A protecting-group-free route to chiral BINOL-phosphoric acids

Article abstract of DOI:10.1002/ejoc.201100328

A two-step, protecting group-free route for the synthesis of 3,3′-disubstituted and 6,6′-disubstituted chiral BINOL-phosphoric acids has been realized starting from commercially available brominated BINOLs. This synthesis relies on the direct Suzuki coupl

Full text of DOI:10.1002/ejoc.201100328

FULL PAPER
DOI: 10.1002/ejoc.201100328
A Protecting-Group-Free Route to Chiral BINOL–Phosphoric Acids
Baojian Li[a] and Pauline Chiu*[a]
Keywords: Phosphorus / Cross-coupling / Asymmetric synthesis / Protecting groups
A two-step, protecting group-free route for the synthesis of
3,3Ј-disubstituted and 6,6Ј-disubstituted chiral BINOL–phos-
phoric acids has been realized starting from commercially
available brominated BINOLs. This synthesis relies on the
direct Suzuki coupling of brominated BINOL phosphoric ac-
ids. This synthetic strategy is more efficient compared to pre-
vious circuitous strategies involving protections and depro-
tections, and the process is higher yielding relative to the
alternative two-step synthesis involving Suzuki coupling of
the BINOL.
Introduction
cycloaddition cascade reaction.[6,7] The rare-earth com-
plexes of BNP and 6,6Ј-disubstituted BNP were studied as
catalysts for enantioselective Diels–Alder reactions.[8] The
sodium salts of BNP derivatives have been investigated for
the catalysis of the enantioselective Strecker reaction of ket-
imines.[9] More recently, asymmetric counteranion-directed
catalysis (ACDC) has used chiral BNP in reactions medi-
ated by gold, silver, and manganese complexes to effect
enantioselectivity.[10]
BINOL–phosphoric acids (BNPHs) have emerged as an
important and privileged family of compounds in asymmet-
ric catalysis. Pioneering research by Akiyama[1] and Ter-
ada[2] have introduced 3,3Ј-disubstituted BNPHs as chiral
Brønsted acid organocatalysts that mediate a spectacularly
wide spectrum of carbon–carbon bond-forming reactions.[3]
A wide variety of 3,3Ј-disubstituted BNPH derivatives has
been designed and synthesized for the catalysis of a range
of reactions.
While the reactions employing BNPH and BNP deriva-
In addition, BINOL–phosphates (BNPs) have been used tives have seen an exponential growth, the strategies for
successfully as chiral ligands of metal complexes to mediate their synthesis have remained consistent throughout the
enantioselective reactions. For example, Pirrung[4] and years. Scheme 1 shows the typical route for the synthesis of
McKervey[5] employed Rh2(BNP)4 for reactions of diazo- 3,3Ј-disubstituted BNPH 7 starting from BINOL (1). Pro-
carbonyl compounds in C–H insertions, cyclopropanations, tection of the hydroxy groups, often as ethers, is followed
and aziridinations. Subsequently, extensive work by Hodg- by ortho-lithiation to functionalize the 3- and 3Ј-positions.
son investigated both 3,3Ј- and 6,6Ј-disubstituted BNP for The lithiated BINOL derivative is then parlayed to either
the enantioselective rhodium-induced carbene cyclization electrophile 3 through halogenation or nucleophile 4
Scheme 1. Typical synthesis of chiral 3,3Ј-BNPH 7.
through borylation. Substituents are then added by Suzuki–
[a] Department of Chemistry, The University of Hong Kong,
Pokfulam Road, Hong Kong
Miyaura coupling[11] or Kumada reactions.[11e,11k,12] The
synthesis is completed through deprotection of the ethers
and reaction with phosphorus oxychloride to generate the
Fax: +852-2857-1586
E-mail: pchiu@hku.hk
3932
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3932–3937

A Protecting-Group-Free Route to Chiral BINOL–Phosphoric Acids
phosphoric acid functionality. A very similar sequence of pling was complete at a comparable temperature in re-
reactions involving protections and deprotections is utilized fluxing DME to give an 81% yield of 12a (Table 1, En-
for the synthesis of 6,6Ј-disubstituted BNPHs 12, starting try 5). The use of water in the reaction was deleterious to
from commercially available 6,6Ј-dibromo-BINOL (8) as the rate of conversion (Table 1, Entries 6 and 7).
substrate (Scheme 2).[6,13]
Scheme 3. Synthesis of BNPHs 13 and 14.
