Quinoid BINOL-type compounds as a novel class of chiral ligands

Article abstract of DOI:10.1016/j.tetasy.2005.08.026

A short and efficient synthesis of a novel family of quinone-substituted BINOL-type ligands exploiting the chromium-templated [3+2+1]benzannulation reaction as the key step is reported.

Full text of DOI:10.1016/j.tetasy.2005.08.026

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 3256–3267
Quinoid BINOL-type compounds as a novel class of chiral ligandsI
Ana Minatti and Karl Heinz Dotz*
¨
Kekule´-Institut fu¨r Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universita¨t Bonn,
Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany
Received 8 August 2005; accepted 17 August 2005
´
Dedicated to Professor Jose Barluenga on the occasion of his 65th birthday
Abstract—A short and efficient synthesis of a novel family of quinone-substituted BINOL-type ligands exploiting the chromium-
templated [3+2+1]benzannulation reaction as the key step is reported.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Enantiopure BINOL is one of the most prominent C2-
symmetric, axial-chiral ligands for both stoichiometric
and catalytic asymmetric reactions.1 Nevertheless, the
modification of the chiral backbone in a symmetrical
or non-symmetrical fashion is of great interest as substi-
tution of BINOL may affect not only the steric environ-
ment around the coordinated metal centre but also the
electronic properties of the oxygen atoms, which are
common constituents in many Lewis acidic metal com-
plexes.2,3 The most frequently modified positions at
the binaphthol core are those at the aromatic carbon
atoms 3 and 6. To the best of our knowledge, no quinoid
moieties have ever been attached to BINOL. Herein, we
report a novel class of modified BINOL ligands, which
bear redox-active quinoid functionalities either attached
to the binaphthol core in positions 3 and 6 through a
C–C-single bond or directly annulated. We envisaged
to synthesise this new BINOL-type ligand family using
the chromium-templated [3+2+1]benzannulation reac-
tion as the key step in the synthetic approach. Until
now, we are only aware of a single example of this
synthetic strategy applied to the synthesis of the vaulted
2,20-binaphthol- and 3,30-biphenanthrol ligands
VANOL and VAPOL by Wulff et al.4
The chromium-templated [3+2+1]benzannulation reac-
tion between
a pentacarbonylchromium(0)-carbene
complex A and an alkyne B provides one of the most
powerful tools for generating densely substituted benze-
noid compounds (Scheme 1).5
This unique type of metal carbene reaction proceeds via
a formal [3+2+1] cycloaddition, which involves an a,b-
unsaturated carbene ligand, an alkyne and a carbonyl
ligand and takes place within the coordination sphere
of the chromium(0) metal centre, which acts as a
O
RL
C
R'
RL
R'
Cr(CO)5
A
MeO
+
- CO
RS
RS
Cr
MeO
B
CO
OC
CO
O
OH
(OC)3Cr
R'
RL
RS
Ox
RL
RS
R'
q Reactions of Complex Ligands Part 107. For Part 106 see Bennewitz,
J.; Nieger, M.; Lewall, B.; Do¨tz, K. H. J. Organometal. Chem., in
press.
OMe
O
D
C
*
Scheme 1. Atom connectivity in the regioselective [3+2+1]benzannu-
Corresponding author. Tel.: +49 228 73 5608; fax: +49 228 73
lation reaction (RL = large substituent; RS = small substituent).
5813; e-mail: doetz@uni-bonn.de
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.08.026

A. Minatti, K. H. Do¨tz / Tetrahedron: Asymmetry 16 (2005) 3256–3267
3257
template. The initially formed Cr(CO)3-coordinated 4-
methoxyphenol or 4-methoxy-1-naphthol skeleton C
can subsequently be cleaved from the chromium tem-
plate and readily oxidised to the corresponding quinone
D with CAN in a one-pot procedure.6 This highly valu-
able transformation was used to synthesise (R)-BINOL-
derived ligands with either quinoid functionalities
attached to the binaphthol core through a C–C-single
bond or directly annulated quinone moities starting
from commercially available, enantiomerically pure
(R)-BINOL. The two different structural patterns could
be generated depending on the functionalisation of the
binaphthol compound.
syntheses (EtBr vs MeI) and its easy purification by
recrystallisation. The bromination of (R)-2 in positions
6,60 with bromine in CH2Cl2 was achieved in 86%.8
Application of this procedure in the synthesis of com-
pound (R)-3 resulted in an easier protocol compared
to the literature synthesis yielding compound (R)-3 in
95%.9 The brominated derivatives (R)-3 and (R)-4
reacted with trimethylsilyl acetylene in a Sonogashira-
coupling at 80 ꢁC according to the known literature
procedure, to give (R)-5 and (R)-6 in 99% and 79%
yields, respectively.10 Cleavage of the remaining TMS-
group under basic conditions led to the free alkynes
(R)-7 (87%) and (R)-8 (85%), respectively,10a which were
subsequently subjected to a double chromium-templated
[3+2+1]benzannulation reaction. Each alkyne func-
tionality was reacted with 2.2 equiv of pentacarbonyl-
[methoxy(phenyl)carbene]chromium(0) under optimised
reaction conditions to afford the red 6,60-bis(naphtho-
quinone)-substituted binaphthyl compounds (R)-9 and
(R)-10 after in situ oxidation of the initially formed
Cr(CO)3-(g6-hydronaphthoquinone) complexes. The
double benzannulation reaction with (R)-7 was per-
formed in CH2Cl2 at 55 ꢁC to give 73% yield of (R)-9
after oxidation with CAN at room temperature for
12 h. A significant increase of the chemical yield up to
87% was achieved for the benzannulation product
(R)-10, as the benzannulation reaction was performed in
TBME and the final oxidation was carried out at 0 ꢁC
The synthetic approach to chiral ligand (R)-L1 is out-
lined in Scheme 2, and two different strategies concern-
ing the protecting groups are presented. The protection
of the free hydroxy groups as methoxy or ethoxy ethers
was the first step following the strategy of maximum
protection. Compound (R)-1 was synthesised according
to the procedure of Cram et al. in 95% yield.7 The use of
Cs2CO3 instead of K2CO3 allowed for the synthesis of
the ethoxy-protected compound (R)-2 under milder con-
ditions [shorter reaction time (3 vs 36 h) and lower reac-
tion temperature (25 vs 56 ꢁC)] compared to the
literature procedure.8 Compound (R)-2 revealed two
major advantages compared to its methyl analogue
(R)-1: the use of a less toxic alkylation reagent in their
O
R'
R
vi PG = Me
O
iv
vii PG = Et
OPG
OPG
OPG
OPG
OPG
OPG
O
R
R'
v
(R)-3 PG = Me, R = Br
(R)-4 PG = Et, R = Br
(R)-5 PG = Me, R' = TMS
(R)-6 PG = Et, R' = TMS
iii
O
(R)-1 PG = Me, R = H
(R)-2 PG = Et, R = H
(R)-9, PG = Me
(R)-10, PG = Et
(R)-7 PG = Me, R' = H
(R)-8 PG = Et, R' = H
i PG = Me
ii PG = Et
viii
O
(R)-BINOL
ix
R
Br
O
O
OH
OH
x
xii
OH
OH
OH
OH
Br
R
O
(R)-12 R = TMS
(R)-13 R = H
(R)-11
(R)-L1
xi
Scheme 2. Reagents and conditions: (i) K2CO3, MeI, acetone, 36 h, reflux, 95%; (ii) Cs2CO3, EtBr, acetone, 3 h, rt, 99%; (iii) Br2, CH2Cl2, 0 ꢁC to rt,
95% (PG = Me), 86% (PG = Et); (iv) TMSC„CH, Pd(PPh3)2Cl2, CuI, NEt3, 12 h, 80 ꢁC, 99% (PG = Me), 79% (PG = Et); (v) KOH, MeOH/THF,
3 h, rt, 87% (PG = Me), 85% (PG = Et); (vi) (CO)5Cr@C(OMe)Ph, CH2Cl2, 3 h, 55 ꢁC, CAN, H2O, 12 h, 73%; (vii) (CO)5Cr@C(OMe)Ph, TBME,
12 h, 60 ꢁC, CAN, H2O, 1 h, 0 ꢁC, 87%; (viii) BBr3, CH2Cl2, 1 h, À78 ꢁC, 2 h, rt, 84% (PG = Et); (ix) Br2, CH2Cl2, À75 ꢁC to rt, 3 h, 99%; (x)
TMSC„CH, Pd(PPh3)2Cl2, CuI, NEt3, 12 h, 80 ꢁC, 89%; (xi) KOH, MeOH/THF, 3 h, rt, 97%; (xii) (CO)5Cr@C(OMe)Ph, TBME, 12 h, 60 ꢁC,
CAN, H2O, 1 h, 0 ꢁC, 25%.

