Synthesis of planar chiral [2.2]Paracyclophanyl imidazo[1,5-a[pyridinium salts for the rhodium-catalyzed asymmetric arylation

Article abstract of DOI:10.1080/00397911.2011.610548

Several novel flexibility-restricted imidazo[1,5-a]pyridinium triflates (abbreviated as imidazolium salts) were synthesized from (4S _p,13R _p)-()-4-amino-13-bromo[2.2]paracyclophane and pyridylaldehyde. These imidazolium salts can be used as nitrogen-containing heterocyclic carbene precursors in asymmetric catalysis and here they are applied in the Rh-catalyzed asymmetric 1,2-addition of arylboronic acids to aldehydes. After optimizing the catalytic situations and testing a series of substrates, moderate enantioselectivity and good yield were obtained.

Full text of DOI:10.1080/00397911.2011.610548

This article was downloaded by: [University of Calgary]
On: 28 February 2013, At: 12:58
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Synthesis of Planar Chiral
[2.2]Paracyclophanyl Imidazo[1,5-
a]pyridinium Salts for the Rhodium-
Catalyzed Asymmetric Arylation
Dengxia Wang a , Yudao Ma a , Fuyan He a , Wenzeng Duan a , Lei
Zhao a & Chun Song a
a Department of Chemistry, Shandong University, Jinan, Shandong,
China
Accepted author version posted online: 21 Feb 2012.Version of
record first published: 21 Dec 2012.
To cite this article: Dengxia Wang , Yudao Ma , Fuyan He , Wenzeng Duan , Lei Zhao & Chun Song
(2013): Synthesis of Planar Chiral [2.2]Paracyclophanyl Imidazo[1,5-a]pyridinium Salts for the
Rhodium-Catalyzed Asymmetric Arylation, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 43:6, 810-825
To link to this article: http://dx.doi.org/10.1080/00397911.2011.610548
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 43: 810–825, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.610548
SYNTHESIS OF PLANAR CHIRAL
[2.2]PARACYCLOPHANYL IMIDAZO[1,5-a]
PYRIDINIUM SALTS FOR THE RHODIUM-
CATALYZED ASYMMETRIC ARYLATION
Dengxia Wang, Yudao Ma, Fuyan He, Wenzeng Duan,
Lei Zhao, and Chun Song
Department of Chemistry, Shandong University, Jinan, Shandong, China
GRAPHICAL ABSTRACT
Abstract Several novel flexibility-restricted imidazo[1,5-a]pyridinium triflates (abbreviated
as imidazolium salts) were synthesized from (4Sp,13Rp)-(ꢀ)-4-amino-13-bromo[2.2]
paracyclophane and pyridylaldehyde. These imidazolium salts can be used as nitrogen-
containing heterocyclic carbene precursors in asymmetric catalysis and here they are applied
in the Rh-catalyzed asymmetric 1,2-addition of arylboronic acids to aldehydes. After opti-
mizing the catalytic situations and testing a series of substrates, moderate enantioselectivity
and good yield were obtained.
Keywords Aldehyde; asymmetric arylation; N-heterocyclic carbene; [2.2]paracyclo-
phane; planar chirality
INTRODUCTION
N-Heterocyclic carbenes (NHCs) have emerged during the past two decades as
a new type of stable compound,[1,2] and they have become indispensable ligands in
many kinds of transition-metal catalysis.[3–15] The stabilizing properties of NHCs,
expressed by the strong metal–carbene bond and slow dissociation rate, are the
key factors in most of the reactions using NHC complexes as catalysts.[16] The
structure of NHC is easily modified by changing the substitutuents on the carbene
precursor, allowing the design of new ligands with different geometries.[17–20] Much
work has been devoted to the design and development of carbene compounds
with new structures to tune their steric and electronic properties and also to their
application in organometallic catalysis and organocatalysis.[21–25]
Received March 22, 2011.
Address correspondence to Yudao Ma, Department of Chemistry, Shandong University, Shanda
South Road #27, Jinan 250100, Shandong, China. E-mail: ydma@sdu.edu.in
810

RHODIUM-CATALYZED ASYMMETRIC ARYLATION
811
Chiral diarylmethanols are important intermediates for the synthesis of
biologically and pharmaceutically active compounds.[26–32] The Rh-catalyzed
addition of arylboronic acid derivatives to aldehydes for the synthesis of optically
active diarylmethanols deserves particular mention for its high efficiency and wide
tolerance toward polar substitutuents in the substrate.[4,33–37] However, examples
of using chiral N-heterocyclic carbenes in ligand-catalyzed asymmetric arylation of
aldehydes are rare.[38] Developing new chiral N-heterocyclic carbene ligands and
efficient catalytic systems for the asymmetric 1,2-addition of organoboronic acid
to aldehydes is an important synthetic goal.
The backbone structure of [2.2]paracyclophane and the directing effect of its
substitutuents make it possible to design chiral ligands of essentially different
patterns.[39]
diphosphanes,[40–43]
Previous
[2.2]paracyclophanyl-based
oxazoline–phosphanes,[44–46]
ligands
included
imidazoliniums,[38,47–49]
oxazoline–alcohols,[50–52] and imine ligands.[53–56] However, tailor-made imidazo-
lium salts bearing bulky [2.2]paracyclophane-substituted combinations have been
rarely reported[13,57] and their preparation is still a challenge. The construction of
benzannulated derivatives is a very simple strategy to modify Arduengo’s original
imidazolium (Scheme 1, structure A),[1] as was demonstrated in the bipyridine-
derived imidazolium (Scheme 1, structure B),[21,58] and the monopyridine-derived
imidazolium (Scheme 1, structure B).[22,25] Herein, we report the synthesis of a
new series of NHC precursors, [2.2]paracyclophanyl imidazo[1,5-a]pyridinium
(Scheme 1, structure D), which combines imidazo[1,5-a]pyridine and [2.2]paracyclo-
phane. Then, these NHC precursors were used as ligands for the rhodium-NHC-
catalyzed asymmetric 1,2-addition of arylboronic acids to aldehydes.
RESULTS AND DISCUSSION
Synthesis of N-[(4Sp,13Rp)-13-R-4-[2.2]Paracyclophanyl]-imidazo
[1,5-a]pyridinium Triflates [5a–e]
A range of substituted pyridine-derived NHC precursors was synthesized from
pyridine carboxaldehydes 3 and sterically hindered 4-amino-[2.2]paracyclophane
Scheme 1. Representative N-heterocyclic carbene precursors.

812
D. WANG ET AL.
derivative 2, which was prepared by Suzuki–Miyaura coupling reaction from
(4Sp,13Rp)-4-amino-13-bromo[2.2]paracyclophane and arylboronic compounds.[39]
The condensation of 4-amino[2.2]paracyclophane derivative 2 and pyridine carbox-
aldehyde 3 in toluene afforded the corresponding imine 4 in excellent yield
(Scheme 2).[25] Then, treatment of pyridine imines 4 with a reagent formed from
equal amounts of AgOTf and chloromethyl pivalate in tetrahydrofuran (THF)
resulted in the formation of the desired imidazolium triflates 5a–e in good yields
(Scheme 2).[18] However, imidazolium triflates 5f–g could not be prepared from
4f–g, although we changed the reaction conditions, such as temperature and sol-
vents. Their lack of reactivity may be ascribed to the steric hindrance of the R0 group
at the 6-position of the pyridinyl group.
Catalytic Addition of Arylboronic Acids to Aromatic Aldehydes
Imidazolium salts 5a–e were used as precursors for Rh-NHC complexes and
applied in the catalytic asymmetric addition of arylboronic acids to aromatic
aldehydes (Table 1). To develop an effective Rh-NHC catalysis for the reaction, sev-
eral experimental variables were investigated. Foremost among the factors that can
influence the rate and enantioselectivity of the reaction are the solvents and catalysts.
Therefore, a systematic study of these two variables was performed. The 1,2-addition
of phenylboronic acid to 1-naphthaldehyde with a catalyst generated in situ from
imidazolium salt 5d (3 mol%) and [Rh(OAc)2]2 (3 mol%) in the presence of KOBu-t
Scheme 2. Synthesis of imidazolium triflates 5.

