Aminophosphonates as organocatalysts in the direct asymmetric aldol reaction: Towards syn selectivity in the presence of Lewis bases

Article abstract of DOI:10.1039/b605091c

Chiral α-aminophosphates as a new class of efficient organocatalysts for the asymmetric direct aldol reaction was investigated. These biological compounds were synthesized and high enantioselectivities were achieved for a range of substituted cyclo-hexano

Full text of DOI:10.1039/b605091c

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Aminophosphonates as organocatalysts in the direct asymmetric aldol
reaction: towards syn selectivity in the presence of Lewis bases
Peter Dine´r and Mohamed Amedjkouh*
Received 4th October 2005, Accepted 18th April 2006
First published as an Advance Article on the web 9th May 2006
DOI: 10.1039/b605091c
Chiral a-aminophosphonates have been synthesized and their
performance was evaluated as organocatalysts in the direct
asymmetric aldol reaction. High enantioselectivities (up to
99% ee) were achieved for a range of substituted cyclo-
hexanones and benzaldehydes. Several organic bases, such
Fig. 1
as DBU, DBN, and TMG, were used together with the a-
aminophosphonates in the aldol reactions and were found to
favor syn-selectivity.
nitrobenzaldehyde, using the a-aminophosphonate 1 as a catalyst
at the B3LYP/6-31G(d) level of theory, in order to explore the
potential of the a-aminophosphonates.
a-Aminophosphonates and their derivatives are important com-
pounds possessing diverse and useful biological activities.1 a-
Aminophosphonates are analogous to amino acids and have
found applications ranging from medicine to agriculture, e.g.
as antibiotics,2 enzyme inhibitors,3 anti-cancer agents,4 and
herbicides.5 These biological properties are mostly associated with
the tetrahedral structure of the phosphonyl group acting as a
“transition-state analogue”.6 Cyclic a-aminophosphonates have
found promising applications as surrogates of proline, increasing
the need for their syntheses in enantiomerically pure form.7
However, despite the similarities with proline, to our knowledge
there is only one report of their use as a ligand for catalysis.8
Proline has recently re-emerged as a highly enantioselective
catalyst for the direct asymmetric aldol reaction as one of the most
powerful methods for the construction of complex chiral polyol
architectures. Early developments for the intramolecular aldol
cyclisations were independently reported by Hajos and Parrish9
and by Wiechert and co-workers10 in 1971, and paved the way
for the development of the concept of small organic molecules
as catalysts. Barbas, List and co-workers demonstrated that L-
proline was a powerful catalyst in the asymmetric intermolecular
direct aldol reaction.11 However, a rather high catalyst loading
(around 20 mol%) is usually required to effect the reaction in a
reasonable timescale. Other proline-based compounds including
diamines, small peptides, tetrazole and sulfonamides were found to
catalyze the aldol reaction. Sulfonamides are modular catalysts,
which allowed for an enantioselectivity of up to 98% ee while
maintaining high activity at low catalyst loadings.12
We report herein that a-aminophosphonates catalyze the
enantioselective aldol reaction between unmodified ketones and
aldehydes to provide aldol adducts with up to 99% ee.
Computational investigation of enantioselectivity
Several computational investigations of the potential energy
surface of the aldol reactions between L-proline and aldehydes
have been performed and the reaction is suggested to go via the
enamine mechanism.13 Therefore, we have investigated possible
activated complexes in the addition of 4-nitrobenzaldehyde to
the syn- and anti-enamine of aminophosphonate 1 and acetone
involving the enamine mechanism (Scheme 1).
Cyclic (2S)-pyrrolidin-2-ylphosphonic acid 1 shown below
(Fig. 1) is an analog of D-proline, and could be readily prepared
from diethyl (2S)-pyrrolidin-2-ylphosphonate 2. It was thought
that the replacement of the carboxyl group in proline by a
phosphonate would result in a functional group of sufficient
acidity to catalyze the aldol reaction.
Therefore, we found it interesting to computationally investigate
the enantioselectivity of the aldol reaction between acetone and 4-
Organic Chemistry, Department of Chemistry, Go¨teborg University, SE-412
96, Go¨teborg, Sweden. E-mail: mamou@chem.gu.se; Fax: +46 31 772 3840
Scheme 1
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Both the syn- and anti-enamine derived from aminophos-
phonate 1 and acetone have been calculated at the B3LYP/6-
31G(d) level of theory and the difference in enthalpy was found
to be only 0.3 kcal mol−1 in favor of the anti-enamine. This
shows that the aldehyde possibly could react with both the
syn- and anti-enamine of the aminophosphonate 1 and acetone.
