Syntheses of chiral hybrid O,N-donor ligands for the investigation of lanthanide complex reactivities in direct aldol condensations

Article abstract of DOI:10.1016/j.tetasy.2005.02.023

A method for the synthesis of new chiral α/β-dimethylamino esters and β-amino ethers from (S,S)-hydrobenzoin is described. These new O,N-donor ligands are expected to prove a useful platform for exploring the relationship between the ligand structure and

Full text of DOI:10.1016/j.tetasy.2005.02.023

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 1521–1526
Syntheses of chiral hybrid O,N-donor ligands for the
investigation of lanthanide complex reactivities in direct
aldol condensations
Jacek Mlynarski,* Joanna Jankowska and Bartosz Rakiel
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Received 21 January 2005; accepted 18 February 2005
Available online 18 March 2005
Abstract—A method for the synthesis of new chiral a/b-dimethylamino esters and b-amino ethers from (S,S)-hydrobenzoin is
described. These new O,N-donor ligands are expected to prove a useful platform for exploring the relationship between the ligand
structure and stereoselective direct aldol condensation catalyzed by their lanthanide complexes. The initial survey of the catalytic
utility of newly synthesized complexes in the unique aldol-Tishchenko reaction of aldehydes and aliphatic ketones is also presented.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
the most versatile.11 In this case two parts of catalyst:
Lewis acid and Brønsted base are necessary for the alde-
hyde acceptor activation and the enolization of the
ketone substrate. To date, the scope of possible
substrates and the selection of applicable catalytic sys-
tems remains still limited. In general, the elaborated
methodology offers a versatile access to aldol-type prod-
ucts from methyl ketones8–11 and the development of
catalytic systems applicable to their methylene ana-
logues12 is more challenging and restricted mainly to
a-hydroxymethyl ketones.6,8b,11c
Lewis acid catalyzed reactions belong to one of the most
powerful methods in modern synthetic chemistry.1
Among the many Lewis acids developed so far, lantha-
nide triflates have received growing attention because
of the unique combinations of their strong Lewis acidity
mixed with mildness and usually high selectivity.2 There-
fore, not only Ln(OTf)3 but also Sc(OTf)3 and Y(OTf)3
(rare earth metal triflates RE(OTf)3) have been used for
numerous processes including carbon–carbon bond
forming reactions and other transformations.3 An enan-
tioselective version of all of these catalytic reactions
would be of great value.4 Despite the enormous develop-
ment in lanthanide elements chemistry the knowledge
about their interaction with a chiral ligands remains nar-
row, and a number of tested structures is still restricted.5
This problem has been solved recently by Shibasaki
et al., who presented an application of the bifunctional
catalyst to the unique stereo- and enantioselective
aldol-Tishchenko reaction.13 In a one-step process, alde-
hydes were reacted with methylene ketones to give
1,3-diol monoesters, which were formed with a simulta-
neous creation of three adjacent stereogenic centers14
as a result of bond reorganization in the cyclic Evans
intermediate.15 This methodology requires activated
aromatic ketones, hence its application to aliphatic
substrates needs further exploration.
On the other hand, metal-catalyzed asymmetric direct
aldol reactions of aldehydes with unmodified ketones
still remain a challenge for synthetic chemists.6 Remark-
able success in this area is a result of ShibasakiÕs work
on homo- and heterobimetallic catalysts.7 Despite some
promising reports on other metals (e.g., zinc,7b,8 bar-
ium,9 and calcium10) heterobimetallic catalyst contain-
ing lanthanides as the catalyst core turned out to be
At around the same time, we reported the first example
of the aldol-Tishchenko reaction of aliphatic ketone, for
example, 3-pentanone (Scheme 1).16 Although not yet
selective enough, this catalytic system is applicable to
aliphatic substrates, which makes this methodology
interesting in terms of natural product synthesis. This
premise encouraged us to carry on with our research.
*
Corresponding author. Tel.: +48 223432130; fax: +48 226326681;
e-mail: mlynar@icho.edu.pl
Student of Warsaw University of Technology.