RHODIUM-CATALYZED ASYMMETRIC ARYLATION
813
Table 1. Solvent effect on the arylationa
Entry
Solvent
Yield (%)b
ee (%)c
1
2
3
4
5
6
CH3CN=DME (5:1)
Pyridine
DMF
12
0
0
MeOCH2CH2OH=DME (5:1)
MeOH=DME (1:1)
MeOH=DME (5:1)
62
98
92
16 (R)
17 (R)
20 (R)
aReaction conditions: [Rh(OAc)2]2 (3 mol%), 5d (3 mol%), KOBu-t (1 eq), arylboronic acids (2 eq), N2,
80 ꢁC, 2 h.
bIsolated yield.
cDetermined by chiral HPLC (CHIRALPAK IA Columns) analysis.
was examined in different solvents at 80 ꢁC for 2 h (Table 1). The results showed that
the solvent had a great impact on both the yield and the enantioselectivity of this
catalyzed addition reaction. The rapid rate and good enantioselectivity of the
addition in MeOH=DME (5:1) (Table 1, entry 6) compared to other solvents clearly
identified it as the solvent of choice for this transformation. Next, various precata-
lysts, such as [Rh(nbd)Cl]2, [Rh(COD)Cl]2, RhCl3 ꢂ xH2O, and [Ru(p-cymene)Cl2]2
were subjected to the same reaction, but none of them exhibited any catalytic activity.
Then we tested different bases, such as NaOH, K2CO3, and Cs2CO3, in place of
KOBu-t, but none of these bases improved the yield or enantiomeric excess. Finally,
we investigated the effect of the amount of the catalyst on this reaction. The catalytic
activity decreased significantly when the catalyst loading was reduced to 1.0 mol%.
Based on these results, we chose MeOH=DME (5:1) as the solvent system,
KOBu-t as the base, and [Rh(OAc)2]2 (3 mol%) as the precatalyst. Other imidazo-
lium salts 5a, 5b, 5c, and 5e were screened in the phenylation of 1-naphthaldehyde
(Table 2), which showed that all the Rh-NHC complexes prepared by combining
[Rh(OAc)2]2 with the corresponding imidazolium salts could afford the desired dia-
rylmethanol in good yield and moderate enantioselectivity (Table 2, entries 1, 3, 4
and 5). Among them, imidazolium salt 5d gave the best enantioselectivity. The lowest
ee (Table 2, entry 2), obtained using imidazolium salt 5b, may be explained by too
much congestion around the ligand, preventing complete complexation of the ligand
to the rhodium center. The ligand screening revealed that ligand substitution can
greatly affect the enantioselectivity.
The optimized catalyst system was tested in the asymmetric arylation of
aldehydes with different steric and electronic properties (Table 3). The system was com-
patible with a wide variety of functional groups on both reaction partners, and in most
cases, the reaction could proceed with notable efficiency (up to 98% isolated yield) with

814
D. WANG ET AL.
Table 2. Evaluation of ligand effectsa
Entry
Ligand
Yield (%)b
ee (%)c
1
2
3
4
5
5a
5b
5c
5d
5e
89
45
76
92
87
14.5 (R)
0.8 (S)
16 (R)
20 (R)
18 (R)
aReaction conditions: [Rh(OAc)2]2 (3 mol%), ligand 5 (3 mol%), KOBu-t (1 eq), arylboronic acids (2 eq),
N2, MeOH=DME (5:1), reflux, 2 h.
bIsolated yield.
cDetermined by chiral HPLC (CHIRALPAK IA Columns) analysis.
Table 3. Evaluation of different reaction partnersa
Entry
Ar1
1-naphthyl (6a)
1-naphthyl (6a)
Ar2
Phenyl (7b)
Yield (%)b
ee (%)c
1
2
92 (8ab)
98 (8ac)
60 (8ad)
69 (8ba)
65 (8ca)
43 (8db)
57 (8dc)
62 (8dd)
88 (8da)
37 (8eb)
76 (8ea)
79 (8fa)
93 (8fb)
97 (8 fc)
85 (8fd)
20 (R)
27 (ꢀ)
57 (þ)
16 (S)
30 (ꢀ)
17 (S)
12 (ꢀ)
22 (R)
13 (R)
24 (R)
10 (þ)
18 (þ)
45 (ꢀ)
22 (ꢀ)
32 (þ)
2-Methoxyphenyl (7c)
3-Methoxyphenyl (7d)
1-naphthyl (7a)
3
1-naphthyl (6a)
Phenyl (6b)
4
5
2,4,6-trimethylphenyl (6c)
4-chlorophenyl (6d)
4-chlorophenyl (6d)
1-naphthyl (7a)
Phenyl (7b)
6
7
2-MethoxyPhenyl (7b)
3-Methoxyphenyl (7d)
1-naphthyl (7a)
8
4-chlorophenyl (6d)
4-chlorophenyl (6d)
9
10
11
12
13
14
15
2-Methoxyphenyl (6e)
2-Methoxyphenyl (6e)
4-(methoxylcarbonyl)phenyl (6f)
4-(methoxylcarbonyl)phenyl (6f)
4-(methoxylcarbonyl)phenyl (6f)
4-(methoxylcarbonyl)phenyl (6f)
Phenyl (7b)
1-naphthyl (7a)
1-naphthyl (7a)
Phenyl (7b)
2-Methoxyphenyl (7c)
3-Methoxyphenyl (7d)
aReaction conditions: [Rh(OAc)2]2 (3 mol%), ligand 5d (3 mol%), KOBu-t (1 eq), arylboronic acids (2
eq), N2, MeOH=DME (5:1), reflux, 2 h.
bIsolated yield.
cDetermined by chiral HPLC (CHIRALPAK IA Columns) analysis.

