Catalyzed enantioselective synthesis of allyl alcohols from aldehydes and alkenylboronic acids

Article abstract of DOI:10.1055/s-2006-950287

Enantiomerically enriched (E)-allyl alcohols can be prepared in good yields by asymmetric alkenylation of aldehydes with alkenylboronic acids catalyzed by a chiral ferrocene-based agent. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950287

PAPER
3625
Catalyzed Enantioselective Synthesis of Allyl Alcohols from Aldehydes and
Alkenylboronic Acids
Allyl
A
lcohols
r
fromA
a
ldehydes
a
n
n
d Alkenylbo
k
ronic
A
cids Schmidt, Jens Rudolph, Carsten Bolm*
Institut für Organische Chemie der RWTH Aachen, Landoltweg 1, 52074 Aachen, Germany
E-mail: Carsten.Bolm@oc.rwth-aachen.de
Received 3 August 2006
Dedicated to Professor Dr. Marty Semmelhack on the occasion of his 65th birthday
we reported a general catalytic asymmetric aryl transfer to
Abstract: Enantiomerically enriched (E)-allyl alcohols can be pre-
pared in good yields by asymmetric alkenylation of aldehydes with
alkenylboronic acids catalyzed by a chiral ferrocene-based agent.
aromatic aldehydes with arylzinc species formed in situ
from arylboronic acids and diethylzinc.13 The presence of
catalytic amounts of methoxy polyethylene glycols im-
proved the enantioselectivities of these reactions.14 Pro-
Key words: C–C bond formation, allyl alcohols, enantioselective
catalysis, vinylboronic acid, zinc organyls, vinylation
pan-2-ol also had
enantioselectivity.
a
beneficial effect on the
These results encouraged us to investigate the applicabil-
ity of alkenylboronic acids 1 (see Table 1) in the prepara-
tion of enantioenriched allyl alcohols. Starting from
commercially available reagents 1, in situ boron-to-zinc
exchange was expected to afford alkenylzincs, which we
hoped would serve as alkenyl sources in catalyzed asym-
metric addition reactions to aldehydes. To test this hy-
pothesis, boronic acids 1 were stirred in toluene in the
presence of a threefold excess of ZnEt2 at –2 °C for five
minutes. Subsequently, 10 mol% of ferrocene 4 and alde-
hydes 2 were added at –2 °C. To our delight, allyl alcohols
3 formed in yields ranging from 37–79%. Table 1 and
Figure 1 summarize the results of this study.
Since chiral allyl alcohols are important intermediates in
the synthesis of numerous biologically active compounds,
enantioselective approaches towards their preparation
have recently attracted significant attention. Most strate-
gies are either based on asymmetric carbonyl reductions
of a,b-unsaturated ketones1 or enantioselective additions
of alkenylzinc reagents to carbonyl compounds.2–11 The
latter transformations are of particular interest due to the
generation of a stereogenic center with concomitant for-
mation of a new C–C bond. Early work in this area stems
from Oppolzer and Radinov, who employed alkenylzinc
reagents prepared in situ by the reaction of either ethenyl
Grignard or alkenyllithium reagents with ZnCl2 or ZnBr2.2
Later, the same authors used the reaction of terminal
alkynes with dicyclohexylborane and subsequent boron–
zinc exchange for the preparation of the alkenylzinc re-
agents. With Noyori’s 3-exo-dimethylaminoborneol
(DAIB)3 as catalyst, asymmetric alkenylations of alde-
hydes were achieved.4 Bräse introduced [2.2]paracyclo-
phane-based N,O-ligands for the asymmetric addition of
alkenylzinc species to aldehydes.5 Other amino alcohols
were successfully applied by Walsh,6 Chan,7 and Soai.8
Tseng and Yang investigated the use of b-amino thiols in
Oppolzer’s protocol,9 and the efficiency of N-acylethyl-
enediamines in asymmetric additions of alkenylzinc spe-
cies to aldehydes was screened by Seto.10 Wipf developed
a protocol for the hydrozirconation of alkynes using
Cp2ZrHCl (Schwartz reagent) for the preparation of alke-
nylzirconocenes, which were then transmetalated in situ
with dimethylzinc to give the corresponding zinc re-
agents.11
Initially, commercial samples of boronic acids 1a and
1c were used in the catalyzed addition reactions with
4-methylbenzaldehyde (2b) and 4-chlorobenzaldehyde
(2c), respectively (Table 1, entries 5 and 14). Unfortu-
nately, all attempts afforded addition products 3b and 3i
as racemates. To obtain chemically homogeneous boronic
acids and to minimize the presence of boroxines in the
commercial samples, boronic acids 1a and 1c were re-
fluxed in water for four hours, and the excess water was
then removed prior to use (entries 3 and 13). To our de-
light, those modified conditions led to the formation of al-
lyl alcohols 3b and 3i in good yields and in
enantioselectivities of 28% and 56%, respectively. Fur-
ther improvements in both yield and enantioselectivity
were achieved when one equivalent of propan-2-ol was
used as additive. In the reaction of boronic acid 1a and 4-
methylbenzaldehyde (2b) (entries 3 and 2), this effect in-
creased the enantioselectivity from 28% to 34% ee, while
the yield remained constant. The reaction between alke-
nylboronic acid 1c and aldehyde 2e was affected similarly
(entries 13 and 12), with the yield increasing from 58% to
79% and the ee from 56% to 61%. Interestingly, the use of
dimethoxy polyethylene glycol (DiMPEG) was detrimen-
tal, and the corresponding product was obtained in only
trace amounts (<10%; Table 1, entry 4). The best result
was achieved in the formation of 3h (entry 11), which was
In our previous studies, ferrocene 4 (see Table 1) was
found to be an excellent catalyst for the asymmetric syn-
thesis of diarylmethanols where either diphenylzinc or
triphenylborane was used as the phenyl source.12 In 2002
SYNTHESIS 2006, No. 21, pp 3625–3630
x
x.
