New class of amino-phosphinite chiral catalysts for the highly enantioselective addition of arylzinc reagents to aldehydes

Article abstract of DOI:10.1016/j.tet.2009.12.009

A new class of amino-phosphinite chiral ligands was prepared and applied in zinc-catalyzed addition of aryl boronic acids to aldehydes; the reaction furnished the diarylmethanols in excellent yields and with a high level of enantioselectivity (up to 93% ee).

Full text of DOI:10.1016/j.tet.2009.12.009

Tetrahedron 66 (2010) 1341–1345
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
New class of amino-phosphinite chiral catalysts for the highly
enantioselective addition of arylzinc reagents to aldehydes
Marcelo Godoi a, Eduardo E. Alberto b, Marcio W. Paixa˜o c, Liliana A. Soares d,
,
a,
*
Paulo H. Schneider d , Antonio L. Braga
*
a
´
´
Departamento de Quımica, Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil
b Departamento de Qu´ımica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
c Departamento de Qu´ımica, Universidade Federal de S˜ao Carlos, S˜ao Carlos, SP, Brazil
d Instituto de Qu´ımica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
A new class of amino-phosphinite chiral ligands was prepared and applied in zinc-catalyzed addition of
aryl boronic acids to aldehydes; the reaction furnished the diarylmethanols in excellent yields and with
a high level of enantioselectivity (up to 93% ee).
Received 9 September 2009
Received in revised form 1 December 2009
Accepted 2 December 2009
Available online 6 December 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Dedicated to Professor Joa˜o Valdir
Comasseto on the occasion of his
60th birthday
1. Introduction
can be prepared using the same chiral ligand, just through the
appropriate choice of the two reaction partners: aryl boronic acid
A survey of the recent chemical literature reveals an explosion of
interest in the development and design of chiral auxiliaries and
catalysts to access pure or enriched chiral compounds.1 De-
velopment of new or improved methods for the asymmetric
preparation of chiral diarylmethanols has gained considerable
significance in recent years because they are useful building blocks
for the synthesis of various biologically active and structurally
interesting compounds.2,3
One of the key issues in aryl transfer reactions is the selective
formation of an appropriate aryl-metal intermediate. In this con-
text, boronic acids have been used as a source of nucleophilic aryl
species, obtained through a boron-to-zinc exchange reaction with
diethylzinc.4 This procedure, which takes advantage of the readily
available aryl boronic acids, is very promising for effecting such
a transformation, since it allows the easy preparation of several
substituted arylzinc reagents and therefore the synthesis of a wide
range of substituted chiral diarylmethanols. Another interesting
feature of this reaction is that both enantiomers of a given product
and aldehyde (Scheme 1).
B(OH)2
CHO
OH
chiral catalyst
Et2Zn
R1
R1
R1
R2
R2
R2
CHO
B(OH)2
chiral catalyst
Et2Zn
R1
R2
OH
both enantiomers, same chiral catalyst
Scheme 1. Catalytic arylation of aldehydes with aryl boronic acids.
The catalytic activity and enantioselectivity of the reaction is
highly dependent on the properties of the chiral ligand, and con-
sequently the design of efficient chiral ligands has become one of
the most intensively studied areas of research. Various chiral
bidentate ligands with two different heterodonor atoms and dif-
ferent donor–acceptor strengths, such as oxygen–nitrogen and
sulfur–nitrogen, form effective catalysts to induce high enantiose-
lectivities.5 Some representative examples are given in Figure 1.
*
Corresponding authors. Tel.: þ55 48 37218650; fax: þ55 48 37216427 (A.L.B.);
tel.: +55 51 33086286 (P.H.S.).
E-mail addresses: paulos@iq.ufrgs.br (P.H. Schneider), albraga@qmc.ufsc.br (A.L.
Braga).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.12.009

1342
M. Godoi et al. / Tetrahedron 66 (2010) 1341–1345
Table 1
Et
O
Catalytic arylation of p-tolualdehyde with phenylboronic acida
Et
OH
Ph
Ph
OH
N
PhB(OH)2
Et2Zn
OH
Ph
N
Fe
N
Ph
Ph
Ph
O
60 °C, 15 min
N
O
OH
PPh2
Braga 20055b
Braga 20055a
Bolm 20024f
Ph
Ph
H
Catalyst 3a
Toluene, 30 min
Ph
3a
O
PPh2
No.
