Development and scope of the phenolic aldol reaction of 2-formylpyridines

Article abstract of DOI:10.1055/s-0029-1217325

2-Formylpyridines have been shown to be suitable electrophiles for the magnesium-promoted phenolic aldol reaction. Exceptionally mild reaction conditions have been developed and a brief survey of the reaction scope has been conducted. This process gives straightforward access to a range of functionalised 2-hydroxyphenyl-2-pyridylmethanols and 2-hydroxyphenyl-2- pyridylmethanes via their subsequent reduction. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217325

LETTER
1609
Development and Scope of the Phenolic Aldol Reaction of 2-Formylpyridines
Phenolic
A
ldol Reactio
a
nof 2-Form
t
ylpyri
t
dines hew Whiting,* Mark C. Wilkinson, Kathy Harwood1
Synthetic Chemistry, Chemical Development, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK
Fax +44(1438)764869; E-mail: matthew.p.whiting@gsk.com
Received 9 January 2009
plex.5 Phenolic aldol-type reaction with aldehydes or ke-
Abstract: 2-Formylpyridines have been shown to be suitable elec-
tones generally occurs under quite forcing conditions,
initially providing ortho-hydroxyalkylated products,
trophiles for the magnesium-promoted phenolic aldol reaction. Ex-
ceptionally mild reaction conditions have been developed and a
which then often react further under the reaction condi-
brief survey of the reaction scope has been conducted. This process
gives straightforward access to a range of functionalised 2-hydroxy- tions to produce a variety of products dependent upon the
nature of the reaction partners.4,6 A number of aldehydic
and ketonic compounds containing a-coordinating func-
tionalities, including a-alkoxy aldehydes,3b,d suitably pro-
tected a-amino aldehydes,3b,c,g,h glyoxal,3a and isatins3f
have been shown to undergo the corresponding reaction
under much milder conditions enabling selective forma-
phenyl-2-pyridylmethanols
and
2-hydroxyphenyl-2-pyridyl-
methanes via their subsequent reduction.
Key words: phenolic aldol reaction, arylation, magnesium phenox-
ides, 2-formylpyridines, 2-hydroxyphenyl-2-pyridylmethanols
A cheap and scalable synthesis of diarylmethane 1a or 1b tion of the initial ortho-hydroxyalkylated phenol products
was required as part of a program towards the develop- (Scheme 2).
ment of novel EP1 antagonists.2 Initial work revealed that
a direct Friedel–Crafts alkylation could be accomplished,
OMgBr
OH OH
O
XR4
however, the electron-deficient nature of both coupling
partners necessitated the use of extreme conditions (a melt
consisting of 4 equiv AlCl3 at 180 °C for 6 h). These con-
ditions were not considered suitable for further scale-up,
leading us to investigate alternative options, including the
phenolic aldol reaction3 of 2-formylpyridine (4a) with
4-chlorophenol (2a), followed by reduction of the initially
formed diarylmethanol to the desired diarylmethane 1a
(Scheme 1).
XR4
R2
R2
+
R3
R3
R1
R1, R2, R3 = various
XR4 = O-alkyl, N-Boc or =O
R1
Scheme 2 Phenolic aldol reaction of magnesium phenoxides
We postulated that the pyridyl nitrogen of 2-formyl-
pyridines could act as a suitable a-coordinating substitu-
ent, thereby facilitating the desired reaction. The only
example we were able to find in the literature was the re-
action of 2-methylphenoxymagnesium bromide with 2-
formylpyridine itself. This reaction was said to proceed in
only 8% yield, though the precise reaction conditions
were not given.7
OH
OH
O
O
AlCl3 (4 equiv)
180 °C
N
N
OR
+
OH
Cl
70%
Cl
2a
Cl
3
1a (R = Et), 1b (R = H)
Given this limited precedent we were pleased to find that
4-chlorophenoxymagnesium bromide, generated by addi-
tion of one equivalent of EtMgBr in Et2O to a solution of
4-chlorophenol in CH2Cl2, underwent rapid phenolic al-
dol reaction upon addition of aldehyde 4a at room temper-
ature to give 50% conversion to the desired
diarylmethanol 5a (Table 1, entry 1). Use of 2.2 equiva-
lents of the magnesium phenoxide enabled the reaction to
progress to completion, presumably as one equivalent is
required to deprotonate the relatively acidic product
(Table 1, entry 2). Use of a 1 M MTBE solution of the
Grignard reagent8 still gave high conversion albeit at a
slightly reduced rate (Table 1, entry 3), though using a 1
M THF solution gave a much reduced reaction rate and
lower product formation due to competing side reactions
(Table 1, entry 4). Use of EtMgCl (Table 1, entry 5) gave
identical conversion compared to the bromide. A number
of metal alkoxide bases gave only low conversion to prod-
OH
O
O
1) phenolic aldol
2) benzylic reduction
N
+
OEt
Cl
2a
4a
Scheme 1 Friedel–Crafts and proposed phenolic aldol–reduction
route to diarylmethanes 1a and 1b
Magnesium phenoxides are known to undergo selective
reaction at the ortho position with a wide range of electro-
philes to provide a variety of ortho-substituted phenol
derivatives,4 presumably via an initial coordination com-
SYNLETT 2009, No. 10, pp 1609–1613
Advanced online publication: 02.06.2009
DOI: 10.1055/s-0029-1217325; Art ID: D01409ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
0
9