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.02.023

1522
J. Mlynarski et al. / Tetrahedron: Asymmetry 16 (2005) 1521–1526
2. Results and discussion
O
O
N
N
O
O
N
N
N
N
O
O
O
O
O
O
Previously, we revealed that a hydrobenzoin, ytter-
bium(III) triflate, and tertiary amine combination pro-
vided the highest level of asymmetric induction (up to
75% ee) observed to date in the addition of 3-pentanone
to aldehydes (Scheme 1).16 As we supposed, binding of
the amine to the hydroxyl group (type-1 structure) is
essential for catalytic activity of this species.17 We
assumed that the existence of two active centers in this
structure making possible simultaneous donor and
acceptor activation toward direct aldol condensation is
a condition sine qua non of the reaction. We presumed
that the amino group fixed to molecule would exhibit
catalytic activity as well, and that such a defined archi-
tecture would form a more efficient catalyst. To realize
this concept and make use of the general principle of
the two-center ligand, we herein report the synthesis of
new compounds as promising ligands for stereoselective
direct aldol condensation.
5
7
6
Figure 1.
amino ether moieties from commercially available
hydrobenzoin. Our strategy for hindered chiral amino
ether 5 required an optimized Williamson procedure at
the etherification stage (Scheme 2). We applied double
coupling of diol 8 with dimethylamino ethanol trans-
formed previously into appropriate tosyl derivative.
Considering the fact that the synthesis of the required
tosylate is delicate and not suitably described in the lit-
erature,21 probably because of high instability of the
structure with leaving group in the b-position to amino
function, we decided, nevertheless, to chance it this way.
NR3
H
N
N
O
O
O
OH
OH
O
b
a
Yb(OTf)3
OH
O
Ar
N
O
H
8
5
9
1
O
H
Ar
ArCHO +
Scheme 2. Reagents and conditions: (a) KH, 18-crown-6, THF, then
Me2N(CH2)2OTs, rt; (b) reflux, 89%.
O
O
M
2
Despite the instability of the tosylate toward all isol-
ation methods tested, it survived the substitution reac-
tion conditions. Thus freshly prepared tosylate was
cannulated into hydrobenzoin dianion solution at rt.
To generate the dianion, potassium, and sodium hydride
were tested. In both cases, after combining with the
tosylate, only monosubstituted ether 9 was detected in
the reaction mixture. Much better results were obtained
when an improved Aspinall et al.20 methodology was
applied. The nucleophilicity of the hydrobenzoin anion
was increased by solvation of the ion pair with 15-
crown-5 (for Na+) or 18-crown-6 (for K+). In our hands,
the application of potassium hydride was very promis-
ing. Under optimized conditions the desired diether 5
was isolated in 89% yield after 1-h reflux of the reaction
mixture.
O
O
OH
O
Ar
Ar
O
OH
Ar
Ar
4
3
Scheme 1. Aldol-Tishchenko reaction of 3-pentanone with aldehydes.
While many structurally diverse architectures have been
introduced in recent years to enantioselective reactions
catalyzed by lanthanide elements,4 there exists a paucity
of reported variation in complexes containing Ln(OTf)3
combined with mixed O,N-donor neutral ligands.5 More-
over, the presented examples have been applied to an-
other type of C–C bond forming reactions18 and to the
best of our knowledge such neutral ligands have never
been applied to direct aldol condensation. In this regard,
tuning of chiral hybrid ligands is necessary for reaction
optimization. We addressed this deficiency by preparing
a family of (S,S)-hydrobenzoin-based ligands possessing
both O- and N-heteroatoms located along the catalyst
arms. To enable a comprehensive study of the ligand ef-
fect we designed syntheses of diether 5 and diesters 6
and 7 equipped with dimethylamino groups (Fig. 1).
A similar protocol was applied for the acylation of 8
with dimethylcarbamoyl chloride. While all standard
conditions (HunigÕs base, DMAP, reflux in pyridine)
¨
failed in the case of such a hindered ester, application
of crown ether/NaH resulted in the formation of mono-
ester 11 transformed after short reflux in THF into dies-
ter 7 with 71% yield (Scheme 3).
DCC-promoted esterification was applied for obtaining
diester 6. When hydrobenzoin were treated with dimeth-
ylaminoglycine, DCC, and DMAP 6 was formed as the
main product accompanied with some amount of 10.
After procedure optimization, when only a catalytic
amount of DMAP was loaded, 6 was isolated with
97% yield.
We decided to test two types of ligands, that is, having
N-centers by two and one carbon atoms removed from
oxygen atoms. Syntheses of the target ligands require a
routine preparation of hindered ethers/esters in high
yields from optically active precursors.19,20 Our first
aim was to synthesize the catalyst, which possess two

J. Mlynarski et al. / Tetrahedron: Asymmetry 16 (2005) 1521–1526
1523
important to stress that homogeneous solutions were
obtained from all ligands–Yb(OTf)3 combinations in
THF. When 20 mol % of ligand 5 was used, desired
esters 14 and 15 were formed in 75% overall yield,
albeit in racemate forms.