3258
A. Minatti, K. H. Do¨tz / Tetrahedron: Asymmetry 16 (2005) 3256–3267
for 1 h. This excellent chemical yield was obtained even
at high scale up to 10 mmol. Compound (R)-10 afforded
the enantiopure 6,60-bis(naphthoquinone)-BINOL-type
ligand (R)-L1 in 84% yield after cleavage of the ethoxy
groups within 3 h with BBr3 in CH2Cl2 at À78 ꢁC to
room temperature. These time- and temperature-con-
trolled conditions were necessary as cleavage of the eth-
oxy groups with BBr3 under standard conditions
resulted only in decomposition. In conclusion, ligand
(R)-L1 was synthesised in six steps with an overall yield
of 46% following the ÔmaximisedÕ protecting group strat-
egy (PG = Et).
sented. As observed for the synthesis of (R)-L1, the
ethoxy-protected derivatives generally showed higher
solubility than their methoxy analogues and could be
easily purified by recrystallisation. This prompted us
to synthesise ligand (R)-L2 starting from ethoxy-pro-
tected BINOL-(R)-2, as a successful directed ortho-lith-
iation demands complete solubility in limited amounts
of solvent. Elementary iodine proved to be the electro-
phile of choice to react with the in situ ortho-lithiated
species as the use of Br2 or (BrCl2C)2 afforded only mix-
tures of bis- and monobrominated species. Bisiodide
(R)-14 was synthesised in 88% yield by lithiation of
(R)-2 with n-BuLi in the presence of TMEDA in Et2O
at room temperature and subsequent reaction with I2.
Subsequent Sonogashira-coupling in positions 3,30 with
trimethylsilyl acetylene at 40 ꢁC in NEt3 as solvent gave
compound (R)-15 in 78% yield. The cleavage of the
TMS-groups to afford the terminal alkyne (R)-16 was
effected under basic conditions with 90% yield. The
double benzannulation reaction of 3,30-bisalkyne (R)-16
and an excess of pentacarbonyl[methoxy(phenyl)car-
bene]-chromium was performed under different reaction
conditions. The best result was obtained in CH2Cl2 at
55 ꢁC with an in situ oxidation with CAN at room tem-
perature for 12 h, affording an orange 3,30-bis(naphtho-
quinone)-substituted binaphthyl compound (R)-17 in
24% yield even at a 10 mmol scale. Several deprotecting
reagents were tested for the cleavage of the ethoxy
groups in (R)-17. The use of the common Lewis-acids
We were also interested in whether BINOL-bisquinone
(R)-L1 could be obtained without the introduction of
any protecting groups. The bisalkyne-substituted
binaphthyl compound (R)-13 was synthesised according
to the literature procedures involving the bromination of
(R)-BINOL (99%),9 the Sonogashira-coupling with
trimethylsilyl acetylene (89%)11 and the cleavage of the
TMS-groups under basic conditions (97%).11 Bisalkyne
(R)-13 was reacted in a double benzannulation reaction
with 4.5 equiv of pentacarbonyl[methoxy(phenyl)car-
bene]chromium(0) to give bisquinone (R)-L1 in 25%
yield. This demonstrates that the benzannulation reac-
tion is compatible with the presence of the free hydroxy
groups, although this results in a decrease in chemical
yield. Thus, the syntheis of (R)-L1 could be shortened
to four steps providing an overall yield of 21% in the
absence of any protecting groups.
12
BB3 and BI3 did not meet with success, and TMSI
seemed to be an inappropriate choice as previous experi-
ments have indicated a preference for furanohelicene
cyclisation under these conditions.13 Quantitative reac-
tion was observed with AlCl3,14 although only analytical
The synthetic route to the regioisomeric chiral ligand
(R)-L2 is outlined in Scheme 3; again two complemen-
tary strategies concerning the protecting groups are pre-
O
R
I
O
i
ii
iv
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
O
I
R
(R)-17
(R)-2
(R)-14
(R)-15 R = TMS
(R)-16 R = H
O
O
iii
v
vi
R
I
O
O
OH
OH
ix
vii
OH
OH
OH
OH
I
R
(R)-L2
(R)-18
(R)-19 R = TMS
(R)-20 R = H
O
viii
Scheme 3. Reagents and conditions: (i) n-BuLi, TMEDA, Et2O, 6 h, rt, I2, À78 ꢁC to rt, 88%; (ii) TMSC„CH, Pd(PPh3)2Cl2, CuI, NEt3, 20 h, 40 ꢁC,
78%; (iii) KOH, MeOH/THF, 3 h, rt, 90%; (iv) (CO)5Cr@C(OMe)Ph, CH2Cl2, 5 h, 55 ꢁC, CAN, H2O, 12 h, rt, 24%; (v) AlCl3, CH2Cl2, 12 h, rt; (vi)
BBr3, CH2Cl2, 12 h, À40 ꢁC to rt, 99%; (vii) TMSC„CH, Pd(PPh3)2Cl2, CuI, NEt3, 20 h, 40 ꢁC, 99%; (viii) KOH, MeOH/THF, 3 h, rt, 99%; (ix)
(CO)5Cr@C(OMe)Ph, CH2Cl2, 12 h, 55 ꢁC, CAN, H2O, 1 h, 0 ꢁC, 0%.

A. Minatti, K. H. Do¨tz / Tetrahedron: Asymmetry 16 (2005) 3256–3267
3259
amounts of the enantiopure 3,30-bis(naphthoquinone)-
BINOL-type ligand (R)-L2 could be isolated after col-
umn chromatography. Again, the possibility of applying
a ÔminimisedÕ protecting group strategy was studied —
ÔminimisedÕ as the absence of any protecting group is
incompatible with the ortho-lithiation step. The eth-
oxy-groups were removed after the iodination in posi-
tions 3,30 with BBr3 in CH2Cl2 to yield compound
(R)-1815 quantitatively. Sonogashira-coupling with tri-
methylsilyl acetylene and subsequent cleavage of the
TMS-groups under basic conditions gave bisalkynes
(R)-1916 and (R)-2017 in quantitative yields, respectively.
Although quantitative consumption of the alkyne was
observed, unfortunately, no product arising from the
double benzannulation of (R)-20 and pentacar-
bonyl[methoxy(phenyl)carbene]chromium could be iso-
lated after in situ oxidation with CAN. As already
observed for (R)-L1, the benzannulation reaction pro-
ceeded with significantly lower yield in the presence of
free hydroxy groups compared to the hydroxy protec-
tion situation (87% vs 25%). Unfortunately, this trend
was confirmed for the benzannulation approach to
(R)-L2, and reduced the 24% yield obtained for the pro-
tected BINOL derivative (R)-16 to virtually 0% for its
unprotected analogue (R)-20.
view of the last step — the deprotection of the hydroxy
groups — an orthogonal protecting group strategy was
necessary in order to cleave the hydroxy protecting
group in the presence of the methoxy-groups of the
hydro(naphthoquinone)-functionalities (Scheme 4).
Following this approach, (R)-BINOL was cyclopro-
tected with diiodomethane in DMF and K2CO3 as base
to give acetal (R)-21 in 87% yield.19 Iodination of (R)-21
in positions 3,30 was achieved in 65% yield following the
experimental protocol established for compound (R)-14.
A subsequent Sonogashira-coupling with trimethylsilyl
acetylene under standard conditions gave compound
(R)-23 in 84% yield; deprotection of the TMS-groups
under basic conditions yielded (R)-24 nearly quanti-
tatively. Bisalkyne (R)-24 was reacted with penta-
carbonyl[methoxy(phenyl)carbene]chromium in a double
[3+2+1]benzannulation reaction in TBME at 60 ꢁC;
after in situ oxidation with CAN at 0 ꢁC for 1 h the
3,30-bis(naphthoquinone)-substituted binaphthyl, com-
pound (R)-25, was isolated in 22% yield. The reductive
methylation of the naphthoquinone moieties proceeded
nicely under phase transfer catalytic conditions.20 The
bis(naphthoquinone) (R)-25 was reduced in the first step
with Na2S2O4 to the bis(naphthohydroquinone), which
was subsequently deprotonated with KOH and methyl-
ated with Me2SO4 to give a 76% yield of the methyl-
BINOL-derived ligands bearing an alkyl-protected ben-
zohydroquinoid moiety in positions 3,30 have proven to
be highly effective in asymmetric catalysis.18 These func-
tional groups are introduced via a Suzuki-coupling
between the halogenated binaphthol and the corre-
sponding arylboronic acids. As an alternative synthetic
approach to those types of ligands, we envisaged to
attach a naphthohydroquinone to the binaphthol core
by following our [3+2+1]benzannulation protocol. In
protected
3,30-bis(naphthohydroquinone)-substituted
binaphthyl compound (R)-26, which represents a direct
precursor of bis(naphthohydroquinoid) derivative
(R)-L3.21
The NMR-data of ligands (R)-L1, (R)-L2 and com-
pound (R)-26 revealed that these structures suffer from
a strong distortion of the naphthoquinone and the
R
I
i
iii
ii
O
O
O
O
O
O
(R)-BINOL
I
R
(R)-23 R = TMS
(R)-24 R = H
(R)-21
(R)-22
iv
v
O
OMe
OMe
O
O
OMe
OMe
OMe
vi
OH
OH
O
O
O
O
OMe
(R)-L3
(R)-26
(R)-25
O
OMe
OMe
Scheme 4. Reagents and conditions: (i) I2CH2, K2CO3, DMF, 16 h, 80 ꢁC, 87%; (ii) n-BuLi, TMEDA, Et2O, 6 h, rt, I2, À78 ꢁC to rt, 65%; (iii)
TMSC„CH, Pd(PPh3)2Cl2, CuI, NEt3, 20 h, 40 ꢁC, 84%; (iv) KOH, MeOH/THF, 3 h, rt, 98%; (v) (CO)5Cr@C(OMe)Ph, TBME, 12 h, 60 ꢁC, CAN,
H2O, 1 h, 0 ꢁC, 22%; (vi) Na2S2O4, THF/H2O, n-Bu4NBr, KOH, Me2SO4, 76%.