RHODIUM-CATALYZED ASYMMETRIC ARYLATION
815
a catalyst generated in situ from the same amount of imidazolium salt 5d (3 mol%) and
[Rh(OAc)2]2 (3 mol%). The substitution of the substrate has an important effect on the
enantioselectivity of the catalytic reaction. Aromatic aldehydes or arylboronic acids
bearing meta-substituents afforded chiral diarylmethanols with greater enantiomeric
excess than those bearing ortho-substituents (Table 3, entries 2 and 3, 7 and 8, and
14 and 15). An interesting feature of this methodology is that in most cases both enan-
tiomers of a given diarylmethanol can be easily prepared with the same chiral ligand,
just by appropriate choice of the reaction partners—the arylboronic acid and aldehyde.
CONCLUSIONS
A new type of planar-chiral NHC precursor, 2H-imidazo[1,5-a]pyridin-4-ium
triflate, has been synthesized in good yield from 4-amino-13-bromo[2.2]paracyclo-
phane and pyridylaldehyde. Their application in rhodium-catalyzed asymmetric
1,2-additions of arylboronic acids to aromatic aldehydes has been demonstrated.
The system was shown to be widely compatible with many functional groups in both
reaction partners and the enantiomeric excess of the corresponding diarylmethanols
reached 57%. Future investigations are in progress, aiming at modification of the
[2.2]paracyclophane-based NHC ligands to improve the catalytic performance in
terms of activity and enantioselectivity.
EXPERIMENTAL
All nonaqueous reactions were carried out in flame-dried glassware under a
slight positive pressure of nitrogen. THF, dioxane, dimethoxyethane (DME), and
toluene were dried by sodium benzophenone ketyl and distilled under nitrogen before
use. CH2Cl2 was dried by P2O5 and distilled under nitrogen before use. Other
commercially available solvents were used without further purification. Commer-
cially available reagents were used without further purification unless otherwise
noted. (4Sp,13Rp)-4-Amino-13-bromo[2.2]paracyclophane 1 and (4Sp,13Rp)-4-amino-
12-aryl-[2.2]paracyclophane 2 were prepared according to the literature procedures.[49]
Pyridylaldehyde 3 was purchased from J&K Chemical Ltd. Reactions were magneti-
cally stirred and monitored by thin-layer chromatography (TLC) on silica-gel
0.25-mm precoated plates. All thin-layer chromatography (TLC) plates were visua-
lized by ultraviolet (UV) fluorescence quenching. Yields refer to chromatographically
and spectroscopically pure material unless otherwise noted. Melting points were
recorded on a melting-point apparatus and are uncorrected. 1H and 13C NMR spectra
were recorded on a 300-MHz spectrometer. Chemical shifts were reported as d values
in parts per million (ppm) and were referenced to residual solvent signals: CDCl3 (H
7.26 ppm and C 77.0 ppm) and dimethylsulfoxide (DMSO-d6) (H 2.50 and C 39.5)
using tetramethylsilane (TMS) as an internal standard. Data are reported as [d shift]
([s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet, m ¼ multiplet]). The electropray
ionization–mass spectrometry (ESI-MS) spectra were recorded on a mass spec-
trometer. Optical rotations were measured on a polarimeter with a wavelength of
589 nm: the concentration ‘‘c’’ has units of g=100 mL unless otherwise noted. Enantio-
meric and diastereomeric analyses were determined by chiral high-performance liquid
chromatography (HPLC) (Chiralpak IA column).

816
D. WANG ET AL.
General Procedure for the Synthesis of Planar Chiral (4,13)-
Disubstituted [2.2]Paracyclophanyl Imidazo[1,5-a]pyridinium Triflate
5a–e
4-Amino-[2.2]paracyclophane derivative 1 or 2 (1 mmol) and pyridylaldehyde 3
(1.1 mmol) were dissolved in dry toluene (4 mL), and anhydrous MgSO4 (240 mg,
2 mmol) was added as dehydration agent. The resulting mixture was heated to
90 ꢁC for 30–60 min. After filtration of MgSO4, evaporation of the solvent in vacuo,
and crystallization from EtOH, imine 4 was obtained as a yellow solid (yield >90%).
To a suspension of AgOTf (308 mg, 1.2 mmol) in THF (2 mL), chloromethyl
pivalate (170 mL, 1.2 mmol) was added and the resulting suspension was stirred in a
sealed tube in the dark at 40 ꢁC for 1 h. Then imine 4 (0.9 mmol) was added to the
tube. The resulting mixture was stirred at 40–80 ꢁC for 5–6 h. After the suspension
was cooled to room temperature, the solvent was removed in vacuum. The resulting
oil was chromatographed on silica gel (2.5 ꢃ 20 cm, CH2Cl2=MeOH ¼ 50:1 to 10:1),
and the pure product was isolated. The resulting foam was crystallized from EtOH
to give imidazolium triflate 5 as colorless crystals.
Imidazolium triflate 5a. Compound 4a: 95.5% yield. Compound 5a: 84%
20
yield. Mp: 229–231 ꢁC (decomp), Rf ¼ 0.45 (CH2Cl2=MeOH ¼ 10:1); ½aꢄD ¼ þ113.9
(c 0.13, DMSO); 1H NMR (300 MHz, DMSO, rt): d 10.10 (s, 1 H), 8.54 (d, J ¼ 1.5 Hz,
Hz, 1 H), 7.80 (d, J ¼ 9.0 Hz, 1 H), 7.67 (d, J ¼ 7.2 Hz, 1 H), 7.47 (s, 1 H), 7.36 (d,
J ¼ 6.3 Hz, 2 H), 7.22 (dd, J ¼ 9.3 Hz, J ¼ 7.2 Hz, 1 H), 7.11–6.98 (m, 6 H), 6.89 (d,
J ¼ 7.8 Hz, 1 H), 6.77 (d, J ¼ 7.8 Hz, 1 H), 3.15–3.35 (m, 8 H); 13C NMR (75 MHz,
DMSO, rt): d 142.7, 140.0, 139.5 139.2, 138.2, 136.9, 136.5, 135.9, 134.1, 132.8,
132.1, 131.1, 131.0, 128.8, 128.5, 127.4, 126.5, 126.0, 125.4, 123.1, 121.1 (q,
J ¼ 319 Hz), 118.1, 116.7, 112.6, 34.9, 34.6, 34.4, 34.3. HRMS (ESI): calcd for
C29H24BrN2 (M–OTf)þ 479.1123; found 479.1118.
Imidazolium triflate 5b. Compound 4b: 92% yield. Compound 5b: 78% yield.
20
Mp: 146–148 ꢁC (decomp), Rf ¼ 0.44 (CH2Cl2=MeOH ¼ 10:1); ½aꢄD ¼ þ69.9 (c 0.39,
1
CHCl3); H NMR (300 MHz, CDCl3, rt): d 8.98 (s, 1 H), 8.28 (s, 1 H), 7.83 (d,
J ¼ 9.3 Hz, 1 H), 7.76 (d, J ¼ 8.4 Hz, 2 H), 7.54 (d, J ¼ 8.1 Hz, 1 H), 7.49 (s, 1 H),
7.39–7.23 (m, 5 H), 7.08–7.03 (m, 1 H), 6.91–6.78 (m, 6 H), 3.33–3.14 (m, 6 H),
2.91–2.87 (m, 2 H); 13C NMR (75 MHz, CDCl3, rt): d 143.7, 140.5, 138.0, 137.7,
137.6, 137.2, 135.7, 135.0, 133.8, 133.1, 132.6, 132.5, 132.0, 131.6, 130.5, 128.5,
128.4, 127.1, 126.5, 126.0, 125.7, 125.4, 124.2, 124.1, 122.7, 121.0 (q, J ¼ 318 Hz),
118.2, 116.8, 111.7, 35.1, 34.9, 34.6, 33.2. HRMS (ESI): calcd. for C33H26BrN2 (M–
OTf)þ 529.1279; found 529.1266.
Imidazolium triflate 5c. Compound 4c: 97.2% yield. Compound 5c: 92%
20
yield. Mp: 215–217 ꢁC (decomp), Rf ¼ 0.47 (CH2Cl2=MeOH ¼ 10:1); ½aꢄD ¼ þ83.7
(c 0.47, CHCl3); 1H NMR (300 MHz, CDCl3, rt): d 10.57 (s, 1 H), 8.84 (d, J ¼ 7.2 Hz,
Hz, 1 H), 7.77 (s, 1 H), 7.67 (d, J ¼ 9.3 Hz, 1 H), 7.33 (s, 1 H), 7.25–7.20 (m, 1 H),
7.12–7.04 (m, 2 H), 6.78–6.65 (m, 4 H), 3.50–2.80 (m, 8 H); 13C NMR (75 MHz,
CDCl3, rt): d 142.8, 142.6, 138.0, 137.5, 136.4, 136.1, 135.5, 134.1, 131.6, 131.5,
129.6, 126.4, 125.3, 125.2, 124.5, 124.4, 120.7 (q, J ¼ 319 Hz), 118.3, 114.3, 36.9,
34.8, 34.2, 28.6. HRMS (ESI): calcd. for C23H20BrN2 (M–OTf)þ 403.0810; found
403.0816.