x
x
.
2
0
0
6
Advanced online publication: 09.10.2006
DOI: 10.1055/s-2006-950287; Art ID: Z16506SS
© Georg Thieme Verlag Stuttgart · New York

3626
F. Schmidt et al.
PAPER
Table 1 Catalyzed Asymmetric Alkenylzinc Addition to Aldehydesa
O
OH
ZnEt2, 4 (10 mol%)
B(OH)2
+
i-PrOH
toluene, –2 °C, 12 h
Ar
R
Ar
R
1
2
3
O
N
OH
Fe
Ph
Ph
4
Entry
1d
Ar (1)
R (2)
Product 3
3a
Yieldb (%)
eec (%)
43 (R)
34 (R)
28 (R)
n.d.g
Ph (1a)
Ph (2a)
70
71
72
<10
41
62
69
72
53
55
62
79
58
37
67
2d
Ph (1a)
4-Tol (2b)
4-Tol (2b)
4-Tol (2b)
4-Tol (2b)
Mes (2c)
3b
3b
3b
3b
3c
3d,e
4d–f
5h
Ph (1a)
Ph (1a)
Ph (1a)
rac
6d
Ph (1a)
29 (R)
12 (R)
55 (R)
51 (R)
33 (S)
75 (R)
61 (R)
56 (R)
rac
7d
Ph (1a)
C6Me5 (2d)
3d
3e
8d
Ph (1a)
4-ClC6H4 (2e)
2-BrC6H4 (2f)
Cy (2g)
9d
Ph (1a)
3f
10d
11d
12d
13d,e
14h
15d
Ph (1a)
3g
4-Tol (1b)
4-ClC6H4 (1c)
4-ClC6H4 (1c)
4-ClC6H4 (1c)
4-ClC6H4 (1c)
4-ClC6H4 (2e)
4-ClC6H4 (2e)
4-ClC6H4 (2e)
4-ClC6H4 (2e)
C6Me5 (2d)
3h
3i
3i
3i
3j
9 (R)
a Reagents and conditions: 1 (0.6 mmol), 2 (0.25 mmol), 4 (10 mol%), Et2Zn (1.8 mmol), i-PrOH (0.25 mmol), toluene, –2 °C, 12 h.
b Yield after column chromatography.
c The enantiomer ratios were determined by HPLC on a chiral stationary phase. The absolute configuration of 3a was established by comparing
its rotational values with literature data.8b,15 Otherwise, the stereochemistry was assigned by assuming identical reaction pathways for the cata-
lyzed product formation.
d Boronic acid 1 was stirred in H2O at 100 °C for 4 h prior to use.
e Without i-PrOH.
f With DiMPEG (1.0 equiv) as additive.
g n.d. = not determined.
h Boronic acid 1 was not pretreated in H2O.
obtained in 75% ee in 62% yield from 1b and 4-chlo- major differences in yield and enantioselectivity were ob-
robenzaldehyde (2e). The reactions between pentamethyl- served. This effect was particularly pronounced in reac-
benzaldehyde (2d) and boronic acids 1a and 1c gave the tions with boronic acid 1a.
corresponding products 3d and 3j in low enantioselectiv-
ities (12 and 9%; entries 7 and 15). 2-Bromobenzaldehyde
(2f), also an ortho-substituted aldehyde, reacted well and
gave 3f in 51% ee and 53% yield (entry 9). The alkenyla-
tion of aliphatic aldehyde 2g with boronic acid 1b (entry
10) furnished the corresponding allyl alcohol 3g in 33%
ee and a respectable yield of 55%. Noticeable is that the
quality of the boronic acid was important in all reactions.
