Catalytic asymmetric arylation of aliphatic aldehydes using a B/Zn exchange reaction

Article abstract of DOI:10.1016/j.tet.2015.01.014

Herein we describe the arylation of aliphatic aldehydes using the boron/zinc exchange reaction for the generation of transferable aryl groups, in the presence of chiral amino alcohol ligands. For the first time, a systematic investigation of this reaction

Full text of DOI:10.1016/j.tet.2015.01.014

Tetrahedron 71 (2015) 1202e1206
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Catalytic asymmetric arylation of aliphatic aldehydes using a B/Zn
exchange reaction
Andressa M.M. Carlos, Maria Eduarda Contreira, Bruna S. Martins, Maira F. Immich,
*
ꢀ
€
Angelica V. Moro, Diogo S. Ludtke
Instituto de Química, Universidade Federal do Rio Grande do Sul, UFRGS, Av. Bento Gonc¸ alves 9500, 91501-970 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:
Herein we describe the arylation of aliphatic aldehydes using the boron/zinc exchange reaction for the
generation of transferable aryl groups, in the presence of chiral amino alcohol ligands. For the first time,
a systematic investigation of this reaction using aliphatic aldehydes was developed and we have found
that it proved to be significantly more challenging than the arylation of aromatic aldehydes. The cor-
responding chiral secondary alcohols were obtained in up to 73% ee.
Received 26 November 2014
Received in revised form 8 January 2015
Accepted 9 January 2015
Available online 14 January 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Boron/zinc exchange
Amino alcohols
Stereoselectivity
Chiral secondary alcohols
1. Introduction
conformational flexibility that decreases the relative energies of the
diastereomeric transition states that ultimately lead to the two
The catalytic asymmetric addition of organozinc reagents to
aldehydes using is a powerful methodology for the synthesis of
enantiopure chiral alcohols.1 For instance, the reaction of dieth-
ylzinc with aldehydes proceeds slowly in the absence of any li-
gands. However, the addition of substoichiometric amount of
a chiral ligand results in the formation of a new catalytic species
that accelerates the ethyl transfer to aldehydes and might render it
enantioselective.2 The catalytic asymmetric addition of arylzinc
reagents to aldehydes though, poses additional challenges since the
uncatalyzed background aryl transfer reaction competes with the
catalyzed pathway, requiring an efficient ligand turnover.3 One of
the best ways to perform such a reaction is through the generation
mixed arylalkylzinc reagents through a boron/zinc exchange re-
action between arylboronic acids and diethylzinc.4 Using these
conditions, a number of aryl groups can be stereoselectively
transferred to aldehydes in the presence of catalytic amounts of
chiral ligands.5 Despite the success achieved in such reaction in
recent years,6 the main focus has been the asymmetric arylation of
aromatic aldehydes and only scattered examples of the outcome of
the arylation of aliphatic aldehydes have been described, usually
with diminished enantioselectivities.7 The main challenge associ-
ated with the addition to aliphatic aldehydes is their higher
enantiomers of a given product. Intrigued by the lack of data on the
behavior of such aldehydes as electrophiles in asymmetric aryla-
tions, we decided to systematically investigate this reaction using
easily synthesized chiral ligands that were already successfully
employed in the synthesis of diarylmethanols. The ligands chosen
possess different chiral backbones, which are based on acyclic
amino acids,8 pyrrolidine9 and aziridine10 derivatives, sugar-based
amino alcohols,11 and amino naphthols (Fig. 1).12
2. Results and discussion
We started our investigation by examining the impact of the
ligand structure on the yield and enantioselectivity of the reaction.
The phenyl transfer reaction to n-hexanal was selected as our
standard reaction in order to compare the activities of our selected
ligand set (Table 1). In all reactions, the B/Zn exchange was per-
formed using arylboronic acid and diethylzinc, at 60 ꢀC for 0.5 h.
We first tested ligands L1 and L2, derived from
L-phenylalanine
and -valine, respectively (Table 1, entries 1 and 7). The phenyl
L
transfer reaction to hexanal was performed in the presence of
20 mol % of the amino alcohol, at 0 ꢀC. Ligand L1 resulted in better
results of yield and enantiomeric excess, delivering the 1-phenyl-1-
hexanol product in 80% isolated yield and 62% ee. With this
promising result in hands, we changed the reaction conditions in an
attempt to improve the performance of our catalytic system.