3260
A. Minatti, K. H. Do¨tz / Tetrahedron: Asymmetry 16 (2005) 3256–3267
naphthohydroquinone moieties with respect to the BI-
NOL naphthol unit as the remaining H-atom in the
ortho-position to the quinone or the methoxy group,
respectively, indicating an enhanced upfield shift com-
pared to the aromatic H-atoms [(R)-L1: 6.93 vs 7.2–
8.2 ppm; (R)-L2: 7.20 vs 7.2–8.1 ppm; and (R)-26: 6.7 vs
7.3–8.2 ppm]. This finding suggests that the H-atom
points onto the aromatic system resulting in shielding
due to the ring current effect. MM3-minimised molecular
models of compounds (R)-L1 and (R)-L2, which are in
agreement with this argument, are shown in Figure 1.
O
OMe
Cr(CO)5
O
OH
OH
OMe
OMe
O
Cr(CO)5
OMe
O
(R)-30
(R)-L5
Finally, the synthesis of the C2-symmetric bis(phenan-
threnequinone) ligand (R)-L4 was envisaged following
a different synthetic strategy as the alkyne component
for the [3+2+1]benzannulation reaction is no longer
attached to the binaphthol core. Instead, the chromium
carbene functionality is incorporated into the binaph-
thol moiety and properly placed to allow for an angular
benzannulation regiochemistry (Scheme 5). There have
been two preliminary reports on the synthesis of struc-
turally related compounds, for example, chiral ligand
(R)-L5, which has been synthesised starting from biscar-
bene complex (R)-30 and racemic compound 32 gener-
ated from the racemic biscarbene complex precursor
31 (Scheme 6).13,22 BINOL bisbromide (R)-3 was
applied to the classical Fischer-Route; lithiation with
t-BuLi in THF for 30 min at À78 ꢁC, treatment with
Cr(CO)6 at À20 ꢁC to give the non-stable bis(acylmeta-
late), and in situ methylation with Me3OBF4 in water
afforded the bis(carbene) complex (R)-27 in 80% yield.
O
O
O
O
(OC)5Cr
(OC)5Cr
O
O
O
O
OMe
OMe
X
X
31
32
Scheme 6. Retrosynthetic approach to bisquinones (R)-L5 and 32.
The use of water in the methylating step is crucial for
a high yield; the syntheses of the related biscarbene com-
plexes (R)-30 and 31, in which the alkylation was per-
formed in dichloromethane, resulted in yields of only
56% and 48%, respectively. Double [3+2+1]benzannula-
tion of bis(carbene) complex (R)-27 with 3-hexyne in
Figure 1. MM3-minimised 3D representation of (R)-L1 and (R)-L2.
O
O
Cr(CO)5
MeO
O
O
O
O
iii
i
ii
OMe
OMe
OR
OMe
OMe
(R)-3
OR'
MeO
Cr(CO)5
(R)-27
O
O
(R)-28
(R)-L4, R, R' = H
(R)-29, R = OMe, R' = H
Scheme 5. Reagents and conditions: (i) t-BuLi, THF, 30 min, À78 ꢁC, Cr(CO)6, 40 min, À20 ꢁC to rt, Me3OBF4, H2O, 30 min, rt, 80%; (ii) 3-hexyne,
CH2Cl2, 12 h, 55 ꢁC, CAN, H2O, 1 h, 0 ꢁC, 40%; (iii) BBr3, CH2Cl2, À12 h, 10 ꢁC to rt, 70% [(R)-L4], 30% [(R)-29].

A. Minatti, K. H. Do¨tz / Tetrahedron: Asymmetry 16 (2005) 3256–3267
3261
CH2Cl2 at 55 ꢁC afforded — after in situ oxidation with
CAN at 0 ꢁC — the bis(phenanthrenquinone) (R)-28 in
40% yield. As expected, the exclusive formation of the
bis-angular benzannulation product was observed.23
chiral catalyst was generated in situ by adding ZnEt2
to the (R)-L2. The results of the Hetero-Diels–Alder
reaction between DanishefskyÕs diene and benzaldehyde
are shown in Table 2.
The C2-symmetric free ligand (R)-L4 was isolated in
70% yield after cleavage of the methoxy groups with
BBr3 in CH2Cl2; in addition, the non-symmetrical
monodentate ligand (R)-29 was isolated in 30% yield.
The synthesis of (R)-L4 was accomplished in five steps
with 18% overall yield providing the missing comple-
mentary structure to the already existing compounds
(R)-L5 and 32.
1) 10 mol% (R)-L2
12 mol% ZnEt2
toluene, 12 h
2) TFA
OMe
O
O
+
Ph
O
Ph
TMSO
Scheme 8. Zinc-mediated enantioselective hetero-Diels–Alder reaction.
In order to test the potential of the chiral ligands (R)-L1
and (R)-L2 in an enantioselective catalysis, two model
reactions were chosen. The catalytic activity of ligand
(R)-L1 was probed in the zinc-mediated asymmetric
epoxidation of chalcone (Scheme 7).24,25 The reaction
was performed in different solvents by the sequential
treatment of chiral ligand (R)-L1 with ZnEt2, chalcone
and tert-butyl hydroperoxide (TBHP) as the terminal
oxidant. The epoxidation proceeded in all cases with
perfect diastereoselectivity; only the trans-epoxide was
formed (Table 1). The solvent has a significant effect
on both the yield and the enantioselectivity. An excep-
tionally high reactivity was observed when the reaction
was conducted in Et2O, and the epoxide was isolated
in 99% yield and 32% enantiomeric excess (Table 1,
entry 3). A slight enantiomeric excess was observed for
CH2Cl2 (40% ee), although the yield dropped dramati-
cally to 45% (Table 1, entry 1). Toluene gave only a
modest yield (27%), while the asymmetric induction re-
mained nearly unchanged (38% ee) (Table 1, entry 2).
No epoxidation was observed when the reaction was
performed in THF (Table 1, entry 4).
Table 2. Enantioselective hetero-Diels–Alder reaction catalysed by a
chiral Zn-(R)-L2 complex
Entry
T (ꢁC)
Yield (%)a
ee (%)b
1
2
25
0
99
99
20
10
a Yield of isolated product.
b Determined by HPLC analysis on a chiral stationary phase.
The 2-phenyl-substituted 2,3-dihydro-4H-pyran-4-one
was isolated in quantitative yield and low ee when con-
ducting the reaction either at room temperature or at
0 ꢁC (Table 2, entries 1 and 2). Remarkably, the ee
was further decreased when the reaction temperature
was lowered from 25 to 0 ꢁC.
3. Conclusion
In summary, the (R)-BINOL-derived quinoid ligands
(R)-L1, (R)-L2, (R)-L4 and ligand precursor (R)-26 were
synthesised in a straightforward manner employing the
[3+2+1]benzannulation reaction as the key step.
Depending on the functionalisation of the binaphthol
compound, two different structural patterns could be
generated. The alkyne-functionalised binaphthol com-
pounds generated quinone-funtionalities, which were
attached to the binaphthol core through a C–C-single
bond [(R)-L1, (R)-L2], while a chromium carbene-func-
tionalised binaphthol was reacted to give directly annu-
lated quinone moieties [(R)-L4]. Preliminary results have
shown moderate activity of these ligands in enantioselec-
tive epoxidation and Hetero-Diels–Alder catalysis. Fur-
ther studies aimed at the elucidation of the scope of
these ligands in other metal-catalysed enantioselective
reactions are currently in progress.
The chiral ligand (R)-L2 has been used in the zinc-med-
iated Hetero-Diels–Alder reaction (Scheme 8).27,28 The
20 mol% (R)-L1
36 mol% ZnEt2
1.2 eq TBHP
O
O
Ph
Ph
Ph
Ph
0˚C - r.t., 12 h
O
Scheme 7. Zinc-mediated enantioselective epoxidation of chalcone.
Table 1. Enantioselective epoxidation of chalcone catalysed by a chiral
Zn-(R)-L1 complex
Entry
Solvent
Yield (%)a
de (%)b
ee (%)c,d
1
2
3
4
CH2Cl2
Toluene
Et2O
45
27
99
—
>99
>99
>99
—
40
38
32
—
4. Experimental
4.1. General procedures
THF
a Yield of isolated epoxide.
Reactions involving moisture- or/and air-sensitive inter-
mediates were performed under argon atmosphere.
Dichloromethane was distilled from CaH2 under argon.
Diethyl ether and tetrahydrofuran were freshly distilled
from benzophenone ketyl radical under argon prior to
use. Column chromatography was performed with silica
b Only the trans-isomer was formed as determined from the H NMR
coupling constant of the vicinal protons on the oxirane ring.
c Determined by HPLC analysis on a chiral stationary phase.
d Absolute configuration of the major enantiomer was determined to
be (2S,3R) by comparison of the specific rotation and HPLC reten-
tion times with those reported in the literature.26
1

