Ligand effects in aluminium-catalyzed asymmetric Baeyer-Villiger reactions

Article abstract of DOI:10.1016/j.tet.2005.12.080

Asymmetric Baeyer-Villiger oxidations of racemic and prochiral cyclobutanones can be performed with chiral aluminium-based Lewis acids resulting in products with good enantioselectivities in high yields. By employing substituted BINOL derivatives as ligan

Full text of DOI:10.1016/j.tet.2005.12.080

Tetrahedron 62 (2006) 6700–6706
Ligand effects in aluminium-catalyzed asymmetric
Baeyer–Villiger reactions
Jean-C e´ dric Frison, Chiara Palazzi and Carsten Bolm
*
Insitut f u€ r Organische Chemie der RWTH Aachen, Landoltweg 1, 52074 Aachen, Germany
Received 1 December 2005; revised 28 December 2005; accepted 29 December 2005
Available online 26 May 2006
Abstract—Asymmetric Baeyer–Villiger oxidations of racemic and prochiral cyclobutanones can be performed with chiral aluminium-based
Lewis acids resulting in products with good enantioselectivities in high yields. By employing substituted BINOL derivatives as ligands, re-
markable catalyst efficiencies have been achieved and g-butyrolactones with up to 84% ee were obtained. The relation between the electronic
properties of the ligand and the enantioselectivity of the reaction has been investigated, leading to a better understanding of the requirements
for achieving a good enantioselectivity in this aluminium-catalyzed oxidative transformation.
Ó 2006 Elsevier Ltd. All rights reserved.
1
. Introduction
80% ee (Eq. 1). For example, Katsuki utilizes chiral salen
metal complexes 3 (with M¼Zr or Hf) as catalysts for asym-
4
The Baeyer–Villiger reaction is a highly useful oxidative
transformation in synthetic organic chemistry, which allows
the conversion of ketones into esters and lactones. The latter
represents core structures of a number of biologically active
compounds and, in particular, g-butyrolactones have proven
to be useful intermediates for the synthesis of complex target
molecules. Since the first reports on metal-catalyzed asym-
metric transformations of 1a (ee ¼87%). Another system
max
stems from our group and is based on chiral BINOL-type
ligands in combination with aluminium reagents. For exam-
1
5
0
when treated with equimolar amounts of Me AlCl promoted
6
ple, we found that VANOL (4) or 6,6 -dibromo-BINOL (5)
2
the Baeyer–Villiger oxidation of cyclobutanone 1a to give
lactone 2a with good enantioselectivity (83 and 77% ee,
respectively) in excellent yield.
2
metric Baeyer–Villiger reactions in 1994, numerous chiral
catalysts have been developed for this transformation. To
3
date, however, only very few of them allow the conversion
of simple substrates such as 1-phenylcyclobutanone (1a)
into the corresponding g-butyrolactone 2a with more than
Several optimizationstudieshavealreadybeen conductedand
the appropriate choice of reagents and reaction parameters
such as the solvent, the oxidant, the aluminium source and
the temperature proved to be essential for achieving an effi-
O
O
Catalyzed asymmetric
Baeyer-Villiger reaction
6
cient catalysis. In order to further improve the promising re-
O
sult obtained with simple BINOL derivative 5, we decided to
determine the influence of the ligand structure on the catalyst
activity and the enantioselectivity in more detail. The results
of this study are presented here. Unless noted otherwise, all
enantioselectivities and yields mentioned in this article refer
to the Baeyer–Villiger reaction of 3-phenylcyclobutanone
(1)
1a
2a
(
1a)togiveg-butyrolactone2a(Eq. 1), whichweusedasstan-
Br
Br
N
N
O
dard test. In cases, where incomplete reactions are reported,
prolongations of the reaction time did not lead to higher
conversions. Thus, the indicated reaction time corresponds
to the point at which maximum conversion was reached.
M
O
Ph
Ph
OH
OH
OH
OH
Ph Ph
2. Results and discussion
3
(with M = Zr or Hf)
4
5
2
.1. Effects of substituted ligands
Keywords: Aluminium; Baeyer–Villiger oxidation; BINOL; Catalysis;
Oxidation.