Depending on the nature (and purity) of the boronic acid,
The reaction between alkenylboronic acid 1a and alde-
hyde 2b at –10 °C led to an interesting observation. The
yield of the expected product 3b decreased to 33%, and
the presence of a new compound was detected. The dou-
ble set of signals in both the 1H and 13C NMR spectra in-
dicated the formation of a compound structurally very
similar to 3b, and which finally was identified as allyl al-
cohol 6b, an isomer of 3b (Scheme 1). Two-dimensional
NMR experiments of the isomer mixture measured in deu-
Synthesis 2006, No. 21, 3625–3630 © Thieme Stuttgart · New York

PAPER
Allyl Alcohols from Aldehydes and Alkenylboronic Acids
3627
support this hypothesis and to ensure that the rearrange-
ment was not caused by the presence of aldehyde 2b, two
experiments were carried out. First, (racemic) 3b was
treated with boronic acid 1a and diethylzinc, and the re-
sulting mixture was kept at –10 °C for 12 hours. Second,
the same experiment was performed, but the boronic acid
was substituted by the aldehyde. Supporting our suggest-
ed scenario, traces of isomerized product 6b were only
formed in the first experiment, whereas no 6b was found
in the second.
OH
OH
Me
3a
3b
OH Me
OH Me
Me
Me
Me
3d
Me
Me
Me
OH
3c
OH
In conclusion, we developed a new strategy for the syn-
thesis of enantiomerically enriched allyl alcohols starting
from aldehydes and commercially available alkenylbo-
ronic acids. The synthetic pathway is very flexible, allow-
ing the introduction of structural diversity in a single
reaction step.
Cl
Br
3e
3f
OH
OH
OH
All air-sensitive manipulations were carried out under an inert at-
mosphere of argon and using sealed vials. Toluene was distilled un-
der N2 from sodium/benzophenone ketyl radical. Et2O and pentane
Me
Cl
3g
3h
OH Me
1
for column chromatography were distilled before use. H and 13C
NMR spectra were recorded on a Varian Gemini 300 spectrometer
(300 MHz and 75 MHz, respectively) and on a Varian Inova 400
spectrometer (400 MHz and 100 MHz, respectively). IR spectra of
samples prepared as KBr pellets or neat samples (liquid com-
pounds) were measured on a Perkin-Elmer PE 1760 FT instrument;
absorptions are given in wave numbers (cm–1). MS spectra were re-
corded on a Varian MAT 212 or Finnigan MAT 95 spectrometer
with EI ionization. Optical rotation measurements were conducted
at room temperature with a Perkin-Elmer PE 241 polarimeter at a
wavelength of 589 nm. HPLC measurements were performed on a
Dionex HPLC system (previously Gynkothek) with autosampler
Gina 50, UV detector UVD 170S, degasser DG 503, and gradient
pump M480G.
Me
Cl
Cl
Cl
Me
3j
Me
Me
3i
Figure 1 Allyl alcohols 3 obtained by alkenyl transfer onto aldehy-
des
terated dichloromethane and deutero-pyridine confirmed
the assignments of both isomers 3b and 6b.16
Although the precise mechanism of the formation of 6b is
unknown, we assume that deprotonated 3b (e.g., alkoxide
3b-H+) reacts with the excess of the boron reagent (the bo-
ronic acid or its metalated counterpart) to give an interme-
diate such as 5b (Scheme 1). The latter then rearranges,
Pretreatment of Alkenylboronic Acids 1a–c; General Proce-
dure
The alkenylboronic acid 1 was suspended in H2O and the mixture
was refluxed for 4 h. Then the aqueous soln was extracted with
leading, after hydrolysis, to isomeric allyl alcohol 6b. To EtOAc, the organic layer was dried (MgSO4) and filtered, and the
solvent was removed under reduced pressure; this afforded the bo-
ronic acids 1a–c used in the reactions below.
R
B
Allyl Alcohols 3a–j; General Procedure
XO
OX
A 10-mL vial was charged with alkenylboronic acid 1 (0.6 mmol,
2.4 equiv), flushed with argon, and sealed with a septum. Freshly
distilled toluene (1.5 mL) was added at –2 °C, followed by 1 M
ZnEt2 in heptane (1.8 mL, 1.8 mmol, 7.2 equiv) and i-PrOH (20 mL,
0.25 mmol, 1 equiv). The mixture was stirred for 5 min at this tem-
perature. Another vial was charged with ferrocene 4 (12.5 mg,
0.025 mmol, 10 mol%), sealed with a septum, and flushed with ar-
gon. Toluene (1 mL) was added and the mixture was cooled to
–2 °C. The soln was transferred by syringe to the first one and stir-
ring was continued for 2 min at –2 °C. In a third vial, aldehyde 2
(0.25 mmol) was dissolved in toluene (1 mL), and the soln was
cooled to –2 °C and transferred by syringe to the other soln. The
mixture was stirred for 12 h at 0 °C. Then the reaction was
quenched with H2O (0.7 mL). The mixture was placed on a pad of
Celite, and eluted with CH2Cl2. The organic layer was extracted
with a sat. NaHCO3 soln (1 × 50 mL) and brine (2 × 50 mL), dried
(MgSO4), and filtered, and the solvent was removed under reduced
pressure. Purification of the product by column chromatography
gave allyl alcohol 3.17
–
OH
O
Me
Me
3b–H+
6b
rearrangement
then: hydrolysis
OX
R
–
B
O
XO
Me
5b
Scheme 1 Formation of isomeric products 3b and 6b during the al-
kenyl transfer from 1a to 2b at –10 °C (X = H or a metal species)
Synthesis 2006, No. 21, 3625–3630 © Thieme Stuttgart · New York