* Corresponding author. Tel.: þ55 51 3308 9637; e-mail address: dsludtke@iq.
€
ufrgs.br (D.S. Ludtke).
http://dx.doi.org/10.1016/j.tet.2015.01.014
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

A.M.M. Carlos et al. / Tetrahedron 71 (2015) 1202e1206
1203
with good yield and modest ee (entry 11). Finally, Chan’s amino
naphthol ligands L7 and L8 were also used and L8, with a free NeH
group delivered the best results in terms of both yield and ee
(entries 12e16). Notably, using L8, the ligand loading could be re-
duced to 10 mol % without any loss of yield and enantioselectivity
(entry 16). With L1 and L8 identified as the most effective ligands,
we next examined their performance in the arylation of a broader
range of aliphatic aldehydes. The results of these studies are pre-
sented in Table 2.
We first examined the impact of aldehydes with longer alkyl
chains. Therefore, n-octanal and n-decanal were employed (Table 2,
entries 3e6), and we observed that with ligand L8 the ee was
decreased with these longer chain aldehydes, while with L1 a de-
crease in the ee was observed for octanal, but essentially the same
level of enantioselectivity was obtained with decanal and alcohol 1c
was isolated in 85% yield and 64% ee (entry 5). The same trend was
observed with the use of the a-branched aldehyde iso-butyralde-
hyde (entries 7 and 8) whose phenylation resulted in the corre-
sponding alcohol 1d in 61% ee for L1 and 40% ee for L8. An increase
in the bulky of the side chain, by using pivalaldehyde, resulted in
sluggish arylation and alcohol 1e was obtained in disappointingly
low yields, alongside with decomposition of the aldehyde (entries 9
and 10). On the other hand, cyclo-hexylcarboxaldehyde and trans-
cinnamaldehyde underwent smooth arylation (entries 11e14) and
the best results were achieved using ligand L8, which resulted in
products 1f and 1g in 71% and 73% ee, respectively. Finally, we
examined the scope of the arylation reaction regarding the sub-
stitution pattern of the starting arylboronic acid. Therefore, we
performed the arylation of hexanal and cyclo-hexylcarboxaldehyde
using 4-methoxyphenyl boronic acid, 4-chlorophenyl boronic acid,
and 2-tolyl boronic acid, in order to evaluate the influence of
electronic and steric effects on the arylation reagent. We have found
that the presence of substituents at the transferable aryl group was
best tolerated when using ligand L1 and hexanal as the electrophile.
When the electron-donating group methoxy was present, we ob-
served an increase in the reactivity of the arylating agent and the
products were obtained with higher yields, albeit with decreased
ees (see entries 16, 21, and 22). Exception to this trend was observed
with the reaction between 4-methoxyphenyl boronic acid and
hexanal in the presence of L1, which resulted in product 1h in 90%
yield and an increased ee of 69% (entry 15). For the transfer of
a 4-chlorophenyl group to hexanal, L1 has shown the best results
(entry 17, 65% yield, 69% ee) while for cyclo-hexylcarboxaldehyde
L8 was the most efficient (entry 24, 88% yield, 62% ee). Finally, the
enantioselectivity of the reaction proved to be sensitive to steric
effects at the aryl group and in all cases studied the products 1j and
1m were isolated in very low enantiomeric excesses (see entries 19,
20 and 25, 26).
Fig. 1. Structures of ligands L1eL8 evaluated.
However, decreasing the arylation temperature from 0 ꢀC to ꢁ20 ꢀC
(entry 2) or ꢁ40 ꢀC (entry 3) resulted in decreased yields and ees.
Similarly, keeping the temperature at 0 ꢀC and increasing the ary-
lation time from 1 h to 2 h, resulted in an erosion of the ee of the
product (entry 4). We also tried to decrease the ligand loading to
15 mol %, but a sharp decrease of the ee was observed (entry 6).
