2,8'-Disubstituted-1,1'-Binaphthyls: A New Pattern in Chiral Ligands

Article abstract of DOI:10.1002/1521-3765(20021018)8:20<4633::AID-CHEM4633>3.0.CO;2-N

The title binaphthyls 19 and 26, which are the positional isomers of 2-methoxy-2'-(diphenylphosphino)-1,1'-binaphthyl (MOP, 19) and 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN, 26), have been synthesized by Suzuki coupling as the key step (10 + 15 -> 18), followed by functional group transformations, involving C-P and C-N bond formation (18 -> 19 and 18 -> 23). Racemic intermediate 22 was resolved by cocrystallization with N-benzylcinchonidinium chloride and the absolute configuration determined by X-ray crystallography. These novel binaphthyls are configurationally stable and, as such, potentially usable as chiral ligands in asymmetric reactions. Michael addition of the glycine-derived enolate 40 to methyl acrylate, carried out in the presence of (R)-(-)-27 as the chiral phase-transfer catalyst, afforded L-glutamic acid (S)-(+)-43 of 92% ee (after hydrolysis of the primary product).

Full text of DOI:10.1002/1521-3765(20021018)8:20<4633::AID-CHEM4633>3.0.CO;2-N

FULL PAPER
2,8'-Disubstituted-1,1'-Binaphthyls: A New Pattern in Chiral Ligands
Steœpa¬n Vyskocœil,*[a, b] Ludeœk Meca,[b] Iva Tisœlerova¬,[b] Ivana CÌsarœova¬,[b] Miroslav Pola¬sœek,[c]
œ
Syuzanna R. Harutyunyan,[d] Yuri N. Belokon,*[d] Russel M. J. Stead,[e] Louis Farrugia,[a]
Stephen C. Lockhart,[a] William L. Mitchell,[f] and Pavel Kocœovsky*[a]
¬
œ
Dedicated to the memory of Professor Otakar Cervinka
Abstract: The title binaphthyls 19 and
26, which are the positional isomers of
2-methoxy-2'-(diphenylphosphino)-1,1'-
binaphthyl (MOP, 19) and 2-amino-2'-
hydroxy-1,1'-binaphthyl (NOBIN, 26),
have been synthesized by Suzuki cou-
pling as the key step (10 ‡ 15 ! 18),
followed by functional group transfor-
mic intermediate 22 was resolved by co-
figurationally stable and, as such,
potentially usable as chiral ligands in
asymmetric reactions. Michael addition
of the glycine-derived enolate 40 to
methyl acrylate, carried out in the pres-
ence of (R)-(À)-27 as the chiral phase-
transfer catalyst, afforded l-glutamic
acid (S)-(‡)-43 of 92% ee (after hydrol-
ysis of the primary product).
crystallization with N-benzylcinchonidi-
nium chloride and the absolute config-
uration determined by X-ray crystallog-
raphy. These novel binaphthyls are con-
Keywords: amination ¥ binaphthyls
¥
chirality
¥ chiral resolution ¥
À
À
mations, involving C P and C N bond
Suzuki coupling
formation (18 ! 19 and 18 ! 23). Race-
identical substituents X and Y [e.g., 2,2'-dihydroxy-1,1'-
binaphthyl 2,2'-diamino-1,1'-binaphthyl
(BINOL),[2]
Introduction
2,2'-Substituted 1,1'-binaphthyls (1)[1] have played a major
role in the development of chiral catalysts for asymmetric
synthesis. Whilst the classical first generation possessed
(BINAM),[3] and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl
(BINAP);[4] 1a 1c], new development is characterized by
non-identical groups [e.g., 2-amino-2'-hydroxy-1,1'-binaphth-
yl (NOBIN),[5, 6] 2-methoxy-2'-(diphenylphosphino)-1,1'-bi-
naphthyl (MOP),[7] and 2-(N,N-dimethylamino)-2'-(diphenyl-
phosphino)-1,1'-binaphthyl (MAP);[5m, 8] 1d 1 f].