Our previous studies had shown that axially chiral BINOL-
type ligands gave high enantioselectivities. However, in the
*
Corresponding author. Tel.: +49 241 8094675; fax: +49 241 8092391;
e-mail: carsten.bolm@oc.rwth-aachen.de
0
040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.12.080

J.-C. Frison et al. / Tetrahedron 62 (2006) 6700–6706
6701
light of the successful applications of other chelating mole-
cules in metal-catalyzed oxidations, the current optimization
study was started by investigating the effect of Schiff-bases
Table 1. Application of steroidal BINOLs in Baeyer–Villiger oxidations of
1
a
a
b
0
Entry Ligand
R
R
Conv. Abs config. ee (%)
c
(%) of 1a of 2a
7
8
9
6
, 7 and 8 on the transformation shown in Eq. 1. Whereas
of 2a
the former two compounds are axially chiral as 5, the latter
has only a stereogenic centre. Unfortunately, however, the
presence of none of these compounds (in combination
1
2
3
4
5
6
7
8
9
1
(S
a
)-14a
H
H
H
H
100
100
60
(+)
(ꢀ)
(+)
67
68
8
rac
67
60
68
69
69
73
(R )-14a
a
(S
a
)-14b
N–NH
N–NH
N–NHTos
2
(R
(R
a
)-14b
)-14c
2
40
with Me AlCl) allowed the oxidations of 1a with cumene
2
a
100
100
100
100
100
100
(ꢀ)
(+)
hydroperoxide (CHP) as oxidant under standard reaction
conditions. Since additives such as amines or phosphine ox-
ides can inhibit the oxidation, we hypothesized that the pres-
ence of multiple coordination sites in 6–8 was responsible
for this low catalyst activity. Consequently, the use of axially
(S
a
)-14d
)-14d
SCH
SCH
2
CH
CH
2
S
S
(R
a
(S )-14e
(R
(R
a
2
2
(ꢀ)
OH
H
H
(+)
a
)-14e OH
)-14f
(ꢀ)
(ꢀ)
0
a
O
1
0
11
a
b
c
chiral N,N- and N,O-chelates 9 and 10 was attempted.
Those compounds resemble BINOLs, but distinguish them-
selves by the presence of one or two triflated amino groups.
Also the presence of these compounds had a detrimental
effect on the catalyst activity, which was now attributed to
the electronic properties of the ligand.
Reaction conditions: 1a (0.5 mmol), 14 (50 mol %), Me AlCl (50 mol %),
2
ꢁ
CHP (1.5 equiv), toluene, ꢀ25 C to rt.
Only the axial chirality is indicated. The stereogenic centres relate to the
natural steroid skeleton.
Determined by GC using a chiral column: Lipodex B (25ꢂ0.25 mm),
ꢁ ꢁ ꢁ ꢁ
2
0 kPa N , at 140 C; 140 C, 15 min, 2 C/min, 160 C, 50 min;
6
tR¼65.0 min (S), 66.6 min (R).
I
NHTf
NHTf
I
NHTf
OH
OH
OH
N
N
N
N
HO
I
OH HO
HO
I
6
7
8
9
10
Based on these observations we decided to focus our atten-
tion on the use of substituted BINOLs. Previous studies
with diastereomeric ligands, the additional stereogenic cen-
tres in the ligand backbone had only a minor influence on
the enantioselectivity of the oxygen insertion. Only with
the two diastereomeric ligands of 14d a difference of 8%
ee (60 vs 68% ee; entries 6 and 7, respectively) in the forma-
tion of product 2a was detected. In all cases the absolute con-
figuration of lactone 2a was determined by the chiral axis.
Again, the presence of an additional coordinating group
(such as the hydrazone moiety in 14b; Table 1, entries 3
1
2
had revealed that BINOLs 11 with substituents at the 3-
and 3 -positions were less efficient compared to their 6,6 -di-
0
substituted counterparts (such as 5) giving lactones with
0
6
very low enantioselectivity. To our surprise it was now
found that 4,4 ,6,6 -tetrabromo-BINOL 12 gave racemic
0
0
a. BINOL 13 having bromo substituents at the 7,7 -posi-
13
0
2
tions afforded 2 in good ee of 64%.
1
4
R'
R
Me
H
Br
Br
R
Br
Br
OH
OH
OH
OH
Br
Br
OH
OH
OH
OH
H
R
R'
Me
R
11
12
13
14
1
5
Steroidal BINOLs 14 have previously been applied in
various enantioselective metal-catalyzed reactions including
and 4) was detrimental to both catalytic activity and enantio-
selectivity.
1
5b
the asymmetric oxidation of sulfides. There, use of such
BINOL derivatives resulted in higher enantioselectivities
than with BINOL. In contrast, no major improvement in ee
was found, when steroidal BINOLs 14 were applied in the
Baeyer–Villiger reaction of 1a, and out of a range of deriva-
tives only a single compound (14f) performed better than
BINOL leading to 2a with 73% ee (Table 1). As revealed
by the similar ee-values of products obtained in reactions
Since at this stage BINOL derivative 5 with two bromo
0
substituents at the 6,6 -positions had led to the best enantio-
selectivity, this type of substitution pattern was investigated
in more detail. Assuming that the bromo substituents
exhibited an electronic effect on the ligand, the application
of other BINOLs with electronically modified arenes
was studied. A particular emphasis was put on BINOLs

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J.-C. Frison et al. / Tetrahedron 62 (2006) 6700–6706
0
3
with electron-withdrawing substituents, since those were ex-
pected to positively affect the catalytically active metal cen-
tre by increasing its Lewis acidity. Starting point was the
substituents at the 6,6 -positions and the sp hybridized car-
bons in the ligand framework, respectively. Presumably, due
to these steric effects in combination with the lack of activat-
ing substituents the catalysts bearing 19 and 20 showed only
a moderate efficiency (with full conversions of 1a after 24
and 16 h, respectively) affording lactone 2a with 76 and
73% ee, respectively.