RHODIUM-CATALYZED ASYMMETRIC ARYLATION
817
Imidazolium triflate 5d. Compound 4d: 93.4% yield. Compound 5d: 86%
20
yield. Mp: 208–211 ꢁC (decomp), Rf ¼ 0.42 (CH2Cl2=MeOH ¼ 10:1); ½aꢄD ¼ þ62.1
(c 0.12, CHCl3); 1H NMR (300 MHz, CDCl3, rt): d 9.82 (s, 1 H), 8.43 (d, J ¼ 1.2 Hz,
Hz, 1 H), 7.84 (d, J ¼ 9.3 Hz, 1 H), 7.41 (s, 1 H), 7.32 (d, J ¼ 6.9 Hz, 1 H), 7.10 (dd,
J ¼ 9.3 Hz, J ¼ 7.2 Hz, 1 H), 6.97 (s, 1 H), 6.69–6.63 (m, 3 H), 6.48 (d, J ¼ 7.8 Hz, 1
H), 3.46–3.08 (m, 6 H), 2.92–2.78 (m, 2 H); 13C NMR (75 MHz, CDCl3, rt): d
142.7, 137.8, 137.4, 136.5, 136.1, 135.4, 133.9, 131.8, 131.5, 130.8, 126.3, 126.1,
125.2, 124.7, 124.5, 122.6, 120.9 (q, J ¼ 319 Hz), 118.3, 117.7, 112.5, 36.9, 34.5,
34.1, 28.6. HRMS (ESI): calcd. for C23H19Br2N2 (M–OTf)þ 480.9909; found
.480.9918.
Imidazolium triflate 5e. Compound 4e: 96.0% yield. Compound 5e: 95%
20
yield. Mp: 214–215 ꢁC (decomp), Rf ¼ 0.47 (CH2Cl2=MeOH 10:1); ½aꢄD ¼ ꢀ26.7 (c
1
2.21, CHCl3); H NMR (300 MHz, CDCl3, rt): d 9.36 (s, 1 H), 8.68 (s, 1 H), 8.11
(d, J ¼ 9.0 Hz, 1 H), 7.42 (d, J ¼ 7.2 Hz, 1 H), 7.26–7.18 (m, 1 H), 7.04 (s, 1 H),
6.87 (d, J ¼ 7.8 Hz, 1 H), 6.72–6.63 (m, 3 H), 6.55 (d, J ¼ 7.8 Hz, 1 H), 6.50–6.47
(d, J ¼ 8.1 Hz, 1 H), 3.42–2.89 (m, 7 H), 2.74–2.71 (m, 1 H); 13C NMR (300 MHz,
CDCl3, rt): d 144.0, 140.3, 138.4, 137.4, 136.2, 133.9, 133.4, 132.8, 132.5, 132.3,
128.6, 127.3, 125.1, 124.6, 123.0, 119.1, 116.8, 35.0, 34.8, 34.5, 31.9. HRMS (ESI):
C23H20BrN2 (M–OTf)þ 403.0810; found 403.0796.
General Procedure for the Solvent Effect on the Arylation (Table 1)
[Rh(OAc)2]2 (3.3 mg, 7.5 ꢃ 10ꢀ3 mmol, 3 mol%) was weighted into a flame-dried
tube equipped with a condenser under an argon atmosphere. The solvent (1.0 mL)
was added and the suspension was stirred at room temperature for 5 min. Then,
NHC precursor 5d (4.8 mg, 7.5 ꢃ 10ꢀ3 mmol, 3 mol%), phenylboronic acid
(61.0 mg, 0.50 mmol), KOBu-t (28.0 mg, 0.25 mmol, 1 eq), and 1-naphthaldehyde
(34.0 mg, 0.25 mmol) were successively added. The resulting mixture was stirred at
80 ꢁC for 3 h. The reaction mixture was concentrated under reduced pressure, and
the residue was purified by chromatography (ethyl acetate = hexane), yielding the
desired secondary alcohol as a yellowish oil, which crystallized upon standing at
low temperature (ꢅ4 ꢁC in the refrigerator).
General Procedure for the Evaluation of Ligand Effects (Table 2)
[Rh(OAc)2]2 (3.3 mg, 7.5 ꢃ 10ꢀ3 mmol, 3 mol%) was weighted in a flame-dried
tube equipped with a condenser under an argon atmosphere. MeOH=DME (5:1)
(1.0 mL) was added, and the suspension was stirred at room temperature for 5 min.
Then, NHC precursor 5 (7.5 ꢃ 10ꢀ3 mmol, 3 mol%), phenylboronic acid (61.0 mg,
0.50 mmol), KOBu-t (28.0 mg, 0.25 mmol), and 1-naphthaldehyde (34.0 mg,
0.25 mmol) were successively added. The resulting mixture was stirred at reflux for
3 h. The reaction mixture was concentrated under reduced pressure, and the
residue was purified by chromatography (ethyl acetate = hexane), yielding the desired
secondary alcohol as a slightly yellow oil, which crystallized upon standing at low
temperature (ꢅ4 ꢁC in the refrigerator).

818
D. WANG ET AL.
General Procedure for the Evaluation of Different Reaction Partners
(Table 3)
[Rh(OAc)2]2 (3.3 mg, 7.5 ꢃ 10ꢀ3 mmol, 3 mol%) was weighted into a flame-
dried tube equipped with a condenser under an argon atmosphere. MeOH=DME
(5:1) (1.0 mL) was added, and the suspension was stirred at room temperature for
5 min. Then, NHC ligand precursor 5d (4.8 mg, 7.5 ꢃ 10ꢀ3 mmol, 3 mol%) arylboro-
nic acid (0.50 mmol), KOBu-t (28.0 mg, 0.25 mmol), and aryl aldehyde (0.25 mmol)
were successively added. The resulting mixture was stirred at reflux for 3 h. The reac-
tion mixture was concentrated under reduced pressure, and the residue was purified
by preparative thin, layer chromatography (ethyl acetate = hexane), yielding the
desired secondary alcohol as a yellowish oil, which crystallized upon standing at
low temperature (ꢅ4 ꢁC in the refrigerator).
(1-Naphthyl)phenylmethanol (8ab and 8ba)
20
R-(þ)-8ab. Yield 92%; ½aꢄD ¼ þ5.5 (c 0.5, CHCl3) with 20% ee. The ee value
was determined by HPLC analysis using a chiral column (Chiralpak IA column,
n-hexane=chloroform ¼ 3:1, flow 1.0 mL=min, detection at 254 nm), retention times
18.8 min (minor) and 20.1 min (major).
20
S-(–)-8ba. Yield 69%; ½aꢄD ¼ ꢀ4.2 (c 0.5, CHCl3) with 16% ee. The ee value
was determined by HPLC analysis using a chiral column (Chiralpak IA column,
n-hexane=chloroform ¼ 3:1, flow 1.0 mL=min, detection at 254 nm), retention times
18.7 min (major) and 20.0 min (minor).
1H NMR (300 MHz, CDCl3, rt): d 8.03 (d, J ¼ 3.3 Hz, 1 H), 8.01–7.80 (m, 2 H),
7.64 (d, J ¼ 6.9 Hz, 1 H), 7.50–7.35 (m, 5 H) 7.34–7.24 (m, 3 H), 6.53 (s, 1 H), 2.35 (s,
1 H). 13C NMR (75 MHz, CDCl3, rt): d 143.1, 138.7, 133.9, 130.7, 128.8, 128.6,
128.5, 127.7, 127.06, 126.1, 125.6, 125.3, 124.6, 123.9, 73.6. HRMS (ESI): calcd.
for C17H13 (M–OH)þ 217.1017; found 217.1022.
(1-Naphthyl) (2-methoxyphenyl)methanol (8ac and 8ea)
20
(–)-8ac. Yield 98%; ½aꢄD ¼ ꢀ14.7 (c 0.6, CHCl3) with 27% ee; The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column, n-
hexane=chloroform ¼ 3:1, flow 1.0 mL=min, detection at 254 nm), retention times
15.6 min (minor) and 18.3 min (major).
20
(þ)-8ea. Yield 76%; ½aꢄD ¼ þ4.9 (c 0.6, CHCl3) with 10% ee; The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column, n-
hexane=chloroform ¼ 3:1, flow 1.0 mL=min, detection at 254 nm), retention times
13.7 min (major) and 14.7 min (minor).
1H NMR (300 MHz, CDCl3, rt): d 8.00 (d, J ¼ 7.8 Hz 1 H), 7.86–7.78 (m, 2 H),
7.65 (d, J ¼ 7.2 Hz, 1 H), 7.50–7.38 (m, 3 H) 7.28–7.23 (m, 1 H), 6.96–6.78 (m, 4 H),
3.89 (s, 3 H), 3.05 (s, 1 H). 13C NMR (75 MHz, CDCl3, rt): d 156.9, 138.0, 133.7, 131.3,
131.0, 129.0, 128.6, 128.4, 125.9, 125.5, 125.4, 124.3, 124.2, 120.8, 110.5, 101.1, 72.6,
68.4, 55.5. HRMS (ESI): calcd. for C18H15O (M–OH)þ 247.1123; found 247.1116.