œ
œ
¬
œ
[a] Prof. P. Kocovsky, Dr. S. Vyskocil, Dr. L. Farrugia, S. C. Lockhart
Department of Chemistry, University of Glasgow
Glasgow G12 8QQ (UK)
Fax : (‡44)141-330-4888
E-mail: p.kocovsky@chem.gla.ac.uk
stepanv@natur.cuni.cz
œ
œ
œ
¬
œ
¬
[b] Dr. S. Vyskocil, L. Meca, Dr. I. Tislerova, Dr. I. CÌsarova
Department of Organic Chemistry, Charles University
128 40 Prague 2 (Czech Republic)
2
8
1
1
X
Y
Y
X
1'
1'
8'
2'
Fax : (‡420)2-2195-2323
[c] Dr. M. Polasek
¬ œ
¬
J. Heyrovsky Institute of Physical Chemistry
1a, X = Y = OH
2a, X = Y = OH
Academy of Sciences of the Czech Republic
182 23 Prague 8 (Czech Republic)
1b, X = Y = NH2
2b, X = Y = OXZ
2c, X = Y = COOH
2d, X = Y = Me
1c, X = Y = PPh2
1d, X = OH, Y = NH2
1e, X = OMe, Y = PPh2
1f, X = NMe2, Y = PPh2 2f, X = COOH, Y = H
1g, X = Y = H
1h, X = OH, Y = H
1i, X = OH, Y = NHCOMe
[d] Prof. Yu. N. Belokon, Dr. S. R. Harutyunyan
A. N. Nesmeyanov Institute of Organo-Element Compounds
Russian Academy of Sciences
2e, X = OMe, Y = PPh2
N
R
Vavilova 28, 117813 Moscow (Russian Federation)
E-mail: yubel@ineos.ac.ru
OXZ =
O
[e] R. M. J. Stead
Department of Chemistry, University of Leicester
Leicester LE1 7RH (UK)
Further locations in the binaphthyl skeleton, available to
accommodate the ligating groups, would be the 8,8'- and 2,8'-
positions.[9] While the former pattern (2) has been synthe-
sized[10] and shown to give high levels of asymmetric induction
in selected cases,[11] the latter series (3; Scheme 1) remains
[f] Dr. W. L. Mitchell
Department of Chemistry, GlaxoSmithKline PLC
The Frythe, Welwyn, Herts. AL6 9AR (UK)
Supporting information for this article is available on the WWW under
http://chemeurj.org/ or from the author.
Chem. Eur. J. 2002, 8, No. 20
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4633

œ
œ
¬
œ
P. Kocovsky, S. Vyskocil, Y. N. Belokon et al.
FULL PAPER
additional, bulky groups in 3,3'-positions;[1, 14] however, this
increases the synthetic complexity of the ligands. By contrast,
binaphthyl complexes with ligating groups located at 8,8'- or
2,8'-positions (2/M[10, 11] or 3/M) appear to offer a chiral
environment directly created by the binaphthyl skeleton so
that the binaphthyl moiety itself can be expected to exercise
asymmetric control, which may have interesting implications
in the level of asymmetric induction. The 8,8'-system (2/M)
has recently been shown to behave along these lines,[10, 11] but
the practicality of these ligands is somewhat hampered by
their low configurational stability (as compared to the 2,2'-
substituted binaphthyls).[11, 15] Herein, we report on the first
synthesis of 2,8'-disubstituted-1,1'-binaphthyls (3; X ˆ OMe,
OH, Yˆ PPh2, NH2) and demonstrate their configurational
stability.
2
1
X
Y
X
Y
X
Y
Br
(HO)2B
(HO)2B
Br
or
1'
8'
3
A
B
Scheme 1. Retrosynthetic analysis of 3.
unexplored. Yet another molecular architecture encompasses
a shift of the classical 1,1'-chiral axis into the 2,2'-position.[12]
Although these VAPOL-type ligands (e.g. 2,2'-diphenyl-(3,3'-
biphenanthrene)-4,4'-diol) require further substituents to
prevent rotation about the chiral axis, this complication is
compensated by excellent enantioselectivities attained in
selected asymmetric reactions.[12]
The common feature of 1,1'-binaphthyls is the chiral axis
between C-1 and C-1', which creates a chiral cavity. However,
when the coordinating atoms are located in the 2,2'-position,
this molecular architecture fails to offer a chiral environment
in the immediate vicinity of the reaction center (1/M), so that
the high degree of enantioselection reported for these ligands
has to be attributed to additional effects. Thus, for instance, in
Results and Discussion
Construction of 2,8'-disubstituted 1,1'-binaphthyls by Suzuki
coupling: The synthesis of the 2,8'-disubstituted 1,1'-binaphth-
yls 3 can be envisaged by the Suzuki[16] or related coupling
(Scheme 1) as the key step to construct the 1,1'-bond. This
approach would require two building blocks, namely a 1,2-
disubstituted naphthalene and its 1,8-disubstituted partner.
The substituents at the 1-position in each block would have to
be suitable for the intended coupling, for example, a halogen
and boron, with the choice of polarity (A or B). Availability of
the starting materials appeared to favor the alternative A,
since the naphthalene derivative with an electron-rich 2-sub-
stituent can be brominated at the 1-position (note that
1-bromo-2-naphthol is commercially available) and the syn-
thesis of the boronic partner can be envisaged through the
chelation-controlled deprotonation of a 1-substituted naph-
thalene in 8-position.
M
X
X
M
Y
Chiral
core
M
X
Chiral Y
core
ChiralY
core
Complex 3/M
Complex 2/M
Complex 1/M
1-Methoxynaphthalene is known to be deprotonated by
nBuLi at 2-position,[17 20] whereas tBuLi prefers the 8-position
(though the conversion seems rather low and the primary
product tends to equilibrate to the more thermodynamically
stable 2-Li isomer).[20, 21] By contrast, 1-(dimethylamino)naph-
thalene (4) is selectively deprotonated at 8-position both with
nBuLi and tBuLi.[21, 22] Therefore, we have first focused on 4 as
a precursor.