3a (mol %)
T (ꢀC)
Yieldb (%)
eec (%)
Ph
N
Ph
OH
OH
1
2
3
4
5
6
7
1
2.5
5
25
25
25
25
25
0
ꢁ20
65
70
98
95
88
99
97
8 (S)
51 (S)
71 (S)
81 (S)
83 (S)
93 (S)
93 (S)
O
N
SAc
PPh2
O
10
SH
20
10
10
Jin 20085d
Uang 20065c
Ishihara 20055e
a
Figure 1. Examples of chiral ligands used in aryl transfer to aldehydes.
Reactions were performed on
a 0.5 mmol scale of aldehyde, PhB(OH)2
(2.4 equiv), and Et2Zn (7.2 equiv) in toluene.9
b
Isolated yield of the corresponding product.
Enantiomeric excess was determined by comparison of the HPLC retention
c
On the other hand, ligands based on phosphorous–nitrogen
chelating atoms have been extensively studied and applied in the
enantioselective palladium-catalyzed nucleophilic alkylation of
allylic esters. Many examples have been found due to the excellent
ability of phosphorous to stabilize palladium(0).6 Despite their
well-known effectiveness in this type of reaction, bidentate ligands
with phosphorus as the donor atom have not been screened as
chiral ligands in the catalytic arylation of aromatic aldehydes with
aromatic boronic acids. To the best of our knowledge this is the first
time that amino-phosphinite ligands have been successfully
employed in this area.
times with those in the literature.4f,10
At first the reaction was carried out with 1 mol % of catalyst,
affording the desired product in 65% yield and only 8% ee (entry 1).
However, on increasing the catalyst amount to 2.5 mol %, the diaryl-
methanol was obtained with 70% yield and the enantiomeric excess
was enhanced to 51% (entry 2). In the same way, when 5 mol % of
chiral catalyst was added the ee value increased to 71% with almost
quantitative yield (entry 3). When 10 mol % of ligand 3a was used the
corresponding product was delivered in high yield (95%) with an
enantiomeric excess of 81% (entry 4). Interestingly, the ee value was
not increased when the loading of ligand was increased to 20 mol %
(entries 4 vs 5). Carrying out the reaction at 0 ꢀC, with 10 mol % of
ligand, increased the ee valueto 93% inquantitativeyield (entry 6). No
changes in the ee values were observed when the temperature of the
reaction was decreased from 0 ꢀC to ꢁ20 ꢀC (entry 7).
2. Results and discussion
As part of our broader program to explore the preparation and
use of chiral catalysts in asymmetric synthesis, we describe in this
article the synthesis of a new class of chiral phosphinite-amines
(Scheme 2) and their application in arylzinc addition to aldehydes.
The chiral amino-phosphinite ligands can be conveniently pre-
pared from aziridine-2-methanol.
Once we had established the amount of catalyst and the reaction
temperature, we evaluated the electronic and steric effects based
on the different structures of ligand 3. When compounds 3b and 3c,
having a soft electron-donor group on the aromatic ring, were used,
a slight decrease in the ee values was observed (Table 2, entries 2
and 3). By using ligands with strong electron-donor and electron-
withdrawing groups, the desired product was obtained with a sig-
nificant lost of enantioselectivity (entries 4 and 6). Interestingly,
when ligand 3g (R1¼C2H5) was applied, a considerable decrease in
the enantioselectivity was observed (entry 7). In order to in-
vestigate the influence of the aziridine ring on the catalytic system,
we synthesized an analogous ligand (4a) with a five-membered
O
O
R1
R1
(i)
O
HO
OH
O
N
(ii)
N
Trt
NH2
PPh2
Trt
2
1
3a-g
3a: R1 = C6H5
3e: R1 = 4-ClC6H4
3b: R1 = 2-MeC6H4
3c: R1 = 4-MeC6H4
3d: R1 = 4-MeOC6H4
3f: R1 = 3-CF3C6H4
3g: R1 = C2H5
ring, derived from L-proline. Unfortunately, the desired product was
obtained with low enantioselectivity (Table 2, entry 8).