Next, we evaluated three ligands possessing the nitrogen atom
embedded in smaller rings: aziridino amino alcohol L3 and the
pyrrolidine amino alcohols L4 and L5, which are derived from L-
proline (entries 8e10). These ligands resulted in good conversions
to the product, but no further improvement in the enantiose-
lectivity of the arylation reaction was observed. Notably, the chiral
secondary alcohol with the opposite absolute configuration was
formed as the major product, despite the fact that the all ligands
were prepared from the corresponding L-amino acids, the sense of
enantioinduction is the opposite for ligands derived from acyclic
and cyclic amino acids.13 The sugar-based 1,3-amino alcohol ligand
L6 was also tested in the reaction and the product was obtained
Table 1
Effect of the ligand structure on the arylation of n-hexanal
OH
B(OH)2
1) Et2Zn, 60 oC, 0.5 h
2) hexanal, conditions
1a
Entry
Ligand (mol %)
Time (h)
Temperature (ꢀC)
Yielda (%)
eeb (%)
3. Conclusions
1
2
3
4
5
6
7
8
L1 (20)
L1 (20)
L1 (20)
L1 (20)
L1 (20)
L1 (15)
L2 (20)
L3 (20)
L4 (20)
L5 (20)
L6 (20)
L7 (20)
L8 (20)
L8 (20)
L8 (20)
L8 (10)
1
4
4
2
1
1
1
2
1
1
1
2
1
1
2
2
0
ꢁ20
ꢁ40
0
25
0
0
0
0
0
0
0
25
0
0
80
60
24
85
60
74
60
86
60
58
73
73
68
85
88
84
62 (S)
55 (S)
40 (S)
49 (S)
36 (S)
36 (S)
36 (S)
61 (R)
45 (R)
56 (R)
40 (R)
52 (S)
45 (S)
62 (S)
61 (S)
60 (S)
In summary, we have studied the arylation of aliphatic alde-
hydes using the boron/zinc exchange reaction for the generation of
transferable aryl groups, in the presence of chiral amino alcohol
ligands. For the first time, a systematic investigation of this reaction
using aliphatic aldehydes was developed and we have found that it
proved to be significantly more challenging than the arylation of
aromatic aldehydes. The lower reactivity toward nucleophilic ad-
dition, together with the higher conformational flexibility of the
alkyl side chain, imposed additional hurdles that are reflected in
small energetic differences in the diastereomeric transition states
that lead to each enantiomers of the chiral secondary alcohol. Of
significant note is that all ligands tested have been previously used
in the arylation of aryl aldehydes, delivering the corresponding
diarylmethanols in ees higher than 90%, therefore confirming that
the arylation of more conformationally flexible electrophiles is far
9
10
11
12
13
14
15
16
0
a
Isolated yield.
b
Enantiomeric excesses were determined by chiral HPLC, see Supplementary
data for details.

1204
A.M.M. Carlos et al. / Tetrahedron 71 (2015) 1202e1206
Table 2 (continued)
Table 2
Scope of the arylationa
Entry
Product
Ligand (mol %) Yieldb (%) eec (%)
OH
B(OH)2
1) Et2Zn, 60 oC, 0.5 h
2) ligand, aldehyde, 0 o
R
R1
R1
25
26
L1 (20)
L8 (10)
37
83
21 (S)
14 (R)
C
1
Entry
Product
Ligand (mol %) Yieldb (%) eec (%)
n.d.¼not determined. Absolute configurations were assigned based on comparison
with the literature.
a
1
L1 (20)
L8 (10)
L1 (20)
L8 (10)
L1 (20)
L8 (10)
L1 (20)
L8 (10)
L1 (20)
L8 (10)
L1 (20)
L8 (10)
L1 (20)
L8 (10)
L1 (20)
L8 (10)
L1 (20)
L8 (10)
L1 (20)
L8 (10)
L1 (20)
L8 (10)
L1 (20)
L8 (10)
80
84
70
75
85
83
60
57
<10
<10
96
80
68
73
90
63
65
88
76
90
80
97
75
88
62
60
51
41
64
51
61
40
n.d.
n.d.
68
71
24
73
69
41
69
53
21
2
All reactions were performed on a 0.5 mmol scale with PhB(OH)2 (2.4 equiv),
Et2Zn (7.2 equiv) in toluene. For reactions performed using ligand L1 (20 mol %) the
reaction mixture was stirred at 0 ꢀC for 1 h. For ligand L8 (10 mol %), the reaction
mixture was stirred at 0 ꢀC for 2 h.
2
b
Isolated yield.
c
Enantiomeric excesses were determined by chiral HPLC, see Supplementary
3
data for details.