the case of BINAP (1c), the binaphthyl moiety serves merely
as a chiral scaffold, which dictates the orientation of the Ph
groups adjacent to the phosphorus atoms.[13] It is this relayed
effect, which then controls the enantioselection of the
catalytic reactions.[13] With these systems, the chiral environ-
ment at the reaction center can be further enhanced by
Deprotonation of 1-(dimethylamino)naphthalene (4)[22]
occurred at room temperature over a period of three days
(Scheme 2) and was evidenced by a gradual precipitation of
the yellow lithiated species, commencing about 18 24 hours
after the setup of the reaction. The latter, in situ generated
species was treated with (MeO)3B and the resulting borate
was hydrolyzed under the standard acidic conditions (HCl) to
afford the corresponding boronic acid 6 (44%). However, the
attempted Suzuki coupling of 6 with either 1-bromo-2-
naphthol or its methyl ether 9 (vide infra), under a variety
of conditions, was unsuccessful. Only the starting boronic acid
and the dehalogenated 2-naphthol and 2-methoxynaphtha-
lene were isolated after a prolonged reaction time. Appa-
Abstract in Czech: 2,8'-Disubstituovanÿ-1,1'-binaftyly, zejmÿ-
na polohovÿ isomery MOPu (19) a NOBINu (26), byly
¬
œ
œ
syntetizovany s pouzitÌm Suzukiho reakce jako klÌcovÿho
œ
œ
¬
kroku (10 ‡ 15 ! 18), po nemz nasledovala transformace
œ
funkcnÌch skupin, zahrnujÌcÌ tvorbu C-P a C-N vazeb (18 !
¬
œ œ
19 a 18 ! 23). Racemicky meziprodukt 22 byl rozstepen na
enantiomery krystalizacÌ s N-benzylcinchonidinium chloridem
a jeho absolutnÌ konfigurace byla stanovena pomocÌ rentgeno-
œ
strukturnÌ krystalografie. Tyto novÿ binaftyly jsou konfigurac-
œ
œ
¬
œ
œ
¬
ne stabilnÌ a tudÌz potencialne vyuzitelnÿ jako chiralnÌ ligandy
¬
¬
v asymetrickych reakcÌch. Michaelova adice enolatu 40, od-
¬
¬ œ
¬
vozenÿho z glycinu, na methyl metakrylat, provadena v
œ
¬
¬
¬
prÌtomnosti (R)-(À)-27 jako chiralnÌho katalyzatoru fazovÿho
rently, this failure to react is associated with the B
N
œ
prenosu, poskytla l-glutamovou kyselinu (S)-(‡)-43 s 92% ee
interaction (acid base), evidenced by 11B NMR spectroscopy,
¬
¬
(po hydrolyze primarnÌho produktu).
which showed the boron signal in 6 at d ˆ 10.56 ppm, that is,
4634
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Chem. Eur. J. 2002, 8, No. 20

Disubstituted Binaphthyls
4633 4648
NMe2
a
Li
NMe2
X
NMe2
OMe
b, c
or
55%
a
11
11
+
+
14
15
d
X
4
5
6, X = (HO)2B
7, X = Me3Sn
68%
16, X = NHAc
17, X = Br
e - g
(X = Br)
h-j
Scheme 4. a) [Pd(PPh3)4] (5 mol%), DME, H2O, Na2CO3, reflux 18 h.
OMe
OMe
X
B(OH)2
8, X = H
9, X = Br
10
(X = H or Br)
This last result suggested that, indeed, lowering the Lewis
basicity of the neighboring group improved the reactivity in
the 8-position. However, the reaction also required that steric
hindrance be minimized, as in boronic acid 11, which lacks the
interference of the peri-hydrogen, characteristic of its isomer
10. Apparently, the combined steric hindrance in 10 and 14
(particularly the peri-proton in 10) is prohibitive. Since the
steric architecture of the boronic acid cannot be altered
(boron must be located in 1-position), any alteration can only
be attempted in the electrophilic partner. Therefore, 1,8-
dibromide[32] 15 was prepared from diamine 12 by a double
Sandmeyer-type transformation and subjected to the coupling
with 10. On this occasion, the Suzuki reaction was successful
(Scheme 5), affording the desired 1,1'-binaphthyl 18 (76%),
whose structure was confirmed by X-ray crystallography (vide
infra). However, a fair amount of optimization was required
here; the highest yield (76%) of the desired product was
obtained when the coupling was carried out with [Pd(Ph3P)4]
as the catalyst (3.5 5 mol%) and K2CO3 as a base in a 2:1
DME/H2O mixture at reflux temperature for 24 hours.[33]
B(OH)2
OMe
11
Scheme 2. a) nBuLi, Et2O, RT, 3 d; b) (MeO)3B, RT, overnight; c) HCl,
H2O, RT, 2 h, 44% overall; d) Me3SnCl, RT, overnight, 53%; e) from 9,
Mg, THF, 30 min; f) (iPrO)3B (1.5 equiv), À788C, 1 h, then RT, 12 h;
g) HCl, H2O, RT, 30 min, 67% overall; h) from 9, nBuLi, THF, À788C, 2 h;
i) (iPrO)3B, À788C to RT, 18 h; j) dil. HCl, RT, 30 min.
ꢀ8 ppm upfield relative to other boronic acids, such as
PhB(OH)2, whose 11B signal appears at d ˆ 2.36 ppm.[23, 24]
Attempted Stille coupling of 9 with the tin analogue 7,[25]
obtained on quenching of the organolithium derivative 5 with
Me3SnCl, proved equally unsuccessful.