3628
F. Schmidt et al.
PAPER
(1R,2E)-1,3-Diphenylprop-2-en-1-ol (3a)18
13C NMR (100 MHz, CD2Cl2): d = 20.5 (2 CH3), 20.6 (CH3), 71.1
(CH), 126.3 (2 CH), 127.3 (CH), 128.4 (2 CH), 129.1 (CH), 129.9
(2 CH), 130.6 (CH), 135.2 (2 C), 136.4 (2 C), 136.9 (C).
MS (EI, 70 eV): m/z (%) = 252 (19) [M+], 234 (71), 133 (74), 132
(100), 105 (44).
Alcohol 3a was obtained from trans-boronic acid 1a (88.7 mg, 0.6
mmol, 2.4 equiv) and benzaldehyde (2a; 25.4 mL, 0.25 mmol, 1
equiv). Column chromatography (silica gel, pentane–Et2O–
Et3N, 7:2.7:0.3) gave 3a as a pale yellow oil. The absolute configu-
ration of 3a was established by comparing its rotational values with
literature data.8b,15
HRMS (EI): m/z calcd for C18H20O: 252.1514; found 252.1514.
Yield: 36.7 mg (70%); [a]D20 +11.2 (c 1.7, CH2Cl2).
(1R,2E)-1-(Pentamethylphenyl)-3-phenylprop-2-en-1-ol (3d)
Alcohol 3d was obtained from trans-boronic acid 1a (88.7 mg, 0.6
mmol, 2.4 equiv) and pentamethylbenzaldehyde (2d; 44.0 mg, 0.25
mmol, 1 equiv). Column chromatography (silica gel, pentane–
Et2O–Et3N, 7:2.7:0.3) gave 3d as a pale yellow oil. The absolute
configuration of 3d was assigned assuming an identical reaction
pathway for the catalyzed product formation as for 3a.
HPLC (Chiralcel OD, 254 nm, heptane–i-PrOH, 90:10, 1.0 mL/
min): tR = 15.3 min (S), 20.1 min (R).
IR (KBr): 3369, 1491, 1448, 1013, 965, 745, 695 cm–1.
1H NMR (400 MHz, CD2Cl2): d = 2.17 (br s, 1 H, OH), 5.26 (d,
J = 6.6 Hz, 1 H, CH), 6.28 (dd, J = 15.7, 6.6 Hz, 1 H, CH), 6.58 (d,
J = 15.9 Hz, 1 H, CH), 7.11–7.35 (m, 10 H, HAr).
13C NMR (100 MHz, CD2Cl2): d = 75.0 (CH), 126.2 (2 CH), 126.5
(2 CH), 127.6 (CH), 127.7 (CH), 128.5 (2 CH), 128.5 (2 CH), 130.1
(CH), 131.8 (CH), 136.6 (C), 143.0 (C).
Yield: 36.7 mg (69%); [a]D20 +4.9 (c 2.4, CH2Cl2).
HPLC (Chiralcel OD-H, 230 nm, heptane–i-PrOH, 90:10, 0.5 mL/
min): tR = 13.4 min (S), 22.5 min (R).
IR (CHCl3): 3388, 3009, 2925, 1450, 1217, 966, 757, 695 cm–1.
MS (EI, 70 eV): m/z (%) = 210 (54) [M+], 105 (100), 91 (14), 77
(21).
1H NMR (400 MHz, CD2Cl2): d = 1.97 (br s, 1 H, OH), 2.12 (s, 6 H,
2 CH3), 2.15 (s, 3 H, CH3), 2.24 (s, 6 H, 2 CH3), 5.90 (dd, J = 4.4,
1.9 Hz, 1 H, CH), 6.37 (dd, J = 16.5, 1.9 Hz, 1 H, CH), 6.50 (dd,
J = 15.9, 4.4 Hz, 1 H, CH), 7.10–7.14 (m, 1 H, HAr), 7.16–7.22 (m,
2 H, HAr), 7.24–7.29 (m, 2 H, HAr).
13C NMR (100 MHz, CD2Cl2): d = 16.5 (2 CH3), 16.9 (CH3), 17.2
(2 CH3), 71.6 (CH), 126.2 (2 CH), 127.2 (CH), 128.4 (2 CH), 128.9
(CH), 132.0 (CH), 132.1 (2 C), 133.1 (2 C), 134.3 (C), 135.9 (C),
137.1 (C).