Initially, 4-nitrobenzaldehyde forms a complex with either the
syn- or anti-enamine in which the phosphate hydroxyl group is
hydrogen bonded to the carbonyl group in 4-nitrobenzaldehyde.
These enamine-aldehyde complexes are 12.5 kcal mol−1 (anti)
and 11.0 kcal mol−1 (syn) more stable than free enamine and 4-
nitrobenzaldehyde.
to (S)- and (R)-aldol products have been considered. For example,
different hydrogen bonding from the two acid functions to the
carbonyl oxygen in the aldehyde with aminophosphonate 1 and
different conformations around the forming C–C bond have been
considered (Fig. 2).
In the transition states for the reaction between the enamine
and aldehyde, the hydrogen of the hydroxyl group is simulta-
neously transferred to the carbonyl oxygen along with carbon–
carbon bond formation. The calculations show that the activation
enthalpy for the most stable transition state (R-TSc) for the
addition of 4-nitrobenzaldehyde to the anti-enamine is 9.3 kcal
mol−1 relative to the anti-enamine–4-nitrobenzaldehyde complex.
The major geometrical differences between the two most stable
transitions states in the addition of 4-nitrobenzaldehyde to the
anti-enamine, R-TSc and S-TSc, originates from the different
orientation of the phenyl ring, which leads to a tilt in the aldehyde
In order to investigate the enantioselectivity of the catalyst, the
activated complexes for the reaction between 4-nitrobenzaldehyde
and the syn- and anti-enamine of aminophosphonate 1 and
acetone were calculated. Different activated complexes leading
Fig. 2
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in the S-TSc due to the interaction between the phenyl and the
methyl group in the enamine part of the catalyst. The second
difference is seen in the distance of the carbon–carbon bond
formation. In all the calculated transition states leading to (R)-
product, the C–C distances are longer than those found in the
The enthalpy difference between the most stable activated
complexes leading to (R)- and (S)-product, R-TSe and S-TSd, is
1.93 kcal mol−1, favoring the (R)-product. Thus, the calculations
predict (R)-aldol adduct in 97% ee for addition of aldehyde to the
syn-enamine.
Most of the calculations of the transition states were performed
as a predicted tool for the enantioselectivity for aminophospho-
nate 1, and thus, the calculation of the transition states were
performed by analogy to L-proline. However, the aminophospho-
nate 1 is the analogue of D-proline, and this explains the differ-
ence in stereochemistry between the calculated and synthesized
aminophosphonate.
˚
transition states leading to (S)-product (R-TSc: 1.95 A, S-TSc:
˚
1.90 A). All the computed transition states for the addition of
aldehyde to anti-enamine are arranged to form a six-membered
chair-like ring similar to Zimmerman–Traxler.
At the B3LYP/6-31G(d) level of theory, the difference in
enthalpy of activation between the two most stable activated
complexes, R-TSc and S-TSc, is 1.64 kcal mol−1, favoring the
formation of (R)-products. Thus, the calculations predict (R)-aldol
adduct in 88% ee for addition of aldehyde to the anti-enamine.
The transition states for the addition of 4-nitrobenzaldehyde to
the syn-enamine are generally one to a few kcal mol−1 higher in
energy than for the transition states for the addition to the anti-
enamine. However, the most stable transition state for addition
to the syn-enamine, R-TSe, is merely 0.87 kcal mol−1 higher in
energy than R-TSc. This shows that both the syn- and anti-
enamine could play a role in the aminophosphonate catalyzed
aldol reaction. In R-TSe, the C–C distance of the forming C–C
Evaluation of aminophosphonates
Aminophosphonate 2 was prepared according to the method
described by Katritzky et al.14 Starting from oxazolopyrrolidine 3
and subsequent Arbuzov reaction in the presence of the Lewis acid,
ZnBr2 (10 mol%), converted 3 into the desired oxazolopyrrolidine
phosphonate 4 as single diastereoisomer. Aminophosphonic acid
1 was finally obtained in 88% yield, as a white powder, by cleavage
of the ester functions in acidic medium (6 M HCl) followed by
treatment with propylene oxide (Scheme 2).15
The efficiency of the novel aminophopshonates 1 and 2 as
organocatalysts was evaluated in the direct aldol reaction of 4-
nitrobenzaldehyde and acetone using DMSO as solvent. In the
initial experiments, the catalyst was employed at 20 mol% with
respect to the aldehyde and an excess of acetone 20 vol% (27 mol
equiv.) (Scheme 3).16 The results for different reaction conditions
are summarized in Table 1.