RHODIUM-CATALYZED ASYMMETRIC ARYLATION
819
(1-Naphthyl) (3-methoxyphenyl)methanol 8ad
20
(þ)-8ad: Yield 60%; ½aꢄD ¼ þ34 (c 0.4, CHCl3) with 57% ee; The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column, n-
hexane=chloroform ¼ 3:1, flow 1.0 mL=min, detection at 254 nm), retention times
1
29.8 min (minor) and 32.3 min (major). H NMR (300 MHz, CDCl3, rt): d 8.06–8.03
(m, 1 H), 7.86–7.78 (m, 2 H), 7.60 (d, J ¼ 7.2 Hz, 1 H), 7.48–7.40 (m, 3 H),
7.25–7.20 (m, 1 H), 6.98–6.98 (m, 1 H), 6.80 (d, J ¼ 8.1 Hz, 1 H), 6.49 (s, 1 H), 3.75
(s, 3 H), 2.36 (s, 1 H). 13C NMR (75 MHz, CDCl3, rt): d 159.8, 144.8, 138.7, 133.9,
130.7, 129.5, 128.8, 128.5, 126.2, 125.6, 125.3, 124.7, 123.9, 119.4, 113.0, 112.7, 73.5,
55.2. HRMS (ESI): calcd. for C18H15O (M–OH)þ 247.1123; found 247.1118.
(2-Methoxyphenyl)phenylmethanol (8eb)
20
R-(þ)-8eb: 95% yield; ½aꢄD ¼ þ9.3 (c 0.4, CHCl3) with 24% ee; The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column, n-
hexane=chloroform ¼ 3:1, flow 1.0 mL=min, detection at 254 nm), retention times
13.2 min (minor) and 14.1 min (major). 1H NMR (300 MHz, CDCl3, rt): d
7.39–7.26 (m, 7 H), 6.95–6.85 (m, 2 H), 6.04 (d, J ¼ 4.5 Hz, 1 H), 3.78 (s, 3 H),
3.05 (s, 1 H). 13C NMR (75 MHz, CDCl3, rt): d 156.7, 143.3, 132.0, 128.7, 128.1,
127.8, 127.1, 126.6, 120.8, 110.8, 72.1, 55.4. HRMS (ESI): calcd. for C14H13O (M–
OH)þ 197.0966; found 197.0960.
(4-Chlorophenyl)(1-naphthyl)methanol (8da)
20
R-(–)-8da: 88% yield; ½aꢄD ¼ ꢀ10.2 (c 07, CHCl3) with 13% ee. The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column, n-
hexane=chloroform ¼ 3:1, flow 1.0 mL=min, detection at 254 nm); retention times
23.8 min (major) and 25.1 min (minor).
1H NMR (300 MHz, CDCl3, rt): d 7.95–7.76 (m, 3 H), 7.51–7.20 (m, 8 H), 6.37
(s, 1 H), 2.56 (s, 1 H). 13C NMR (75 MHz, CDCl3, rt): d 141.6, 138.4, 134.0, 133.3,
130.6, 128.8, 128.7, 128.6, 128.3, 126.3, 125.7, 125.3, 124.8, 123.8, 73.0. HRMS (ESI):
calcd for C17H12Cl (M–OH)þ 251.0628, found 251.0622.
(4-Chlorophenyl) (2-methoxyphenyl)methanol (8dc)
20
(–)-8dc: 57% yield; ½aꢄD ¼ ꢀ4.5 (c 0.7, CHCl3) with 12% ee. The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column,
n-hexane=chloroform ¼ 3:1, flow 1.0 mL=min, detection at 254 nm), retention times
15.1 min (major) and 15.9 min (minor). 1H NMR (300 MHz, CDCl3, rt): d
7.32–7.19 (m, 6 H), 6.96–6.85 (m, 2 H), 6.00 (s, 1 H), 3.79 (s, 3 H), 3.03 (s, 1 H).
13C NMR (75 MHz, CDCl3, rt): d 156.6, 141.9, 132.8, 131.5, 128.9, 128.2, 127.9,
127.7, 120.9, 110.8, 71.6, 55.4. HRMS (ESI): calcd. for C14H12ClO (M–OH)þ
231.0577; found 231.0573.