4
from being just a mere extension of substrate scope. Further studies
toward a better understanding of this behavior are underway.
5
4. Experimental
4.1. General
6
7
Hydrogen nuclear magnetic resonance spectra (1H NMR) were
obtained at 300 MHz and 400 MHz. Spectra were recorded in CDCl3
solutions. Chemical shifts (d) are reported in parts per million
(ppm), referenced to the solvent peak of residual CHCl3 or tetra-
methylsilane (TMS) as reference. Data are reported as follows:
chemical shift (d), multiplicity, coupling constant (J) in hertz (Hz),
8
9
and integrated intensity. Carbon-13 nuclear magnetic resonance
spectra (13C NMR) were obtained at 75 and 100 MHz. Spectra were
recorded in CDCl3 solutions. Chemical shifts are reported in parts
per million (ppm), referenced to the solvent peak CDCl3. Abbrevi-
ations to denote the multiplicity of a particular signal are s (singlet),
d (doublet), t (triplet), dd (double doublet), m (multiplet), and br s
(broad singlet). Optical rotations were obtained on a Perkin Elmer
341 Polarimeter. Column chromatography was performed using
silica gel (230e400 mesh) following the methods described by
Still.14 Thin layer chromatography (TLC) was performed using silica
gel GF254, 0.25 mm thickness. For visualization, TLC plates were
either placed under ultraviolet light, or phosphomolibdic acid,
followed by heating. Air- and moisture-sensitive reactions were
conducted in oven-dried glassware equipped with tightly fitted
rubber septa and under a positive atmosphere of dry argon. Re-
agents and solvents were handled using standard syringe tech-
niques. The chiral ligands used were prepared according to the
following literature procedures, which are also described
in Supplementary data: L1 and L2;8 L3;11a L4;9 L5; L6;10 L715 and
L8.12d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
4.2. General experimental procedure for the arylation
reaction
In an atmosphere of argon 1.5 M solution of Et2Zn (7.2 equiv,
3.6 mmol, 2.4 mL) was slowly added to a solution of arylboronic
acid (2.4 equiv, 1.2 mmol, 146 mg) in dry toluene (2 mL). The
mixture was stirred at 60 ꢀC for 0.5 h and after this period, cooled at
room temperature and a solution of ligand (20 mol % L1 and
10 mol % L8) in 1 mL of dry toluene was added. The reaction mix-
ture was stirred for 15 min followed by addition of the aldehyde
(0.5 mmol). After stirred at 0 ꢀC for the time indicate in Table 2 the
reaction mixture was carefully quenched at 0 ꢀC by the addition of
NH4Cl solution (satd, 10 mL) or HCl 1 M solution (L8). The aqueous
layer was extracted with dichloromethane (3ꢂ15 mL). The com-
bined organic layers were dried with anhydrous MgSO4, filtered,
27
21
23
62

A.M.M. Carlos et al. / Tetrahedron 71 (2015) 1202e1206
1205
20
and the solvent was evaporated in vacuum. The crude product was
purified by flash chromatography using hexane/ethyl acetate
(90:10) when L1 was used or dichloromethane, when L8 was used.
With L8: yield: 66%, 41% ee; [
a
]
ꢁ18 (c 1, CHCl3).
D
HPLC conditions: Chiracel OB-H, hexane/IPA¼95:5, 1.0 mL/min,
UV, 254 nm, (S): 9.34; (R): 10.8 min.
1H NMR (300 MHz, CDCl3):
d
7.27 (d, J¼8.1, 2H), 6.88 (d, J¼8.1,
4.2.1. (S)-1-Phenyl-1-hexanol (1a). Colorless liquid.7
2H), 4.61 (t, J¼6.7, 1H), 3.81 (s, 3H), 1.85e1.56 (m, 4H), 1.34e1.27 (m,
20
With L1: yield: 80%, 62% ee; [
With L8: yield: 84%, 60% ee; [
a
a
]
]
ꢁ20 (c 1, CHCl3).
5H), 0.86 (t, J¼6.9, 3H). 13C NMR (75 MHz, CDCl3):
d 159.0, 137.1,
D
20
D
ꢁ20 (c 1, CHCl3).
127.1, 113.8, 74.3, 55.3, 38.9, 31.7, 25.6, 22.6, 14.0.