(1R,2E)-3-Phenyl-1-(p-tolyl)prop-2-en-1-ol (3b)19
Alcohol 3b was obtained from trans-boronic acid 1a (88.7 mg, 0.6
mmol, 2.4 equiv) and 4-methylbenzaldehyde (2b; 29 mL, 0.25
mmol, 1 equiv). Column chromatography (silica gel, pentane–
Et2O–Et3N, 7:2.7:0.3) gave 3b as a pale yellow solid. The absolute
configuration of 3b was assigned assuming an identical reaction
pathway for the catalyzed product formation as for 3a.
Yield: 31.7 mg (56%); mp 74.0–75.7 °C; [a]D20 +8.0 (c 1.4,
CH2Cl2).
MS (EI, 70 eV): m/z (%) = 280 (12) [M+], 265 (100), 147 (15), 91
(5).
HPLC (Chiralcel OD, 254 nm, heptane–i-PrOH, 90:10, 1.0 mL/
min): tR = 13.6 min (S), 19.6 min (R).
HRMS (EI): m/z calcd for C20H24O: 280.1827; found 280.1827.
IR (KBr): 3393, 3025, 1509, 1448, 1021, 963, 815, 763, 692 cm–1.
(1R,2E)-1-(4-Chlorophenyl)-3-phenylprop-2-en-1-ol (3e)20
Alcohol 3e was obtained from trans-boronic acid 1a (88.7 mg, 0.6
mmol, 2.4 equiv) and 4-chlorobenzaldehyde (2e; 35.1 mg, 0.25
mmol, 1 equiv). Column chromatography (silica gel, pentane–
Et2O–Et3N, 7:2.7:0.3) gave 3e as a pale yellow solid. The absolute
configuration of 3e was assigned assuming an identical reaction
pathway for the catalyzed product formation as for 3a.
1H NMR (400 MHz, CD2Cl2): d = 2.16 (br s, 1 H, OH), 2.33 (s, 3 H,
CH3), 5.31 (d, J = 6.6 Hz, 1 H, CH), 6.36 (dd, J = 15.9, 6.5 Hz, 1 H,
CH), 6.66 (d, J = 15.8 Hz, 1 H, CH), 7.14–7.25 (m, 3 H, HAr), 7.26–
7.34 (m, 4 H, HAr), 7.35–7.41 (m, 2 H, HAr).
13C NMR (100 MHz, CD2Cl2): d = 21.2 (CH3), 75.1 (CH), 126.4 (2
CH), 126.7 (2 CH), 127.8 (CH), 128.7 (2 CH), 129.4 (2 CH), 130.1
(CH), 132.2 (CH), 136.9 (C), 137.7 (C), 140.3 (C).
20
Yield: 44.6 mg (72%); mp 58.2–59.0 °C; [a]D +8.9 (c 1.6,
CH2Cl2).
MS (EI, 70 eV): m/z (%) = 224 (34) [M+], 209 (24), 119 (100), 105
(19), 91 (18).
HPLC (Chiralcel OD, 254 nm, heptane–i-PrOH, 90:10, 1.0 mL/
min): tR = 14.9 min (S), 22.2 min (R).
IR (KBr): 3293, 1089, 1012, 964, 828, 751, 694 cm–1.
HRMS (EI): m/z calcd for C16H16O: 224.1201; found: 224.1201.
(1R,2E)-1-Mesityl-3-phenylprop-2-en-1-ol (3c)
1H NMR (400 MHz, CD2Cl2): d = 1.17 (br s, 1 H, OH), 5.23 (d,
J = 6.6 Hz, 1 H, CH), 6.22 (dd, J = 15.7, 6.6 Hz, 1 H, CH), 6.55 (d,
J = 15.7 Hz, 1 H, CH), 7.11–7.45 (m, 9 H, HAr).
13C NMR (100 MHz, CD2Cl2): d = 74.3 (CH), 126.5 (2 CH), 127.7
(2 CH), 127.8 (CH), 128.5 (2 CH), 128.6 (2 CH), 130.6 (CH), 131.3
(CH), 133.1 (C), 136.4 (C), 141.5 (C).
Alcohol 3c was obtained from trans-boronic acid 1a (88.7 mg, 0.6
mmol, 2.4 equiv) and 2,4,6-trimethylbenzaldehyde (2c; 37 mL, 0.25
mmol, 1 equiv). Column chromatography (silica gel, pentane–
Et2O–Et3N, 7:2.7:0.3) gave 3c as a pale yellow oil. The absolute
configuration of 3c was assigned assuming an identical reaction
pathway for the catalyzed product formation as for 3a.
MS (EI, 70 eV): m/z (%) = 244 (65) [M+], 209 (17), 141 (32), 139
(100), 105 (31).
Yield: 39.2 mg (62%); [a]D20 +11.1 (c 1.9, CH2Cl2).
HPLC (Chiralcel OD-H, 254 nm, heptane–i-PrOH, 90:10, 0.5 mL/
min): tR = 17.9 min (S), 27.9 min (R).
IR (CHCl3): 2921, 1217, 966, 852, 758, 694 cm–1.