O
O
O
N
N
N
OH
OH
O
O
O
a
+
OH
10
8
6
b
Unsymmetrical ligand 9 failed to react. In contrast,
unsymmetrical monoester 10 delivered Tishchenko
products in good yield, but in small enantiomeric excess
(5% ee). Its acetyl derivative Ac-10 showed similar reac-
tivity and selectivity. When diester 6 was added as a chi-
ral ligand, the reactivity and stereoselectivity increased,
and both products were isolated in 96% yield after 2 h
with 24 ee. Next we tried to reduce the catalyst loading,
with the reaction carried out with 10% of 6/Yb(OTf)3
combination (entry 8). The yield, as well as stereoselec-
tivity, remained at the same level. Interestingly, the ste-
reoselectivity dropped when the reaction was run at
À20 ꢁC, and remained untouched at 40 ꢁC. To check
the role of the ligand arms structure we tested acetylated
hydrobenzoin, which gave only unpromising results (en-
try 10) even with amine as additive. This observation
shows that both the structural part of the ligand (ester
moiety and amino group) is necessary for this reaction.
Ligands with longer amino acid chains were tested (from
hippuric acid and Z-Gly-OH) albeit with less promising
results. Despite its reactivity, ligand 13 was unselective
(entry 11), which suggests that the presence of benzyl-
type hydrogen atom is necessary in catalyst structure.
Both ligands with shorter arms, that is, 7 and 11,
failed.
O
N
N
O
O
O
O
c
OH
O
N
11
7
Scheme 3. Reagents and conditions: (a) dimethylaminoglycine, DCC,
DMAP, DCM, rt, 97%; (b) NaH, 15-crown-5, dimethylcarbamoyl
chloride, THF, rt; (c) reflux, 71%.
To test a broad range of ligands we decided to apply an
elaborated methodology to the esterification of the chi-
ral 2,3-butanediol 12. In this case, diester 13 was isolated
in 63% yield (Scheme 4).
O
N
OH
OH
O
a
O
12
N
O
13
Scheme 4. Reagents and conditions: (a) dimethylaminoglycine, DCC,
DMAP, DCM, rt, 63%.
With the best ligand in hand, we tested various metal
sources. A systematic evaluation of RE(OTf)3 in the
condensation of benzaldehyde with 3-pentanone re-
vealed a consistent increase in enantioselectivity as a
function of the lanthanide atomic number, with the
highest ee of 24% obtained with Yb(OTf)3 (Table 2).
Having the new ligands in hand, we tested their catalytic
activity with ytterbium triflate, which was found as the
most promising metal salt during previous screenings.16
Preliminary results are summarized in Table 1. It is
Table 1. Direct aldol-Tishchenko reaction promoted by O,N-ligands/ytterbium triflate
O
O
O
Yb(OTf)3 / L
OH
O
Ph
Ph
O
OH
THF / rt
+
+
Ph
Ph
2 PhCHO
14
15
Entry
Ligand
Catalyst loading, mol %/time, h
Yield, % (14/15)
Ee
1
5
10/20
20/20
Trace
75 (1/2)
ND
—
0
2
5
3
9
10
20/20
20/20
—
5
4
74 (1/3.3)
62 (1/7)
96 (2/1)
90 (3/1)
97 (2/3)
90
5
Ac-10
6
20/20
20/2
7
6
24
10
24
20
0
7
6
20/4 (À20 ꢁC)
10/4
8
6
9
6
10/4 (40 ꢁC)
20/20
10/20
10
11
12
13
Ac-8/EtiPr2N
13 (1/0)
84 (2/1)
ND
13
11
7
0
20/20
20/20
—
—
ND

1524
J. Mlynarski et al. / Tetrahedron: Asymmetry 16 (2005) 1521–1526
Table 2. Optimization on the aldol-Tishchenko reaction of 3-pentanone and benzaldehyde catalyzed by 6 and RE(OTf)3 (10 mol %)
RE(OTf)3
Sc
La
Pr
Sm
Eu
Dy
Er
YbY
In
Yield (%)
De (%)
Ee (%)
ND
—
ND
—
15
40
8
35
20
8
62
28
10
83
80
15
94
95
20
97
99
24
95
93
8
ND
—
—
—
—
In the case of the more reactive 4-chloropropiophenone,
as little as 5 mol % of catalyst is sufficient enough for
obtaining 63% yield. When 10 mol % of catalyst was
used, 98% of the desired product was isolated after 4 h
at rt albeit with only 19% ee.