Since strategy A (Scheme 1) failed, we turned to the
partners with swapped polarity (B). To this end, boronic
acid[26] 10 was prepared as the nucleophilic partner from
1-bromo-2-methoxynaphthalene (9) from the corresponding
Grignard reagent[26
(Scheme 2) and borate ester.[27] I t is
28]
pertinent to note that 10 cannot be prepared directly from
2-methoxynaphthalene (8) through ortho-directed metalla-
tion or from 9 by lithiation, since these routes lead to the
™wrong∫ boronic acid 11.[29]
Br Br
+
OMe
B(OH)2
As an electrophilic partner, 1-amino-8-bromonaphtha-
lene[30] (13) was synthesized from the commercially available
1,8-diamine 12 by the Sandmeyer reaction (Scheme 3).
However, the attempted coupling of 13 with boronic acid
10[27] also failed.
10
15
a
OMe
Br
Br NHR
NH2 NH2
Br Br
d, e
a - c
18
Scheme 5. a) [Pd(PPh3)4] (3.5 5.0 mol%), Na2CO3, DME, H2O, reflux,
24 h; 76%.
13, R = H
14, R = MeCO
12
15
Scheme 3. a) NaNO2 (1 equiv), HCl, À58C, 2 h, 108C, 18 h; b) HBr
(excess), Cu bronze (0.66 equiv), 608C; 27%; c) Ac2O, pyridine, 1008C,
1 h, 80%; d) NaNO2 (2.3 equiv), conc. H2SO4, 08C; e) HBr (excess), CuBr
(1.3 equiv), RT; 25%.
A control experiment showed that, as expected, dibromide
15 also coupled with the isomeric boronic acid 11 to afford
1,2'-binaphthyl 17 (Scheme 4).
Since the presence of an electron-rich substituent in the
peri-position proved detrimental to the Suzuki coupling, we
set out to explore the possibility of using a less Lewis basic
group. To this end, bromoacetamide[31] 14 was prepared by
acetylation of 13 and subjected to the coupling with 10, but,
again, was found to be inert. On the other hand, amide 14 did
couple with the isomeric boronic acid 11 (unlike the amine 13,
which was still inert) to produce 1,2'-binaphthyl 16 (Scheme 4).
Substituent variation in 2,8'-disubstituted 1,1'-binaphthyls:
We envisaged that the availability of bromide 18 would open
the routes to methoxyphosphine 19, which can be regarded as
the 2,8'-isomer of MOP[7] (Scheme 6), and to amino alcohol
26, an isomer of NOBIN[5, 6] (Scheme 7). Indeed, replacement
of bromine in 18 with the PPh2 group did occur as expected by
using the Ager protocol,[34] affording 19, though in a modest
yield (32%), owing to the competing reduction to 2-meth-
Chem. Eur. J. 2002, 8, No. 20
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P. Kocovsky, S. Vyskocil, Y. N. Belokon et al.
FULL PAPER
In the synthesis of iso-NOBIN (26), Hartwig Buchwald
amination[40] was employed as the key step (Scheme 7). Thus,
following the protocol developed by Buchwald for an alter-
native synthesis of NOBIN,[40] methoxy bromide 18 was
converted into imine 23 (97%). Interestingly, the analogous
hydroxy bromide 22, obtained on the BBr3-mediated depro-
tection of 18 (96%), proved inert under the same conditions,
demonstrating the importance of the protecting group.
Hydrolysis of imine 23 afforded methoxy amine 25 (92%),
whose deprotection with BBr3 furnished the desired iso-
NOBIN (26, 95%). Alternatively, oxygen deprotection of 23
resulted in the formation of hydroxy imine 24 (95%),
demonstrating the stability of the imine functionality to Lewis
acids in the absence of water; the structure of 24 was
confirmed by X-ray crystallography (vide infra). Subsequent
hydrolysis of 24 with Br˘nsted acid gave rise to 26 (89%),
identical with the compound obtained from the first route.
The overall yields of these two routes were practically
identical. A two-step N-acetylation[5g] of 26 afforded acet-
amide 27 (94%).
OMe
Br
OMe
PPh2
a
19
18
OMe
OMe
+
20
21
Scheme 6. a) Ph2PCl, Zn, DMF, (dppe)NiCl2 (5 mol%), 1058C, 48 h.
The N,N-dimethylation of NOBIN (1d) by reductive
amination with formaldehyde and NaBH4 has been shown
by us to occur uneventfully and with high yield.[5g,i] Interest-
ingly, under the same conditions, iso-NOBIN (26) afforded a
mixture (Scheme 8) of the expected dimethylamino derivative
29 (33%) and the ipso-product 30 (59%), whose structure was
determined by the NMR spectroscopy with the full assign-
ment of all protons and carbons. The spirocycle 30 apparently
results from an electrophilic attack of the intermediate
immonium ion 28 at C-1'.
a
OMe
Br
OH
Br
b
22
18
c
OMe
OH
N
a
N
CPh2
CPh2
..