1610
M. Whiting et al.
LETTER
uct (Table 1, entries 6–9). Importantly, generation of the
magnesium phenoxide using Et3N in the presence of
MgCl2 also gave efficient product formation; in the ab-
sence of MgCl2 no reaction was observed (Table 1, entries
10 and 11).
OH
O
Et3N, MgCl2
N
CO2Et
9
+
CH2Cl2, r.t., 16 h
Cl
2a
4a
OH OH
OH
Table 1 Phenolic Aldol Reaction Using Various Basesa
N
CO2Et
+
N
CO2Et
OH
O
OH OH
N
CO2Et
base, CH2Cl2
r.t.
N
CO2Et
Cl
5a
7
+
OH
O
4a
HO2C
N
CO2Et
Cl
2a
N
CO2Et
Cl
5a
+
+
Entry
Base
Time (h)
Conversion to 5a
8
6
(%)b
Cl
Scheme 3 Byproducts arising from the Et3N/MgCl2 process
1c
2
EtMgBrd
EtMgBrd
EtMgBre
EtMgBrf
EtMgClg
Mg(OEt)2
Al(OEt)3
Ti(Oi-Pr)4
Ca(Oi-Pr)2
Et3N/MgCl2
Et3N
2
1
50
98 (95)
Ketone 6 is formed by magnesium promoted Oppenauer
oxidation of the initial product using the starting aldehyde
as the oxidant, concomitantly generating alcohol 7. Acid
8 and alcohol 7 are also generated by a mild MgCl2/Et3N
promoted Cannizzarro-type disproportionation.10 To try
and improve the reaction selectivity we investigated use
of a range of alternative bases (Table 2).
3
2
97
62
97
14
8
4
16
2
5
6
16
16
16
16
16
16
7
Table 2 MgCl2-Promoted Phenolic Aldol Reaction Base Screena
8
4
OH
OH OH
O
MgCl2, base,
CO2Et CH2Cl2
N
CO2Et
9
8
N
+
r.t., 16 h
10
11
68
0
Cl
2a
Cl
5a
4a
a 2a (2.5 equiv) and base (2.2 equiv) were stirred in CH2Cl2 for 30
min, 4a (1 equiv) was then added as a solution in CH2Cl2.
b Determined by LC-UV analysis; isolated yield after chromatogra-
phy is given in parentheses.
Entry
1
Base
Et3N
Conversion to 5a (%)b
67
27
20
67
78
72
62
64
80
0
c 1 equiv of 2a and base used.
2
K2CO3
d 3 M soln in Et2O.
e 1 M soln in MTBE.
3
NaHCO3
DIPEA
f 1 M soln in THF.
g 2 M soln in Et2O.