HPLC conditions: Chiralcel OD-H, hexane/IPA¼99:1, 0.9 mL/min,
UV 254 nm, (R): 19.2; (S): 22.4 min.
4.2.8. (S)-1-(4-Chlorophenyl)hexan-1-ol (1i). White solid.21
1H NMR (300 MHz, CDCl3):
d
7.33e7.26 (m, 5H), 4.62 (t, J¼6.0,
With L1: yield: 65%, 69% ee; [
With L8: yield: 63%, 53% ee; [
a
a
]
]
ꢁ19 (c 1, CHCl3).
20
D
20
D
1H), 2.08 (br s, 1H), 1.78e1.66 (m, 2H), 1.30e1.26 (m, 6H), 0.87
ꢁ18 (c 1, CHCl3).
(t, J¼6.8, 3H). 13C NMR (75 MHz, CDCl3):
d
144.9, 128.3, 127.3, 125.8,
HPLC conditions: Chiralcel AD-H, hexane/IPA¼98:2, 0.5 mL/min,
74.6, 39.0, 31.6, 25.4, 22.5, 14.0.
UV 254 nm, 36.32, 40.68 min.
1H NMR (300 MHz, CDCl3):
d
7.31e7.23 (m, 4H), 4.62 (t, J¼6.6,
4.2.2. (S)-1-Phenyl-1-octanol (1b). Colorless liquid.16
1H), 2.00 (br s, 1H), 1.77e1.61 (m, 2H), 1.40e1.26 (m, 6H), 0.86
With L1: yield: 70%, 51% ee; [
With L8: yield: 75%, 41% ee; [
a
a
]
]
20 ꢁ16 (c 1, CHCl3).
(t, J¼6.6, 3H). 13C NMR (75 MHz, CDCl3):
d 143.3, 133, 128.5, 127.2,
D
20 ꢁ8 (c 1, CHCl3).
73.9, 39, 31.6, 25.3, 22.5, 13.9.
D
HPLC conditions: Chiralcel OD-H, Hexane/IPA¼99:1, 0.9 mL/min,
UV 254 nm, (R): 19.2; (S): 22.4 min.
4.2.9. (S)-1-(2-Methylphenyl)hexan-1-ol (1j). White solid.21
1H NMR (300 MHz, CDCl3):
d
7.38e7.22 (m, 5H), 4.64 (t, J¼5.8,
With L1: yield: 76%, 21% ee; [
a
]
20 ꢁ15 (c 1, CHCl3).
D
20
1H), 2.00 (br s, 1H), 1.88e1.59 (m, 2H), 1.51e1.16 (m, 10H), 0.86 (t,
With L8: yield: 68%, 2% ee; [
a
]
ꢁ7 (c 1, CHCl3).
D
J¼6.8, 3H). 13C NMR (75 MHz, CDCl3):
d
144.9, 128.3, 127.4, 125.8,
HPLC conditions: Chiralcel AD-H, hexane/IPA¼99:1, 0.8 mL/min,
74.6, 39.0, 31.8, 29.4, 29.1, 25.8, 22.6, 14.0.
UV 254 nm, 15.70, 18.58 min.
1H NMR (300 MHz, CDCl3):
d
7.44 (d, J¼7.3, 1H), 7.23e7.09
4.2.3. (S)-1-Phenyl-1-decanol (1c). Colorless liquid.17
(m, 3H), 4.90 (dd, J¼7.3, 5.3, 1H), 2.32 (s, 3H), 1.89 (br s, 1H),
With L1: yield: 85%, 64% ee; [
a
]
]
20 ꢁ14 (c 1, CHCl3).
1.73e1.62 (m, 2H), 1.41e1.25 (m, 6H), 0.88 (t, J¼6.5, 3H). 13C NMR
D
20
With L8: yield: 83%, 51% ee; [
a
ꢁ7 (c 1, EtOH).
(75 MHz, CDCl3): d 143.0, 134.3, 130.2, 127.0, 126.0, 125.0, 70.6, 38.0,
D
HPLC conditions: Chiralcel OD-H, hexane/IPA¼98:2, 1.0 mL/min,
31.7, 25.7, 22.5, 19.0, 14.0.
UV 254 nm, (R): 7.4 min; (S): 8.6 min.