820
D. WANG ET AL.
(4-Chlorophenyl) (3-methoxyphenyl)methanol (8dd)
20
R-(–)-8dd: 62% yield; ½aꢄD ¼ ꢀ1.6 (c 1.2, CHCl3) with 22% ee. The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column,
n-hexane=chloroform ¼ 3:1, flow 1.0 mL=min, detection at 254 nm), retention times
33.1 min (major) and 36.1 min (minor). 1H NMR (300 MHz, CDCl3, rt): d
7.33–7.21 (m, 5 H), 6.91–6.79 (m, 3 H), 5.76 (s, 1 H), 3.77 (s, 3 H), 2.27 (s, 1 H).
13C NMR (75 MHz, CDCl3, rt): d 159.8, 145.0, 142.1, 133.3, 129.6, 127.8, 118.8,
113.1, 112.1, 75.5, 55.2. HRMS (ESI): calcd for C14H12ClO (M–OH)þ 231.0577,
found 231.0579.
(4-Chlorophenyl) Phenylmethanol (8db)
20
S-(–)-8db: 43% yield; ½aꢄD ¼ þ5.7 (c 0.36, CHCl3) with 24% ee. The ee value
was determined by HPLC analysis using a chiral column (Chiralpak IA column,
n-hexane=chloroform ¼ 3:1, flow 1.0 mL=min, detection at 254 nm), retention times
19.6 min (minor) and 23.4 min (major). 1H NMR (300 MHz, CDCl3, rt): d
7.35–7.25 (m, 9 H), 5.81 (s, 1 H), 2.23 (s, 1 H); 13C NMR (75 MHz, CDCl3, rt): d
143.4, 142.2, 133.3, 128.7, 128.6, 127.9, 127.86, 126.5, 75.6. HRMS (ESI): calcd.
for C13H12ClO (M þ H)þ 219.0532; found 219.0249.
(1-Naphthyl)(2,4,6-trimethylphenyl)methanol (8ca)
20
(–)-8ca: 65% yield; ½aꢄD ¼ ꢀ12.4 (c 1.1, CHCl3) with 30% ee. The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column,
n-hexane=chloroform ¼ 3:1, flow 1.0 mL=min, detection at 254 nm), retention times
1
24.9 min (major) and 26.2 min (minor). H NMR (300 MHz, CDCl3, rt): d 8.22 (d,
J ¼ 3.3 Hz, 1 H), 7.89 (d, J ¼ 5.2 Hz, 1 H), 7.87 (d, J ¼ 6.9 Hz, 1 H), 7.80–7.86 (m,
7 H) 6.53 (s, 1 H), 2.30 (s, 9 H), 2.15 (s, 1 H); 13C NMR (75 MHz, CDCl3, rt): d
137.2, 137.1, 137.06, 135.4, 134.1, 131.5, 130.4, 128.8, 128.5, 126.2, 125.6, 125.1,
125.0, 124.4, 70.9, 21.2, 20.9. HRMS (ESI): calcd. for C20H19 (M–OH)þ 259.1487;
found 259.1493.
(1-Naphthyl) [4-(methoxylcarbonyl)phenyl] Methanol (8fa)
20
(þ)-8fa: 79% yield; ½aꢄD ¼ þ11.6 (c 0.45, CH2Cl2) with 18% ee. The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column,
n-hexane=i-propanol ¼ 4:1, flow 1.0 mL=min, detection at 254 nm), retention times
15.7 min (major) and 18.0 min (minor). 1H NMR (300 MHz, CDCl3, rt): d
8.04–8.00 (t, 1 H), 7.97 (d, J ¼ 6.0 Hz, 2 H), 7.87–7.80 (m, 2 H), 7.53–7.40 (m, 6 H),
6.53 (s, 1 H), 3.87(s, 3 H), 2.55 (s, 1 H); 13C NMR (75 MHz, CDCl3, rt): d 166.9,
148.2, 138.3, 134.1, 130.6, 129.8, 129.3, 128.9, 128.8, 126.8, 126.3, 125.8, 125.3,
125.2, 123.9, 73.5, 52.1. HRMS (ESI): calcd. for C19H15O2 (M-OH)þ 275.1072; found
275.1079.

RHODIUM-CATALYZED ASYMMETRIC ARYLATION
821
[4-(Methoxylcarbonyl)phenyl]phenylmethanol (8fb)
20
(–)-8fb: 93% yield; ½aꢄD ¼ ꢀ12.2 (c 0.38, CH2Cl2) with 45% ee. The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column,
n-hexane=i-propanol ¼ 4:1, flow 1.0 mL=min, detection at 254 nm), retention times
13.2 min (major) and 14.3 min (minor). 1H NMR (300 MHz, CDCl3, rt): d
8.05–7.97 (m, 3 H), 7.98–7.81 (m, 2 H), 7.54–7.40 (m, 6 H), 6.55 (s, 1 H), 3.88 (s, 3
H), 2.50 (d, J ¼ 3.0 Hz, 2 H); 13C NMR (75 MHz, CDCl3, rt): d 166.9, 148.1, 138.3,
134.1, 130.6, 129.8, 129.3, 128.9, 126.8, 126.4, 125.8, 125.3, 125.2, 123.9, 73.6, 52.1.
HRMS (ESI): calcd. for C15H13O2 (M-OH)þ 225.0916; found 225.0910.
(2-Methoxyphenyl)[4-(methoxylcarbonyl)phenyl]methanol (8fc)
20
(–)-8 fc: 97% yield; ½aꢄD ¼ ꢀ9.2 (c 0.25, CH2Cl2) with 22% ee. The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column,
n-hexane=i-propanol ¼ 4:1, flow 1.0 mL=min, detection at 254 nm), retention times
14.7 min (major) and 16.2 min (minor). 1H NMR (300 MHz, CDCl3, rt): d
8.00–7.97 (d, 2 H), 7.47 (d, J ¼ 9.0 Hz, 2 H), 7.31–7.20 (m, 2 H), 6.97–6.88 (m, 2
H), 6.08 (s, 1 H), 3.90 (s, 3 H), 3.80 (s, 3 H), 3.08 (s, 1 H); 13C NMR (75 MHz, CDCl3,
rt): d 156.7, 148.5, 131.4, 129.5, 129.1, 128.9, 127.9, 126.4, 120.9, 110.9, 72.1, 55.4,
52.0. HRMS (ESI): calcd. for C16H15O3 (M-OH)þ 255.1021; found 255.1010.
(3-Methoxyphenyl)[4-(methoxylcarbonyl)phenyl]methanol (8fd)
20
(þ)-8fd: 85% yield; ½aꢄD ¼ þ20.1 (c 0.23, CH2Cl2) with 32% ee. The ee value was
determined by HPLC analysis using a chiral column (Chiralpak IA column,
n-hexane=i-propanol ¼ 4:1, flow 1.0 mL=min, detection at 254 nm), retention times
1
16.4 min (major) and 20.0 min (minor). H NMR (300 MHz, CDCl3, rt): d 7.99 (d,
J ¼ 6.0 Hz, 2 H), 7.46 (d, J ¼ 6.0 Hz, 2 H), 7.28–7.22 (m, 1 H), 6.92 (d, J ¼ 6.0 Hz, 2
H), 6.83–6.79 (m, 1 H), 5.84 (s, 1 H), 3.89 (s, 3 H), 3.77 (s, 3 H), 2.38 (s, 1 H); 13C
NMR (75 MHz, CDCl3, rt): d 166.9, 159.9, 148.5, 144.9, 129.8, 129.7, 129.3, 126.3,
118.9, 113.3, 112.2, 75.8, 55.2, 52.1. HRMS (ESI): calcd. for C16H15O3 (M-OH)þ
255.1021; found 255.1031.
ACKNOWLEDGMENTS
Financial support from the National Natural Science Foundation of China
(Grant Nos. 20441004 and 20671059) and the Department of Science and
Technology of Shandong Province is gratefully acknowledged
REFERENCES
1. Arduengo, A. J.; Harlow, R. L.; Kline, M. A stable crystalline carbene. J. Am. Chem. Soc.
1991, 113(1), 361–363.
2. Bourissou, D.; Guerret, O.; Gabbai, F. P.; Bertrand, G. Stable Carbenes. Chem. Rev.
2000, 100(1), 39–92.