1H NMR (400 MHz, CD2Cl2): d = 1.97 (br s, 1 H, OH), 2.16 (s, 3 H,
CH3), 2.31 (s, 6 H, 2 CH3), 5.75 (d, J = 2.7 Hz, 1 H, CH), 6.43 (d,
J = 3.0 Hz, 2 H, 2 CH), 6.75 (s, 2 H, HAr), 7.12 (tt, J = 6.3, 1.4 Hz,
1 H, HAr), 7.17–7.23 (m, 2 H, HAr), 7.25–7.30 (m, 2 H, HAr).
HRMS (EI): m/z calcd for C15H13ClO: 244.0654; found 244.0655.
Anal. Calcd for C15H13ClO: C, 73.62; H, 5.35. Found: C, 73.57; H,
5.43.
(1R,2E)-1-(2-Bromophenyl)-3-phenylprop-2-en-1-ol (3f)
Alcohol 3f was obtained from trans-boronic acid 1a (88.7 mg, 0.6
mmol, 2.4 equiv) and 2-bromobenzaldehyde (2f; 29 mL, 0.25 mmol,
1 equiv). Column chromatography (silica gel, pentane–Et2O–Et3N,
7:2.7:0.3) gave 3f as a pale yellow oil. The absolute configuration
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PAPER
Allyl Alcohols from Aldehydes and Alkenylboronic Acids
3629
of 3f was assigned assuming an identical reaction pathway for the
catalyzed product formation as for 3a.
Yield: 38.0 mg (53%); [a]D20 +54.1 (c 1.9, CH2Cl2).
13C NMR (100 MHz, C6D6): d = 20.9 (CH3), 74.0 (CH), 126.5 (2
CH), 127.1 (CH), 127.1 (CH), 128.4 (2 CH), 129.2 (2 CH), 130.4
(CH), 130.5 (CH), 132.9 (C), 133.8 (C), 137.3 (C), 141.8 (C).
MS (EI, 70 eV): m/z (%) = 258 (73) [M+], 243 (15), 139 (100), 119
(52), 105 (53).
HPLC (Chiralcel OD-H, 254 nm, heptane–i-PrOH, 90:10, 0.5 mL/
min): tR = 33.1 min (R), 36.9 min (S).
HRMS (EI): m/z calcd for C16H15ClO: 258.0811; found: 258.0810.
IR (CHCl3): 3358, 1467, 1440, 966, 753, 694 cm–1.
Anal. Calcd for C15H13BrO (258.08): C, 74.24; H, 5.84. Found: C,
74.25; H, 5.97.
1H NMR (400 MHz, CD2Cl2): d = 1.17 (br s, 1 H, OH), 5.67 (d,
J = 6.3 Hz, 1 H, CH), 6.27 (dd, J = 15.9, 6.3 Hz, 1 H, CH), 6.65 (d,
J = 15.9, 6.3 Hz, 1 H, CH), 7.05–7.32 (m, 7 H, HAr), 7.45–7.55 (m,
2 H, HAr).
13C NMR (100 MHz, CD2Cl2): d = 73.3 (CH), 122.3 (C), 126.0 (2
CH), 127.7 (CH), 127.8 (CH), 128.0 (CH), 128.5 (2 CH), 129.1
(CH), 129.9 (CH), 130.7 (CH), 132.7 (CH), 136.5 (C), 141.8 (C).
(1R,2E)-1,3-Bis(4-chlorophenyl)prop-2-en-1-ol (3i)22
Alcohol 3i was obtained from trans-boronic acid 1c (109 mg, 0.6
mmol, 2.4 equiv) and 4-chlorobenzaldehyde (2e; 35.1 mg, 0.25
mmol, 1 equiv). Column chromatography (silica gel, pentane–
Et2O–Et3N, 7:2.7:0.3) gave 3i as a pale yellow solid. The absolute
configuration of 3i was assigned assuming an identical reaction
pathway for the catalyzed product formation as for 3a.
MS (EI, 70 eV): m/z (%) = 288 (35), 209 (100) [M+], 184 (99), 182
(98), 104 (40), 91 (35).
20
Yield: 43.5 mg (79%); mp 82.0–85.7 °C; [a]D +15.4 (c 2.2,
HRMS (EI): m/z calcd for C15H13BrO: 288.0149; found: 288.0149.
CH2Cl2).
Anal. Calcd for C15H13BrO: C, 62.30; H, 4.53. Found: C, 62.35; H,
4,79.
HPLC (Chiralcel OD, 254 nm, heptane–i-PrOH, 90:10, 1.0 mL/
min): tR = 10.1 min (R), 11.7 min (S).
IR (capillary): 3383, 1489, 1089, 1013, 968, 822 cm–1.