Scheme 2. Synthesis of the aziridine compounds from L-serine. Reagents and condi-
With 3a identified as the most effective ligand, we then exam-
ined the scope of our system in reactions with several aromatic
aldehydes with diverse electronic and steric properties. The results
listed in Table 3 confirm that ligand 3a is a suitable catalyst for this
asymmetric reaction. Reactions with 2- and 4-tolualdehyde, as well
as 2-anisaldehyde, underwent smooth aryl addition in very high
enantiomeric excesses and with nearly quantitative yields (Table 3,
entries 1–3). Only 4-anisaldehyde obtained a lower enantiose-
lectivity (entry 4). Additionally, electron-withdrawing groups
present in the aldehyde did not have a significant influence on the
enantioselectivity (entries 5–7). With regard to steric effects, these
do not play an important role in determining the degree of enan-
tioselection. For instance, ortho-substituted benzaldehydes
underwent aryl addition with similar ee values as their para
analogues (compare entries 1 vs 2 and entries 5 vs 6).
tions: (i): R1MgBr/THF; (ii): PPh2Cl, Et3N, DMAP and toluene.
The aziridine 2 was prepared in high yields starting from
L
-serine, following procedures described previously.7 A simple
transformation of 2 into the amino-phosphinites (3a–g) was ach-
ieved by reaction with ArMgBr and subsequent treatment with
PPh2Cl.8
With the target ligands in hand, we focused our attention to-
ward the optimization of the arylation reactions. Our study started
with the addition of PhZnEt to p-tolualdehyde in the presence of
ligand 3a, using toluene as the solvent. In order to establish the best
conditions, we screened several parameters of the reaction condi-
tions; the effect of catalyst loading and temperature was first
investigated in some detail for ligand 3a (Table 1, entries 1–7).

M. Godoi et al. / Tetrahedron 66 (2010) 1341–1345
1343
Table 2
amino-phosphinite ligands. This is the first time that this type of
catalyst is applied in the asymmetric arylation of aromatic alde-
hydes. In the presence of 10 mol % of chiral catalyst, the corre-
sponding diarylmethanols were obtained in excellent yields and
with high levels of enantioselectivity (up to 93% ee).
Evaluation of chiral relay ligands in catalytic arylation of p-tolualdehyde with phe-
nylboronic acida
PhB(OH)2
Et2Zn
R1
R1
O
We believe that the chemistry described here represents a new
direction for the design of bidentate, chiral amino-phosphinite li-
gands and their application in asymmetric catalysis. Intensive
research in this area is in progress in our laboratory.
60 °C, 15 min
N
O
OH
PPh2
Ph
Ph
H
Catalyst (10 mol%)
Toluene, 0 °C, 30 min
Ph
4. Experimental
4.1. General
No.
Ligand
R1
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
C6H5
99
75
75
97
70
60
93
80
93 (S)
91 (S)
86 (S)
77 (S)
78 (S)
75 (S)
25 (S)
27 (S)
2-Me–C6H4
4-Me–C6H4
4-MeO–C6H4
4-Cl–C6H4
3-CF3–C6H4
C2H5
Hydrogen nuclear magnetic resonance spectra (1H NMR) were
obtained at 400 MHz or 200 MHz. Spectra were recorded in CDCl3
solutions. Data are reported as follows: chemical shift (d), multi-
3g
4a
plicity, coupling constant (J) in hertz and integrated intensity.
Carbon-13 nuclear magnetic resonance spectra (13C NMR) were
obtained at 100 MHz or 75 MHz. Spectra were recorded in CDCl3
solutions. Chemical shifts are reported in parts per million relative
to the TMS (1H NMR) and to the solvent (13C NMR). Air- and
moisture-sensitive reactions were conducted in flame-dried or
oven dried glassware equipped with tightly fitted rubber septa and
under a positive atmosphere of dry argon. Reagents and solvents
were handled using standard syringe techniques.
C6H5
a
Reactions were performed on a 0.5 mmol scale with PhB(OH)2 (2.4 equiv) and
Et2Zn (7.2 equiv) in toluene (first at 60 ꢀC for 15 min, then at 0 ꢀC for 30 min).9
b
Isolated yield of the corresponding product.
Enantiomeric excess was determined by comparison of the HPLC retention
c
times with those in the literature.4f,10
In order to examine whether different aryl groups could be
transferred to aldehydes with the same stereoselectivity, the aryl
transfer reactions of some substituted aryl boronic acids with
benzaldehyde were performed and high yields and enantiomeric
excesses were obtained (entries 8–10). For example, the aryl
transfer reaction of 4-chlorophenyl boronic acid to benzaldehyde
occurred in the same range of ee values (entries 5 versus 10). This is
the most interesting feature of the methodology employed here,
since both enantiomers of a given product can be easily prepared
with excellent yield and high enantiomeric excess using the same
chiral catalyst.