Scheme 2. Typical synthesis of chiral 6,6Ј-BNPH 12.
Herein we describe a straight-forward, protecting-group-
free route for the synthesis of this important family of com-
pounds, which employs direct Suzuki coupling in the pres-
ence of the phosphoric acid functionality.
Table 1. Optimization of Suzuki coupling of 13.
Results and Discussion
In the course of our work on the application of the rho-
dium carbene cyclization–cycloaddition cascade reaction to
synthesis,[14] the rhodium complex of 12a as a chiral catalyst
was required. The literature preparation of 12a (Scheme 2)
from 3a involved multiple steps; moreover, Kumada cou-
pling with dodecylmagnesium bromide provided 10 with
variable yields.[6]
Our synthesis is based on the idea that the Suzuki cou-
pling of brominated derivatives of BNPH would straight-
forwardly yield the corresponding substituted derivatives
without necessitating the protection of any of the interme-
diates. This less circuitous route to 7 or 12 has not been
reported in the literature and requires the Suzuki coupling
to proceed successfully in the presence of the phosphoric
acid or phosphate functionality. It is worthwhile to note
that, while there have been some examples of Suzuki cou-
pling reactions of alkyl phosphate, diphosphate, and tri-
phosphate derivatives, proceeding generally in moderate
yields,[15] the Suzuki coupling of aryl phosphates or phos-
phoric acid diesters have not been reported.[16]
Entry
Base
(equiv.)
Solvent
T
[°C]
t
[h]
Yield
[%]
1
2
3
4
5
6
7
NaOH (5)
K2CO3 (9)
K2CO3 (9)
K2CO3 (9)
K2CO3 (9)
1,4-dioxane
THF
101 (reflux) 24
dec.
43
39
dec.
81
N.R.
N.R.
66 (reflux)
66 (reflux)
90
85 (reflux)
reflux
60
60
24
60
16
24
THF[a]
DMF
DME
K2CO3 (5) THF/H2O (10:1)
K2CO3 (9) DME/H2O (10:1)[b]
reflux
[a] Ag2O (3 equiv.). [b] Pd(PPh3)4 used as catalyst.
Thus, 12a was synthesized efficiently in two high-yielding
steps from 3a. Using the optimized conditions, we exam-
ined the Suzuki coupling of both 13 and 14 (Scheme 3) with
various boronic acids (Table 2). Phenylboronic acid reacted
Table 2. Suzuki coupling of brominated BNPHs 13 and 14.
We first explored the Suzuki coupling for the synthesis
of 6,6Ј-disubstituted BNPH 12a. BINOL 3a is readily con-
verted into corresponding BNPH 13 according to a litera-
ture procedure (Scheme 3).[11k] The optimizations of the Su-
zuki coupling of 13 are shown in Table 1. Initially, Suzuki
coupling using the commercially available PdCl2(dppf)·
CH2Cl2 complex (15) was tried, but it was not effective and
resulted in decomposition of 13 (Table 1, Entry 1).[17] Upon
changing to a weaker base (K2CO3), the reaction proceeded
but was incomplete even after 60 h of refluxing in THF
(Table 1, Entry 2). The application of Falck’s conditions by
the addition of Ag2O failed to improve the reaction in this
case (Table 1, Entry 3).[18] We then examined the reaction
at higher temperatures in other solvents. While the use of
Entry X1 X2
R1
R2
t
[h]
Yield
[%]
[α]D20
1
2
3
4
Br
Br
H
H
H
H
H
H
Br
Br
Br
Br
n-C12H25
H
H
Ph
60 12a, 81
48 12b, 92
48 7a, 93
48 7b, 95
48 7b, 68[b]
96 7c, 61
–285.1
–278.8
–328.5
–343.1
n.d.