(1S,2E)-1-Cyclohexyl-3-phenylprop-2-en-1-ol (3g)9
Alcohol 3g was obtained from trans-boronic acid 1a (88.7 mg, 0.6
mmol, 2.4 equiv) and cyclohexanecarbaldehyde (2g; 30 mL, 0.25
mmol, 1 equiv). Column chromatography (silica gel, pentane–
Et2O–Et3N, 7:2.7:0.3) gave 3g as a pale yellow solid. The absolute
configuration of 3g was assigned assuming an identical reaction
pathway for the catalyzed product formation as for 3a.
1H NMR (400 MHz, CD2Cl2): d = 2.20 (br s, 1 H, OH), 5.28 (d,
J = 6.3 Hz, 1 H, CH), 6.25 (dd, J = 15.9, 6.6 Hz, 1 H, CH), 6.57 (d,
J = 15.9 Hz, 1 H, CH), 7.20–7.33 (m, 8 H, HAr).
13C NMR (100 MHz, CD2Cl2): d = 74.2 (CH), 127.7 (2 CH), 127.8
(2 CH), 128.6 (2 CH), 128.6 (2 CH), 129.2 (CH), 132.0 (CH), 132.2
(C), 133.3 (C), 135.0 (C), 141.3 (C).
20
Yield: 30.0 mg (55%); mp 60.4–61.7 °C; [a]D +2.5 (c 1.6,
CH2Cl2).
MS (EI, 70 eV): m/z (%) = 278 (31) [M+], 243 (12), 139 (100), 125
(21).
HPLC (Chiralcel OD-H, 230 nm, heptane–i-PrOH, 90:10, 0.5 mL/
min): tR = 15.0 min (R), 21.3 min (S).
HRMS (EI): m/z calcd for C15H12Cl2O: 278.0265; found: 278.0264.
IR (KBr): 3925, 2851, 1493, 1448, 1011, 969, 752 cm–1.
(1R,2E)-3-(Chlorophenyl)-1-(pentamethylphenyl)prop-2-en-1-
ol (3j)
1H NMR (400 MHz, CD2Cl2): d = 0.89–1.25 (m, 5 H, HCy), 1.34–
1.45 (m, 1 H, HCy), 1.53–1.72 (m, 5 H, HCy/OH), 1.77–1.85 (m, 1 H,
CH), 3.90 (t, J = 7.1 Hz, 1 H, CH), 6.15 (dd, J = 15.9, 6.7 Hz, 1 H,
CH), 6.45 (d, J = 15.9 Hz, 1 H, CH), 7.11–7.17 (m, 1 H, HAr), 7.19–
7.26 (m, 2 H, HAr), 7.28–7.32 (m, 2 H, HAr).
13C NMR (100 MHz, C6D6): d = 26.2 (CH2), 26.3 (CH2), 26.7
(CH2), 28.7 (CH2), 29.0 (CH2), 44.1 (CH), 77.3 (CH), 126.3 (2 CH),
127.4 (CH), 128.5 (2 CH), 130.5 (CH), 131.6 (CH), 136.9 (C).
Alcohol 3j was obtained from trans-boronic acid 1c (109 mg, 0.6
mmol, 2.4 equiv) and pentamethylbenzaldehyde (2d; 44.0 mg, 0.25
mmol, 1 equiv). Column chromatography (silica gel, pentane–
Et2O–Et3N, 7:2.7:0.3) gave 3j as a pale yellow oil. The absolute
configuration of 3j was assigned assuming an identical reaction
pathway for the catalyzed product formation as for 3a.
Yield: 44.9 mg (63%); [a]D20 +5.52 (c 2.2, CH2Cl2).
MS (EI, 70 eV): m/z (%) = 216 (23) [M+], 133 (100), 115 (15), 91
(7).
HPLC (Chiralcel OD-H, 254 nm, heptane–i-PrOH, 90:10, 0.5 mL/
min): tR = 12.3 min (S), 14.5 min (R).
IR (KBr): 3398, 2925, 1489, 1456, 1011, 969 cm–1.
HRMS (EI): m/z calcd for C15H20O: 216.1514; found: 216.1514.
1H NMR (400 MHz, CD2Cl2): d = 1.11 (s, 6 H, 2 CH3), 2.13 (s, 1 H,
OH), 2.14 (s, 3 H, CH3), 2.23 (s, 6 H, 2 CH3), 5.89 (dd, J = 4.1, 1.9
Hz, 1 H, CH), 6.34 (dd, J = 15.9, 1.9 Hz, 1 H, CH), 6.47 (dd,
J = 15.9, 4.1 Hz, 1 H, CH), 7.13–7.23 (m, 4 H, CHAr).
13C NMR (100 MHz, CD2Cl2): d = 16.5 (2 CH3), 16.9 (CH3), 17.2
(2 CH3), 71.5 (CH), 127.5 (2 CH), 127.6 (CH), 128.5 (2 CH), 132.1
(2 C), 132.6 (C), 132.8 (CH), 133.2 (2 C), 134.4 (C), 135.8 (2 C).