4
6
4-methylmorpholine
N-methylpiperidine
N-ethylmorpholine
4-ethyliperidine
Me2NEt
Phenolic aldol-type reactions have generally been con-
ducted by formation of the magnesium phenoxide in an
ethereal solvent followed by removal of the ether and re-
placement with a nondonating solvent, typically benzene
or CH2Cl2, to promote the required complexation.3a–d,3f–h,5
Our finding in the current example that reactions proceed
readily in a mixture of CH2Cl2 and MTBE was already a
large step forward, enabling us to scale the chemistry
without serious issues. The necessity for a large amount of
the expensive and reactive Grignard reagent, however,
prompted us to further investigate phenoxide generation
using simple bases in combination with cheap magnesium
salts. Analysis of the Et3N/MgCl2 promoted reaction
(Table 1 entry 10) showed the observed yield reduction
was due to competing redox reactions (Scheme 3) along
with the presence of residual starting aldehyde which we
postulate could be trapped under the reaction conditions
as an unreactive acetal.
7
8
9
10
11
12
13
14
15
16
DABCO
Bu2NH
0
2,6-lutidine
1
TMEDA
33
0
triethanolamine
tetramethylguanidine
58
Synlett 2009, No. 10, 1609–1613 © Thieme Stuttgart · New York

LETTER
Phenolic Aldol Reaction of 2-Formylpyridines
1611
Table 2 MgCl2-Promoted Phenolic Aldol Reaction Base Screena
OH OH
OH
N
CO2Et
H2, Pd/C, ZnBr2
EtOAc, H2SO4
N
CO2Et
OH
OH OH
O
MgCl2, base,
CO2Et CH2Cl2
N
CO2Et
N
+
r.t., 16 h
Cl
Cl
5a
1a 82%
Cl
2a
Cl
Scheme 4 Reduction to give diarylmethane 1a
5a
4a
Conversion to 5a (%)b
creased MgCl2, reduced base, and slow addition of the al-
dehyde), 4-chlorophenol (2a) gave 92% solution yield,
and 5a was isolated in 86% yield after chromatography;
alternatively, isolation by crystallisation from 1:1 EtOH–
H2O gave 78% yield (cf. 83% for the Grignard-promoted
process; Table 3, entry 1). The highly electron-deficient
4-nitrophenol (2e) only gave poor conversion (Table 3,
entry 5), however, the reasonably electron-deficient ethyl-
4-hydroxybenzoate (2d) still furnished the desired prod-
uct 5d in good yield (Table 3, entry 4).
Entry
Base
a Compound 2a (2.5 equiv), MgCl2 (3 equiv), and base (3 equiv) were
stirred in CH2Cl2 for 30 min, 4a (1 equiv) was then added as a solution
in CH2Cl2.
b Determined by LC-UV analysis.
Use of inorganic bases gave greatly reduced reactivity
(Table 2, entries 2 and 3); however, use of alternative tri-
alkylamines maintained high conversion. Diisopropyl-
ethylamine (Table 2, entry 4) behaved similarly to Et3N,
use of 4-methylmorpholine or N-methylpiperidine gave
slightly improved selectivity (Table 2, entries 6 and 7),
whereas use of their ethyl derivatives gave slightly lower
yields (Table 2, entries 8 and 9). N,N-Dimethylethyl-
amine (Me2NEt) gave the highest observed selectivity
(Table 2, entry 10), and a range of alternative organic
bases gave lower or no reactivity (Table 2, entries 11–16).
It therefore appears that for efficient conversion a trial-
kylamine is required as base, with smaller (and also less
basic) derivatives seemingly giving higher selectivities
for reasons which are not currently fully understood. In-
vestigation of a range of alternative solvents gave no im-
provement.11 Use of strongly donating or protic solvents
had an adverse effect on the reactivity, whereas ethers and
a number of other hydrocarbon solvents were not suffi-
ciently polar to solubilise the reaction intermediates. After
optimisation of the Me2NEt process we briefly surveyed
the scope of the reaction (Table 3 and Table 4).
Whilst the parent 2-formylpyridine (4b) underwent effi-
cient reaction with chloromagnesium phenoxide generat-
ed from phenol, MgCl2, and Me2NEt (Table 4, entry 1),
replacement of the 2-pyridyl group with either a benzene
ring or a 3-pyridyl substituent gave no conversion under
the reaction conditions (Table 4, entries 2 and 3). This
supports the hypothesis that the 2-pyridyl nitrogen is
required for efficient chelation of the magnesium centre
prior to reaction. A range of further substituted 2-
formylpyridines (4e–h) all underwent smooth conversion
to provide 5i–l (Table 4, entries 4–7).