˚
bond is significantly longer (2.19 A) than in all other transition
states. Another feature present in the R-TSe transition state is
the short distance between the aldehyde proton and the non-
˚
hydroxy oxygen in the phosphonate group (2.344 A), which could
contribute to electrostatic stabilization of R-TSe. In contrast to the
anti-enamine transition states, R-TSe can be viewed as a transition
state with the conformation of a boat-like six-membered ring and
cannot be rationalized to a chair-like transition state similar to
Zimmerman–Traxler.
Scheme 2 Reagents and conditions: a) P(OEt)3 (2 eq.), ZnBr2 (0.3 eq.), CH2Cl2, 0 ◦C, overnight. b) H2, Pd/C, HCl–EtOH, overnight. c) 6 M HCl, reflux
12 h. d) Propylene oxide EtOH, reflux, 3 h.
Table 1 Aminophosphonate-catalyzed aldol reaction of acetone and 4-nitrobenzaldehydea
Entry
Cat.
Conditions
Time/h
Conv. (%)b
Ee (%)c
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
2e
2
2
—
43
24
24
63
21
66
40
83
30
68
69
35
35
82
76
52
62
44
52
52
82
72
76
1% H2O
1% PBSd
0.1% PBSd
20% DBU
0.2% DBU
5% DBU–Tol : IPA (9 : 1)
—
19
(15 min)
2.5
1
24
24
1% H2Od
0.1% PBSd
10
19
a Unless otherwise stated, all reactions were carried out using 0.1 M aldehyde and 20 mol% catalyst in 1 mL DMSO : acetone (4 : 1). b The yields were
determined by 1H NMR spectroscopy. c The ee was determined by chiral HPLC analysis using a Kromasil CHI-TBB. The major enantiomer was assigned
to be (S) by comparison with literature. d Phosphate buffer at pH 7.1. e The reaction was performed using 5 mol% catalyst 2.
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The cyclic ketones (Scheme 4, Table 2) were found to be suitable
substrates for this aldol reaction with both catalysts, 1 and 2,
giving aldol products in good yield after 24 h, although with
moderate diastereocontrol. Excellent enantioselectivities up to
99% were observed for both syn and anti isomers in the reaction
of cyclohexanone derivatives. Typically, aminophosphonic acid
1 (20 mol%) catalyzed the reaction of cyclohexanone with 4-
nitrobenzaldehyde to produce adducts syn-11 and anti-11 in up to
97% ee (entry 3). This also represents a significant improvement of
enantioselectivity relative to reactions catalyzed with proline and
its derived compounds with a maximum of 90% ee for anti and
74% ee for syn products.11,12 Catalyst 2 (20 mol%) promoted the
reaction with a higher reaction rate than 1 and with up to 97% ee
(entry 4).
Scheme 3
Thus, aminophosphonic acid 1 catalyzed the asymmetric forma-
tion of aldol adduct (S)-5 in 82% ee with good yield and practical
reaction time. Catalyst 2 was found to be more reactive and typical
catalyst loading of 5 mol% provided the aldol product in 69% yield
with a 82% ee after 24 h (entry 8).
Recently, we and others have found that addition of water at low
concentration (1–2 vol%) resulted in an increase of the reaction
rates of the aldol reaction.17 Water is thought to participate in a
proton relay that could allow for enamine formation in organic
solvents. We reported remarkable effects on enantioselectivity and
reactivity under aqueous reaction conditions. However, addition
of water (1 mol%) to catalyst 1 resulted in lower reactivity
providing (S)-5 in only 76% ee (entry 2). Furthermore, while
there was an increase in reactivity in the presence of 1 vol%
PBS in DMSO with aminophosphonic acid catalyst 1, it had a
deleterious effect on the enantioselectivity, which decreased from
82% to 52% ee. In addition, using 0.1 vol% PBS resulted in an
improved ee of 62%, while keeping a high reactivity (entries 3,
4). The same trend in enantioselectivity could be observed with
the aminophosphonate ester catalyst 2 under similar conditions
as shown in entries 9 and 10.