3262
A. Minatti, K. H. Do¨tz / Tetrahedron: Asymmetry 16 (2005) 3256–3267
gel 60 (0.063–0.2 mm). All yields given refer to as iso-
lated yields. Optical rotation data [c = g/100 ml] were
measured on a Perkin–Elmer 431 polarimeter. NMR
spectra were recorded on a 300 MHz spectrometer.
The chemical shifts reported are in parts per million
relative to TMS. IR spectra [cmÀ1] were recorded on a
Nicolet Magna 550 FT-IR spectrometer. MS (EI) [m/z
(%)] and HRMS measurements were performed on a
Kratos MS 50. MS (FAB) [m/z (%)] was performed on
a Kratos Concept 1H-spectrometer.
and a 0.25 M solution of (NH4)2Ce(NO3)6 in H2O
(40 ml) slowly added. The mixture was stirred for 12 h
and extracted with Et2O (50 ml). The organic layer
was washed with NaHCO3 and NaCl, and finally dried
over MgSO4. After removing the solvents under reduced
pressure, the residue was purified by column chromato-
graphy (CH2Cl2; Rf = 0.5) to afford the title compound
23
9 (0.48 g, 73%) as a red solid; ½aŠ ¼ À286 (c 0.048,
CHCl3); 1H NMR (300 MHz, CDDCl3) d 3.81 (s, 6H,
OCH3), 7.15 (s, 2H), 7.19 (d, 2H, J = 9 Hz), 7.41 (dd,
2H, J = 9, 2 Hz), 7.51 (d, 2H J = 9 Hz), 7.75 (m, 4H),
8.08 (d, 2H, J = 9 Hz), 8.10–8.22 (m, 4H), 8.23 (d, 2H,
J = 2 Hz); 13C NMR (75 MHz, CDCl3) d 185.72
(C@O), 185.43 (C@O), 156.99 (C2), 148.56 (C200),
135.36, 135.29, 134.42, 133.32, 132.85, 131.49, 131.08,
129.32, 129.06, 127.71, 127.39, 126.58, 126.12, 119.63,
115.13, 57.34 (OCH3); MS (EI): m/z 626 (199), 580
(10); HRMS (EI) calcd for C42H26O6 626.1729, found
626.1706; IR (KBr) m 3066, 2935, 2836, 1730, 1654,
1618, 1592, 1573, 1477, 1332, 1303, 1249, 1099, 1064,
1022, 889, 804, 779, 719.
The following compounds were prepared according
to the literature procedures: (R)-2,20-dimethoxy-1,10-
binaphthyl,7 (R)-6,60-dibrom-2,20-diethoxy-1,10-binaph-
thyl,8 (R)-6,60-di[(trimethylsilyl)ethynyl]-2,20-diethoxy-
1,10-binaphthyl,10 (R)-6,60-di[(trimethylsilyl)ethynyl]-2,20-
dimethoxy-1,10-binaphthyl,10 (R)-6,60-diethynyl-2,20-di-
ethoxy-1,10-binaphthyl,10a (R)-6,60-diethynyl-2,20-dimeth-
oxy-1,10-binaphthyl,10a (R)-6,60-dibrom-2,20-dihydroxy-
1,10-binaphthyl,9 (R)-6,60-di[(trimethylsilyl)ethynyl]-2,20-
dihydroxy-1,10-binaphthyl,11 (R)-6,60-diethynyl-2,20-dihy-
droxy-1,10-binaphthyl,11 pentacarbonyl[methoxy(phenyl)-
carbene]chromium,29 borontriodide,12 (R)-2,20-methyl-
enedioxy-1,10-binaphthyl.19
4.5. (R)-6,60-Di(naphthalene-1,4-dione-2-yl)-2,20-
diethoxy-1,10-binaphthyl, 10
4.2. (R)-2,20-Diethoxy-1,10-binaphthyl, 2
A solution of compound 8 (3.9 g, 10 mmol) and
(CO)5Cr@C(OMe)(Ph) (14.1 g, 45 mmol) in t-BuOMe
(50 ml) was degassed by three freeze–pump–thaw cycles
and warmed to 60 ꢁC for 12 h under an inert atmo-
sphere. The benzannulation reaction mixture was cooled
to 0 ꢁC, and a 0.25 M solution of (NH4)2Ce(NO3)6 in
H2O (400 ml) was slowly added. The mixture was stirred
for 1 h at 0 ꢁC and extracted with Et2O (500 ml). The
organic layer was washed with NaHCO3 and NaCl
and finally dried over MgSO4. After removing the sol-
vents under a reduced pressure, the residue was purified
by column chromatography (CH2Cl2; Rf = 0.5) to afford
Ethylbromide (24 ml, 315 mmol) was added to a solu-
tion of (R)-BINOL (6.0 g, 21 mmol) and Cs2CO3
(27.4 g, 84 mmol) in acetone (250 ml). After stirring
the solution at room temperature for 3 h, the reaction
mixture was poured into H2O (300 ml) and extracted
with CH2Cl2 (3 · 100 ml). The combined organic layers
were dried over MgSO4 and the solvent was removed
under reduced pressure. The product was purified by
recrystallisation from PE to give compound 2 (7.1 g,
99%) as colourless crystals; the spectroscopic and chir-
optical data were in agreement with those reported in
the literature.8
the title compound 10 (5.72 g, 87%) as a red solid;
23
½aŠ ¼ À265 (c 0.022, CHCl3); 1H NMR (300 MHz,
D
CDCl3) d 1.01 (t, 6H, J = 7 Hz, CH3), 4.00 (m, 4H,
OCH2), 7.05 (s, 2H,), 7.10 (d, 2H, J = 9 Hz), 7.29 (dd,
2H, J = 9, 2 Hz), 7.37 (d, 2H, J = 9 Hz), 7.64 (m, 4H),
7.93 (d, 2H, J = 9 Hz), 8.00–8.10 (m, 4H), 8.11 (d, 2H,
J = 2 Hz); 13C NMR (75 MHz, CDCl3) d 185.13
(C@O), 184.84 (C@O), 155.75 (C2), 147.97 (C200),
137.82, 134.67, 133.79, 132.71, 132.22, 130.60, 130.40,
128.68, 128.35, 128.29, 127.08, 126.51, 125.95, 125.71,
119.86, 115.91, 65.00 (OCH2), 14.98 (CH3); MS (EI):
m/z 654 (100); HRMS (EI) calcd for C44H30O6
654.2042, found 654.2042; IR (KBr) m 2975, 2919,
1730, 1664, 1654, 1616, 1590, 1572, 1466, 1342, 1302,
1247, 1113, 888, 779, 717.
4.3. (R)-6,60-Dibromo-2,20-dimethoxy-1,10-binaphthyl, 3
(R)-2,20-Dimethoxy-1,10-binaphthyl 1 (4.7 g, 15 mmol)
was dissolved in CH2Cl2 (250 ml) and stirred at 0 ꢁC.
Bromine (1.68 ml, 33 mmol) was added in one portion
with stirring and a stream of argon was bubbled through
the solution to remove the evolving HBr. The reaction
mixture was stirred for 5 h while the flask was allowed
to warm to room temperature. During this procedure,
the product precipitated as a white solid and was filtered
off and dried in vacuo to give compound 3 (4.9 g, 95%)
as a white powder; the spectroscopic and chiroptical
data were in agreement with those reported in the
literature.9
4.6. (R)-6,60-Di(naphthalene-1,4-dione-2-yl)-2,20-
dihydroxy-1,10-binaphthyl, (R)-L1
4.4. (R)-6,60-Di(naphthalene-1,4-dione-2-yl)-2,20-di-
methoxy-1,10-binaphthyl, 9
A stirred solution of compound 10 (0.65 g, 1 mmol) in
CH2Cl2 (40 ml) was cooled to À78 ꢁC and BBr3
(0.52 ml, 5.5 mmol) was added dropwise under an inert
atmosphere. After the reaction mixture was stirred for
1 h at À78 ꢁC, it was warmed to room temperature
and stirred for a further 2.5 h. H2O (20 ml) was then
added, and the reaction mixture was vigorously stirred
A solution of compound 7 (0.38 g, 1 mmol) and
(CO)5Cr@C(OMe)(Ph) (1.41 g, 4.5 mmol) in CH2Cl2
(20 ml) was degassed by three freeze–pump–thaw cycles
and warmed to 55 ꢁC for 3 h under an inert atmosphere.
The benzannulation reaction mixture was cooled to 0 ꢁC