Reduction of diarylmethanol 5a to the desired diaryl-
methane 1a was readily achieved by palladium-catalysed
hydrogenolysis. Conducting the reaction in ethyl acetate
with catalytic ZnBr2 proved key to controlling competi-
tive reduction of the aryl chloride (Scheme 4).12
In summary, 2-formylpyridines have been demonstrated
to be suitable substrates for the magnesium-promoted
phenolic aldol reaction. This enables a very mild and
A range of functionalised phenols was well tolerated
(Table 3, entries 1–4). Under the optimised conditions (in-
Table 3 Scope of Phenol Componenta
OH
O
OH OH
N
CO2Et
N
CO2Et
MgCl2, Me2NEt, CH2Cl2
r.t., 16 h
+
R
R
4a
2a–e
5a–e
Entry Phenol
Conversion to 5 (%)b
1
2
3
4
5
2a, R = 4-Cl
5a
5b
5c
5d
5e
92 (86)
96 (85)
93
2b, R = H
2c, R = 2-Cl
2d, R = 4-CO2Et
2e, R = 4-NO2
87 (81)
26
a Phenol (2.5 equiv), MgCl2 (4 equiv), and Me2NEt (2.2 equiv) were stirred in CH2Cl2 for 30 min, 4a (1 equiv) was then added as a solution
in CH2Cl2 over 3 h.
b Determined by LC-UV analysis; isolated yield after chromatography is given in parentheses.
Synlett 2009, No. 10, 1609–1613 © Thieme Stuttgart · New York

1612
M. Whiting et al.
LETTER
Table 4 Scope of Aldehyde Componenta
cautiously added to the resultant suspension at a rate which main-
tained the internal temperature below 30 °C (caution, 2-stage exo-
therm observed). The reaction mixture was equilibrated to 23 °C,
and a soln of the aldehyde 4a (5 g, 28 mmol) in CH2Cl2 (10 mL) was
added over 4 h. The resulting orange suspension was stirred at r.t.
for 15 h before being cooled to 0 °C and cautiously quenched by ad-
dition of HCl (30 mL of a 2 M aq soln, 60 mmol) followed by
KHSO4 (18 mL of a 0.54 M aq soln, 9.7 mmol). The organic phase
was separated and the aqueous phase back extracted with CH2Cl2 (5
mL). The combined organics were washed with H2O (20 mL) and
the aqueous phase again back extracted with CH2Cl2 (5 mL). The
combined organic phases were concentrated to 15 mL by atmo-
spheric pressure distillation before EtOH (50 mL) was added, and
the soln further concentrated to 35 mL. H2O (35 mL) was slowly
added at reflux. The solution was cooled to 70 °C, seeded with 5a,
held for 1 h, and then cooled to 0 °C over 2 h. The resultant slurry
was held for 1 h before the product was collected by filtration and
washed with EtOH–H2O (1:1, 3 × 10 mL) at 0 °C. The fluffy white
solid was dried overnight under vacuum at 40 °C to furnish 5a (6.7
g, 78%, >99.9% a/a purity by LC-UV). 1H NMR (400 MHz,
CDCl3): d = 10.34 (br s, 1 H), 8.01 (d, J = 7.5 Hz, 1 H), 7.91 (t,
J = 7.5 Hz, 1 H), 7.75 (d, J = 7.5 Hz, 1 H), 7.37 (d, J = 2.5 Hz, 1 H),
7.10 (dd, J = 8.5, 2.5 Hz, 1 H), 6.89 (d, J = 8.5 Hz, 1 H), 6.10 (s, 1
H), 4.45 (q, J = 7.0 Hz, 2 H), 3.98 (br s, 1 H), 1.44 (t, J = 7.0 Hz, 3
H). ESI-HRMS: m/z calcd for C15H15NO435Cl [MH+]: 308.0684;
found: 308.0691.