Next we studied the influence of organic bases on the aldol
reaction between acetone and 4-nitrobenzaldehyde and using
exclusively catalyst 1 (20 mol%). We presumed that addition of
organic base would facilitate enamine formation and thus accel-
erate the reaction. The organic base could also solvate the acidic
proton in the Zimmerman–Traxler transition state. Differences in
reaction rates became clearly visible: in the presence of 20 mol%
DBU with respect to aldehyde in DMSO, the reaction was driven
to 83% conversion after only 15 min. Even at 0.2 mol% DBU, the
conversion was at 30% after 2.5 h (entries 5,6). Similarly, 5 mol%
DBU in toluene: isopropanol (IPA) (9 : 1) resulted in 68% conver-
sion after 1 h (entry 7). However this observed base-accelerating
effect was at the expense of the enantioselectivity. This observation
suggests that DBU could participate in the transition state.
Scheme 4
Aminophosphonate 2 was found to be very efficient and could
be used with only 2 mol% catalyst loadings with respect to the
aldehyde acceptor without deleterious effect on enantioselectivity.
Additionally, 2 was still very efficient even with only 2 mol
equivalents of the corresponding ketone donor. Thus, under these
conditions, i.e. 2 (5 mol%) and ketone (2 mol equiv.), a range of
cyclohexanones were explored, although a longer reaction time
is needed (entries 5–11). Equally high enantioselectivities (up to
99%) were observed (entries 3–9), with a slightly lower 89% ee for
anti-12 (entry 7).
It also appears that catalyst 2 favors the formation of the anti
isomer. Noteworthy examples include anti-12 and anti-13 (entries
7–8). In the case of 4-tert-butylcyclohexanone, the aldol reaction
produced only two diastereoisomers, anti-trans-14 and syn-trans-
14, out of four possible in a 1 : 1 ratio.18 Thus, after 44 h the
aldol product was obtained in 52% yield and with 96% ee for
Table 2 Aminophosphonate-catalyzed aldol reaction of cyclic ketones and 4-nitrobenzaldehydea
Entry
Aldol product
Cat (mol%)
Time/h
Yield (%)b (syn : anti)
Ee (%)c syn : anti
1
2
3
4
5
6
7
8
9
10
10
11
11
11
11
12
13
14
15
16
1 (20)
2 (20)
1 (20)
2 (20)
2 (5)
2 (2)
2 (5)
2 (5)
2 (5)
2 (5)
2 (5)
23
27
21
21
96
144
120
120
44
96
96
51 (1 : 1)
51 (3 : 2)
47 (1 : 1)
91 (1 : 2)
73 ( 1: 2)
68 (2 : 3)
79 (1 : 4)
36 (1 : 9)
52 (1 : 1)
51 (2 : 3)
68 (1 : 1)
46 : nd
rac : nd
97 : 97
97 : 96
96 : 96
96 : 94
nd : 89
nd : 99
nd : 96
97 : 97
nd : 98
10
11
a Unless otherwise stated, all reactions were carried out using 0.2 M aldehyde, 0.4 M ketone and corresponding amount catalyst (see the table) in 1 mL
DMSO. b The yields are based on isolated product. c The ee was determined by chiral HPLC analysis using a Chiralcel-OD column or a Kromasil
CHI-TBB. d Reactions were carried out at 0.05 M.
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Table 3 Effect of additives on the aminophosphonate-catalyzed aldol reaction of cyclohexanone with 4-nitrobenzaldehydea
Entry
Aldol product
Cat. (mol%)
Additives (mol%)
Time/h
Conv. (%)b (syn : anti)
ee (%)c syn : anti
1
2
3
4
5
6
7
8
9
11
11
11
11
11
11
11
11
11
1 (5)
Pro (5)
1 (5)
Pro (5)
1 (5)
Pro (5)
1 (5)
2 (5)
2 (5)
DBU (5)
DBU (5)
DBN (5)
DBN (5)
TMG (5)
TMG (5)
H2O (200)
PNP (20)
H2O (200)
72
24
72
24
72
24
24
24
24
60 (2 : 1)
82 (1 : 1)
56 (2 : 1)
quant.