822
D. WANG ET AL.
3. Lai, R.; Daran, J. C.; Heumann, A.; Zaragori-Benedetti, A.; Rafii, E. The synthesis and
x-ray structure of a chiral rhodium-NHC complex: Implications for the use of NHCs in
asymmetric hydroformylation catalysis. Inorg. Chim. Acta 2009, 362(13), 4849–4852.
´
4. Gois, P. M. P.; Trindade, A. F.; Veiros, L. F.; Andre, V.; Duarte, M. T.; Afonso, C. A.
M.; Caddick, S.; Cloke, F. G. N. Tuning the reactivity of dirhodium(II) complexes with
axial N-heterocyclic carbene ligands: The arylation of aldehydes. Angew. Chem., Int.
Ed. 2007, 46(30), 5750–5753.
5. Ma, Y.; Song, C.; Jiang, W.; Wu, Q.; Wang, Y.; Liu, X.; Andrus, M. B. Sonogashira
coupling using bulky palladium-phenanthryl imidazolium carbene catalysis. Org. Lett.
2003, 5(18), 3317–3319.
6. Burstein, C.; Lehmann, C. W.; Glorius, F. Imidazo[1,5-a]pyridine-3-ylidenes—Pyridine-
derived N-heterocyclic carbene ligands. Tetrahedron. 2005, 61, 6207–6217.
7. Trnka, T. M.; Grubbs, R. H. The development of L2X2RuCHR olefin metathesis
catalysts: An organometallic success story. Acc. Chem. Res. 2000, 34(1), 18–29.
8. Kuriyama, M.; Soeta, T.; Hao, X.; Chen, Q.; Tomioka, K. N-Boc-l-valine-connected
amidomonophosphane rhodium(I) catalyst for asymmetric arylation of N-tosylarylimines
with arylboroxines. J. Am. Chem. Soc. 2004, 126(26), 8128–8129.
9. Chen, J.; Zhang, X.; Feng, Q.; Luo, M. Novel hexadentate imidazolium salts in the rhodium-
catalyzed addition of arylboronic acids to aldehydes. J. Organomet. Chem. 2006, 691(3),
470–474.
10. Kuriyama, M.; Shimazawa, R.; Enomoto, T.; Shirai, R. Palladium-catalyzed 1,2-addition
of potassium aryl- and alkenyltrifluoroborates to aldehydes using thioether-imidazolinium
carbene ligands. J. Org. Chem 2008, 73(17), 6939–6942.
11. Kuriyama, M.; Shimazawa, R.; Shirai, R. Efficient 1,2-addition of aryl- and alkenylboro-
nic acids to aldehydes catalyzed by the palladium=thioether-imidazolinium chloride
system. J. Org. Chem. 2008, 73(4), 1597–1600.
12. Roland, S.; Mangeney, P. Chiral diaminocarbene complexes: Synthesis and application
in asymmetric catalysis; In Chiral Diazaligands for Asymmetric Synthesis; Springer Berlin=
Heidelberg: 2005; vol. 15, pp. 191–229.
13. Ma, Y.; Song, C.; Ma, C.; Sun, Z.; Chai, Q. B.; Andrus, E. Asymmetric addition of aryl
boron reagents to enones with rhodium dicyclophane imidazolium carbene catalysis.
Angew. Chem., Int. Ed. 2003, 42(47), 5871–5874.
14. Zinner, S. C.; Zhang-Presse, M.; Herrmann, W. A.; Kuehn, F. E. Enantioselective hydro-
silylation with a chiral N-heterocyclic carbene complex of rhodium(I). J. Chem. Sci. 2009,
64(11=12), 1607–1611.
15. Trindade, A. F.; Gois, P. M. P.; Veiros, L. F.; Andrev, V.; Duarte, M. T.; Afonso, C. A.
M.; Caddick, S.; Cloke, F. G. N. Axial coordination of NHC ligands on dirhodium(II)
complexes: Generation of a new family of catalysts. J. Org. Chem. 2008, 73(11), 4076–4086.
16. Herrmann, W. A. N-Heterocyclic carbenes: A new concept in organometallic catalysis.
Angew. Chem., Int. Ed. 2002, 41(8), 1290–1309.
17. Gsto¨ttmayr, C. W. K.; Bo¨hm, V. P. W.; Herdtweck, E.; Grosche, M.; Herrmann, W. A. A
defined N-heterocyclic carbene complex for the palladium-catalyzed Suzuki cross-coupling
of aryl chlorides at ambient temperatures. Angew. Chem., Int. Ed. 2002, 41(8),
1363–1365.
18. Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F. An N-heterocyclic carbene
ligand with flexible steric bulk allows Suzuki cross-coupling of sterically hindered aryl
chlorides at room temperature. Angew. Chem., Int. Ed. 2003, 42(31), 3690–3693.
19. Eckhardt, M.; Fu, G. C. The first applications of carbene ligands in cross-couplings of
alkyl electrophiles: Sonogashira reactions of unactivated alkyl bromides and iodides.
J. Am. Chem. Soc. 2003, 125(45), 13642–13643.

RHODIUM-CATALYZED ASYMMETRIC ARYLATION
823
20. Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F. Sterically demanding,
bioxazoline-derived N-heterocyclic carbene ligands with restricted flexibility for catalysis.
J. Am. Chem. Soc. 2004, 126(46), 15195–15201.
21. Robert, W.; Silvia, R.; Matthias, H.; Frank, H. Generation and trapping reactions of a
formal 1:1 complex between singlet carbon and 2,20-bipyridine. Angew. Chem., Int. Ed.
1998, 37(3), 344–347.
22. Alcarazo, M.; Roseblade, S. J.; Cowley, A. R.; Fernandez, R.; Brown, J. M.; Lassaletta, J.
M. Imidazo[1,5-a]pyridine: A versatile architecture for stable N-heterocyclic carbenes.
J. Am. Chem. Soc. 2005, 127(10), 3290–3291.
23. Furstner, A.; Alcarazo, M.; Krause, H.; Lehmann, C. W. Effective modulation of the
¨
donor properties of N-heterocyclic carbene ligands by through-spaced communication
within a planar chiral scaffold. J. Am. Chem. Soc. 2007, 129(42), 12676–12677.
24. Farman, U.; Gabor, B.; Tamas, V.; Peterv, J.; Joachimv, H. Stabilization of unsymmetri-
cally annelated imidazol-2-ylidenes with respect to their higher group 14 homologues by
n-=pi-HOMO inversion. Angew. Chem., Int. Ed. 2007, 46(15), 2697–2700.
25. Burstein, C.; Lehmann, C. W.; Glorius, F. Imidazo[1,5-a]pyridine-3-ylidenes—pyridine-
derived N-heterocyclic carbene ligands. Tetrahedron 2005, 61(26), 6207–6217.
26. Hite, G.; Barouh, V.; Dall, H.; Patel, D. Stereochemical aspects of antihistamine action, 4:
Absolute configuration of carbinoxamine antipodes. J. Med. Chem. 1971, 14(9), 834–836.
27. Schmidt, F.; Stemmler, R. T.; Rudolph, J.; Bolm, C. Catalytic asymmetric approaches
towards enantiomerically enriched diarylmethanols and diarylmethylamines. Chem. Soc.
Rev. 2006, 35(5), 454–470.
28. Welch, W.; Kraska, A.; Sarges, R.; Koe, B. Nontricyclic antidepressant agents derived
from cis- and trans-1-amino-4-aryltetralins. J. Med. Chem. 1984, 27, 1508–1515.
29. Chatelain, P.; Massingham, R. Cardiac ischaemia: Possibilities for future drug therapy.
Eur. J. Med. Chem. 1997, 32(9), 687–707.
30. Nilvebrant, L.; Andersson, K. E.; Gillberg, P. G.; Stahl, M.; Sparf, B. Tolterodine—A
new bladder-selective antimuscarinic agent. Eur. J. Pharmacol. 1997, 317, 195–207.
31. Astles, P. C.; Brown, T.; Halley, F.; Handscombe, C.; Harris, N.; Majid, T.; McCarthy, C.;
McLay, I.; Morley, A.; Porter, B.; Roach, A.; Sargent, C.; Smith, C.; Walsh, R. Selective
ETA antagonists, 5: Discovery and structure–activity relationships of phenoxyphenylacetic
acid derivatives. J. Med. Chem. 2000, 43, 900–910.
32. Meguro, K.; Aizawa, M.; Sohda, T.; Kawamatsu, Y.; Nagaoka, A. New 1,4-dihydropyr-
idine derivatives with potent and long-lasting hypotensive effect. Chem. Pharm. Bull. 1985,
33, 3787–3797.
33. Yamamoto, Y.; Kurihara, K.; Miyaura, N. Me-bipam for enantioselective ruthenium(II)-
catalyzed arylation of aldehydes with arylboronic acids. Angew. Chem., Int. Ed. 2009,
48(24), 4414–4416.
34. Trindade, A. F.; Gois, P. M. P.; Veiros, L. F.; Vania, A.; Duarte, M. T.; Afonso, C. A.
M.; Caddick, S.; Cloke, F. G. N. Axial coordination of NHC ligands on dirhodium(II)
complexes: Generation of a new family of catalysts. J. Org. Chem. 2008, 73(11),
4076–4086.
35. Nishimura, T.; Kumamoto, H.; Nagaosa, M.; Hayashi, T. The concise synthesis of chiral
tfb ligands and their application to the rhodium-catalyzed asymmetric arylation of
aldehydes. Chem. Commun. 2009, 38, 5713–5715.
36. Duan, H. F.; Xie, J. H.; Shi, W. J.; Zhang, Q.; Zhou, Q. L. Enantioselective rhodium-
catalyzed addition of arylboronic acids to aldehydes using chiral spiro monophosphite
ligands. Org. Lett. 2006, 8(7), 1479–1481.
37. Xing, C. H.; Liu, T. P.; Zheng, J. R.; Ng, J.; Esposito, M.; Hu, Q. S. Rh(I)=
diene-catalyzed addition reactions of aryl=alkenylboronic acids with aldehydes. Tetra-
hedron Lett. 2009, 50(35), 4953–4957.