1'
OH
OH
NH2
23
a
N+R
24
d
d, a
28, R = H or Me
26
OR
NH2
OH
NHCOMe
e, f
O
OH
NMe2
NMe
25, R = Me
26, R = H
27
Scheme 7. a) BBr3, CH2Cl2, RT, overnight; b) MeI, K2CO3, Me2CO,
ˆ
reflux, 24 h, 97%; c) Ph2C NH, [Pd(dba)2], (2-Ph2P-C6H4)2O, tBuONa,
toluene, 1008C, 24 h; d) 35% aq HCl, CH2Cl2, RT, overnight; e) AcCl,
29
30
Scheme 8. a) 35% aq CH2O, NaBH4, H2SO4, THF, RT, 15 min.
C5H5N, CH2Cl2, RT, overnight; f) MeONa (cat.), MeOH, RT, overnight.
The electrophilic ipso-attack is not confined to this series.
Thus, tosylate 31 is known to produce the tetrahydropyrane
derivative 32 in alkaline medium rather than the expected
eight-membered crown ether (Scheme 9).[41, 42] Similarly,
MAP (1 f) reacts with the electrophilic PdCl2 to generate
the five-membered P,C-chelate 33 rather than the seven-
membered P,N-complex,[8c,g,h] and analogous results were
reported for reactions of PdII with bisphenanthrol[43] and PtII
with Me2BINOL.[44]
oxy-1,1'-binaphthyl (20, 6%)[35] and an insertion reaction
resulting in the formation of 1-methoxyperylene (21,
26%),[36, 37] whose structure was proved by single-crystal
X-ray analysis. Other attempts, such as the lithiation of 18
using tBuLi, followed by addition of Ph2PCl,[8d] the Pd0-
catalyzed coupling of 18 with Ph2P(O)H,[8a, 38] and the Ni0-
catalyzed coupling with Ph2PH[34, 39] were entirely unsuccess-
ful.
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Chem. Eur. J. 2002, 8, No. 20

Disubstituted Binaphthyls
4633 4648
Table 1. Racemization of selected 2,2'-disubstituted 1,1'-binaphthyls (1).
O
2
..
1
Entry
X
Y
T [8C] Solvent
t1/2(rac) DG=rac
Ref.
O-
1
[min] [kcalmolÀ1
]
OTs
O
1
2
3
4
5
6
CO2H CO2H 208
tetralin
> 900 > 39.4
[46]
[41, 47]
[47]
1'
O
1'
OH
NH2
II315
OH
H
OH
NH2
195
220
naphthalene
caprolactam
270
240
37.1
38.7
32
31
caprolactam
77
45.5
[47]
H
H
80
40
benzene
benzene
2600
102
29.4
24.0
[48]
[49]
Cl
-
Cl
2
Pd
1
..
PdCl2 Ph
Ph
NMe2
1
2
P
PPh2
1'
N+
1'
Me
Me
Table 2. Racemization of selected 8,8'-disubstituted 1,1'-binaphthyls (2).
Entry
X
Y
T
[8C]
Solvent t1/2(rac) DG=rac
[min] [kcalmolÀ1
Ref.
1f
33
]
Scheme 9. Reaction scheme for the formation of compounds 32 and 33.
1
2
3
4
5
6
7
8
CO2H
CO2Me CO2Me
CO2H CO2Me
CH2OH CH2OH 100 DMF
CO2Me CH2OH 100 DMF
CH3
CO2H
H
CO2H
50 DMF
50 DMF
50 DMF
51.5 24.4
23 23.8
18.3 23.7
[50]
[50]
[51]
[51]
[51]
[51]
[50]
[50]
Substituent variation in 8,3'-disubstituted 1,2'-binaphthyls:
The straightforward synthesis of methoxy acetamide 16 by
Suzuki coupling (Scheme 4) prompted us to establish a
suitable deprotection of both heterosubstituents, aiming at
the synthesis of another isomer of NOBIN. However, in
contrast to the straightforward deprotection of 23, this
molecule proved to be more difficult to deal with. Thus,
although the initial demethylation afforded the expected
hydroxy acetamide 34 in 92% yield (Scheme 10), the sub-
sequent attempt at hydrolysis of the N-acetyl group gave rise
to dibenzoxanthene 36 (50%) as the only isolable product.
Hydrazinolysis[45] of 34 was equally unsuccessful, furnishing
dibenzoacridine 37 (78%). Finally, reaction of 34 with
trichlorosilane produced the desired amino alcohol 35, though
in mere 16% yield.
395
29.7
14.1 27.3
CH3
H
H
100 DMF
50 DMF
50 DMF
679
30.4
15.4 23.4
14.5 23.4
have the racemization barrier at the level of unsubstituted
1,1'-binaphthyl (Table 1, entry 6). By contrast, sp3-substituents
(Table 2, entries
ꢀ6 kcalmolÀ1.[11e]
4 and 6) increase the barrier by
Configurational stability of 2,8'-disubstituted 1,1'-binaphthyls
18, 25, and 26 and 8,3'-disubstituted 1,2'-binaphthyls 16, 17,
and 35: Racemic binaphthyl derivatives 16, 17, and 35 were
resolved into enantiomers by means of analytical HPLC on
Daicel Chiralpak AD; the quantities thus obtained were
sufficient for the racemization experiments. Preparative
resolution has been achieved for hydroxy bromide (Æ)-22
(vide infra),[52, 53] from which enantiopure 18, 25, and 26 were
synthesized (vide infra).