47 (2 : 1)
quant.
no reaction
35 (1 : 2)
40 (1 : 2)
91 : 45
rac
90 : 45
rac
90 : 45
rac
—
96 : 97
96 : 98
a Unless otherwise stated, all reactions were carried out using 0.2 M aldehyde, 0.4 M ketone and the corresponding amount of catalyst (see the table) in
1 mL DMSO. b Conversion as determined by 1H NMR. c The ee was determined by chiral HPLC analysis using a Chiralcel-OD column or a Kromasil
CHI-TBB, after flash chromatography.
the isomer anti-trans-14 (entries 9).19 This high enantioselectivity
is also observed for other aromatic aldehydes to produce aldol
adducts 15 with 97% ee for both diastereomers, and 16 with 98%
ee for the anti isomer (entries 10–11).20
The effectiveness of catalyst 2 over catalyst 1 may be attributed
to a higher solubility of 2 in organic solvents. Moreover, it is not yet
clear whether catalyst 2 is involved as a dimer in a dual catalyst–
enaminium transition-state, suggesting a second order reaction
with respect to catalyst 2. Such a transition-state model has been
previously discussed.21
Perhaps most importantly, we have found that organic bases
can be employed as co-catalysts to enforce syn-selectivity. From the
above-mentioned results in Table 1, we envisioned that a transition
state stabilized with an organic base, in a boat conformation,
would favor the syn product. As shown in Table 3, a combination
of aminophosphonic acid 1 and one of the organic bases (DBU,
DBN or TMG) in 5 mol% of each allows the addition of
cyclohexanone to 4-nitrobenzaldehyde with 2 : 1 syn-selectivity.
Remarkably, syn-11 and anti-11 aldol products are isolated with 91
and 45% ee, respectively—while still using only 2 mol equivalents
of ketone donor (entries 1, 3, 5). In a stark contrast, a similar
catalyst combination incorporating proline (as the catalyst) and
one organic base produced a 1 : 1 mixture of anti-11 and syn-
11 aldol adducts. Although a remarkable increase of the reaction
rate was observed, the aldol products are obtained in racemic
form for both diastereomers (entries 2, 4, 6). We also examined
the impact of the protic additives. However, with added water
aminophosphonic acid 1 did not promote the reaction (entry
7). On the other hand, addition of 4-nitrophenol (PNP) did
not influence significantly the selectivity of the reaction with
aminophosphonate 2 as the catalyst (entry 8). Interestingly,
the asymmetric aldol reaction proceeded efficiently in aqueous
organic solvent (200 mol% water), keeping excellent level of
enantioselectivity.
Both enantiomers of catalysts 1 and 2 can be easily prepared
on a large scale from commercially available compounds. For the
first time, excellent enantioselectivity is achieved for both anti and
syn isomers of aldol adducts derived from cyclohexanone, while
maintaining low catalyst loadings (2 mol%). Furthermore, organic
bases can be employed as co-catalysts to enforce syn-selectivity
while keeping a high level of enantioselectivity.
B3LYP/6-31G(d) calculations of structures and energies of
possible, diastereoisomeric activated complexes showed the de-
cisive role of the tetrahedral phosphonate group in catalyst 1
on the enantioselectivity. The predicted enantioselectivities were
in agreement with the experimental values, although the present
model does not account for reactivity of 2 or the influence of
organic bases.
The syn-directing effects of organic bases together with the
possibility of substituent variation on the phosphonyl part are
expected to allow for appropriate tuning of the aminophosphonate
catalysts. A study aimed at the understanding of the mechanism
is currently under way.
Acknowledgements
This work was supported by the Swedish Research Council
(Veteskapsra˚det), The Wilhelm and Martina Lundgrens Veten-
skapsfond, and The Royal Society of Arts and Sciences (KVVS).
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Moreover, the high enantioselectivity in aqueous media alludes to
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J. Org. Chem., 1999, 64, 1979–1985.
17 (a) F. Tanaka, R. Thayumanavan, N. Mase and C. F. Barbas, III,
Tetrahedron Lett., 2004, 45, 325–328; (b) H. Torii, M. Nakadai, K.
Ishihara, S. Saito and H. Yamamoto, Angew. Chem., Int. Ed., 2004,
43, 1983–1986; (c) M. Amedjkouh, Tetrahedron: Asymmetry, 2005, 16,
1411–1414.
