yl)-2-methylpropyl)-2-methylpropane-2-sulfinamide:
A dry 25 mL RB flask under N2 was charged with the sulfonamide (14) (100 mg, 0.301 mmol), Cs2CO3
(294.2 mg, 0.903 mmol), and the boronic acid (63.1 mg, 0.421 mmol). The flask is purged and back-filled
with N2, then a 1:1 solution of DME:H2O (4.3 mL) was added via syringe. The stirred suspension was
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degassed with N2 (x3) , then charged with Pd(PPh3)4 (34.7 mg, 0.030 mmol). The reaction flask was fitted
with a reflux condenser and then degassed with N2 again. The reaction was heated to reflux overnight,
cooled to RT, diluted with 10 mL H2O, and extracted into DCM (3X10mL). Combined organics washed
with brine, dried over Na2SO4, filtered, and purified by column (30% EtOAc:Hex). [α] = -165.4 (0.02
CHCl3). 1H NMR (500 MHz, CDCl3): 0.64-0.66 (d, 2H), 0.87-0.88 (d,2H), 1.23 (s, 9H), 1.90-1.97 (m,
1H), 3.51-3.52 (d, 1H), 4.18-4.21 (t, 1H), 7.21 -7.23 (d, 1H), 7.287-7.295 (t, 1H), 7.37-7.39 (m, 7H). 13C
NMR (125 MHz, CDCl3): 19.5, 19.6, 22.7, 36.5, 15.2, 62.5, 126.3, 126.7, 127.0, 127.8, 128.1, 129.8,
130.4, 140.1, 141.3, 141.8. . LCMS m/z calcd for C20H27NOS 329.2 found 327.9 (M+-H+).
15a (R)-1-([1,1'-biphenyl]-2-yl)-2-methylpropan-1-amine:
In a dry 10 mL rb flask under N2, methanol (0.5 mL) was cooled to 0oC, then Acetyl Chloride (0.04 mL,
0.526 mmol) was added to generate the acidic methanol solution. The acidic methanol solution was
warmed to RT, then added to N-(1-([1,1'-biphenyl]-2-yl)-2-methylpropyl)-2-methylpropane-2-
sulfinamide in another dry flask under N2 via syringe. The solution was stirred for 2 hours, then basified
with 10% wt. aq. NaOH, extracted into DCM (3 X 10 mL). Combined organics washed with brine, dried
over Na2SO4, filtered and solvent removed, purified by column (10% MeOH:DCM) to yield product as a
light yellow oil. (83%). [α] = -33.5 (0.01, CHCl3). 1H NMR (500 MHz, CDCl3): 0.60-0.61 (d, 3H), 0.94-
0.95 (d, 3H), 1.66 (bs, 2H), 1.83-1.89 (m, 1H), 3.67-3.70 (d, 1H), 7.20-7.21 (d, 1H), 7.22-7.28 (m, 3H),
7.29-7.40 (m, 4H), 7.41-7.42 (d, 1H). 13C NMR (125 MHz, CDCl3): 14.2, 29.2, 35.4, 27.5, 126.0, 126.2,
126.8, 127.8, 128.0, 129.4, 129.9, 141.7, 141.8, 143.2. . LCMS m/z calcd for C16H19N 225.2 found 224.3
(M+-H+).
18a 1,3-bis((R)-1-([1,1'-biphenyl]-2-yl)-2-methylpropyl)-1H-imidazol-3-ium chloride:
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Following the general procedure for 16a, 18a was obtained as a light brown, glassy solid (62%).
[α] = -60.4 (0.01, CHCl3). 1H NMR (500 MHz, CDCl3): 0.68-0.69 (d, 6H), 0.86-0.87 (d, 6H), 3.21-3.26
(m, 2H), 4.83-4.85 (d, 2H), 6.85 (s, 2H), 7.00 (bs, 4H), 7.10-7.14 (d, 2H), 7.29-7.34 (m, 10H), 7.49-7.52
(m, 2H), 10.01 (s, 1H). 13C NMR (125 MHz, CDCl3): 19.8, 20.1, 31.5, 53.4, 38.3, 121.2, 127.2, 127.9,
128.7, 128.8, 128.9, 129.4, 130.3, 134.2, 134.3, 137.8, 142.6. LCMS m/z calcd for C35H37N2Cl 520.3
found 485.6 (M+-Cl-).
21a (1,3-bis((R)-1-([1,1'-biphenyl]-2-yl)-2-methylpropyl)-2,3-dihydro-1H-imidazol-2-yl)gold(I)
chloride:
Following the general procedure for 19a, 21a was isolated as a white foam (43%). [α] = +100.0 (0.02,
CHCl3). 1H NMR (500 MHz, CDCl3): 0.77-0.78 (d, 6H), 0.97-0.98 (d, 6H), 2.70-2.76 (m, 2H), 5.46-5.48
(d, 2H), 6.48 (s, 2H), 6.98 (bs, 4H), 7.22-7.23 (d, 2H), 7.24-7.41 (m, 8H), 7.47-7.48 (t, 2H), 7.78-7.81 (d,
2H). 13C NMR (125 MHz, CDCl3): 14.2, 20.4, 20.6, 21.1, 31.9, 60.4, 67.3, 118.5, 126.9, 127.8, 128.2,
128.3, 128.8, 129.1, 131.1, 134.8, 139.7, 144.4, 170.1.
15b (R)-1-(3',5'-dimethyl-[1,1'-biphenyl]-2-yl)-2-methylpropan-1-amine:
Following the general procedure for 15a, 15b was obtained as a yellow oil (78%). [α] = -15.7 (0.02,
CHCl3). 1H NMR (500 MHz, CDCl3): 7.54 (d, 1H), 7.34 (t, 1H), 7.23 (t, 1H), 7.20 (d, 1H), 7.03 (s, 1H),
6.94 (s, 2H), 3.73 (d, 1H), 2.39 (s, 6H), 1.89 (m, 1H), 0.98 (d, 3H), 0.65 (d, 3H). 13C NMR (125 MHz,
CDCl3): 18.6, 18.7, 21.4, 36.7, 64.5, 124.8, 125.5, 126.0, 126.7, 129.0, 129.9, 133.1, 136.0, 138.8, 141.1.
LCMS m/z calcd for C18H23N 253.2 found 251.4 (M+-2H+).
14