16
BBr3
OH
NHCOMe
OH
NH2
Cl3SiH
Racemization of the individual derivatives was monitored
at the given temperature (Tables 3 and 4) by chiral HPLC.
The racemization barriers were calculated from the rate
constants by using Eyring equation.[54] The data obtained
indicate that the 2,8'-disubstituted 1,1'-binaphthyls (Table 3)
are sufficiently stable (as demonstrated for 18, 25, and 26) to
be employed as chiral ligands in asymmetric catalysis. Note
that their barriers (ꢀ40 kcalmolÀ1) are comparable with those
reported for BINOL and other 2,2'-disubstituted binaphthyls
(Table 1), which should allow their application in asymmetric
catalysis at temperatures ꢁ1508C.[15] By contrast, 1,2'-bi-
34
35
N2H4
H3O+
O
H
N
36
37
Scheme 10. a) BBr3, CH2Cl2, 08C, 14 h, 92%; b) aq. HCl, EtOH, reflux,
16 h, 50%; c) N2H4, amyl alcohol, reflux, 40 h, 78%; d) Cl3SiH, Et3N,
xylene, 1208C, 15 h, 16%.
Table 3. Racemization of 2,8'-disubstituted 1,1'-binaphthyls 18, 25, and
26.[a]
Configurational stability of 2,2'- and 8,8'-disubstituted 1,1'-
binaphthyls 1 and 2: Scalemic 2,2'-disubstituted 1,1'-binaphth-
yls are known to be configurationally more stable than their
8,8'-disubstituted counterparts. Selected data are summarized
in Tables 1 and 2.
Entry
Com-
pound
T
[8C]
Solvent
krac
t1/2(rac)
DG=rac
[10À6 sÀ1
]
[min]
[kcalmolÀ1
]
1
2
3
18
25
26[b]
250
225
190
Ph2O
Ph2O
Ph2O
59
12
< 9.7
200
960
> 1200
41.3
40.9
> 38.1
Interestingly, the 8,8'-disubstituted 1,1'-binaphthyls (2) with
the substituents possessing an sp2-hybridized carbon adjacent
to the 8-position (and 8') (Table 2, entries 1 3) appear to
[a] The accuracy of the measurement of DG=rac is Æ0.2 kcalmolÀ1. [b] Com-
pound 26 undergoes gradual decomposition at high temperature, which
precludes a more accurate measurement.
Chem. Eur. J. 2002, 8, No. 20
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FULL PAPER
Table 4. Racemization of 8,3'-disubstituted 1,2'-binaphthyls 16, 17, and
35.[a]
Entry Compound
T
[8C]
Solvent krac
[10À6 sÀ1
t1/2(rac) DG=rac
[min]
]
[kcalmolÀ1
]
1
2
3
4
5
16
17
35
35
35
22
22
20
30
40
DME
DME
DME
DME
DME
2.1
2.4
66
300
700
5400
4800
180
38
24.8
24.8
22.7
22.7
22.8
17
[a] The accuracy of the measurement of DG=rac is Æ0.1 kcalmolÀ1
.
naphthyls have their barriers around 23 kcalmolÀ1, as shown
for 16, 17, and 35 (Table 4), which is comparable with 8,8'-
disubstituted-1,1'-binaphthyls with sp2 substituents (Table 2,
entries 1 3) and unsubstituted 1,1'-binaphthyl (Table 1,
entry 6).
Quantum chemistry calculations, carried out for 18 (DFT-
B3LYP with 6-31G** basis set), gave the racemization barrier
of 39.2 kcalmolÀ1 (expressed as an energy difference between
ground and transition state); the less accurate calculation
(DFT-B3LYP at 6-31G level) gave 40.4 kcalmolÀ1.[55] In both
cases, the calculations are in an excellent agreement with the
experimental value of DG=rac (41.3 kcalmolÀ1; Table 3, en-
try 1).
Figure 2. ORTEP diagram of (Æ)-24 showing the atom labeling scheme.
Displacement parameters are shown at the 50% probability level.
carrying the hydroxy group, whereas the other phenyl is
practically perpendicular to the remaining ring of the same
naphthalene unit. The latter orientation suggests a T-type H
p interaction of the ortho proton of the phenyl group with the
p-system of the distal naphthalene ring.[57, 58]
Crystallographic characterization of racemic binaphthyls 18
and 24: A single-crystal X-ray analysis showed the bond
lengths and angles in 18 (Figure 1) to be rather standard, with
Enantiomerically pure 2,8'-disubstituted 1,1'-binaphthyls: The
key compound of this novel series to be successfully resolved
on a preparative scale (ꢀ10 g) was hydroxy bromide (Æ)-22.