1H NMR (300 MHz, CDCl3):
d
7.35e7.23 (m, 5H), 4.61 (t, J¼6.5,
4.2.10. (S)-1-(4-Methoxyphenyl)cyclohexan-1-ol
(1k). White
1H), 2.11 (br s, 1H), 1.79e1.63 (m, 2H), 1.38e1.24 (m, 14H), 0.88
solid.22
20
(t, J¼6.5, 3H). 13C NMR (75 MHz, CDCl3):
d
144.9, 128.3, 127.3, 125.8,
With L1: yield: 80%, 27% ee; [
With L8: yield: 97%, 21% ee; [a]
D
a
]
ꢁ13 (c 1, THF).
ꢁ21 (c 1, THF).
D
20
74.6, 39.0, 31.8, 29.5, 29.2, 25.8, 22.6, 14.0.
HPLC conditions: Chiralcel AS-H, hexane/IPA¼97:3, 0.5 mL/min,
4.2.4. (R)-2-Methyl-1-phenylpropan-1-ol (1d). Colorless liquid.18
UV 254 nm, 12.5, 18.3 min.
With L1: yield: 60%, 61% ee; [
With L8: yield: 57%, 40% ee; [
a
a
]
]
20 ꢁ15 (c 1, AcOEt).
1H NMR (300 MHz, CDCl3):
d
7.20 (d, J¼8.5, 2H), 6.86 (d, J¼8.5,
D
20 ꢁ30 (c 1, CHCl3).
2H), 4.27 (d, J¼7.4, 1H), 3.78 (s, 3H), 2.07e1.97 (m, 2H), 1.77e1.51
D
HPLC conditions: Chiracel OD-H, hexane/IPA¼90:10, 0.5 mL/min,
(m, 4H),1.36e0.84 (m, 6H). 13C NMR (75 MHz, CDCl3):
d 158.8,135.7,
UV 254 nm, (R): 11.8; (S): 10.8 min.
127.7, 113.4, 78.9, 55.1, 44.8, 29.1, 29.0, 26.3, 26, 25.9.
1H NMR (300 MHz, CDCl3):
d
7.33e7.25 (m, 5H), 4.34 (d, J¼6.9,
1H), 2.02e1.87 (m, 2H), 0.99 (d, J¼6.7, 3H), 0.78 (d, J¼6.8, 3H). 13
C
4.2.11. (S)-1-(4-Chlorophenyl)cyclohexan-1-ol (1l). Colorless oil.23
20
NMR (75 MHz, CDCl3):
18.2.
d
143.5, 128.1, 127.3, 126.5, 80.0, 35.2, 18.9,
With L1: yield: 75%, 23% ee; [
With L8: yield: 88%, 62% ee; [
a
a
]
]
ꢁ9 (c 1, CHCl3).
D
20
D
ꢁ19 (c 1, CHCl3).
HPLC conditions: Chiralcel OD-H, hexane/IPA¼98:2, 0,5 L/min,
4.2.5. (R)-1-Phenyl-1-cyclohexanol (1f). White solid.19
UV 254 nm, (S) 19.83, (R) 25.02 min.
With L1: yield: 96%, 68% ee; [
With L8: yield: 80%, 71% ee; [
a
]
20 ꢁ26 (c 1, CHCl3).
1H NMR (300 MHz, CDCl3):
d
7.29 (d, J¼8.4, 2H), 7.20 (d, J¼8.4,
D
a]
20 ꢁ28 (c 1, CHCl3).
2H), 4.32 (d, J¼6.9, 1H), 2.10 (br s, 1H), 1.93e1.89 (m, 1H), 1.77e1.48
D
HPLC conditions: Chiracel OD-H, hexane/IPA¼99:1, 0.4 mL/min,
(m, 4H),1.38e0.87 (m, 6H). 13C NMR (75 MHz, CDCl3):
d 141.9, 132.9,
UV 254 nm, (S): 46.0, (R): 60.1 min.
128.2, 127.9, 78.5, 44.9, 29.1, 28.6, 26.3, 25.98, 25.90.