A. Minatti, K. H. Do¨tz / Tetrahedron: Asymmetry 16 (2005) 3256–3267
3263
23
D
for 30 min and extracted with CH2Cl2 (100 ml). The
organic phase was washed with H2O and dried over
MgSO4. After removing the solvents under reduced
pressure, the residue was purified by column chromatog-
raphy [PE/AcOEt, 3/1 (v/v); Rf = 0.8] to afford the title
½aŠ ¼ À50 (c 0.36, CHCl3); 1H NMR (300 MHz,
CDCl3) d 0.28 (s, 18H, Si(CH3)3), 0.92 (t, 6H,
J = 7 Hz, CH3), 3.71 (m, 2H, OCHAHB), 4.03 (m, 2H,
OCHAHB), 7.06 (d, 2H, J = 8 Hz), 7.22 (m, 2H), 7.36
(m, 2H), 7.80 (d, 2H, J = 8 Hz), 8.14 (s, 2H); 13C
NMR (75 MHz, CDCl3) d 156.24 (C2), 135.23, 134.73,
130.59, 128.41, 127.78, 126.50, 125.87, 125.73, 118.26,
102.92 (C„C), 99.23 (C„C), 70.13 (OCH2), 16.29
(CH3), 0.63 (Si(CH3)3); MS (EI): m/z 534 (100), 461
(5); HRMS (EI) calcd for C34H38O2Si2 534.2410, found
534.2405; IR (KBr) m 3061, 2955, 2929, 2163, 1621, 1591,
1492, 1434, 1382, 1254, 1170, 1111, 840, 760.
compound (R)-L1 (0.5 g, 84%) as
a red solid;
23
½aŠ ¼ À310 (c 0.06, CHCl3); 1H NMR (300 MHz,
D
CDCl3) d 5.8 (br s, 2H, OH), 6.93 (s, 2H), 7.17 (d, 2H,
J = 9 Hz), 7.37 (m, 4H), 7.74 (m, 4H), 7.92 (d, 2H,
J = 9 Hz), 8.04 (m, 2H), 8.11 (m, 2H), 8.15 (s, 2H);
13C NMR (75 MHz, CDCl3) d 185.57 (C@O), 185.25
(C@O), 155.10 (C2), 148.02 (C200), 135.24, 134.96,
134.56, 134.51, 133.18, 133.09, 132.67, 131.37, 129.56,
129.36, 128.36, 127.75, 126.69, 125.23, 119.55, 111.72;
MS (EI): m/z 598 (100); HRMS (EI) calcd for
C40H22O6 598.1416, found 598.1408; IR (KBr) m 3416,
3066, 1664, 1618, 1591, 1571, 1473, 1276, 1250, 1214,
1154, 887, 815, 779, 717.
4.9. (R)-3,30-Diethynyl-2,20-diethoxy-1,10-binaphthyl, 16
A 1 M solution of KOH (81 ml) was added dropwise to
a solution of compound 15 (14.4 g, 27 mmol) in MeOH/
THF [540 ml, 1/1 (v/v)]. After stirring the reaction mix-
ture for 3 h at room temperature, the solvents were
removed under reduced pressure, and the residue was
dissolved in AcOEt (30 ml). The organic phase was
washed with H2O and dried over MgSO4. The solvent
was removed under reduced pressure. Purification by
column chromatography [PE/CH2Cl2, 2/1 (v/v);
Rf = 0.3] afforded compound 16 (9.5 g, 90%) as a yellow
4.7. (R)-3,30-Diodo-2,20-diethoxy-1,10-binaphthyl, 14
TMEDA (0.55 ml, 3.7 mmol) and a 1.6 M solution of n-
BuLi in n-hexane (2.3 ml, 3.7 mmol) were subsequently
added at room temperature to a solution of compound
2 (0.34 g, 1 mmol) in Et2O (15 ml) under an inert atmo-
sphere. After stirring the solution for 6 h at room tem-
perature, the reaction mixture was cooled to À78 ꢁC,
and a solution of iodine (1 g, 4 mmol) in Et2O (8 ml)
was added. The reaction mixture was warmed to room
temperature and stirred for an additional 10 h. The
excess iodine was reduced with 1 M NaS2O5 (5 ml). The
organic layer was separated, washed with NaCl and
dried over MgSO4. The solvent was removed under
reduced pressure. Purification by column chromatogra-
23
23
solid; ½aŠ ¼ À7:5 (c 0.39, CHCl3); ½aŠ ¼ À25 (c 0.39,
D
436
CHCl3); 1H NMR (300 MHz, CDCl3) d 0.75 (t, 6H,
J = 7 Hz, CH3), 3.17 (s, 2H, C„H), 3.61 (m, 2H,
OCHAHB), 3.87 (m, 2H, OCHAHB), 6.92 (d, 2H,
J = 8 Hz), 7.08 (m, 2H), 7.22 (m, 2H), 7.66 (d, 2H,
J = 8 Hz), 8.02 (s, 2H); 13C NMR (75 MHz, CDCl3) d
155.63 (C2), 135.01, 134.15, 129.90, 127.77, 127.35,
125.82, 125.24, 125.22, 116.60, 81.17 (C„H), 80.90
(C„C), 69.71 (OCH2), 15.55 (CH3); MS (EI): m/z 390
(100); HRMS (EI) calcd for C28H22O2 390.1619, found
390.1618; IR (KBr) m 3286, 3056, 2975, 2928, 2102,
1733, 1618, 1587, 1490, 1427, 1384, 1349, 1235, 1097,
phy [PE/CH2Cl2, 2/1 (v/v); Rf = 0.4] afforded compound
23
14 (0.52 g, 88%) as a white solid; ½aŠ ¼ À78 (c 0.35,
D
CHCl3), 1H NMR (300 MHz, CDCl3) d 0.84 (t, 6H,
J = 7 Hz, CH3), 3.33 (m, 2H, OCHAHB), 3.73 (m, 2H,
OCHAHB), 7.00 (d, 2H, J = 8 Hz), 7.18 (m, 2H), 7.32
(m, 2H), 7.70 (d, 2H, J = 8 Hz), 8.44 (s, 2H); 13C
NMR (75 MHz, CDCl3) d 154.28 (C2), 139.67, 133.96,
132.01, 126.98, 126.93, 125.88, 125.55, 125.48, 93.07
(C3), 69.74 (OCH2), 15.43 (CH3); MS (EI): m/z 594
(100), 566 (10), 538 (35), 468 (30); HRMS (EI) calcd
for C24H20I2O2 593.9552, found 593.9551; IR (KBr) m
3052, 2975, 2933, 2885, 1560, 1490, 1413, 1382, 1344,
1226, 1149, 1041, 1022, 885, 748.
1022, 890, 752, 617 cmÀ1
.
4.10. (R)-3,30-Di(naphthalene-1,4-dione-2-yl)-2,20-
diethoxy-1,10-binaphthyl, 17
A solution of compound 16 (0.5 g, 1.3 mmol) and
(CO)5Cr@C(OMe)(Ph) (1.83 g, 5.85 mmol) in CH2Cl2
(25 ml) was degassed by three freeze–pump–thaw cycles
and warmed to 55 ꢁC for 5 h under inert atmosphere.
The benzannulation reaction mixture was cooled to
0 ꢁC and a 0.25 M solution of (NH4)2Ce(NO3)6 in
H2O (52 ml) was slowly added. The mixture was stirred
for 12 h and extracted with Et2O (50 ml). The organic
layer was washed with NaHCO3 and NaCl and finally
dried over MgSO4. After removing the solvents under
reduced pressure, the residue was purified by column
chromatography (CH2Cl2; Rf = 0.4) to afford the title
4.8. (R)-3,30-Di[(trimethylsilyl)ethynyl]-2,20-diethoxy-
1,10-binaphthyl, 15
To a stirred solution of compound 14 (1.6 g, 2.7 mmol),
PdCl2(PPh3)2 (0.11 g, 6 mol %), CuI (0.05 g, 6 mol %) in
NEt3 (18 ml) and under an inert atmosphere, freshly dis-
tilled trimethylsilyl acetylene (2.16 ml, 16.2 mmol) was
added in one portion. After heating the reaction mixture
to 40 ꢁC for 20 h, it was cooled to room temperature and
filtered through a pad of Celite. Additionally, the resi-
due was washed with Et2O (50 ml). The organic layers
were combined and the solvents removed under reduced
pressure. The remaining solid was purified by column
chromatography [PE/CH2Cl2, 2/1 (v/v); Rf = 0.6] to
yield the title compound 15 (1.1 g, 78%) as a white solid;
compound 17 (0.2 g, 24%) as an orange solid;
23
½aŠ ¼ À110 (c 0.05, CHCl3); 1H NMR (300 MHz,
D
CDCl3) d 0.70 (t, 6H, J = 7 Hz, CH3), 3.40 (m, 2H,
OCHAHB), 3.54 (m, 2H, OCHAHB), 7.14 (s, 2H), 7.24
(d, 2H, J = 8 Hz), 7.28 (m, 2H), 7.37 (m, 2H), 7.70 (m,
4H), 7.84 (d, 2H, J = 8 Hz), 7.87 (s, 2H), 8.10 (m,
4H); 13C NMR (75 MHz, CDCl3) d 185.77 (C@O),
184.81 (C@O), 154.46 (C2), 149.49 (C200), 137.24,
135.72, 134.56, 134.42, 133.22, 132.94, 131.53, 130.57,