4.2. General procedure for the synthesis of amino-
phosphinite ligand
To
a solution of aziridine-2-methanol (0.5 mmol), Et3N
(0.5 mmol) and a catalytic amount of DMAP in dry toluene (5 mL),
chlorodiphenylphosphine (0.5 mmol) was added under argon. The
mixture was stirred for 24 h and then filtered through basic alu-
mina. After removal of the solvent under pressure the desired
product was afforded.
Table 3
Catalytic arylation of aldehydes with aryl boronic acids using ligand 3aa
22
4.2.1. Amino-phosphinite 3a. White powder. Yield: 85%; [
(c 1, CH2Cl2); mp 78.1–80.0 ꢀC. 1H NMR (400 MHz, CDCl3):
a
d
]
ꢁ10
D
Ar1B(OH)2
Et2Zn
Ph
Ph
O
¼7.44–
7.10 (m, 35H); 2.36 (dd, 1H, J1¼6.0 Hz; J2¼3.2 Hz); 2.08 (d, 1H,
60 °C, 15 min
J¼3.2 Hz); 1.34 (d, 1H, J¼6.0 Hz). 13C NMR (100 MHz, CDCl3):
N
O
OH
Ar2
PPh2
d
¼147.02; 144.08; 143.90; 142.33; 141.39; 137.46; 134.51; 134.10;
Ar2
H
Ar1
Ph
Ph
Catalyst 3a (10 mol%)
Toluene, 0 °C, 30 min
Ph
3a
132.26; 131.53; 131.32; 131.15; 130.29; 129.88; 129.44; 128.82;
128.59; 128.44; 128.30; 128.13; 127.95; 127.12; 126.76; 126.27;
88.74 (J¼8.78 Hz); 75.08; 42.00 (J¼3.66 Hz); 24.46. 31P NMR
(CDCl3):
d
¼26.66. HRMS-ESI m/z calcd for C11H16NO2P: [M]þ
No.
Ar1
Ar2
Yieldb (%)
eec (%)
667.2640, found: 667.2697.
1
2
3
4
5
6
7
8
9
10
C6H5
4Me-C6H4
99
80
70
76
72
88
98
90
93
71
93 (S)
91 (S)
92 (S)
61 (S)
82 (S)
91 (S)
93 (S)
81 (R)
33 (R)
82 (R)
C6H5
2-Me–C6H4
22
C6H5
C6H5
C6H5
C6H5
2-MeO–C6H4
4-MeO–C6H4
4-Cl–C6H4
2-Cl–C6H4
2-Br–C6H4
C6H5
4.2.2. Amino-phosphinite 3b. Yellow oil. Yield: 71%; [
a
]
ꢁ3 (c 1,
D
CH2Cl2). 1H NMR (200 MHz, CDCl3):
d
¼7.63–6.72 (m, 33H); 2.24
(dd, 1H, J1¼6.4 Hz; J2¼3.2 Hz); 2.11 (d, 1H, J¼3.2 Hz); 1.77 (s, 3H);
1.67 (s, 3H); 1.41 (d, 1H, J¼6.4 Hz). 13C NMR (100 MHz, CDCl3):
C6H5
4-Me–C6H4
4-MeO–C6H4
4-Cl–C6H4
d
¼145.66; 145.66; 143.47; 143.02; 141.92; 135.80; 135.22; 131.57;
C6H5
C6H5
131.28; 130.74; 130.66; 130.54; 129.05; 128.87; 128.75; 128.49;
128.24; 127.72; 127.59; 127.46; 127.20; 126.71; 126.51; 126.47;
125.90; 124.74; 124.29; 88.15 (J¼8.02 Hz); 74.30; 41.42; 23.52;
a
Reactions were performed on a 0.5 mmol scale with PhB(OH)2 (2.4 equiv) and
Et2Zn (7.2 equiv) in toluene (first at 60 ꢀC for 15 min, then at 0 ꢀC for 30 min).9
21.31; 18.56. 31P NMR (CDCl3):
d
¼24.11. HRMS-ESI m/z calcd for
b
Isolated yield of the corresponding product.
c
C48H42NOP: [M]þ 679.3004, found: 679.3046.