Its single co-crystallization with N-benzylcinchonidinium
chloride in acetonitrile[52, 53] afforded a crystalline inclusion
complex that contained (‡)-22 (99.4% ee), while the mother
liquor was enriched in the (À)-enantiomer (84% ee). The
pure (‡)-enantiomer was released by chromatography on
silica gel using dichloromethane as eluent. Although we failed
to purify the enriched (À)-enantiomer directly by crystalliza-
tion of this material, we have found that, after its trans-
formation into (‡)-26 (84% ee), this material could be
crystallized from toluene to give racemic crystalline product,
leaving (‡)-26 (94% ee) in the solution. Crystallization of the
mother liquor from a dichloromethane-hexane mixture pro-
duced (‡)-26 (>99% ee). Even more efficient is the crystal-
lization of the enantiomerically enriched amide (À)-27
(ꢀ84% ee) from toluene, which gives an enantiopure product
in a single operation.
The absolute configuration of 22 was established by a
single-crystal X-ray analysis as (S)-(‡)-22 (Figure 3).[59]
Figure 1. ORTEP diagram of (Æ)-18 showing the atom labeling scheme.
Methylation of (S)-(‡)-22 (>99% ee, MeI , KCO3, acetone,
2
Displacement parameters are shown at the 50% probability level.
reflux) produced (‡)-18 (95%), for which the absolute
configuration was confirmed by X-ray crystallography as
(S)-(‡)-18 (Figure 4).[60] The remaining members of the series
were then synthesized by using the protocols developed for
their racemic counterparts.[61]
From the absolute configuration of 18 and 22, established
by X-ray crystallography, the whole series of the generically
related 2,8'-disubstituted 1,1'-binaphthyls can be inferred as
À
a notable deformation about the C Br bond imposed by the
bulky bromine atom that is repulsed by the naphthalene
unit.[56] In both 18 and 24, the two naphthalene units are
almost perpendicular. Interesting characteristics were noted
for imine 24 (Figure 2), in which one of the phenyl rings
adjacent to the imine group is roughly parallel to the ring
4638
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Chem. Eur. J. 2002, 8, No. 20

Disubstituted Binaphthyls
4633 4648
O
O
N
O
Ni
N
N
a
H
N
N
O
O
O
38
39
b
MeO2C
R
O
O−
O
*
N
N
Ni
Ni
N
N
N
N
O
O
slow
41, R = H
42, R = CH3
40
MeO2C
O−
− NiCl2
− 38
c
O
N
HO2C
CO2H
Ni
*
N
N
R
NH2
O
(S)-43, R = H (94% ee)
44, R = CH3
Figure 3. ORTEP diagram of (S)-(‡)-22 showing the atom labeling
45
scheme. Displacement parameters are shown at the 50% probability level.
Scheme 11. a) Ni(NO3)2, MeONa, MeOH, reflux 20 min, 91%; b) solid
ˆ
NaH, catalyst (10 15 mol%), CH2 C(R)CO2Me, CH2Cl2, RT, 2 3 min;
c) 6m HCl, MeOH, reflux for several min.
positive nonlinear effect have also been demonstrated for this
reaction.[6k, 64] As an extension of this methodology, we elected
to briefly study asymmetric Michael addition of 39 to methyl
ˆ
acrylate and methyl methacrylate CH2 C(R)CO2Me
(Scheme 11 and Table 5). To this end, nonchiral ligand 38,
obtained from o-aminobenzophenone and a-picolinic acid
chloride (Et3N, CH2Cl2, RT, overnight; 85%),[6k] was con-
densed with glycine and to afford complex 39 (91%).[6k] The
Michael addition of 39 to methyl acrylate (solid NaH, catalyst
(10-15 mol%), in CH2Cl2, RT, 2 3 min), furnished the
expected adduct 41 (for yields and enantioselectivities, see
Table 5. Michael addition of glycine complex 39 to methyl acrylate and methyl
methacrylate catalyzed by 1,1'-binaphthyls (Scheme 11).[a]
Entry
R
Base
[mol%]
Catalyst
[mol%]
T
Time Yield[b] % ee[c]
[8C] [min] [%]
(configuration[d]
)
1
2
3
4
H
H
H
H
H
H
H
NaH (10) (R)-1d (10) 18
NaH (100) (R)-1i (10) 18
NaH (100) (S)-22 (10) 20
NaH (100) (R)-26 (10) 20
NaH (100) (R)-27 (10) 20
NaH (100) (R)-27 (10) 20
NaH (200) (R)-27 (10) 20
3
3
2.5
3
2
2
3
9
40
50
75
40
60
65
70
50
26 (S)
55 (S)
13 (S)
18 (S)
90 (S)
92 (S)
92 (S)
81 (2S,4R)[g]
Figure 4. ORTEP diagram of (S)-(‡)-18 showing the atom labeling
scheme. Displacement parameters are shown at the 50% probability level.
5
6[e]
7[f]
8
follows: (S)-(‡)-18, (S)-(‡)-19, (S)-(‡)-22, (S)-(À)-23, (S)-
(À)-24, (S)-(‡)-25, (S)-(À)-26, and (S)-(‡)-27.
Me NaH (100) (R)-27 (15) 20
[a] The reaction was carried out at 1.0 4.0 mmol scale in CH2Cl2 with six
equivalents of methyl acrylate. The crude product was hydrolyzed with 6m HCl
and 43/44 was isolated by ionex chromatography. [b] Isolated yield. [c] Deter-
mined by chiral GLC for the n-propyl ester of N-trifluoroacetyl derivative.