3264
A. Minatti, K. H. Do¨tz / Tetrahedron: Asymmetry 16 (2005) 3256–3267
129.44, 129.10, 128.22, 127.65, 126.85, 126.59, 125.92,
124.88, 70.15 (OCH2), 16.18 (CH3); MS (EI): m/z 654
(100), 580 (50); HRMS (EI) calcd for C44H30O6
654.2042, found 654.2038; IR (KBr) m 3062, 2974,
2925, 2906, 1664, 1619, 1597, 1426, 1390, 1350, 1302,
1251, 1107, 1045, 1024, 892, 790.
pressure. The remaining residue was dissolved in AcOEt
and filtered through a pad of Celite. The filtrate was
washed with a 1 M solution of HCl and dried over
MgSO4. After removing the solvent under reduced pres-
sure, the remaining residue was dried in vacuo to give
compound 19 (0.34 g, 99%) as a white solid; the spectro-
scopic and chiroptical data were in agreement with those
reported in the literature.16
4.11. (R)-3,30-Di(naphthalene-1,4-dione-2-yl)-2,20-diol-
1,10-binaphthyl, (R)-L2
4.14. (R)-3,30-Diethynyl-2,20-dihydroxy-1,10-binaphthyl,
20
A solution of compound 17 (0.08 g, 0.12 mmol) and
AlCl3 (0.16 g, 1.2 mmol) in CH2Cl2 (5 ml) was stirred
for 12 h at room temperature under an inert atmo-
sphere. After adding a 1 M solution of HCl (20 ml),
the reaction mixture was vigorously stirred for another
12 h. The reaction mixture was extracted with CH2Cl2
(50 ml) and the organic layer subsequently washed with
NaHCO3 and NaCl. The organic phase was dried over
MgSO4 and the solvents were removed under reduced
pressure. The remaining residue was purified by column
chromatography with silica gel 60 (0.015–0.25 mm),
A 1 M solution of KOH (3 ml) was added dropwise to a
solution of compound 19 (0.34 g, 0.7 mmol) in MeOH/
THF [20 ml, 1/1 (v/v)]. After stirring the reaction mix-
ture for 3 h at room temperature, the solvents were
removed under reduced pressure. The residue was
dissolved in AcOEt (30 ml) and washed with a 1 M solu-
tion of HCl and H2O. The organic layer was dried over
MgSO4 and the solvent removed under reduced pres-
sure. Purification by column chromatography (CH2Cl2;
Rf = 0.3) afforded compound 20 (0.23 g, 99%) as a yel-
low solid; the spectroscopic and chiroptical data were
in agreement with those reported in the literature.17
[CH2Cl2/MeOH, 15/0.1 (v/v); Rf = 0.64] to afford the
26
title compound (R)-L2 as an orange solid; ½aŠ ¼ þ63
D
1
(c 0.15, THF); H NMR (300 MHz, CDCl3) d 5.92 (s,
2H, OH), 7.17 (d, 2H, J = 8 Hz), 7.20 (s, 2H), 7.28–
7.37 (m, 4H), 7.73 (d, 2H, J = 6 Hz), 7.74 (d, 2H,
J = 6 Hz), 7.87 (d, 2H, J = 8 Hz), 7.96 (s, 2H), 8.03
(dd, 2H, J = 6, 3 Hz), 8.08 (dd, 2H, J = 6, 3 Hz); 13C
NMR (75 MHz, CDCl3) d 185.04 (C@O), 183.94
(C@O), 150.52 (C2), 147.50 (C200), 137.06, 134.13,
133.90, 133.78, 132.37, 132.29, 132.13, 128.85, 128.73,
128.39, 127.11, 126.13, 124.69, 124.39, 124.21, 112.13;
MS (EI): m/z 598 (33), 597 (38), 596 (91), 580 (100);
IR (KBr) m 3428, 3062, 2962, 2926, 2854, 1662, 1621,
1593, 1446, 1301, 1252, 1128, 893, 785, 737.
4.15. (R)-3,30-Diiodo-2,20-methylenedioxy-1,10-binaphthyl,
22
TMEDA (3.5 ml, 23.5 mmol) and a 1.6 M solution of n-
BuLi in n-hexane (14.6 ml, 23.5 mmol) were subse-
quently added at room temperature to a solution of
compound 21 (1.89 g, 6.34 mmol) in Et2O (95 ml) under
an inert atmosphere. After stirring the solution for 6 h at
room temperature, the reaction mixture was cooled to
À78 ꢁC and a solution of iodine (6.34 g, 25.4 mmol) in
Et2O (50 ml) added. The reaction mixture was warmed
to room temperature and stirred for an additional
10 h. The excess iodine was reduced with 1 M NaS2O5
(20 ml). The organic layer was separated, washed with
NaCl and dried over MgSO4. The solvent was removed
under reduced pressure. Purification by column chroma-
4.12. (R)-3,30-Diiodo-2,2-dihydroxy-1,10-binaphthyl, 18
A solution of compound 14 (0.42 g, 0.7 mmol) in
CH2Cl2 (10 ml) was cooled to À40 ꢁC and a 1 M solu-
tion of BBr3 in CH2Cl2 (7 ml) was added dropwise under
an inert atmosphere. The solution was warmed to room
temperature and stirred for 12 h. H2O (30 ml) was added
and the reaction mixture vigorously stirred for 30 min.
The solution was extracted with CH2Cl2 (50 ml) and
the organic layer dried over MgSO4. After removing
the solvent under reduced pressure, the remaining resi-
due was purified by column chromatography [PE/
AcOEt, 5/1 (v/v); Rf = 0.5] to afford the title compound
18 (0.38 g, 99%) as a pale yellow solid; the spectroscopic
and chiroptical data were in agreement with those
reported in the literature.15
tography [PE/CH2Cl2, 3/1 (v/v); Rf = 0.5] afforded com-
23
pound 22 (2.26 g, 65%) as a white solid; ½aŠ ¼ À542 (c
D
0.35, CHCl3); 1H NMR (300 MHz, C6D6) d 5.51 (s, 2H,
CH2), 6.91 (m, 2H), 7.08 (m, 2H), 7.35 (m, 4H), 8.23 (s,
2H); 13C NMR (75 MHz, C6D6) d 150.26 (C2), 140.02,
133.37, 132.21, 127.62, 127.08, 126.95, 126.79, 125.86,
102.20 (OCH2O), 90.46 (C3); MS (EI): m/z 550 (40),
424 (70), 298 (100); HRMS (EI) calcd for C21H12I2O2
549.8927, found 549.8928; IR (KBr) m 3056, 2966,
2906, 1571, 1496, 1384, 1344, 1236, 1201, 1153, 1152,
1041, 997, 888, 749.
4.13. (R)-3,30-Di[(trimethylsilyl)ethynyl]-2,20-dihydroxy-
4.16. (R)-3,30-Di[(trimethylsilyl)ethynyl]-2,20-methyl-
1,10-binaphthyl, 19
enedioxy-1,10-binaphthyl, 23
To
a
stirred solution of compound 18 (0.38 g,
To a stirred solution of compound 22 (5.6 g,
0.7 mmol), PdCl2(PPh3)2 (0.03 g, 6 mol %), CuI (8 mg,
6 mol %) in NEt3 (20 ml) and under an inert atmo-
sphere, freshly distilled trimethylsilyl acetylene (0.6 ml,
4.2 mmol) was added in one portion. After heating the
reaction mixture to 40 ꢁC for 20 h, it was cooled to room
temperature, and the solvent removed under reduced
10.2 mmol), PdCl2(PPh3)2 (0.44 g, 6 mol %), CuI
(0.12 g, 6 mol %) in NEt3 (65 ml) and under an inert
atmosphere, freshly distilled trimethylsilyl acetylene
(8.7 ml, 61.2 mmol) was added in one portion. After
heating the reaction mixture to 40 ꢁC for 20 h, it was
cooled to room temperature and filtered through a pad