(1R,2E)-1-(4-Chlorophenyl)-3-(p-tolyl)prop-2-en-1-ol (3h)21
Alcohol 3h was obtained from trans-boronic acid 1b (97.0 mg, 0.6
mmol, 2.4 equiv) and 4-chlorobenzaldehyde (2e; 35.1 mg, 0.25
mmol, 1 equiv). Column chromatography (silica gel, pentane–
Et2O–Et3N, 7:2.7:0.3) gave 3h as a pale yellow solid. The absolute
configuration of 3h was assigned assuming an identical reaction
pathway for the catalyzed product formation as for 3a.
20
Yield: 40.6 mg (62%); mp 56.1–58.5 °C; [a]D +11.8 (c 2.2,
MS (EI, 70 eV): m/z (%) = 314 (8) [M+], 175 (100), 147 (12).
CH2Cl2).
HRMS (EI): m/z calcd for C20H23ClO: 314.1437; found: 314.1437.
HPLC (Chiralcel OD-H, 254 nm, heptane–i-PrOH, 90:10, 0.7 mL/
min): tR = 18.0 min (R), 21.8 min (S).
IR (KBr): 3317, 1488, 1088, 1030, 1012, 968 cm–1.
1H NMR (400 MHz, C6D6): d = 1.27 (br s, 1 H, OH), 2.09 (s, 3 H,
CH3), 4.91 (d, J = 6.4 Hz, 1 H, CH), 6.17 (dd, J = 15.9, 6.7 Hz, 1 H,
CH), 6.45 (d, J = 15.9 Hz, 1 H, CH), 6.94 (d, J = 8.0 Hz, 2 H, HAr),
7.01–7.17 (m, 6 H, HAr).
(2E)-1-Phenyl-3-(p-tolyl)prop-2-en-1-ol (6b)
1H NMR (400 MHz, CD2Cl2): d = 2.29 (s, 3 H, CH3), 2.51 (br s, 1
H, OH), 5.29 (d, J = 6.7 Hz, 1 H, CH), 6.29 (dd, J = 15.8, 6.7 Hz, 1
H, CH), 6.59 (d, J = 15.8 Hz, 1 H, CH) 7.07–7.11 (m, 2 H, HAr),
7.22–7.41 (m, 7 H, HAr).
Synthesis 2006, No. 21, 3625–3630 © Thieme Stuttgart · New York

3630
F. Schmidt et al.
PAPER
13C NMR (100 MHz, CD2Cl2): d = 21. 3 (CH3), 75.3 (CH), 126.5 (2
CH), 126.6 (2 CH), 127.7 (CH), 128.7 (2 CH), 129.4 (2 CH), 130.3
(CH), 131.0 (CH), 134.0 (C), 137.9 (C), 143.4 (C).
(9) Tseng, S.-L.; Yang, T.-K. Tetrahedron: Asymmetry 2005,
16, 773.
(10) (a) Sprout, C. M.; Richmond, M. L.; Seto, C. T. J. Org.
Chem. 2005, 70, 7408. (b) Richmond, M. L.; Sprout, C. M.;
Seto, C. T. J. Org. Chem. 2005, 70, 8835.
(11) (a) Wipf, P.; Xu, W. Tetrahedron Lett. 1994, 35, 5197.
(b) Wipf, P.; Xu, W. Org. Synth. 1996, 74, 205. (c) Wipf,
P.; Ribe, S. J. Org. Chem. 1998, 63, 6454.
Acknowledgement
This work was supported by the Fonds der Chemischen Industrie
and the Deutsche Forschungsgemeinschaft (DFG) within the Colla-
borative Research Center (SFB) 380 ‘Asymmetric Synthesis by
Chemical and Biological Methods’. We thank N. Brendgen and S.
Grünebaum for experimental contributions and Dr. J. Runsink for
his advice in the isomer assignment as well as extensive NMR stu-
dies. J.R. acknowledges DaimlerChrysler for a scholarship.
(12) Schmidt, F.; Stemmler, R. T.; Rudolph, J.; Bolm, C. Chem.
Soc. Rev. 2006, 35, 454.
(13) (a) Bolm, C.; Rudolph, J. J. Am. Chem. Soc. 2002, 124,
14850. (b) Rudolph, J.; Schmidt, F.; Bolm, C. Synthesis
2005, 840.
(14) (a) Rudolph, J.; Hermanns, N.; Bolm, C. J. Org. Chem.
2004, 69, 3997. (b) Rudolph, J.; Lormann, M.; Bolm, C.;
Dahmen, S. Adv. Synth. Catal. 2005, 347, 1361.
(15) Duan, H.-F.; Xie, J.-H.; Shi, W.-J.; Zhang, Q.; Zhou, Q.-L.
Org. Lett. 2006, 8, 1479.
(16) In these studies, the NMR solvent forms a hydrogen bond to
the hydroxy group of the product. The thus formed p-
complex (see Figure 2) and the additional ring current effect
lead to a shift of the NMR signals to higher ppm values.
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Figure 2
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Synthesis 2006, No. 21, 3625–3630 © Thieme Stuttgart · New York