Ph
H
H
H
H
4-(tBu)C6H4-
4-(tBu)C6H4-
mesityl
5[a]
6
–155.9
[a] Pd(PPh3)4 used as catalyst. [b] Monoarylated BNPH (27%
DMF resulted in the decomposition of 13, the Suzuki cou- yield) also obtained.
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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3933

B. Li, P. Chiu
FULL PAPER
more readily under similar conditions to generate a very Table 4. Suzuki coupling of brominated BINOLs 3a and 8.
good yield of 12b (Table 2, Entry 2). At the sterically more
congested 3,3Ј-positions, aryl boronic acids still underwent
Suzuki coupling readily in excellent yields (Table 2, En-
tries 3 and 4). However, for a hindered boronic acid such
as mesityl, the coupling reaction was less efficient (Table 2,
Entry 6). The use of Pd(PPh3)4 as catalyst was less effective
(Table 2, Entry 5).
The BNPHs were reduced by using LiAlH4 to afford the
Entry BINOL
t
[h]
R1
R2 Yield of 16 Yield of 17
ee
[%]
corresponding BINOLs in high yield (Table 3).[19] No race-
mization occurred during the synthesis or the reduction, as
shown by the enantiomeric excess values of the BINOLs
thus obtained, determined by chiral HPLC (Table 3).
[%]
16a, 23
16a, 45
[%]
1
2
3
3a
3a
8
42
84
48
C12H25
C12H25
H
H
H
17a, 39
trace
98
98
94
Ph 16c, 79[a]
trace
[a] 18a (9% yield) also obtained.
Table 3. Reduction of BNPHs to BINOLs.
Conclusions
We have shown that chiral BINOL phosphoric acids
could be accessed by a protecting-group-free route from
brominated BINOLs 3a and 8, both of which are commer-
cially available, in two steps through the direct Suzuki cou-
pling of the corresponding BNPH. No loss of ee was ob-
served. This synthesis is much more efficient compared to
previous strategies involving protections and deprotections,
cutting the number of steps required by half, and the pro-
cedure is higher yielding relative to the alternative two-step
synthesis involving the direct Suzuki coupling of the BI-
NOL. The protecting-group-free strategy reported herein
should be useful for the synthesis of chiral, substituted
BNPHs owing to the growing importance, applications, and
versatility of this family of compounds, where a large
number of derivatives are invariably needed in each screen-
ing exercise.
Entry Substrate
R1
R2
t
[h]
Yield
[%]
[α]D20
ee
[%]
1
2
3
12a
12b
7
n-C12H25
H
H
Ph
4
4
8
16a, 93 –44.0
16b, 92 –243.4
16c, 91 +68.7
Ͼ99
Ͼ99
Ͼ99
Ph
H
We then investigated whether the two operations could
be reversed, that is, to subject BINOLs 3a and 8 to Suzuki
coupling followed by phosphate ester formation. We were
cautioned to the known racemization of chiral BINOLs, oc-
curring especially with heating under acidic or basic condi-
tions.[20] Having a similar aim of devising a synthesis of
chiral BNP without the use of protecting groups, Bartoszek
Experimental Section
et al. recently reported the direct Suzuki coupling of 3,3Ј- General Methods: All anhydrous reactions were performed in oven-
dried round-bottomed flasks under a positive pressure of dry ar-
gon. Air- and moisture-sensitive compounds were introduced by
syringes or cannulae using standard inert atmosphere techniques.