480 mg, 10 mmol) was weighed into a Schlenk flask con-
taining a magnetic stirring bar under Ar and washed
with dry THF. To a stirred suspension of the base in
dry THF (5 mL) at 0 ꢁC was added dimethylamino eth-
anol (500 lL, 5 mmol). After 5 min a solution of tosyl
chloride (1.15 g, 6 mmol) in THF (5 mL) was added.
Thus a prepared solution of tosylate was directly trans-
ferred into the hydrobenzoin dianion.
3. Conclusions
In summary, we have demonstrated syntheses of novel
chiral ligands, which enable efficient, diastereoselective
aldol-Tishchenko condensation. A metal/ligand com-
plexes were designed, which possess two sites of opposite
character—a basic site and an acidic site, each capable of
independent activation in close proximity the ketone and
the aldehyde substrate. Such catalytic systems have been
found to be applicable to the difficult aldol reaction of 3-
pentanone providing a powerful method for the simulta-
neous construction of three continuous chiral centers.
Gathered data are useful for designing new effective
ligands. With these complexes in hand, we are now en-
gaged in evaluating their catalytic activity and the scope
of the reaction. These data will be reported elsewhere.
4.2.2. Preparation of ligands. Potassium hydride (30%
dispersion in mineral oil, 480 mg, 3 mmol) was weighed
into a Schlenk flask containing a magnetic stirring bar
under Ar and washed with dry THF. To a stirred sus-
pension of the base in dry THF (5 mL) at 0 ꢁC, (S,S)-
hydrobenzoin (215 mg, 1 mmol) was added. 18-Crown-
6 (790 mg, 3 mmol) was slowly added, and the whole
mixture stirred for 15 min. Then dimethylamino ethanol
tosylate solution (ca. 5–7 mL) was added to the alkoxide
solution. The flask was fitted with a reflux condenser,
and reaction mixture heated to 80 ꢁC for 1 h. The reac-
tion mixture was diluted with ethyl acetate, quenched
with water, and washed twice with water and brine.
The organic phase was evaporated, and the residue sub-
mitted to column chromatography (CH2Cl2–MeOH,
7:3 + 0.5% Et3N) to yield 320 mg (89%) of compound
5; mp 47 ꢁC; [a]D = À0.55 (c 1.00, CHCl3); IR (KBr): m
3031, 2942, 2868, 2819, 2796, 1454, 1272, 1112, 1073,
4. Experimental
4.1. General
1
1043; H NMR (500 MHz): d 2.23 (s, 12H), 2.45–2.56
(m, 4H), 3.39–3.49 (m, 4H), 4.43 (s, 2H), 7.03–7.06
and 7.13–7.17 (m, 10 H, Ar); 13C NMR (125 MHz): d
45.6, 58.7, 67.45, 86.2, 127.3, 127.6, 127.7, 138.6; HRMS
(ESI) calcd for C22H32N2O2 [M+Na]+ 379.2356, found
379.2372. When the above reaction was quenched after
30 min without reflux. (1S,2S)-2-[2-(Dimethylamino)-
ethoxy]-1,2-diphenylethanol 9 was isolated as the main
product. Yield: (94%); colorless oil; [a]D = À20.2 (c
1.00, CHCl3); IR (KBr): m 3369, 3028, 2855, 2822,
2778, 1490, 1453, 1120, 1038, 1024; 1H NMR
(500 MHz): d 2.39 (s, 3H), 2.58–2.64 (m, 1H), 2.67–
2.73 (m, 1H), 3.44–3.50 (m, 1H), 3.60–3.65 (m, 1H),
4.22 (d, 1H, J = 8.3 Hz), 4.71 (d, 1H, J = 8.3 Hz),
6.98–7.20 (m, 10H, Ar); 13C NMR (125 MHz): d 44.8,
58.3, 65.6, 78.7, 88.5, 127.3, 127.3, 127.6, 127.7, 127.7,
127.9, 138.2, 139.9; HRMS (ESI) calcd for C18H23NO2
[M+H]+ 286.1802, found 286.1816.