18 (a) The assignment of the axial stereochemistry of the product 14 is
based on the data from 1H NMR. The spectrum of compound 14
shows a coupling constant J = 9.2 Hz for the resonances at 4.93 and
2.66 ppm of the anti isomer. For reference see: A. I. Nyberg, A. Usano
and P. M. Pihko, Synlett, 2004, 1891–1896; (b) J. Busch-Petersen and
E. J. Corey, Tetrahedron Lett., 2000, 41, 6941–6944.
19 The same reaction in presence of L-proline, under previously reported
conditions,18 provided a 1 : 1 mixture of anti- and syn-trans aldol
products (with 68% ee for the anti-isomer).
20 All new compounds gave satisfactory analytical and spectral data.
Characterization data for selected examples are given below: (2R,1ꢀR)-
[Hydroxy-(4-nitrophenyl)-methyl]-cyclohexanone and (2S,1R)-2-[1 -
hydroxy-(4-nitrophenyl)-methyl]-cyclohexanone. syn and anti Diastere-
omers were separated by flash column chromatography (EtOAc–
hexane, 1 : 5) to yield the title compounds as white solids. anti 1H
NMR (400 MHz, CDCl3) d = 8.20 (2H, d, J = 8.7 Hz, ArH), 7.49
(2H, d, J = 8.7 Hz, ArH), 4.98 (1H, d, CHCHOH), 2.59 (1H, m,
CHCHOH), 2.50–2.37 (2H,m, CH2C(O), 2.16–1.55 (6H, m, c-hex-H).
HPLC: Chiralcel-OD. Hexane–i-PrOH, 95 : 5, 1.5 mL min−1, 254 nm:
t
R (major) = 16.4 min; tR (minor) = 12.8 min. syn 1H NMR (400 MHz,
CDCl3) d = 8.20 (2H, d, J = 8.7 Hz, ArH), 7.51 (2H, d, J = 8.7 Hz,
ArH), 5.49 (1H, m, CHCHOH), 2.63 (1H, m, CHCHOH), 2.47–2.30
(2H, m, CH2C(O), 2.13–1.36 (6H, m, c-hex-H). HPLC: Chiralcel-
OD. Hexane–i-PrOH, 95 : 5, 1.5 mL min−1, 254 nm: tR (major) =
11.5 min; tR (minor) = 12.4 min. (2R,1ꢀR)-[Hydroxy-(4-nitrophenyl)-
methyl]-tetrahydrothiopyran-4-one. anti 1H NMR (400 MHz, CDCl3)
d = 8.23 (2H, d, J = 8.7 Hz, ArH), 7.52 (2H, d, J = 8.7 Hz, ArH),
4.99 (1H, d, CHCHOH), 3.36 (1H, m, CHCHOH), 2.93–2.88 (3H, m),
2.73–2.68 (2H, m), 2.55–2.48 (2H, m). HPLC: Chiralcel-OD. Hexane–
i-PrOH, 90 : 10, 1.5 mL min−1, 254 nm: tR (major) = 31.6 min; tR
(minor) = 20.8 min.
15 (a) C. Maury, T. Gharbaoui, J. Royer and H.-P. Husson, J. Org.
Chem., 1996, 61, 3687–3693; (b) C. Maury, Q. Wang, T. Gharbaoui,
M. Chiadmi, A. Tomas, J. Royer and H.-P. Husson, Tetrahedron, 1997,
53, 3627–3636.
16 Typical procedure for aldol reaction: Aminophosphonate catalyst 1 or
2 (0.2 mmol) and aldehyde (1.0 mmol) were added to a solution of
acetone (0.2 mL) and DMSO (0.8 mL). The mixture was stirred at
rt for the given time. The reaction was then quenched with saturated
aqueous NH4Cl (1 mL) and then extracted with EtOAc (3 × 1 mL).
21 (a) F. R. Clemente and K. N. Houk, Angew. Chem., Int. Ed., 2004, 43,
5766–5768; (b) C. Agami, Bull. Soc. Chim. Fr., 1988, 3, 499–507; (c) L.
Hoang, S. Bahmanyar, K. N. Houk and B. List, J. Am. Chem. Soc.,
2003, 125, 16–17.
2096 | Org. Biomol. Chem., 2006, 4, 2091–2096
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