Reactions were monitored by thin-layer chromatography (TLC)
using E. Merck silica gel plates, Kieselgel 60 F254 with a 0.2-mm
thickness. Components were visualized by illumination with short-
wavelength ultraviolet light and/or staining. Flash column
chromatography was performed with E. Merck silica gel 60 (230–
400 mesh ASTM) or Sigma–Aldrich alumina (activated Al2O3,
neutral, Brockmann I). Solvents and chemicals were purified ac-
dibromo–H8–BINOL, which was followed by esterification
with phosphoryl chloride to yield the substituted BNPH.[21]
This Suzuki coupling of the BINOLs was successfully car-
ried out at ambient temperature using Pd(OAc)2 and
Beller’s ligand, PAd2Bu.[22] Under our present conditions,
although the Suzuki coupling of BINOL 3a with an alkyl-
boronic acid proceeded, the reaction was more sluggish,
and much monosubstituted product 17a was obtained
(Table 4, Entry 1). Attempts to drive the reaction to com-
pletion with prolonged heating resulted in a significantly cording to standard procedures. All solvents used for reactions
were distilled or dried by passing through drying columns. Tetra-
hydrofuran, 1,4-dioxane, DME, pyridine, and DMF (under re-
duced pressure) were additionally distilled from CaH2. BNPHs 13
and 14 were prepared according to literature procedures.[11k] 1H
and 13C NMR spectra were recorded in deuteriochloroform
(CDCl3) or a mixture of deuteriochloroform with [D4]MeOH
(CD3OD), with tetramethylsilane (TMS) as an internal standard
at ambient temperature with a Bruker Avance 400 spectrometer,
lower yield of the desired product (Table 4, Entry 2). With
more reactive phenylboronic acid, Suzuki coupling of 8 oc-
curred more readily but nevertheless with a diminished
yield compared to the reaction of 14 (Table 4, Entry 3). No-
tably, debromination is a side reaction under these condi-
tions, and a slight decrease in the enantiomeric excess of
16c was observed. In contrast, even with prolonged heating,
racemization by rotation about the C1–C1Ј is obviated in
the Suzuki coupling of 14 bearing the phosphoric acid
tether.[20]
1
operating at 400 MHz for H, 100 MHz for 13C, and 162 MHz for
31P. All spectra were calibrated at δ = 0.00 ppm for 1H spectra
(TMS) and at 77.16 ppm for 13C spectra (CDCl3). Splitting pat-
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Eur. J. Org. Chem. 2011, 3932–3937

A Protecting-Group-Free Route to Chiral BINOL–Phosphoric Acids
terns are designated as follows: s = singlet, d = doublet, t = triplet,
q = quartet, m = multiplet, br. = broad. IR absorption spectra
were recorded as solutions in CH2Cl2 with a Bio-Rad FTS 165
spectrometer from 4000 to 400 cm–1. Electron impact (EI) mass
spectrometry was recorded with a Finnigan MAT 95 mass spec-
trometer at low and high resolutions, with accurate mass reported
for the molecular ion [M]+ or the next largest fragment thereof.
Optical rotations were recorded with a Perkin–Elmer 343 Polarime-
ter. Analytical HPLC was carried out with a Waters 1525 Binary
HPLC Pump system, equipped with a Waters 2707 autosampler
operating using Breeze2 software and a Waters 2489 variable wave-
length UV/Vis detector.
134.9, 133.9, 132.0, 130.9, 130.6, 129.4, 128.0, 126.7, 125.9, 125.2,
124.6, 122.9, 34.2, 31.0 ppm. IR (CH Cl ): ν = 3024, 2962, 2360,
˜
2
2
1519, 1427, 1226, 1203, 1111, 972, 841, 795 cm–1. MS (FAB+): m/z
= 652.2, 651.2 [M + K]+, 635.2 [M + Na]+, 612.2 [M]+.
(R)-7c:[11j] Yield: 61%; white solid. [α]2D0 = –155.9 (c = 0.80, CHCl3)
{ref.[11j] [α]2D6 = –93.2 (c = 1.08, CHCl3)}. 1H NMR (400 MHz,
CD3OD/CDCl3 = 1:3): δ = 7.91 (d, J = 8.2 Hz, 2 H), 7.71 (br. s, 2
H), 7.48–7.44 (m, 2 H), 7.31–7.26 (m, 4 H), 6.89 (s, 2 H), 6.81 (s,
2 H), 2.28 (s, 6 H), 2.15 (s, 6 H), 2.00 (s, 6 H) ppm. 13C NMR
(100 MHz, CD3OD/CDCl3 = 1:3): δ = 146.7, 137.0, 136.9, 136.2,
134.4, 132.8, 132.1, 130.8, 130.7, 127.8, 127.0, 126.5, 125.8, 124.8,
122.3, 20.6, 20.5, 19.6 ppm. 31P NMR (162 MHz, CD3OD/CDCl3
= 1:3): δ = 4.1 ppm.