Enantiomeric excess was determined by comparison of the HPLC retention
times with those in the literature.4f,10
22
4.2.3. Amino-phosphinite 3c. Yellow oil. Yield: 75%; [
a]
ꢁ109 (c 1,
D
CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
¼7.47–7.13 (m, 29H); 6.99 (d,
2H, J¼8.4 Hz); 6.96 (d, 2H, J¼8.0 Hz); 3.76 (s, 3H); 3.71 (s, 3H); 2.32
(dd, 1H, J1¼6.0 Hz; J2¼3.6 Hz); 2.11 (d, 1H, J¼3.6 Hz); 1.32 (d, 1H,
6.0 Hz). 13C NMR (75 MHz, CDCl3): 143.80; 143.42; 142.47; 137.32;
136.01; 135.72; 132.29; 131.82; 131.35; 131.04; 130.70; 129.86;
129.47; 129.14; 128.96; 128.50; 128.13; 127.97; 127.81; 127.61;
3. Conclusion
In summary, we have developed a new catalytic system for the
enantioselective arylation of aromatic aldehydes using chiral

1344
M. Godoi et al. / Tetrahedron 66 (2010) 1341–1345
127.07; 126.35; 125.63;
d
¼88.27 (J¼8.84 Hz); 74.41; 42.08
stirring for 15 min the reaction was quenched with water and the
(J¼2.21 Hz); 25.28; 20.77; 20.65. 31P NMR (CDCl3):
d¼25.16. HRMS-
aqueous layer was extracted with dichloromethane. The organic
phase was dried over MgSO4, filtered, and the solvents evaporated
under reduced pressure. Purification by flash chromatography on
silica eluting with a mixture of hexane/ethyl acetate (90:10) affor-
ded the pure diarylmethanols.
ESI m/z calcd for C48H42NOP: [M]þ 679.3004, found: 679.2991.
22
4.2.4. Amino-phosphinite 3d. Viscous oil. Yield: 73%; [
a
]
ꢁ25 (c 1,
D
CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
¼7.329–7.151 (m, 33H); 6.72
(d, 2H, J¼8.8 Hz); 6.69 (d, 2H, J¼8.8 Hz); 3.76 (s, 3H); 3.71 (s, 3H);
2.26 (dd, 1H, J1¼6.0 Hz; J2¼3.6 Hz); 2.11 (d, 1H, J¼3.6 Hz); 1.32 (d,
4.3.1. (4-Methyphenyl)phenylmethanol4f. 1H
CDCl3):
¼7.31–7.08 (m, 9H); 5.68 (s, 1H); 2.55 (s, 1H); 2.29 (s, 3H).
13C NMR (100 MHz, CDCl3):
NMR
(400 MHz,
1H, 6.0 Hz). 13C NMR (100 MHz, CDCl3):
d¼147.08; 145.11; 143.65;
d
143.43; 143.26; 134.18; 133.87; 133.62; 132.75; 131.49; 130.50;
129.34; 129.26; 129.03; 128.39; 128.26; 127.81; 127.60; 127.46;
127.33; 127.15; 126.86; 126.44; 87.98 (J¼8.05 Hz); 74.58; 65.31;
d
¼143.89; 140.89; 137.09; 129.06;
128.32; 127.30; 126.46; 126.39; 75.90; 21.02.
41.86 (J¼2.93 Hz); 23.93. 31P NMR (CDCl3):
d¼29.62. HRMS-ESI m/z
4.3.2. (2-Methyphenyl)phenylmethanol4f. 1H
NMR
(400 MHz,
calcd for C48H38NOP: [M]þ 711.2908, found: 711.2896.
CDCl3):
13C NMR (100 MHz, CDCl3):
128.40; 127.46; 127.05; 126.28; 126.06; 73.31; 19.30.
d
¼7.48–7.12 (m, 9H); 5.94 (s, 1H); 2.26 (s, 1H); 2.21 (s, 3H).
d
¼142.87; 141.42; 135.33; 130.49;
22
4.2.5. Amino-phosphinite 3e. White oil. Yield: 87%; [
a]
ꢁ81 (c 1,
D
CH2Cl2); 1H NMR (400 MHz, CDCl3):
d
¼7.33–7.11 (m, 33H); (dd, 1H,
J1¼6.4 Hz; J2¼3.2 Hz); 2.03 (d, 1H, J¼3.2 Hz); 1.31 (d, 1H, J¼6.4 Hz).