OH
OH OH
O
MgCl2, Me2NEt, CH2Cl2
r.t., 16 h
+
Ar
Ar
4b–h
2b
5f–l
Entry
Aldehyde
Conversion to 5 (%)b
O
O
O
O
O
O
N
1
2
4b
5f
94 (50)c
4c
4d
4e
4f
5g
0
3
4
5
6
7
5h
5i
0
N
N
93
Procedure for the Preparation of 1a
Compound 5a (70 g, 1 equiv) and Pd/C (5.25 g of JM type 487 10
wt% Pd on activated carbon, dry powder, 2.2 mol% Pd) were
charged to a hydrogenation vessel. EtOAc (525 mL) was added, and
further EtOAc (525 mL) was used to wash in ZnBr2 (1.4 g, 2.7
mol%), after which H2SO4 (70 mL, concd) was cautiously added
with vigorous stirring. The vessel was flushed with N2 followed by
H2 at 1 atm (above atmospheric pressure) and the reaction was heat-
ed to 65 °C for 6 h. The reaction was cooled to r.t. and filtered
through a short plug of Celite, washing with EtOAc (3 × 70 mL).
The combined filtrates were added into H2O (700 mL). The aqueous
phase was separated and diluted with further H2O (980 mL) before
being back extracted with EtOAc (350 mL). The combined organic
phases were washed with Na2SO4 (2 × 420 mL of a 10% w/w solu-
tion) followed by H2O (420 mL). The organic phase was concentrat-
ed to 350 mL by atmospheric pressure distillation, diluted with 2-
PrOH (1.4 L), and further concentrated to 490 mL. The resultant so-
lution was cooled to 55 °C, seeded with 1a, then cooled to 0 °C over
2 h, and held for a further 1 h before the product was collected by
filtration and washed with cold 2-PrOH (140 mL). The white solid
was dried overnight under vacuum at 40 °C to furnish 1a (54.6 g,
Br
Br
N
N
5j
5k
5l
97 (81)
93
4g
4h
O
N
86
a Compound 2b (2.5 equiv), MgCl2 (4 equiv), and Me2NEt (2.2 equiv)
were stirred in CH2Cl2 for 30 min, aldehyde (1 equiv) was then added
as a solution in CH2Cl2 over 3 h.
b Determined by LC-UV analysis; isolated yield after chromatogra-
phy is given in parentheses.
c Isolated by precipitation from CH2Cl2–phosphate buffer (pH= 7).
1
82%, >99% a/a purity by LC-UV). H NMR (400 MHz, CDCl3):
straightforward synthesis of a range of 2-hydroxyphenyl-
2-pyridylmethanols, the more functionalised and electron
deficient of which would be problematic or impossible to
d = 11.21 (br s, 1 H), 8.01 (d, J = 7.5 Hz, 1 H), 7.86 (t, J = 7.5 Hz,
1 H), 7.50 (d, J = 7.5 Hz, 1 H), 7.13 (d, J = 2.5 Hz, 1 H), 7.09 (dd,
J = 8.5, 2.5 Hz, 1 H), 6.96 (d, J = 8.5 Hz, 1 H), 4.46 (q, J = 7.0 Hz,
synthesise by more conventional Friedel–Crafts/Fries- 2 H), 4.11 (s, 2 H), 1.47 (t, J = 7.0 Hz, 3 H). ESI-HRMS: m/z calcd
for C15H15NO335Cl [MH+]: 292.0735; found: 292.0738.
type chemistry. Reduction of the initially formed benzylic
alcohols enables access to the corresponding diaryl-
methanes. In addition, new conditions for this reaction
Acknowledgment
have been developed which facilitate reaction scale-up by
We thank Mark Scott for helpful discussions and Gemma Ellison
removing the necessity to use expensive and reactive
and Marco Smith for analytical assistance.
Grignard reagents.
References and Notes
Procedure for the Preparation of 5a
CH2Cl2 (40 mL) was added to 4-chlorophenol (2a, 8.9 g, 69 mmol)
and MgCl2 (10.6 g, 111 mmol). Me2NEt (6.7 mL, 61 mmol) was
(1) Current address: Peakdale Molecular Ltd, Peakdale Science
Park, Sheffield Road, Chapel-en-le-Frith SK23 0PG, UK.
Synlett 2009, No. 10, 1609–1613 © Thieme Stuttgart · New York

LETTER
Phenolic Aldol Reaction of 2-Formylpyridines
1613
(2) For leading references, see: (a) Hall, A.; Billinton, A.;
Giblin, G. M. P. Curr. Opin. Drug Discovery Devel. 2007,
10, 597. (b) Giblin, G. M. P.; Hall, A.; Hurst, D. N.;
Rawlings, D. A.; Scoccitti, T. WO 2006066968, 2006;
Chem. Abstr. 2006, 145, 83231.