General Experimental Procedure for Suzuki Coupling Reactions: A
mixture of 13 or 14 (0.1 mmol), aryl- or alkylboronic acid
(0.395 mmol), 15 (0.010 mmol), and K2CO3 (0.85 mmol) in dry
DME (6 mL) was heated at reflux under an atmosphere of argon
for 48 to 60 h, while the reaction progress was monitored by TLC.
After the reaction was complete, it was cooled to room tempera-
ture. The reaction mixture was adjusted to pH 3 by the addition of
2 m HCl, and it was then filtered and concentrated in vacuo. The
residue was dissolved in acetone (or hexane, in the case of 12a) and
filtered through a pad of Celite. After removing the volatiles in
vacuo, the residue was purified firstly by flash column chromatog-
raphy using a short alumina column (20% MeOH in CH2Cl2/20%
AcOH in MeOH), and secondly by flash chromatography on silica
gel (5–35% MeOH in CH2Cl2) to give 7 or 12 as product.
General Experimental Procedure for the Reduction of Chiral BNPH:
A solution of chiral BNPH (0.06 mmol) in DME (0.8 mL) was
transferred carefully to a suspension of LiAIH4 (0.36 mmol) in
DME (0.8 mL) at 0 °C. The reaction was stirred and warmed to
room temperature. The reaction progress was monitored by TLC.
When the reaction was complete, the excess amount of LiAIH4 was
quenched by the dropwise addition of H2O at 0 °C, and the acidity
of the solution was adjusted to pH 5–6 by the addition of 2 m HCl.
The resultant cloudy mixture was suspended in acetone (10 mL)
and filtered through filter paper. After concentrating under reduced
pressure, the crude product was dissolved in EtOAc (12 mL) and
washed by brine (5 mL). The organic components were dried with
anhydrous MgSO4, and the volatiles were removed in vacuo. The
residue was purified by flash column chromatography using silica
gel (5–20% EtOAc in hexane) to give 16.
(R)-12a:[7b] Yield: 81%; viscous colorless oil. [α]2D0 = –285.1 (c =
1
0.70, CHCl3) {ref.[7b] [α]2D0 = –266.2 (c = 0.7, CHCl3)}. H NMR
(400 MHz, CD3OD/CDCl3 = 1:1): δ = 7.88 (d, J = 8.6 Hz, 2 H),
7.67 (s, 2 H), 7.49 (d, J = 8.4 Hz, 2 H), 7.29 (d, J = 8.7 Hz, 2 H),
7.12 (d, J = 8.1 Hz, 2 H), 2.75 (t, J = 7.6 Hz, 4 H), 1.74–1.66 (m,
4 H), 1.40–1.27 (m, 36 H), 0.88 (t, J = 6.7 Hz, 6 H) ppm. 13C NMR
(100 MHz, CD3OD/CDCl3 = 1:1): δ = 147.8, 139.1, 131.1, 130.5,
129.3, 127.3, 126.5, 126.2, 121.7, 121.0, 35.3, 31.5, 30.8, 29.2, 29.2,
29.2, 29.1, 28.9, 22.2, 13.4 ppm. 31P NMR (162 MHz, CD3OD/
CDCl3 = 1:1): δ = 4.2 ppm.
(R)-16a:[7b] Yield: 93%; viscous colorless oil. [α]D = –44.0 (c = 0.80,
CHCl3) {ref.[7b] [α]2D0 = –51.4 (c = 1.0, CHCl3)}. 1H NMR
(400 MHz, CDCl3): δ = 7.90 (d, J = 8.9 Hz, 2 H), 7.66 (br. s, 2 H),
7.34 (d, J = 8.9 Hz, 2 H), 7.16 (dd, J = 8.6, 1.6 Hz, 2 H), 7.08 (d,
J = 8.6 Hz, 2 H), 4.98 (br. s, 2 H), 2.71 (t, J = 7.7 Hz, 4 H), 1.68–
1.61 (m, 4 H), 1.39–1.23 (m, 36 H), 0.87 (t, J = 6.8 Hz, 6 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 152.2, 138.8, 131.8, 131.0, 129.8,
129.2, 127.0, 124.3, 117.8, 111.0, 36.0, 32.1, 31.6, 29.8, 29.8, 29.8,
29.7, 29.5, 29.5, 22.8, 14.3 ppm. HPLC (Chiralcel OD, hexane/2-
propanol = 48:2, 0.5 mLmin–1): Ͼ99%ee.