4.3.3. (4-Chlorophenyl)phenylmethanol4f. 1H
NMR
(400 MHz,
13C NMR (100 MHz, CDCl3):
d
(ppm) 143.83; 143.33; 143.15; 143.03;
CDCl3):
d
¼7.32–7.22 (m, 9H); 5.74 (s, 1H); 2.39 (s, 1H). 13C NMR
142.69; 142.54; 141.80; 133.42; 130.38; 133.35; 130.27; 130.14;
129.85; 129.28; 128.95; 128.69; 128.25; 128.14; 128.04; 127.93;
127.75; 127.46; 127.22; 99.85; 84.24 (J¼12.44 Hz); 75.03; 42.41
(100 MHz, CDCl3):
127.85; 127.80; 126.50; 75.56.
d
¼143.40; 142.20; 133.24; 128.59; 128.55;
(J¼5.12 Hz); 23.37. 31P NMR (CDCl3):
d¼21.79.
4.3.4. (4-Chlorophenyl)phenylmethanol4f. 1H
NMR
(400 MHz,
CDCl3):
d
¼7.58–7.18 (m, 9H); 6.18 (s, 1H); 2.48 (s, 1H). 13C NMR
22
4.2.6. Amino-phosphinite 3f. Yellow oil. Yield: 90%; [
a]
ꢁ35 (c 1,
(100 MHz, CDCl3):
128.43; 128.17; 128.02; 127.87; 127.71; 127.05; 126.88; 72.63.
d
¼142.23; 140.98; 129.50; 128.70; 128.57;
D
CH2Cl2). 1H NMR (200 MHz, CDCl3):
d
¼7.82–7.08 (m, 33H); 2.35 (dd,
1H, J1¼6.0 Hz; J2¼3.0 Hz); 2.08 (d, 1H, J¼3.0 Hz); 1.37 (d, 1H,
J¼6.0 Hz). 13C NMR (100 MHz, CDCl3):
d
¼147.00; 143.55; 142.56;
4.3.5. (4-Methoxyphenyl)phenylmethanol4f. 1H NMR (400 MHz,
142.50; 141.88; 141.84; 132.53; 131.73; 131.58; 131.56; 131.45;
131.22; 131.07; 131.01; 130.94; 130.88; 129.84; 129.84; 129.42;
129.29; 129.03; 129.03; 128.51; 128.33; 128.21; 128.14; 128.04;
127.89; 127.72; 127.37; 127.02; 126.62; 125.56; 125.27; 124.77;
87.74 (J¼8.84 Hz); 74.77; 41.40 (J¼3.31 Hz); 25.28. 31P NMR (CDCl3):
CDCl3):
d
¼7.35–7.23 (m, 7H); 6.84–6.82 (m, 2H); 5.74 (s, 1H); 3.75
(s, 3H); 3.35 (s, 1H). 13C NMR (100 MHz, CDCl3):
d
¼159.00; 144.01;
136.18; 128.36; 127.87; 127.34; 126.37; 113.84; 75.73; 55.23.
4.3.6. (2-Methoxyphenyl)phenylmethanol4f. 1H NMR (400 MHz,
d
¼29.16. HRMS-ESI m/z calcd for C48H36F6NOP: [M]ꢁ 787.2439,
CDCl3):
d
¼7.33–7.18 (m, 7H); 6.87–6.79 (m, 2H); 5.98 (s, 1H); 3.66
found: 787.2407.
(s, 3H); 3.27 (s, 1H). 13C NMR (100 MHz, CDCl3):
d
¼156.41; 143.23;
131.86; 128.44; 127.93; 127.52; 126.89; 126.37; 120.57; 110.52;
71.65; 55.12.
22
4.2.7. Amino-phosphinite 3g. Colorless oil. Yield: 68%; [
a
]
D
ꢁ9 (c 1,
CH2Cl2); 1H NMR (400 MHz, CDCl3):
d
¼7.75–7.16 (m, 25H); 2.8 (d,
1H, J¼2.6 Hz); 1.95–1.68 (m, 5H); 1.45 (dd, 1H, J1¼5.8 Hz;
4.3.7. (2-Bromophenyl)phenylmethanol4f. 1H
NMR
(400 MHz,
J2¼2.6 Hz); 1.84–1.79 (m, 6H). 13C NMR (75 MHz, CDCl3):
d¼143.90;
CDCl3):
d
¼7.53–7.10 (m, 9H); 6.12 (s, 1H); 2.88 (s, 1H). 13C NMR
131.41; 131.27; 131.20; 131.11; 130.98; 130.82; 130.69; 130.45;
129.25; 128.73; 128.55; 128.06; 127.79; 127.58; 127.08; 126.35;
89.94 (J¼9.94 Hz); 74.36; 38.83 (J¼4.42 Hz); 29.15; 25.43; 24.71;
(100 MHz, CDCl3):
128.95; 128.69; 128.37; 127.65; 126.97; 122.68; 122.38; 74.84.
d
¼142.43; 142.07; 132.72; 132.44; 128.99;
8.52; 7.93. 31P NMR (CDCl3):
d
¼25.49. HRMS-ESI m/z calcd for
Acknowledgements
C38H39NOP: [MþH]þ 556.2769, found: 556.2749.