Ytterbium(III) triflate prepared from ytterbium(III)
oxide (Aldrich) and trifluoromethanesulfonic acid (Flu-
ka), was dried for 24 h at 200 ꢁC under vacuum. All
other metal triflates were used as delivered (Aldrich)
and dried at 200 ꢁC directly before reactions. All reac-
tions were carried out under argon. Optical rotations
were measured with a JASCO Dip-360 Digital Polarim-
1
eter at room temperature. H NMR spectra were re-
corded on Varian-400 and Bruker-500 spectrometers in
CDCl3 with Me4Si as internal standard. High resolution
mass spectra were taken on a Mariner PerSeptive Bio-
systems mass spectrometer with time-of-flight (TOF)
detector. IR spectra were taken with a Perkin Elmer
FT-IR-1600 spectrophotometer. Reactions were con-
trolled using TLC on silica [Merck alu-plates
(0.2 mm)]. All reagents and solvents were purified and
dried according to common methods. All organic solu-
tions were dried over Na2SO4. Reaction products were
purified by flash chromatography using MerckÕs Kiesel-
gel 60 (240–400 mesh).
4.3. (1S,2S)-1,2-Diphenylethyl-1,2-dioxy-bis-N,N-
dimethylaminoacetate 6
Dicyclohexylocarbodiimide (3.09 g, 15 mmol), dimeth-
ylaminoglycine (1.23 g, 12 mmol), and DMAP
(100 mg) were added to a solution of (S,S)-hydrobenz-
oin (860 mg, 4 mmol) in dry DCM at 0 ꢁC under Ar.
The contents were stirred at rt for 20 h. The solution
was diluted with DCM and the precipitate removed by
4.2. (1S,2S)-1,2-Bis[2-(dimethylamino)ethoxy]-1,2-diphen-
ylethanol 5
4.2.1. Preparation of dimethylamino ethanol tosyl-
ate. Sodium hydride (50% dispersion in mineral oil,

J. Mlynarski et al. / Tetrahedron: Asymmetry 16 (2005) 1521–1526
1525
filtration. The solvent was evaporated and the residue
purified on silica gel column (CH2Cl2–MeOH, 95:5).
Yield 97%; mp 83 ꢁC; [a]D = +30.7 (c 1.00, CHCl3); IR
(KBr): m 3037, 2932, 2903, 1724, 1243, 1177, 1150,
t1 = 12.3 min, t2 = 23.3 min. Second fraction contained
1
ester 15:16 yield 58%, H NMR (400 MHz): d 0.75 (d,
3H, J = 6.9 Hz), 0.94 (t, 3H, J = 7.3 Hz), 1.24–1.69 (m,
2H), 2.02–2.20 (m, 1H), 2.52 (br s, 1H, OH), 3.75 (br
t, 1H, J = 6.5 Hz), 5.95 (d, 1H, J = 9.8 Hz), 7.20–7.68
(m, 8H, Ar), and 8.10 (d, 2H, Ar); 13C NMR
(100 MHz): d 8.8, 10.8, 27.3, 43.0, 71.2, 78.8, 127.4,
128.1, 128.3, 128.4, 129.7, 133.1, 139.4, 166.5. Detection
of enantiomers ratio: HPLC on Chiralpak AD-H
column: hexane–iPrOH (95:5), 1 mL/min; t1 =
23.2 min, t2 = 24.3 min.
1
1068; H NMR (500 MHz): d 2.30 (s, 12H), 3.18 and
3.22 (2 · d, 2 · 2H, J = 17.4 Hz), 6.14 (s, 2H), 7.14–
7.22 (m, 10H, Ar); 13C NMR (125 MHz): d 45.0, 60.1,
77.0, 127.4, 128.2, 128.4, 135. 9, 169.4; HRMS (EI) calcd
for C22H28N2O4 [M]+ 384.2049, found 384.2042. When
equimolar amount of DMAP was used some amount
(7–15%) of 2-[(1S,2S)-2-hydroxy-1,2-diphenylethyl]-
oxy-N,N-dimethylaminoacetate 10 was detected as the
first fraction. Mp 93 ꢁC; [a]D = À7.4 (c 1.00, CHCl3);
IR (KBr): m 3307, 3031, 2848, 1738, 1454, 1204, 1163,
Acknowledgements
1
1058; H NMR (500 MHz): d 2.22 (s, 6H), 3.15 and
Financial support by the Polish State Committee for
Scientific Research (KBN Grant 3 T09A 126 27) is
gratefully acknowledged.