1
6
17
synthesis and use of 15, 16 and 17 with iodo, trifluoro-
methyl and nitrilo substituents, respectively, in the 6- and
0
derivative 18 was tested.
6
-positions of the BINOL skeleton. Furthermore, octafluoro
1
8
F
F
C
NC
NC
F
I
3
3
OH
OH
OH
OH
OH
OH
F
F
F
F
OH
OH
I
F
C
F
F
15
16
17
18
OH
OH
OH
OH
19
20
To our delight we found that Baeyer–Villiger oxidation of 1a
with 10 mol % of a catalyst derived from diiodo BINOL 15
Since Shibasaki had demonstrated that BINOLs with acetyl-
enic substituents in the 6,6 -positions were excellent ligands
0
for Lewis acid catalyzed processes, we decided to extend
our studies on the use of BINOL derivatives 21–25.
2
1
(
CHP as oxidant) showed improved properties compared to
and equimolar amounts of Me AlCl in combination with
2
Me Si
H
Ar
3
OH
OH
OH
OH
OH
OH
Me Si
H
Ar
3
21
22
23 Ar = p-MeO-Ph
4 Ar = Ph
5 Ar = 3,5-(CF ) Ph
2
2
3
2
the previous systems affording 2a with 82% ee (at
ꢁ
Gratifyingly, BINOL 21 bearing two trimethylsilylalkynyl
groups at positions 6 and 6 was also highly efficient in the
0
Baeyer–Villiger reaction, and conversion of 1a afforded 2a
ꢀ
30 C). In an attempt to further improve the stereoselectiv-
ity, the reaction was conducted at lower temperatures, but
unfortunately, only a decrease in activity and enantioselec-
with 84% ee. Both the catalyst loading (25 mol %) and the
ꢁ
ꢁ
tivity was observed (59% ee at ꢀ50 C and only 54% con-
temperature (ꢀ30 C) were critical for achieving this enan-
version after 48 h). In contrast to our expectations,
however, use of 16, 17 and 18 led to catalysts with very
low activity, and lactone 2a was formed either as a racemate
tioselectivity at a reasonable reaction rate. Conducting the
reaction with only 5 mol % of the catalyst furnished the lac-
tone with a slightly reduced ee (83%), and the reaction did
not go to completion even after 7 days. As with 15, the enan-
tioselectivity dropped when the catalysis was performed at
(as with a catalyst derived from 16) or with low ee in only
small quantities (best result with 10 mol % of the catalyst
ꢁ
obtained from 17: 45% conversion of 1a, formation of 2a
with 34% ee after 48 h in toluene at ꢀ30 C).
another temperature (81 and 57% ee at ꢀ20 and ꢀ50 C, re-
ꢁ
spectively; in the latter case <10% conversion). Removal of
the trimethylsilyl group of 21 to give BINOL 22 proceeded
1
7
In order to further investigate the impact of the ligand struc-
0
smoothly (K CO in MeOH, 98% yield), but unfortunately,
2
3
ture on the performance of the catalyst, 6,6 -diphenyl-
use of the resulting catalyst (prepared from BINOL 22 and
Me AlCl) did not lead to any improvement of the enantio-
1
9
20
BINOL 19 and octahydro-BINOL 20 were applied in
the Baeyer–Villiger reaction of 1 next. Compared to unsub-
stituted BINOL, 19 and 20 possess a larger torsion angle
between the naphthyl moieties induced by the two phenyl
2
selectivity in the formation of 2a (82% ee). We therefore
concluded that the alkynyl moiety itself and not its terminal
substituent were of importance for the catalyst performance

J.-C. Frison et al. / Tetrahedron 62 (2006) 6700–6706
6703
in the Baeyer–Villiger reaction. In order to confirm this
hypothesis, BINOLs 23–25 with aryl-substituted alkynyl
groups were prepared and applied in the catalysis. Using
substituted substrates occurred in a more enantioselective
manner (Table 2, entries 4 and 5 vs catalyses with
20 mol % of VANOL, which gave 2d and 2e with 41 and
5
2
2 as starting material all three BINOLs could be obtained
37% ee, respectively).
by Sonogashira coupling with the corresponding aryl bro-
mides. By selecting the appropriate aryl moiety the elec-
tronic properties of the alkynyl group (as well as the entire
BINOL) could be varied. Due to the remote position of the
electronic modification we did not expect a major impact
by the inherent steric alternation. Application of BINOLs
Finally, the oxidation of racemic ketone 26 was investigated.