´
We are grateful to the CAPES, CNPq (INCT-Catalise), FAPESC and
22
4.2.8. Amino-phosphinite 4a. Colorless oil. Yield: 70%; [
a]
þ27 (c
D
FAPERGS for financial support. CNPq is also acknowledged for the
doctorate fellowship for E.E.A. and the master’s fellowship for M.G.
1, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d
¼7.55–7.17 (m, 20H); 383
(m, 1H, J¼12 Hz); 376–373 (m, 1H); 1.45 (dd, 1H, J1¼5.8 Hz;
J2¼2.8 Hz); 1.84–1.79 (m, 6H). 13C NMR (75 MHz, CDCl3):
¼146.03;
d
Supplementary data
143.90; 141.41; 140.13; 131.11; 130.98; 130.69; 130.45; 129.25;
128.73; 128.55; 128.48; 128.34; 128.06; 127.79; 127.46; 127.08;
126.35; 87.32 (J¼9.94 Hz); 71.36 (J¼7.32 Hz); 65.69; 48.51; 29.84;
25.47. HRMS-ESI m/z calcd for C30H31NOP: [MþH]þ 452.2143,
found: 452.2151.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.12.009.
References and notes
4.3. General procedure for the asymmetric arylation
of aldehydes
1. (a) Schmidt, F.; Stemmler, R. T.; Rudolph, J.; Bolm, C. Chem. Soc. Rev. 2006, 35,
454; (b) Paixa˜o, M. W.; Braga, A. L.; Lu¨ dtke, D. S. J. Braz. Chem. Soc. 2008, 19,
913; (c) Pu, L.; Yu, H. Chem. Rev. 2001, 101, 757; (d) Suli, M. P.; Manyem, S.
Tetrahedron 2000, 56, 8033; (e) Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed.
Engl. 1991, 30, 49.
2. (a) Meguro, K.; Aizawa, M.; Sohda, T.; Kawamatsu, Y.; Nagaoka, A. Chem. Pharm.
Bull. 1985, 33, 3787; (b) Toda, F.; Tanaka, K.; Koshiro, K. Tetrahedron: Asymmetry
1991, 2, 873; (c) Stanchev, S.; Rakovska, R.; Berova, N.; Snatzke, G. Tetrahedron:
Asymmetry 1995, 6, 183; (d) Botta, M.; Summa, V.; Corelli, F.; Di Pietro, G.;
Lombardi, P. Tetrahedron: Asymmetry 1996, 7, 1263.
Diethylzinc (3.6 mmol toluene solution) was added dropwise to
a solution of aryl boronic acid (1.2 mmol) in toluene (2 mL) under
an argon atmosphere. After stirring for 15 min at 60 ꢀC the mixture
was cooled to room temperature and a solution of the amino-
phosphinite (0.05 mmol) in 1 mL of toluene was added. The
reaction mixture was stirred for 15 min and after cooling to 0 ꢀC
a solution of aldehyde (0.5 mmol) was added with a syringe. After
3. (a) Bolm, C.; Hildebrand, J. P.; Mun˜iz, K.; Hermanns, N. Angew. Chem., Int. Ed.
2001, 40, 3284; (b) Dimitrov, V.; Kostova, K. Lett. Org. Chem. 2006, 3, 176.

M. Godoi et al. / Tetrahedron 66 (2010) 1341–1345
1345
4. For B-to-Zn exchange reactions see: (a) Srebnik, M. Tetrahedron Lett. 1991, 32,
2449; (b) Oppolzer, W.; Radinov, R. N. Helv. Chim. Acta 1992, 75, 170; (c)
Oppolzer, W.; Radinov, R. N. J. Am. Chem. Soc. 1993, 115, 1593; (d) Langer, F.;
Schwink, L.; Devasagayaraj, A.; Chavant, P.-Y.; Knochel, P. J. Org. Chem. 1996, 61,
8229; (e) Boudier, A.; Bromm, L. O.; Lotz, M.; Knochel, P. Angew. Chem., Int. Ed.
2000, 39, 4414; (f) Bolm, C.; Rudolph, J. J. Am. Chem. Soc. 2002, 124, 14850.