A. Minatti, K. H. Do¨tz / Tetrahedron: Asymmetry 16 (2005) 3256–3267
3265
of Celite. Additionally, the residue was washed with
Et2O (250 ml). The organic fractions were combined
and the solvents were removed under reduced pressure.
The remaining solid was purified by column chromato-
graphy [PE/CH2Cl2, 2/1 (v/v); Rf = 0.7] to yield the title
(C200), 137.24, 133.95, 133.87, 132.92, 132.36, 132.19,
131.10, 130.90, 128.69, 127.31, 127.04, 127.01, 126.98,
126.21, 126.02, 125.73, 103.42 (OCH2O); MS (EI): m/z
610 (100), 582 (23); HRMS (EI) calcd for C41H22O6
610.1416, found 610.1418; IR (KBr) m 3057, 2915,
1718, 1672, 1596, 1299, 1251, 993, 725.
compound 23 (4.2 g, 78%) as a light yellow solid;
23
½aŠ ¼ À729 (c 0.28, CHCl3); 1H NMR (300 MHz,
D
CDCl3) d 0.12 (s, 18H, Si(CH3)3), 5.60 (s, 2H, CH2),
7.03–7.25 (m, 6H), 7.65 (d, 2H, J = 8 Hz), 7.97 (s,
2H); 13C NMR (75 MHz, CDCl3) d 150.74 (C2),
134.39, 131.86, 131.04, 128.23, 126.86, 126.71, 126.40,
125.61, 116.44, 102.62 (OCH2O), 100.44 (C„C), 99.10
(C„C), 0.00 (Si(CH3)3); MS (EI): m/z 490 (100), 462
(20); HRMS (EI) calcd for C31H30O2Si2 490.1784, found
490.1787; IR (KBr) m 3054, 2958, 2898, 2156, 1592, 1498,
1411, 1330, 1249, 1151, 1091, 1020, 997, 842, 750.
4.19. (R)-3,30-Di(2-naphthalene-1,4-dimethoxy)-2,20-
methylenedioxy-1,10-binaphthyl, 26
NaS2O4 (1.8 g, 10.4 mmol) was added to a solution of
compound 25 (0.53 g, 0.87 mmol) and (n-Bu)4NBr
(66 mg, 2 mmol) in THF (5 ml) and H2O (2 ml) at room
temperature. After 15 min, KOH (2.25 g, 40 mmol) was
added and after 5 min Me2SO4 (3.48 ml, 36.6 mmol).
The reaction mixture was stirred for 12 h at room tem-
perature and extracted with CH2Cl2 (10 ml). The organ-
ic layer was dried over MgSO4 and the solvent removed
under reduced pressure. Purification by column chroma-
4.17. (R)-3,30-Diethynyl-2,20-methylenedioxy-1,10-binaph-
thyl, 24
tography [PE/CH2Cl2, 3/1 (v/v); Rf = 0.7] afforded com-
23
D
A 1 M solution of KOH (26 ml) was added dropwise to
a solution of compound 23 (4.2 g, 8.6 mmol) in MeOH/
THF [170 ml, 1/1 (v/v)]. After stirring the reaction mix-
ture for 3 h at room temperature, the solvents were
removed under reduced pressure and the residue was
dissolved in AcOEt (45 ml). The organic phase was
washed with H2O and dried over MgSO4. The solvent
was removed under reduced pressure. Purification by
column chromatography [PE/CH2Cl2, 1/1 (v/v);
Rf = 0.6] afforded compound 24 (2.9 g, 98%) as a yellow
pound 26 (0.44 g, 76%) as a yellow solid; ½aŠ ¼ À184 (c
0.2, CHCl3); 1H NMR (300 MHz, CDCl3) d 3.51 (s, 6H,
CH3), 3.85 (s, 6H, CH3), 5.35 (s, 2H, CH2), 6.72 (s, 2H),
7.28 (m, 2H), 7.42 (m, 6H), 7.55 (d, 2H, J = 8 Hz), 7.89
(d, 2H, J = 8 Hz), 8.03 (s, 2H), 8.04 (m, 2H), 8.18 (m,
2H); 13C NMR (75 MHz, CDCl3) d 151.32 (C2),
149.37(C100), 147.60 (C400), 132.10, 131.92, 131.45,
131.20, 128.79, 128.50, 127.06, 127.02, 126.74, 126.37,
126.08, 126.02, 125.72, 125.32, 122.32, 106.97, 102.82
(OCH2O), 61.84 (OCH3), 55.81 (OCH3); MS (EI): m/z
670 (50), 639 (8), 608 (10); HRMS (EI) calcd for
C45H34O6 670.2355, found 670.2351; IR (KBr) m 3068,
2931, 2836, 1625, 1591, 1506, 1456, 1413, 1364, 1228,
1095, 997, 769, 750.
23
1
solid; ½aŠ ¼ À769 (c 0.4, CHCl3); H NMR (300 MHz,
D
CDCl3) d 3.33 (s, 2H, C„H), 5.80 (s, 2H, CH2), 7.26–
7.47 (m, 6H), 7.86 (d, 2H, J = 8 Hz), 8.20 (s, 2H); 13C
NMR (75 MHz, CDCl3) d 150.85 (C2), 135.01, 132.03,
131.05, 128.30, 127.14, 126.77, 126.40, 125.80, 115.42,
103.01 (OCH2O), 81.44 (C„H), 79.28 (C„C); MS
(EI): m/z 346 (100), 318 (36); HRMS (EI) calcd for
C25H14O2 346.0994, found 346.0995; IR (KBr) m 3289,
3052, 2967, 2910, 2100, 1619, 1592, 1498, 1413, 1357,
1328, 1265, 1243, 989, 891, 750, 684, 619.
4.20. (R)-6,60-(2,20-Dimethoxy-1,10-binaphthyl)-bis-
[pentacarbonyl(methoxy)carbene-chromium], 27
A solution of compound 3 (0.94 g, 2 mmol) in THF
(50 ml) was cooled to À78 ꢁC, and 3.5 ml (5.1 mmol)
of a 1.48 M solution of t-BuLi in n-pentane added drop-
wise to the solution under an inert atmosphere. The
resulting yellow solution was stirred for 30 min at
À78 ꢁC and then warmed to À20 ꢁC. After adding
Cr(CO)6 (1.11 g, 5.1 mmol) in one portion at this tem-
perature, the reaction mixture was warmed to room
temperature. The solvent was evaporated under reduced
pressure and the remaining residue dissolved in H2O
(40 ml). Me3OBF4 (0.77 g, 5.1 mmol) was added in one
portion and the resulting red solution was stirred for
30 min. The organic layer was extracted with CH2Cl2
(3 · 30 ml) under an inert atmosphere and the combined
organic layers were filtered through a pad of MgSO4.
The solvent was evaporated under reduced pressure
and the remaining residue was purified by column chro-
matography [Et2O/PE, 3/1 (v/v); Rf = 0.6] to afford the
title compound 27 (1.25 g, 80%) as a red solid; 1H NMR
(300 MHz, CDCl3) d 3.82 (s, 6H, OCH3), 4.85 (s, 6H,
OCH3Carbene), 7.11 (d, 2H, J = 9 Hz), 7.43 (dd, 2H,
J = 9, 1.7 Hz), 7.53 (d, 2H, J = 9 Hz), 8.15 (d, 2H,
J = 9 Hz), 8.22 (s, 2H); 13C NMR (75 MHz, CDCl3) d
345.74 (C@Cr), 224.68 (COtrans), 217.31 (COcis), 157.78
4.18. (R)-3,30-Di(naphthalene-1,4-dione-2-yl)-2,20-methy-
lenedioxy-1,10-binaphthyl, 25
A solution of compound 24 (1.38 g, 4 mmol) and
(CO)5Cr@C(OMe)(Ph) (5.64 g, 18 mmol) in t-BuOMe
(20 ml) was degassed by three freeze–pump–thaw cycles
and warmed to 60 ꢁC for 12 h under an inert atmo-
sphere. The benzannulation reaction mixture was cooled
to 0 ꢁC and a 0.25 M solution of (NO3)6Ce(NH4)2
(160 ml) was slowly added. The mixture was stirred for
1 h at 0 ꢁC and extracted with Et2O (200 ml). The organ-
ic layer was washed with NaHCO3 and NaCl and finally
dried over MgSO4. After removing the solvents under
reduced pressure, the residue was purified by column
chromatography (CH2Cl2; Rf = 0.4) to afford the title
compound 25 (0.53 g, 22%) as an orange solid;
23
½aŠ ¼ À158 (c 0.36, CHCl3); 1H NMR (300 MHz,
D
CDCl3) d 5.50 (s, 2H, CH2), 7.18 (s, 2H), 7.35–7.55
(m, 6H), 7.78 (m, 4H), 7.97 (d, 2H, J = 8 Hz), 7.99 (s,
2H), 8.16 (m, 4H); 13C NMR (75 MHz, CDCl3) d
184.84 (C@O), 184.03 (C@O), 148.69 (C2), 147.84