As in previous studies, this cyclobutanone gave two regio-
3
isomeric lactones 27 and 28 upon Baeyer–Villiger reaction
(83% conversion of 26). Again, the enantioselectivities
(34% ee for 27 and 99% ee for 28) were better than those ob-
tained before with analogous systems (e.g., BINOL-based
2
3–25 in the Baeyer–Villiger oxidation of 1a revealed that
6
the best result was obtained with p-methoxy-substituted li-
gand 23. In this case, a full conversion of 1a was observed
ones ), albeit the ratio between the two products was similar
(27:28¼6.7:1).
ꢁ
equimolar amount of Me AlCl and CHP as oxidant) leading
after 18 h (at ꢀ30 C in toluene with 20 mol % of 23, an
2
O
BINOL 21 (10 mol %),
to lactone 2a with 82% ee. Bis(trifluoromethyl)-substituted
BINOL 25 gave the worst result in this series. Even after
O
Me AlCl (10 Mol %)
O
2
O
+
O
CHP, toluene, –30 °C
4
8 h only 54% of ketone 1a was converted and the resulting
product had only 45% ee. After the same period of reaction
time the catalysis with phenyl-substituted 24 led to full con-
version of 1a yielding lactone 2a with 76% ee. These results
are remarkable since they indicate that catalysts prepared
with these types of BINOLs require electron-rich ligands,
which appear to contradict the first assumption that elec-
tron-poor BINOLs might be more efficient due to the result-
ing increased Lewis acidity at the metal centre. Apparently,
a well-balanced electronic tuning of the ligand is essential
for the success of the reaction, and the background of this
key issue will be discussed below taking mechanistic aspects
into consideration.
26
27
28
Cycloalkanones with larger ring sizes could not be converted
with the BINOL 21/Me AlCl catalyst system.
2
2.3. Mechanistic considerations
For a rational design and targeted search of new ligands it
was considered desirable to get insight into the mechanistic
scenario and to identify relevant intermediates. As a first
step, we probed the existence of nonlinear effects
(NLEs), and determined the relationship between the ee
of the ligand and the ee of product 2. At the outset of this
2
2
2
.2. Substrate scope
investigation, the following observations were made. Upon
addition of Me AlCl to a solution of BINOL in toluene,
Using the catalyst derived from BINOL derivative 21 (in
conjunction with 1 equiv of Me AlCl), the substrate scope
of the asymmetric Baeyer–Villiger oxidation was investi-
gated. Cyclobutanones 1a–e served as test substrates. The
results are summarized in Table 2.
2
the mixture turned into a milky suspension with a white pre-
cipitate. This mixture became clearer after the addition of
the ketone, which we interpreted as indication for a modifica-
tion of the catalyst structure. The NLE studies were then
done with BINOL derivative 21. The positive deviation
from linearity [(+)-NLE] revealed the presence of nonmono-
meric species and their relevance in the stereochemistry-
determining step.
2
Compared to the (so far best) catalyst derived from VANOL
(
4), the system with 21 as ligand proved about equal or
less enantioselective for aryl and alkyl substituted cyclo-
butanones (Table 2, entries 1–3 vs catalyses with 20 mol %
of VANOL, which gave 2a, 2b and 2c with 83, 84 and
Since throughout the catalysis the composition of the reac-
tion media changes with time, we had to ensure that the
5
6
9% ee, respectively). However, the conversion of benzyl-
(enantiomerically enriched) product (here 2a) as well as
the (achiral) ketone (here 1a) did not affect the ongoing
reaction. Therefore a control experiment was performed,
which unequivocally showed that the product was formed
with the same level of enantioselectivity throughout the
entire process. Phenomena such as autocatalysis, auto-
amplification or product inhibition/poisoning were thereby
excluded.
Table 2. Substrate scope of the asymmetric Baeyer–Villiger reaction (in
analogy to Eq. 1)
a
a: R = Ph
O
O
O
b: R = p-ClPh
c: R = n-oct
d: R = Bn
e: R =
R
b
Entry
Substrate
mol % of 21
ee (%) of 2
1
Next, NMR studies were undertaken. A very complex H
NMR spectrum was obtained from a 1:1 mixture of BINOL
1
2
3
4
5
1a
1b
1c
1d
1e
25
10
10
10
10
84
72
70
65
56
23
21 and Me AlCl in toluene-d . Upon addition of 5 equiv
2 8
of 3-phenylcyclobutanone (1a) two singlets appeared at
0.24 and 0.33 ppm, replacing the broad coalescent signal cor-
responding to the TMS groups. Furthermore, clear peaks
resulted in the aromatic region. Although a detailed interpre-
tation of (the spectra and) this behaviour is impossible at the
present stage, it is hypothesized that the sharpening of the
a
Reaction conditions: 1 (0.5 mmol), ratio of 21 and Me
ꢁ
2
AlCl¼1:1,
CHP (1.25 equiv), toluene, ꢀ30 C; in all cases the conversion of 1 was
complete.