824
D. WANG ET AL.
38. Focken, T.; Rudolph, J.; Bolm, C. Planar chiral imidazolium salts in the asymmetric
rhodium-catalyzed 1,2-addition of arylboronic acids to aldehydes. Synthesis 2005, 3,
429–436.
39. Ma, Q.; Ma, Y.; Liu, X.; Duan, W.; Qu, B.; Song, C. Planar chiral imidazolium salts
based on [2.2]paracyclophane in the asymmetric rhodium-catalyzed 1,2-addition of
arylboronic acids to aldehydes. Tetrahedron: Asymmetry 2010, 21(3), 292–298.
40. Zanotti-Gerosa, A.; Malan, C.; Herzberg, D. Phosphonites based on the paracyclophane
backbone: New ligands for highly selective rhodium-catalyzed asymmetric hydrogenation.
Org. Lett. 2001, 3(23), 3687–3690.
41. Dominguez, B.; Zanotti-Gerosa, A.; Hems, W. Electrophilic substitution of dibromopar-
acyclophane: A route to novel paracyclophane phosphine ligands. Org. Lett. 2004, 6(12),
1927–1930.
42. Pye, P. J.; Rossen, K.; Reamer, R. A.; Tsou, N. N.; Volante, R. P.; Reider, P. J. A new
planar chiral bisphosphine ligand for asymmetric catalysis: Highly enantioselective
hydrogenations under mild conditions. J. Am. Chem. Soc. 1997, 119(26), 6207–6208.
43. Pye, P. J.; Rossen, K.; Reamer, R. A.; Volante, R. P.; Reider, P. J. [2.2]Phanephos-
ruthenium(II) complexes: Highly active asymmetric catalysts for the hydrogenation of
b-ketoesters. Tetrahedron Lett. 1998, 39(25), 4441–4444.
44. Wu, X. W.; Yuan, K.; Sun, W.; Zhang, M. J.; Hou, X. L. Novel planar chiral P,N-[2.2]-
paracyclophane ligands: Synthesis and application in palladium-catalyzed allylic alky-
lation. Tetrahedron: Asymmetry 2003, 14(1), 107–112.
45. Whelligan, D. K.; Bolm, C. Synthesis of pseudo-geminal-, pseudo-ortho-, and ortho-
phosphinyl-oxazolinyl-[2.2]paracyclophanes for use as ligands in asymmetric catalysis.
J. Org. Chem. 2006, 71(12), 4609–4618.
46. Stemmler, R. T.; Bolm, C. An unprecedented rhodium-catalyzed asymmetric inter-
molecular hydroacylation reaction with salicylaldehydes. Adv. Synth. Catal. 2007,
349(7), 1185–1198.
47. Bolm, C.; Focken, T.; Raabe, G. Synthesis of iridium complexes with novel planar chiral
chelating imidazolylidene ligands. Tetrahedron: Asymmetry 2003, 14(12), 1733–1746.
48. Focken, T.; Raabe, G.; Bolm, C. Synthesis of iridium complexes with new planar
chiral chelating phosphinyl-imidazolylidene ligands and their application in asymmetric
hydrogenation. Tetrahedron: Asymmetry 2004, 15(11), 1693–1706.
49. Duan, W.; Ma, Y.; Xia, H.; Liu, X.; Ma, Q.; Sun, J. Design and synthesis of planar chiral
heterocyclic carbene precursors derived from [2.2]paracyclophane. J. Org. Chem. 2008,
73(11), 4330–4333.
50. Wu, X. W.; Hou, X. L.; Dai, L. X.; Tao, J.; Cao, B.; X.; Sun, J. Synthesis of novel
N,O-planar chiral [2,2]paracyclophane ligands and their application as catalysts in the
addition of diethylzinc to aldehydes. Tetrahedron: Asymmetry 2001, 12(4), 529–532.
51. Wu, X. W.; Zhang, T. Z.; Yuan, K.; Hou, X. L. Regulation of the flexibility of planar
chiral [2.2]paracyclophane ligands and its significant impact on enantioselectivity in
asymmetric reactions of diethylzinc with carbonyl compounds. Tetrahedron: Asymmetry
2004, 15(15), 2357–2365.
52. Bolm, C.; Whelligan, D. K. The synthesis of pseudo-geminal, pseudo-ortho, and ortho
hydroxy-oxazolinyl[2.2]paracyclophanes for use as ligands in asymmetric catalysis. Adv.
Synth. Catal. 2006, 348(15), 2093–2100.
53. Lauterwasser, F.; Nieger, M.; Mansikkama¨ki, H.; Na¨ttinen, K.; Bra¨se, S. Structurally
diverse second-generation [2.2]paracyclophane ketimines with planar and central chirality:
Syntheses, structural determination, and evaluation for asymmetric catalysis. Chem. Eur.
J. 2005, 11(15), 4509–4525.

RHODIUM-CATALYZED ASYMMETRIC ARYLATION
825
54. Lauterwasser, F.; Gall, J.; Ho¨fener, S.; Bra¨se, S. Second-generation N,O-[2.2]-
paracyclophane ketimine ligands for the alkenylzinc addition to aliphatic and aromatic
aldehydes: Scope and limitations. Adv. Synth. Catal 2006, 348(15), 2068–2074.
55. Bra¨se, S.; Ho¨fener, S. Asymmetric conjugate addition of organozinc compounds to a,
b-unsaturated aldehydes and ketones with [2.2]paracyclophaneketimine ligands without
added copper salts. Angew. Chem., Int. Ed. 2005, 44(48), 7879–7881.
56. Kreis, M.; Nieger, M.; Bra¨se, S. Synthesis of novel planar-chiral [2.2]paracyclophane
derivatives as potential ligands for asymmetric catalysis. J. Organomet. Chem. 2006,
691(10), 2171–2181.
57. Song, C.; Ma, C.; Ma, Y.; Feng, W.; Ma, S.; Chai, Q.; Andrus, M. B. Bis-paracyclophane
N-heterocyclic carbene-ruthenium catalyzed asymmetric ketone hydrosilylation. Tetra-
hedron Lett. 2005, 46(18), 3241–3244.
58. Weiss, R.; Reichel, S. Novel urea derivatives as two-step redox systems. Eur. J. Inorg.
Chem. 2000, 9, 1935–1939.