5. For representative examples, see: (a) Braga, A. L.; Lu¨ dtke, D. S.; Vargas, F.;
Paixao, M. W. Chem. Commun. 2005, 2512; (b) Braga, A. L.; Lu¨dtke, D. S.;
Schneider, P. H.; Vargas, F.; Schneider, A.; Wessjohann, L. A.; Paixao, M. W.
Tetrahedron Lett. 2005, 46, 7827; (c) Wu, P.-Y.; Wu, H.-L.; Uang, B.-J. J. Org. Chem.
2006, 71, 833; (d) Jin, M.-J.; Sarkar, S. M.; Lee, D.-H.; Qiu, H. Org. Lett. 2008, 10,
1235; (e) Hatano, M.; Miyamoto, T.; Ishihara, K. Adv. Synth. Catal. 2005, 347,
1561; (f) Rudolph, J.; Lormann, M.; Bolm, C.; Dahmen, S. Adv. Synth. Catal. 2005,
347, 1361; (g) Paixa˜o, M. W.; Godoi, M.; Rhoden, C. R. B.; Westermann, B.;
Wessjohann, L. A.; Lu¨dtke, D. S.; Braga, A. L. J. Mol. Cat. A: Chem. 2007, 261, 120;
(h) Zhong, J.; Guo, H.; Wang, M.; Yin, M.; Wang, M. Tetrahedron: Asymmetry
2007, 18, 734; (i) Braga, A. L.; Paixa˜o, M. W.; Westermann, B.; Schneider, P. H.;
Wessjohann, L. A. J. Org. Chem. 2008, 73, 2879; (j) Liu, X. Y.; Wu, X. Y.; Chai, Z.;
Wu, Y. Y.; Zhao, G.; Zhu, S. Z. J. Org. Chem. 2005, 70, 7432; (l) Braga, A. L.; Milani,
P.; Vargas, F.; Paixa˜o, M. W.; Sehnem, J. A. Tetrahedron: Asymmetry 2006, 17,
2793; (m) Wu, X.; Liu, X.; Zhao, G. Tetrahedron: Asymmetry 2005, 16, 229; (n)
Yamomoto, Y.; Kurihara, K.; Miyaura, N. Angew. Chem., Int. Ed. 2009, 48, 4414.
6. (a) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921; (b) Trost, B. M.; Van
Vranken, D. L.; Bingel, C. J. Am. Chem. Soc. 1992, 114, 9327; (c) Achiwa, I.;
Yamazaki, A.; Achiwa, K. Synlett 1998, 45; (d) Dierkes, P.; Ramdeehul, S.; Barloy,
L.; De Cian, A.; Fischer, J.; Kamer, P. C. J.; Van Leeuwen, P. W. N. M.; Osborn, J. A.
Angew. Chem., Int. Ed. 1998, 37, 3116; (e) Braga, A. L.; Silveira, C. C.; de Bolster,
M. W. G.; Schrekker, H. S.; Wessjohann, L. A.; Schneider, P. H. J. Mol. Catal. A
2005, 239, 235; (f) Schneider, P. H.; Schrekker, H. S.; Silveira, C. C.; Wessjohann,
L. A.; Braga, A. L. Eur. J. Org. Chem. 2004, 2715.
7. (a) Willems, J. G. H.; Hersmis, M. C.; de Gelder, R.; Smits, J. M. M.; Hammink, J.
B.; Dommerholt, F. J.; Thijs, L.; Zwanenburg, B. J. Chem. Soc., Perkin Trans. 1 1997,
3351; (b) Braga, A. L.; Schneider, P. H.; Paixa˜o, M. W.; Deobald, A. M.; Peppe, C.;
Bottega, D. P. J. Org. Chem. 2006, 71, 4305.
8. (a) Li, S. J.; Jiang, Y. Z.; Mi, A. Q. Tetrahedron: Asymmetry 1992, 3, 1467; (b) Mi, A.
Q.; Lou, R. L.; Jiang, Y. Z.; Deng, J. G.; Qin, Y.; Fu, F. M.; Li, Z.; Hu, W. H.; Chan, A.
S. C. Synlett 1998, 847.
9. Jimeno, C.; Sayalero, S.; Fjermestad, T.; Colet, G.; Maseras, F.; Perica`s, M. A.
Angew. Chem., Int. Ed. 2008, 47, 1098.
10. Schimdt, F.; Rudolph, J.; Bolm, C. Adv. Synth. 2007, 349, 730.