Determined by GC using chiral columns.
b

6704
J.-C. Frison et al. / Tetrahedron 62 (2006) 6700–6706
signals indicates a change from oligomeric to more low-
molecular associates upon addition of the substrate. Treat-
by chelation. Arrangement B would then be a critical inter-
mediate, from which the product needs to be liberated for
further catalysis. The more Lewis acidic the metal is, the
more difficult this step will be, and even a lack of turnover
(as observed with catalysts derived from 16 and 18) can
result.
ꢁ
ment of this mixture with CHP at ꢀ30 C gave lactone 2a
with 80% ee, which is close to the 84% ee obtained under
more diluted conditions.
2
4
As demonstrated in other aluminium-catalyzed processes,
an ageing of the reaction mixture can be crucial for achiev-
ing high enantioselectivities, and presumably, this process
involves the conversion of multiple (mostly unselective)
catalysts into species presenting high enantioselectivities.
In the attempt to make use of this effect, a 1:1 mixture
R
R
R'''
O
R'''
O
Al
H
O
O
H
O
O
O
Cl
Al
R''
O
O
O
Cl
R'
R'
R''
R
of BINOL (11 with R¼H) and (i-Bu) AlCl was stirred at
R
2
room temperature for 30 min prior to the addition of the
ketone. Unfortunately, however, under those conditions
both conversion (80%) and enantioselectivity (68% ee)
were low. Apparently, the ageing of the catalyst mixture
had a negative effect in this case and presumably more
oligomeric species were formed, which were neither active
nor enantioselective. As a consequence, the conversion of
the substrate was slowed down rendering the overall catal-
ysis inefficient.
A
B
3
. Conclusion
In conclusion, we described ligand effects in the aluminium-
catalyzed asymmetric Baeyer–Villiger reaction of cyclo-
butanones. The careful choice of the ligand in combination
with appropriate reaction conditions allows the preparation
of lactones in excellent yields with enantioselectivities that
are among the highest ever obtained in this reaction.
With the goal to achieve a break-up of the oligomers and
to utilize this deoligomerization in the formation of more
active low-molecular species, we decided to submit the
initial reagent mixture to higher temperatures and, further-
more, to use the Lewis-basic substrate (ketone 1a) to sup-
port this cleavage process. Thus, after BINOL (11 with
R¼H) was treated with the aluminium reagent (20 mol %
each), the ketone was added, and the resulting mixture
4. Experimental
4.1. General
Details of the asymmetric Baeyer–Villiger reaction protocol
as well as the analytical data (including ee determinations)
have been reported previously.
ꢁ
5,6
was heated at 70 C for a period of 30 min. After cooling
ꢁ
to ꢀ30 C and addition of the oxidant, the reaction pro-
0
naphthalenyl-2,2 -diol (23). In a Schlenk tube filled with ar-
0
ceeded smoothly to full conversion of 1a (after 24 h),
and lactone 2a was obtained with remarkable 75% ee. A
comparable experiment without this pretreatment at elevated
temperature led to product 2a with only 68% ee. A higher
4.1.1. (R)-6,6 -Bis-(4-methoxyphenylethynyl)-[1,1 ]bi-
0
gon were successively added PdCl (9 mg, 0.05 mmol), PPh
2
3
(55 mg, 0.2 mmol), CuI (11 mg, 0.06 mmol), 22 (334 mg,
1 mmol) and NEt3 (10 mL). 4-Bromoanisole (470 mg,
2.5 mmol) was then added, and the mixture was heated at
ꢁ
temperature (90 C) or prolonged heating times (2–16 h) re-
sulted in a lower catalyst activity. The same procedure was
applied in a catalysis with 19 as ligand, and also in this
case, product 2a was formed with an improved enantioselec-
tivity (80% ee). Catalysts prepared from VANOL (4) and
BINOL derivative 21 behaved differently, and no increase
in ee was found.