(R)-12b:[10] Yield: 92%; white solid. [α]2D0 = –278.8 (c = 0.50,
CH2Cl2). 1H NMR (400 MHz, CD3OD/CDCl3 = 1:2): δ = 8.10 (br.
s, 2 H), 7.95 (d, J = 8.5 Hz, 2 H), 7.71–7.67 (m, 4 H), 7.63 (d, J =
8.7 Hz, 2 H), 7.57 (dd, J = 8.7, 1.3 Hz, 2 H), 7.50 (d, J = 8.9 Hz,
2 H), 7.47–7.42 (m, 4 H), 7.38–7.33 (m, 2 H) ppm. 13C NMR
(100 MHz, CD3OD/CDCl3 = 1:2): δ = 148.8, 148.7, 140.2, 137.4,
131.4, 130.4, 128.7, 127.4, 127.2, 126.9, 125.7, 125.6, 122.0,
121.8 ppm. 31P NMR (162 MHz, CD3OD/CDCl3 = 1:2): δ =
(R)-16b:[24] Yield: 92%; white solid. [α]2D0 = –243.4 (c = 0.65,
1
CHCl3). H NMR (400 MHz, CDCl3): δ = 8.11 (d, J = 1.8 Hz, 2
H), 8.05 (d, J = 8.9 Hz, 2 H), 7.69–7.65 (m, 4 H), 7.60 (dd, J =
8.7, 1.9 Hz, 2 H), 7.49–7.42 (m, 6 H), 7.38–7.34 (m, 2 H), 7.27 (d,
J = 8.7 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.0,
141.0, 137.1, 132.7, 131.9, 129.9, 129.0, 127.4, 127.4, 127.4, 126.5,
2.6 ppm. IR (CH Cl ): ν = 3055, 2360, 1265, 1149, 768, 710 cm–1.
˜
2
2
MS (FAB+): m/z = 523.4 [M + Na]+, 501.1 [M + H]+.
124.9, 118.4, 110.9 ppm. IR (CH Cl ): ν = 3525, 3055, 2361, 1597,
˜
2
2
1497, 1257, 1149, 702 cm–1. HRMS (EI+): calcd. for C32H22O2
[M]+ 438.1620; found 438.1610. HPLC (Chiralpak IC-3, hexane/2-
propanol = 90:10, 1.0 mLmin–1): Ͼ99% ee.
(R)-7a:[11j] Because the monophenylated product was inseparable
from 7a, to ensure complete reaction, extra PhB(OH)2 (2 equiv.),
15 (0.05 equiv.), and K2CO3 (4 equiv.) were used. Yield: 93%; white
solid. [α]2D0 = –328.5 (c = 1.02, CHCl3) {ref.[11j] [α]2D7 = –283.5 (c =
0.99, CHCl3)}. 1H NMR (400 MHz, CD3OD/CDCl3 = 1:3): δ =
7.98 (br. s, 2 H), 7.95 (d, J = 8.2 Hz, 2 H), 7.75–7.72 (m, 4 H),
7.47–7.42 (m, 2 H), 7.35–7.31 (m, 4 H), 7.30–7.22 (m, 6 H) ppm.
13C NMR (100 MHz, CD3OD/CDCl3 = 1:3): δ = 146.6, 146.5,
138.5, 134.8, 132.7, 131.6, 131.4, 130.5, 128.7, 128.4, 127.6, 127.3,
(R)-16c:[12d] Yield: 91%; white solid. [α]2D0 = +69.7 (c = 0.98,
CHCl3) {ref.[12d] [α]D = +69.1 (c = 1.00, CHCl3)}. 1H NMR
(400 MHz, CDCl3): δ = 8.02 (br. s, 2 H), 7.91 (d, J = 7.9 Hz, 2 H),
7.74–7.71 (m, 4 H), 7.50–7.46 (m, 4 H), 7.42–7.36 (m, 4 H), 7.33–
7.29 (m, 2 H), 7.24–7.22 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 150.3, 137.6, 133.1, 131.5, 130.8, 129.7, 129.6, 128.6,
128.6, 127.9, 127.5, 124.5, 124.4, 112.5 ppm. HPLC (Chiralpak IC-
3, hexane/2-propanol = 90:10, 1.0 mLmin–1): Ͼ99% ee.