3266
A. Minatti, K. H. Do¨tz / Tetrahedron: Asymmetry 16 (2005) 3256–3267
(C2), 148.95 (C6), 135.93, 132.88, 128.94, 128.30, 125.46,
123.32, 119.19, 115.24, 67.97 (OCH3Carbene), 57.17
(OCH3); MS (FAB): m/z 782 (10), 698 (5), 642 (100),
613 (42), 586 (8), 558 (10), 502 (20); IR (CH2Cl2) m
2060, 1983, 1944.
4.23. (À)-2,20,3,30-Tetraethyl-(8-hydroxy,80-methoxy)-
7,70-bis(phenanthrene-1,4-dione), 29
Purification by column chromatography (CH2Cl2;
Rf = 0.5) afforded the title compound 29 (19 mg, 30%)
23
D
1
as an orange solid; ½aŠ ¼ À30 (c 0.136, CHCl3); H
NMR (300 MHz, CDCl3) d 1.11 (m, 6H, CH3), 1.21
(m, 6H, CH3), 2.59 (m, 4H, CH2), 2.69 (m, 4H, CH2),
3.84 (s, 3H, OCH3), 5.57 (s, 1H, OH), 7.17 (d, 1H,
J = 9 Hz), 7.32 (d, 1H, J = 9 Hz), 7.52 (d, 1H, J =
9 Hz), 7.61 (d, 1H, J = 9 Hz), 7.80 (d, 1H, J = 9 Hz),
7.85 (d, 1H, J = 9 Hz), 9.60 (d, 1H, J = 9 Hz), 9.72
(d, 1H, J = 9 Hz); 13C NMR (75 MHz, CDCl3) d
188.7 (C@O), 188.4 (C@O), 185.8 (C@O), 185.5
(C@O), 157.7 (C), 153.6 (C), 149.4, 145.4, 145.3, 137.3,
137.2, 132.1, 130.5, 130.4, 130.2, 128.5, 128.2, 125.4,
125.3, 123.7, 122.9, 121.3, 116.3, 115.1, 114.9, 56.4
(OCH3), 20.5 (CH2), 20.5 (CH2), 19.8 (CH2), 14.2
(CH3), 14.0 (CH3), 13.9 (CH3); MS (EI): m/z 572
(100), 529 (9); HRMS (EI) calcd for C37H32O6
572.2199, found 572.2203; IR (KBr) m 3421, 2970,
2935, 2875, 2843, 1650, 1603, 1468, 1308, 1269, 1250,
1093, 812.
4.21. (À)-2,20,3,30-Tetraethyl-8,80-dimethoxy-7,70-
bis(phenanthrene-1,4-dione), 28
A solution of freshly distilled 3-hexyne (0.26 ml,
2.28 mmol) and biscarbene complex 27 (0.3 g,
0.38 mmol) in CH2Cl2 (5 ml) was degassed by three
freeze–pump–thaw cycles and warmed to 55 ꢁC for
12 h under an inert atmosphere. The benzannulation
reaction mixture was cooled to 0 ꢁC and a 0.25 M solu-
tion of (NH4)2Ca(NO3)6 (15 ml) was slowly added. The
mixture was stirred for 1 h at 0 ꢁC and extracted with
Et2O (20 ml). The organic layer was washed with Na-
HCO3 and NaCl and finally dried over MgSO4. After
removing the solvents under reduced pressure, the resi-
due was purified by column chromatography (CH2Cl2;
Rf = 0.67) to afford the title compound 28 (90 mg,
23
40%) as an orange solid; ½aŠ ¼ À10 (c 0.14, CHCl3);
D
1H NMR (300 MHz, CDCl3) d 1.14 (t, 6H, J = 7 Hz,
CH3), 1.21 (t, 6H, J = 7 Hz, CH3), 2.61 (q, 4H,
J = 7 Hz, CH2), 2.70 (q, 4H, J = 7 Hz, CH2), 3.78 (s,
3H, OCH3), 7.32 (d, 2H, J = 9 Hz), 7.61 (d, 2H,
J = 9 Hz), 7.87 (d, 2H, J = 9 Hz), 9.70 (d, 2H,
4.24. General procedure for the enantioselective
epoxidation
(R)-L1 (0.12 g, 0.2 mmol) was dissolved in Et2O (20 ml)
in a Schlenk flask equipped with a magnetic stirring bar
under an inert atmosphere. After cooling to 0 ꢁC with an
ice-bath, ZnEt2 (0.33 ml, 0.36 mmol, 1.1 M solution in
toluene) was added under stirring. After 15 min, chal-
cone (1 mmol) and TBHP(0.24 ml, 1.2 mmol, 5–6 M
in decane) were added, and the resulting mixture
allowed to warm to room temperature overnight. The
reaction was quenched with aq satd NaHSO3 and
extracted with EtOAc. The organic layer was washed
with aq Na2CO3 and brine. The combined organic layers
were dried over MgSO4 and the solvent evaporated in
vacuo. The residue was purified by column chromato-
graphy (CH2Cl2). In all cases, (R)-L1 was recovered
almost quantitatively. The enantiomeric excesses of the
epoxide were determined by HPLC analysis on a sta-
tionary phase: Chiralcel OD column with n-hexane/2-
propanol as eluent (95:5, 0.7 ml/min) and 254 nm UV
detector. The absolute configuration of the product
has been assigned by comparison of specific rotation
with literature values and the elution order of the two
enantiomers on the HPLC column.
J = 9 Hz); 13C NMR (75 MHz, CDCl3)
d 188.8
(C@O), 185.8 (C@O), 156.7 (C8), 149.2, 145.3, 137.2,
130.8, 130.6, 128.4, 125.1, 122.7, 118.9, 116.6, 56.4
(OCH3), 20.5 (CH2), 19.8 (CH2), 14.2 (CH3), 14.0
(CH3); MS (EI): m/z 586 (100), 543 (7); HRMS (EI)
calcd for C38H34O6 586.2355, found 586.2355; IR
(KBr) m 2968, 2935, 2873, 2843, 1651, 1605, 1468,
1309, 1267, 1250, 1095, 1088, 1065, 808.
4.22. (À)-2,20,3,30-Tetraethyl-8,80-dihydroxy-7,70-
bis(phenanthrene-1,4-dione), (R)-L4
A solution of compound 28 (65 mg, 0.11 mmol) in
CH2Cl2 (1 ml) was cooled to À10 ꢁC and BBr3 (0.8 ml)
was added dropwise under an inert atmosphere. The
solution was warmed to room temperature and stirred
for 12 h. H2O (2 ml) was added and the reaction mixture
vigorously stirred for 30 min. The solution was extracted
with CH2Cl2 (10 ml) and the organic layer dried over
MgSO4. After removing the solvent under reduced pres-
sure, the remaining residue was purified by column chro-
matography (Et2O) to afford the title compound (R)-L4
4.25. General procedure for the enantioselective Hetero-
Diels–Alder reaction
23
(43 mg, 70%) as an orange solid; ½aŠ ¼ À160 (c 0.11,
D
CHCl3); 1H NMR (300 MHz, CDCl3) d 1.02 (t, 6H,
J = 7 Hz, CH3), 1.22 (t, 6H, J = 7 Hz, CH3), 2.44 (m,
4H, CH2), 2.64 (m, 4H, CH2), 6.97 (d, 2H, J = 9 Hz),
7.02 (s, 2H, OH), 7.39 (d, 2H, J = 9 Hz), 7.44 (d, 2H,
J = 9 Hz), 9.44 (d, 2H, J = 9 Hz); 13C NMR (75 MHz,
CDCl3) d 188.0, 185.6, 155.6, 149.8, 145.19, 137.3,
131.6, 129.8, 129.7, 127.9, 125.3, 123.6, 121.9, 111.4,
20.6, 19.7, 14.1, 13.8; MS (EI): m/z 558 (100), 515
(10); HRMS (EI) calcd for C36H30O6 558.2042, found
558.2044; IR (KBr) m 3434, 2976, 2935, 2875, 1653,
1603, 1468, 1308, 1281, 1248, 818.
A solution of (R)-L2 (0.06 g, 0.1 mmol) and ZnEt2
(0.11 ml, 0.12 mmol, 1.1 M solution in toluene) in tolu-
ene (4 ml) was stirred in a Schlenk flask equipped with
a magnetic stirring bar under an inert atmosphere for
30 min. Freshly distilled benzaldehyde (0.1 ml, 1 mmol)
was added and after the reaction mixture was kept for
30 min at 0 ꢁC, DanishefskyÕs diene (0.2 ml, 1 mmol)
was charged. The reaction was quenched after 12 h by
introducing TFA (2 ml). The reaction mixture was
extracted with Et2O and the organic layer was washed

A. Minatti, K. H. Do¨tz / Tetrahedron: Asymmetry 16 (2005) 3256–3267
3267
10. (a) Onitsuka, K.; Harada, Y.; Takei, F.; Takahashi, S.
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with aq satd NaHCO3. The organic layer was dried over
MgSO4 and the solvent was evaporated in vacuo. The
residue was purified by column chromatography [PE/
EE, 4/1 (v/v)]. The enantiomeric excess of the product
was determined by HPLC analysis on a stationary
phase: Chiralcel OD column with n-hexane/2-propanol
as eluent (90:10, 1.0 ml/min) and 254 nm UV detector.
13. Tomuschat, P.; Kro¨ner, E.; Steckhan, E.; Nieger, M.;
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Acknowledgements
Support by the German Science Foundation (DFG;
SFB 624) and the Fonds der Chemischen Industrie for
a doctoral fellowship (Ana Minatti) is gratefully
acknowledged.
15. Wu, T. R.; Shen, L.; Chong, J. M. Org. Lett. 2004, 6,
2701–2704.
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H.-U. Synthesis 2004, 9, 1439–1445.
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