ꢁ
70 C for 8 h. When the reaction was complete (controlled
by TLC), the solution was diluted with ethyl acetate and fil-
tered through Celite. The volatiles were removed and the
crude mixture redissolved in ethyl acetate, washed with
1 M HCl, brine and dried (MgSO ). Column chromatography
4
(
silica gel; acetone/pentane 1:4) furnished 498 mg of a
ꢁ
1
The formation of aggregates might also explain the required
electronic fine-tuning of the ligand, which is a key for
achieving high activity and enantioselectivity. On one
hand, a certain level of Lewis acidity is essential for the con-
formational fixation and activation of the substrate. Thus, we
assume that the ketone is coordinated to the metal site of an
intermediately formed chiral aluminium reagent, and upon
oxygen transfer and stereoselective rearrangement the ob-
served Baeyer–Villiger product is formed. Such process
could proceed via the intermediacy of a pentacoordinated
aluminium complex A, which would show structural analo-
gies to other known organoaluminium reagents. If, on the
other hand, the Lewis acidity is (too) high, two other points
become relevant. First, the (spectroscopically observed)
aggregates of the chiral aluminium reagent are difficult to
break, which slows down the catalysis, and second, the
Criegee adduct formed during the reaction might act as
bidentate ligand and thereby block turnover of the catalyst
yellow solid (91% yield); mp¼147–149 C; H NMR
(400 MHz) d 7.99 (s, 2H), 7.86 (d, J¼8.8 Hz, 2H), 7.35–
7.25 (m, 8H), 6.98 (d, J¼8.7 Hz, 2H), 6.80 (d, J¼8.8 Hz,
1
3
2H), 5.06 (br s, 2H), 3.74 (s, 6H); C NMR (100 MHz)
d 159.6, 153.3, 133.1, 132.7, 131.6, 131.4, 130.2, 129.2,
124.3, 119.3, 118.5, 115.4, 114.1, 110.9, 89.8, 88.2, 55.4;
ꢀ
1
IR (KBr): n¼3000 cm ; MS (EI, 70 eV): m/z 546 (100),
273 (50); Anal. Calcd for C H O : C, 83.50; H, 5.21.
3
8 26 4
Found: C, 83.01; H, 5.14.
0
0
4.1.2. (R)-6,6 -Bis-(phenylethynyl)-[1,1 ]binaphthalenyl-
0
21
2,2 -diol (24). In analogy to the synthesis of 23 but with
bromobenzene (425 mg, 2.5 mmol) instead of 4-bromoani-
sole. Column chromatography (silica gel; acetone/pentane
1
1:4) furnished 498 mg of a white solid (91% yield). H
NMR (400 MHz) d 8.04 (d, J¼1.4 Hz, 2H), 7.88 (d,
J¼9.0 Hz, 2H), 7.51–7.46 (m, 4H), 7.37 (m, 10H), 7.04 (d,
1
3
J¼8.5 Hz, 2H), 5.06 (br s, 2H); C NMR (100 MHz)

J.-C. Frison et al. / Tetrahedron 62 (2006) 6700–6706
6705
d 153.4, 132.9, 131.9, 131.6, 131.5, 130.2, 129.1, 128.4,
1
A. K. Yudin, University of Toronto, for providing samples
of BINOL derivatives 14 and 18, respectively.
28.3, 124.3, 123.3, 119.0, 118.6, 110.8, 89.8, 89.3.
0
4
.1.3. (R)-6,6 -Bis-(3,5-bis-trifluoromethylphenyl-
0
0
ethynyl)-[1,1 ]binaphthalenyl-2,2 -diol (25). In analogy
to the synthesis of 23 but with 3,5-bis(trifluoromethyl)-
bromobenzene (732 mg, 2.5 mmol) instead of 4-bromoani-
sole. Column chromatography (silica gel; acetone/pentane
References and notes
1
. (a) Krow, G. R. Org. React. 1993, 43, 251; (b) Hassal, C. H.
Org. React. 1957, 9, 73; (c) Krow, G. R. Comprehensive
Organic Synthesis; Trost, B. M., Fliming, I., Eds.; Pergamon:
Oxford, 1991; Vol. 7, p 671; (d) Bolm, C. Advances in
Catalytic Processes; Doyle, M. P., Ed.; JAI: Greenwich,
1
:4) furnished 728 mg of a yellow solid (96% yield);
H NMR (400 MHz) d 8.18 (d,
ꢁ
1
mp¼117–119 C;
J¼1.6 Hz, 2H), 8.00 (s, 6H), 7.86 (s, 2H), 7.59–7.42 (m,
1
3
4
(
1
H), 7.16 (d, J¼8.6 Hz, 2H), 4.94 (br s, 2H); C NMR
100 MHz) d 154.0, 133.9, 133.4, 131.8, 131.4, 130.3,
29.0, 127.0, 124.5, 121.5, 119.0, 117.5, 110.9, 93.0, 86.7;
1997; Vol. 2, p 43; (e) Renz, M.; Meunier, B. Eur. J. Org.
Chem. 1999, 737.
2
3
. (a) Bolm, C.; Schlinghoff, G.; Weickhardt, K. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 1848; (b) Gusso, A.; Baccin, R.;
Pinna, F.; Strukul, G. Organometallics 1994, 13, 3442.
. (a) Bolm, C.; Luong, T. K. K.; Beckmann, O. Asymmetric
Oxidation Reactions; Katsuki, T., Ed.; University Press:
Oxford, 2001; p 147; (b) Bolm, C. Peroxide Chemistry;
Adam, W., Ed.; Wiley-VCH: Weinheim, 2000; p 494; (c)
Kelly, D. R. Chim. Oggi 2000, 18, 33 and 52; (d) Bolm, C.;
Beckmann, O. Comprehensive Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
Stuttgart, 1999; Vol. 2, p 803; (e) Strukul, G. Angew. Chem.,
Int. Ed. 1998, 37, 1199; (f) Bolm, C. Med. Res. Rev. 1999,
ꢀ1
IR (KBr): n¼3188 cm ; MS (EI, 70 eV): m/z 758.2 (100),
3
79.2 (22), 351.1 (18); Anal. Calcd for C H F O : C,
4
0
20 12
2
6
3.34; H, 2.69. Found: C, 63.21; H, 3.01.