3.19 (2 · d, 2H, J = 15.0 Hz), 4.97 (d, 1H,
J = 7.27 Hz), 5.91 (d, 1H, J = 7.27 Hz), 7.14–7.23 (m,
10H, Ar); 13C NMR (125 MHz): d 45.2, 60.8, 76.8,
80.5, 127.0, 127.3, 127.9, 128.0, 128.1, 137.0, 139.5,
169.4; HRMS (EI) calcd for C18H21NO3 [M]+
299.1521, found 299.1525.
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13
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R. Curr. Org. Chem. 2003, 7, 1713–1723.
15. Evans, D. A.; Hoveyda, A. H. J. Am. Chem. Soc. 1990,
112, 6447.
4.5.1. 1-Hydroxy-2-methyl-1-phenylpentylbenzoate 14
and 3-hydroxy-2-methyl-1-phenylpentylbenzoate 15.
Ytterbium(III) triflate (62 mg 0.10 mmol) was placed
in an oven-dried flask with a magnetic stirring bar and
the flask heated at 200 ꢁC for 10 min in vacuo and then
flushed with argon. After the flask was cooled down to
rt, a solution of ligand 6 (48 mg, 0.12 mmol) in THF
(2 mL) was added. The resulting solution was stirred
for 10 min at rt under an argon atmosphere. To a solu-
tion of the catalyst 3-pentanone (106 lL, 1.00 mmol)
and benzaldehyde (101 lL, 1.00 mmol) were added suc-
cessively. The resulting solution was stirred for 20 h at
rt, then dissolved with MTBE, and washed with water
and brine. The organic layer was dried over Na2SO4,
concentrated, and submitted to column chromatogra-
phy (hexane–ethyl acetate, 9:1). First fraction contained
1
ester 14:16 yield 39%, H NMR (400 MHz): d 0.75 (d,
3H, J = 6.9 Hz), 0.99 (t, 3H, J = 7.4 Hz), 1.55–1.76 (m,
1H), 1.81–2.12 (m, 2H), 3.71 (d, 1H, J = 3.8 Hz, OH),
4.19 (dd, 1H, J = 3.6, 9.8 Hz), 5.62 (ddd, 1H, J = 1.5,
5.6, 8.7 Hz), 7.20–7.64 (m, 8H, Ar), and 8.10 (d, 2H,
Ar); 13C NMR (100 MHz): d 9.9, 10.5, 25.7, 44.3, 75.7,
75.8, 127.0, 127.6, 128.3, 128.4, 129.7, 133.2, 142.8,
167.6. Detection of enantiomers ratio: HPLC on Chir-
alpak AD-H column: hexane–iPrOH (9:1), 1 mL/min;

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J. Mlynarski et al. / Tetrahedron: Asymmetry 16 (2005) 1521–1526
16. Mlynarski, J.; Mitura, M. Tetrahedron Lett. 2004, 45,
7549–7552.
macrocyclic O,N-donors, see: Hamada, T.; Manabe, K.;
Ishikawa, S.; Nagayama, S.; Shiro, M.; Kobayashi, S. J.
Am. Chem. Soc. 2003, 125, 2989–2996.
17. Such a structure was proven by Kobayashi for the
binaphthol-based catalytic system: (a) Kobayashi, S.;
Ishitani, H. J. Am. Chem. Soc. 1994, 116, 4083–4084; (b)
Kobayashi, S.; Ishitani, H.; Araki, M.; Hachiya, I.
Tetrahedron Lett. 1994, 35, 6325–6328; (c) Kobayashi, S.;
Kawamura, M. J. Am. Chem. Soc. 1998, 120, 5840–5841.
18. For binol–amine combination see Ref. 17. For the pybox
ligand family, see: Desimoni, G.; Faita, G.; Quadrelli, P.
Chem. Rev. 2003, 103, 3119–3154, and Ref. 5; For
19. Aspinall, H. C.; Greeves, N.; Lee, W. M.; McIver, E. G.;
Smith, P. M. Tetrahedron Lett. 1997, 38, 4679–4682.
20. Aspinall, H. C.; Greeves, N.; McIver, E. G. Tetrahedron
2003, 59, 10453–10463.
21. For a precedent mesylane synthesis in 15% yield, see: Goff,
D. A.; Koolpe, G. A.; Kelson, A. B.; Vu, H. M.; Taylor,
D. L.; Bedford, C. D.; Musallam, H. M.; Koplovitz, I.;
Harris, R. N., III. J. Med. Chem. 1991, 34, 1363–1368.