(3) (a) Casiraghi, G.; Salerno, G.; Sartori, G. Synthesis 1975,
186. (b) Casiraghi, G.; Cornia, M.; Rassu, G. J. Org. Chem.
1988, 53, 4919. (c) Bigi, F.; Casnati, G.; Sartori, G.; Araldi,
G.; Bocelli, G. Tetrahedron Lett. 1989, 30, 1121.
E.; Messori, R.; Sartori, G. Tetrahedron 1979, 35, 2061.
(f) Casiraghi, G.; Casnati, G.; Pochini, A.; Ungaro, R.
J. Chem. Soc., Perkin Trans. 1 1982, 805. (g) Mibu, N.;
Sumoto, K. Chem. Pharm. Bull. 2000, 48, 1810.
(7) Sartori, G.; Maggi, R.; Bigi, F.; Arienti, A.; Porta, C.;
Predieri, G. Tetrahedron 1994, 50, 10587.
(8) Use of Et2O on scale is complicated by its high volatility and
flammability, MTBE is a much preferred alternative.
(9) For the use of Et3N/MgCl2 to promote selective ortho-
formylation of phenols, see: (a) Hofslokken, N. U.;
Skattebol, L. Acta Chem. Scand. 1999, 53, 258. (b) Hansen,
T. V.; Skattebol, L. Org. Synth. 2005, 82, 64.
(10) This becomes the main reaction pathway if phenol is omitted
from the reaction mixture. For a recent report of a similar
process, see: Abaee, M. S.; Sharifi, R.; Mojtahedi, M. M.
Org. Lett. 2005, 7, 5893.
(d) Cornia, M.; Casiraghi, G. Tetrahedron 1989, 45, 2869.
(e) Saimoto, H.; Yoshida, K.; Tetsuya, M.; Morimoto, M.;
Sashiwa, H.; Shigemasa, Y. J. Org. Chem. 1996, 61, 6768.
(f) Hewawasam, P.; Erway, M. Tetrahedron Lett. 1998, 39,
3981. (g) Rondot, C.; Retailleau, P.; Zhu, J. Org. Lett. 2007,
9, 247. (h) Chen, X.; Zhu, J. Angew. Chem. Int. Ed. 2007, 46,
3962.
(4) For a review, see: Casnati, G.; Casiraghi, G.; Pochini, A.;
Sartori, G.; Ungaro, R. Pure Appl. Chem. 1983, 55, 1677.
(5) For leading references, see: Bocelli, G.; Cantoni, A.; Sartori,
G.; Maggi, R.; Bigi, F. Chem. Eur. J. 1997, 3, 1269.
(6) For selected examples, see: (a) Casiraghi, G.; Casnati, G.;
Cornia, M.; Sartori, G.; Ungaro, R. J. Chem. Soc. Perkin
Trans. 1 1974, 2077. (b) Casnati, G.; Colli, M.; Pochini, A.;
Ungaro, R. Chim. Ind. (Milan) 1977, 59, 764. (c) Casiraghi,
G.; Casnati, G.; Cornia, M.; Pochini, M.; Puglia, G.; Sartori,
G.; Ungaro, R. J. Chem. Soc., Perkin Trans. 1 1978, 318.
(d) Sartori, G.; Casiraghi, G.; Bolzoni, L.; Casnati, G. J. Org.
Chem. 1979, 44, 803. (e) Casiraghi, G.; Casnati, G.; Dradi,
(11) Solvents investigated; acetone, MeCN, MTBE, chloro-
benzene, cyclopentyl methyl ether, CH2Cl2, EtOH, EtOAc,
i-PrOAc, 2-methyltetrahydrofuran, THF, a,a,a-trifluoro-
toluene, and sulfolane.
(12) This reaction will be described in more detail in a future
report. Addition of ZnBr2 does not have a significant effect
on the rate of the desired reduction but greatly reduces the
rate of competitive dechlorination. For a report on the use of
zinc halides to modulate the activity of hydrogenation
catalysts, see: Wu, G.; Huang, M.; Richards, M.; Poirier, M.;
Wen, X.; Draper, R. W. Synthesis 2003, 1657.
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