0
0
carbonitrile (17). Step 1 (synthesis of (R)-2,2 -bis-
0
4
.1.4. (R)-2,2 -Dihydroxy-[1,1 ]binaphthalenyl-6,6 -di-
0
2
1
0
0
methoxymethoxy-[1,1 ]binaphthalenyl-6,6 -dicarbonitrile):
In a Schlenk tube filled with argon were successfully added
Pd(dba) (23 mg, 0.04 mmol), DPPF (44 mg, 0.08 mmol),
(R)-2,2 -bis-methoxymethoxy-[1,1 ]binaphthalenyl-6,6 -di-
bromide (532 mg, 1 mmol), CuCN (540 mg, 5 mmol),
2
0
0
0
n-Bu I (369 mg, 1 mmol) and dioxane (2 mL). The solution
4
was heated at 100 C for 3 h, then cooled to rt, diluted with
1
9, 348; (g) ten Brink, G.-J.; Arends, I. W. C. E.; Sheldon,
ꢁ
R. A. Chem. Rev. 2004, 104, 4105; (h) Bolm, C.; Le Paih, J.;
Frison, J. C. Modern Oxidation Methods; B a¨ ckvall, J. E., Ed.;
Wiley-VCH: Weinheim, 2004; p 253; (i) Bolm, C.; Palazzi,
C.; Beckmann, O. Transition Metals for Organic Synthesis,
ethyl acetate and filtered through Celite. The organic layer
was successively washed with 1 M NaOH, saturated
NaHCO , brine and dried (Na SO ). The solvents were re-
moved, and the crude product was flash chromatographed
with pentane/diethyl ether 1:1 to afford 348 mg of a white
solid (82% yield). H NMR (300 MHz) d 8.20 (d,
3
2
4
2
2
nd ed.; Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim,
004; Vol. 2, p 267.
1
4
. (a) With Zr see: Watanabe, A.; Uchida, T.; Ito, K.; Katsuki, T.
Tetrahedron Lett. 2002, 43, 4481; (b) Watanabe, A.; Uchida, T.;
Irie, R.; Katsuki, T. Proc. Natl. Acad. Sci. U.S.A. 2004, 101,
J¼1.5 Hz, 2H), 7.95 (d, J¼9.2 Hz, 2H), 7.64 (d, J¼
9
8
2
1
1
.2 Hz, 2H), 7.28 (dd, J¼1.5, 8.9 Hz, 2H), 7.07 (d, J¼
.9 Hz, 2H), 5.06 (d, J¼6.9 Hz, 2H), 4.97 (d, J¼6.9 Hz,
5737; (c) With Hf see: Matsumoto, K.; Watanabe, A.; Uchida,
T.; Ogi, K.; Katsuki, T. Tetrahedron Lett. 2004, 45, 2385.
1
3
H), 3.11 (s, 6H); C NMR (75 MHz) d 155.2, 135.4,
34.4, 130.6, 128.5, 127.1, 126.2, 119.8, 119.4, 118.0,
07.6, 94.6, 56.1. This product was utilized in the sub-
5
. Bolm, C.; Frison, J.-C.; Zhang, Y.; Wulff, W. D. Synlett 2004,
1
516.
. (a) Bolm, C.; Beckmann, O.; Palazzi, C. Can. J. Chem. 2001,
9, 1593; (b) Bolm, C.; Beckmann, O.; K u¨ hn, T.; Palazzi, C.;
sequent step without further analysis.
6
7
0
enyl-6,6 -dicarbonitrile (17)):
0
To 2,2 -bis-methoxy-
Step 2 (synthesis of (R)-2,2 -dihydroxy-[1,1 ]binaphthal-
Adam, W.; Rao, P. B.; Saha-M o¨ ller, C. R. Tetrahedron:
Asymmetry 2001, 12, 2441.
0
methoxy-[1,1 ]binaphthalenyl-6,6 -dicarbonitrile (212 mg,
21
0
0
0
7
8
9
. For the aluminium complex, see: Evans, D. A.; Janey, J. M.;
Magomedov, N.; Tedrow, J. S. Angew. Chem., Int. Ed. 2001,
0, 1884.
. (a) Yuan, Y.; Li, X.; Sun, J.; Ding, K. J. Am. Chem. Soc. 2002,
24, 14866; (b) Yuan, Y.; Long, J.; Sun, J.; Ding, K. Chem.—
ꢁ
0
.5 mmol) in CH Cl (1 mL) was added at 0 C a saturated
2
2
methanolic HCl solution (2 mL). The mixture was stirred
for 2 h at rt, and then treated with saturated NaHCO3.