1H NMR (300 MHz, CDCl3):
d
7.34e7.25 (m, 5H), 4.36 (d, J¼5.5,
1H), 2.03e1.92 (m, 1H), 1.82e1.57 (m, 5H), 1.40e0.94 (m, 6H). 13
C
4.2.12. (2-Methylphenyl)cyclohexan-1-ol (1m). White solid.22
20
NMR (75 MHz, CDCl3):
28.8, 26.4, 26.1, 26.0.
d
143.6, 128.1, 127.4, 126.6, 79.3, 44.9, 29.3,
With L1: yield: 37%, 21% ee (S); [
a
]
D
ꢁ21 (c 1, CHCl3).
With L8: yield: 83%, 14% ee (R); [
a
]
20 þ4 (c 1, CHCl3).
D
HPLC conditions: Chiralcel OD-H, hexane/IPA¼97:3, 0.5 L/min,
4.2.6. (S)-(E)-1,3-Diphenyl-prop-2-en-1-ol (1g). Colorless liquid.18
UV 254 nm, (S): 14.77, (R): 16.6 min.
With L1: yield: 68%, 24% ee; [
With L8: yield: 73%, 73% ee; [
a
]
ꢁ15 (c 1, CHCl3).
1H NMR (300 MHz, CDCl3):
d
7.41 (d, J¼7.2, 1H), 7.16e7.13
20
D
20
a
]
ꢁ14 (c 1, EtOH).
(m, 3H), 4.62 (d, J¼7.1, 1H), 2.34 (s, 3H), 2.04e2.01 (m, 1H),
1.80e1.77 (m, 1H), 1.71e1.26 (m, 3H), 1.40e1.37 (m, 1H), 1.26e1.03
D
HPLCconditions: ChiralcelOD-H, hexane/IPA¼88:12,1.0mL/min,
UV 254 nm, (S): 10.6, (R): 13.4 min.
(m, 6H). 13C NMR (100 MHz, CDCl3):
d 141.9, 135.0, 130.2, 127.0,
1H NMR (300 MHz, CDCl3):
d
7.37e7.22 (m, 10H), 6.62
126.2, 126.0, 75.1, 44.5, 29.5, 28.5, 26.4, 26.3, 26.0, 19.5.
(dd, J¼15.8, 0.6, 1H), 6.33 (dd, J¼15.8, 6.5, 1H), 5.30 (d, J¼6.5, 1H),
2.4 (br s, 1H). 13C NMR (75 MHz, CDCl3):
128.5, 128.4, 127.6, 126.5, 126.2, 74.9.
d 142.6, 136.4, 131.4, 130.4,
Acknowledgements
We are grateful to the following agencies for financial support:
4.2.7. (S)-1-(4-Methoxyphenyl)hexan-1-ol (1h). White solid.20
FAPERGS, CNPq, and Coordenac¸ ao de Aperfeic¸ oamento de Pessoal
~
20
With L1: yield: 90%, 69% ee; [
a
]
D
ꢁ20 (c 1, CHCl3).
de Nível Superior.

1206
A.M.M. Carlos et al. / Tetrahedron 71 (2015) 1202e1206
A. M.; Turlington, M.; Ko, J.; Sole, M.; Pu, L. J. Org. Chem. 2010, 75, 2836e2850;
Supplementary data
For the use of the B/Zn exchange reaction in diastereoselective reactions, see:
€
(h) Martins, B. S.; Ludtke, D. S. Eur. J. Org. Chem. 2014, 5364e5369; (i) Wouters,
Copies of NMR and IR spectra and HPLC chromatograms. Sup-
plementary data associated with this article can be found in the
online version, at http://dx.doi.org/10.1016/j.tet.2015.01.014.
€
A. D.; Bessa, A. B.; Sachini, M.; Wessjohann, L. A.; Ludtke, D. S. Synthesis 2013,
€
45, 2222e2233; (j) Wouters, A. D.; Ludtke, D. S. Org. Lett. 2012, 14, 3962e3965;
(k) Stanton, G. R.; Kauffman, M. C.; Walsh, P. J. Org. Lett. 2012, 14, 3368e3371; (l)
Stanton, G. R.; Norrby, P.-O.; Carroll, P. J.; Walsh, P. J. J. Am. Chem. Soc. 2012, 134,
17599e17604; (m) Stanton, G. R.; Koz, G.; Walsh, P. J. J. Am. Chem. Soc. 2011, 133,
7969e7976; (n) Stanton, G. R.; Johnson, C. N.; Walsh, P. J. J. Am. Chem. Soc. 2010,
132, 4399e4408.
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