126.7, 125.9, 123.6 ppm. 31P NMR (162 MHz, CD3OD/CDCl3
=
1:3): δ = 2.3 ppm.
1
(R)-7b:[23] Yield: 95%; white solid. [α]2D0 = –343.1 (c = 1.06, CHCl3).
1H NMR (400 MHz, CD3OD/CDCl3 = 1:3): δ = 7.97 (br. s, 2 H),
7.93 (d, J = 8.2 Hz, 2 H), 7.68–7.65 (m, 4 H), 7.46–7.42 (m, 2 H),
7.36–7.33 (m, 4 H), 7.29–7.24 (m, 4 H), 1.27 (s, 18 H) ppm. 13C
NMR (100 MHz, CD3OD/CDCl3 = 1:3): δ = 149.8, 145.9, 145.8,
(R)-17a: Viscous colorless oil. [α]2D0 = –79.5 (c = 0.61, CH2Cl2). H
NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 2.0 Hz, 1 H), 7.91 (d,
J = 8.9 Hz, 1 H), 7.87 (d, J = 9.0 Hz, 1 H), 7.66 (br. s, 1 H), 7.40
(d, J = 9.0 Hz, 1 H), 7.37–7.32 (m, 2 H), 7.17 (dd, J = 8.6, 1.7 Hz,
1 H), 7.04–6.99 (m, 2 H), 5.11 (s, 1 H), 4.92 (s, 1 H), 2.71 (t, J =
Eur. J. Org. Chem. 2011, 3932–3937
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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B. Li, P. Chiu
FULL PAPER
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7.8 Hz, 2 H), 1.68–1.63 (m, 2 H), 1.32–1.24 (m, 18 H), 0.87 (t, J =
6.8 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.5, 153.1,
152.2, 139.0, 132.2, 131.7, 131.3, 130.8, 130.7, 130.5, 129.8, 129.4,
127.1, 126.3, 124.0, 119.1, 118.0, 117.8, 111.7, 110.2, 35.9, 32.1,
31.6, 29.8, 29.8, 29.7, 29.7, 29.5, 29.5, 22.8, 14.3 ppm. IR (KBr): ν
˜
= 3526, 2932, 2854, 1597, 1504, 1358, 1265, 1180, 895, 748 cm–1.
HRMS: calcd. for C32H37O2Br [M]+ 532.1977; found 532.1971.
(R)-18a:[25] White solid. [α]2D0 = +115.4 (c = 0.14, CH2Cl2) {ref.[25]
1
[α]3D0.5 = +132.0 (c = 1.18, CHCl3)}. H NMR (400 MHz, CDCl3):
[11]
δ = 8.03 (br. s, 1 H), 7.99 (d, J = 8.9 Hz, 1 H), 7.94–7.89 (m, 2 H),
7.74–7.72 (m, 2 H), 7.52–7.47 (m, 2 H), 7.43–7.35 (m, 4 H), 7.34–
7.29 (m, 2 H), 7.23 (d, J = 8.3 Hz, 1 H), 7.16 (d, J = 8.4 Hz, 1 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 152.8, 150.4, 137.5, 133.6,
133.1, 131.6, 131.5, 130.8, 129.7, 129.6, 128.6, 128.6, 128.6, 128.0,
127.6, 124.5, 124.4, 124.3, 124.1, 117.9, 111.9, 111.6 ppm. HRMS
(EI+): calcd. for C26H18O2 [M]+ 362.1307; found 362.1297.
Acknowledgments
This work was supported by the University of Hong Kong and by
the Research Grants Council of the Hong Kong SAR, P. R. China
(General Research Fund 7081/07P, Collaborative Research Fund
HKU1/CRF/08).
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Received: March 8, 2011
Published Online: May 20, 2011
Eur. J. Org. Chem. 2011, 3932–3937
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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