Subsequently, the solution was diluted with CH Cl , ex-
tracted with brine and the organic layer dried (Na SO ).
4
After removal of the solvents, the crude product was recrys-
tallized from CH Cl /pentane to afford 320 mg of 17 as
4
2
2
1
2
Eur. J. 2002, 8, 5033 and references therein.
. For successful applications of this ligand in sulfide oxidations,
see: (a) Pelotier, B.; Anson, M. S.; Campbell, I. B.; Macdonald,
S. J. F.; Priem, G.; Jackson, R. F. W. Synlett 2002, 1055; (b)
Legros, J.; Bolm, C. Angew. Chem., Int. Ed. 2004, 43, 4225;
2
2
1
a white solid (95% yield). H NMR (300 MHz) d 8.15 (s,
H), 7.94 (d, J¼8.9 Hz, 2H), 7.42 (d, J¼8.9 Hz, 2H), 7.31
2
(
2
1
d, J¼8.7 Hz, 2H), 7.05 (d, J¼8.7 Hz, 2H), 5.93 (br s,
(
5
c) Legros, J.; Bolm, C. Angew. Chem., Int. Ed. 2003, 42,
487; (d) Legros, J.; Bolm, C. Chem.—Eur. J. 2005, 11, 1086.
1
3
H); C NMR (75 MHz) d 154.5, 134.4, 133.4, 131.0,
27.2, 127.0, 124.3, 119.0, 118.0, 110.4, 106.1.
1
0. Ooi, T.; Ohmatsu, K.; Uraguchi, D.; Maruoka, K. Tetrahedron
Lett. 2004, 45, 4481.
Acknowledgements
11. Belokon, Y. N.; Bespalova, N. B.; Churkina, T. D.; Cisarova, I.;
Ezernitskaya, M. G.; Harutyunyan, S. R.; Hrdina, R.; Kagan,
H. B.; Kocovsky, P.; Kochetkov, K. A.; Larionov, O. V.;
Lyssenko, K. A.; North, M.; Polasek, M.; Peregudov, A. S.;
Prisyazhnyuk, V. O. V.; Vyskocil, S. J. Am. Chem. Soc. 2003,
125, 12860.
This work was supported by the Fonds der Chemischen
Industrie and the Deutsche Forschungsgemeinschaft
DFG) within the Schwerpunktprogramm 1118. We thank
Dr. M. Schneider, Schering AG, Berlin, and Professor Dr.
(

6706
J.-C. Frison et al. / Tetrahedron 62 (2006) 6700–6706
1
2. Chen, Y.; Yekta, S.; Yudin, A. K. Chem. Rev. 2003, 103,
155.
19. (a) Chen, R.; Qian, C.; de Vries, J. G. Tetrahedron Lett. 2001,
3
42, 6919; (b) Chen, R.; Qian, C.; de Vries, J. G. Tetrahedron
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1
1
3. Gong, L. Z.; Hu, Q. S.; Pu, L. J. Org. Chem. 2001, 66, 2358.
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20. (a) For a review, see: Au-Yeung, T. T.-L.; Chan, S.-S.;
Chan, A. S. C. Adv. Synth. Catal. 2003, 345, 537; (b) For
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21. (a) See Ref. 17; (b) Morita, T.; Arai, T.; Sasai, H.; Shibasaki, M.
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Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: Stuttgart, 1999; Vol. 1, p 101;
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G. K., Ed.; Chapman and Hall: London, 1996; p 9.
1
5. (a) For the preparation of substituted steroidal BINOL-type li-
gands, see: Schneider, M. F.; Harre, M.; Pieper, C. Tetrahedron
Lett. 2002, 43, 8751. For applications of such ligands in asym-
metric catalyses, see: (b) Enev, V. S.; Mohr, J.; Harre, M.;
Nickisch, K. Tetrahedron: Asymmetry 1998, 9, 2693; (c) Bolm,
C.; Dabard, O. Synlett 1999, 360; (d) Kostova, K.; Genov, M.;
Philipova, I.; Dimitrov, V. Tetrahedron: Asymmetry 2000, 11,
3253; (e) Hodgson, D. M.; Stupple, P. A.; Pierard, F. Y. T. M.;
Labande, A. H.; Johnstone, C. Chem.—Eur. J. 2001, 7, 4465.
6. Ishitani, H.; Ueno, M.; Kobayashi, S. J. Am. Chem. Soc. 2000,
1
1
122, 8180.
7. (a) Sasai, H.; Tokunaga, T.; Watanabe, S.; Suzuki, T.; Itoh, N.;
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thetic method, see: Sakamoto, T.; Ohsawa, K. J. Chem. Soc.,
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23. Arai, T.; Sasai, H.; Yamagushi, K.; Shibasaki, M. J. Am. Chem.
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1
8. Yudin, A. K.; Martyn, L. J. M.; Pandiaraju, S.; Zheng, J.;
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