[d] Determined by chiral GLC (by comparison with the known sample). [e] A
fourfold increase in the concentration of the substrate, as compared with entry 4.
[f] The experiment was carried out with (R)-27 recovered from the reaction
mixture (previous batch) in 60% yield. [g] Two diastereoisomers of 44 were
formed: (2S,4R):(2S,4S) ˆ 86:14. The minor diastereoisomer was of 66% ee.
iso-NOBIN-derived acetamide as an asymmetric phase-trans-
fer catalyst: The NiII-complex 39,[62] derived from 38, glycine,
and NiII (Scheme 11), can be alkylated by good electrophiles,
such as PhCH2Br, in the presence of solid NaOH as a base and
NOBIN (1d) as the phase-transfer catalyst, to give, after
hydrolysis, amino acids with very high enantioselectivity (up
‡
to 99% ee).[6k, 63] The crucial role of Na ion and a strong
Chem. Eur. J. 2002, 8, No. 20
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P. Kocovsky, S. Vyskocil, Y. N. Belokon et al.
FULL PAPER
Table 5), whose hydrolysis produced glutamic acid (S)-43.
While (R)-1d gave only 26% ee (Table 5, entry 1), improve-
ment to 55% ee has been attained with the corresponding
acetamide (R)-1i[5g] (entry 2). When the iso-NOBIN-derived
acetamide (R)-(À)-27 was employed, substantial increase in
asymmetric induction was observed (90% ee; entry 5), and
further improvement (to 92% ee) was attained with a four-
fold increase in the concentration of 39 (entry 6). No erosion
of enantioselectivity was observed when 27, regenerated from
a previous batch, was re-employed as catalyst (entry 7). Both
hydroxy bromide (S)-22 and iso-NOBIN (R)-(‡)-26 also
proved to catalyze the reaction, but the enantioselectivity was
low (entries 3 and 4), demonstrating the key role played by
the amide group.[65] With methyl methacrylate (R ˆ Me) as
the Michael acceptor, two diastereoisomers of 44 were formed
in a 6:1 ratio; the major product, identified as the (2S,4R)-
stereoisomer, was obtained in 81% ee (entry 8).
The salient feature of the present protocol is that a second
alkylation of the primary product 41 has not been detected
under the reaction conditions. This selectivity can be under-
stood in terms of steric congestion, which the enolization of 41
to 45 would impose: here, by changing the hybridization at Ca,
the new substituent would be brought into the plane of the
chelate, which is apparently prohibited by the bulky phenyl
group of the imine moiety.[66, 67] The less enantioselective
Michael addition to methyl methacrylate can be attributed to
the effect of the additional methyl group that renders the
transition states less different in energy. The formation of the
second chiral center in 42 (C-4) occurs through protonation of
the corresponding enolate intermediate, arising by Michael
addition. This step is notably diastereoselective (6:1), suggest-
ing an effective 1,3-induction, exercised by the C-2 center.
Another notable feature of the Michael addition is the
strong nonlinear effect[68] (Figure 5)–a behavior that is in line
with the similar effect previously observed for the SN2
alkylation of 39 with PhCH2Br.[6k] In the present case, the
catalyst of only 40% ee still exhibits an impressively high
asymmetric induction (75% ee).
The present experiments show that this chemistry is not
limited to SN2 reactions with reactive electrophiles, as
reported earlier.[6k] Further extensions can be anticipated,
for example, for Michael additions generating two chiral
À
centers at the newly-formed C C bond, aldol condensations,
etc. Moreover, these very fast and mild reactions may be
amenable to the syntheses, for which speed is crucial, such as
those involving 11C and 18F labeling.
Conclusion
In conclusion, we have synthesized a novel class of 1,1'-
binaphthyls with substituents in 2,8'-positions (3), namely, the
methoxy phosphine 19 (iso-MOP) and amino alcohol 26 (iso-
NOBIN), using Suzuki coupling as the key step to construct
the aryl aryl bond (10 ‡ 15 ! 18). This coupling turned out
to be sensitive to the nature of the 8-substituent and the
overall steric congestion in the transition state.
Intermediate 22 was resolved into enantiomers and the
absolute configuration of 18 and 22 was determined by X-ray
crystallography. The new 2,8'-disubstituted binaphthyls 18, 25,
and 26 proved to be as configurationally stable as their 2,2'-
disubstituted counterparts 1 (both experimentally and by
quantum chemistry calculations) and, therefore, suitable for
asymmetric catalysis. By contrast, the 8,3'-disubstituted 1,2'-
binaphthyls 16, 17, and 35 have low racemization barriers,
comparable with that of unsubstituted 1,1'-binaphthyl 1g.
iso-NOBIN 26 and, in particular, its acetamido derivative
27, have been identified as efficient, chiral phase-transfer
catalyst for the Michael addition of the enolate 40, derived
from the NiII complex of glycine-imine, to methyl acrylate,
affording glutamic acid 43 in up to 92% ee.
Experimental Section
General methods: Melting points were determined on a Kofler block and
are uncorrected. The optical rotations were measured in THF with an error
1
of < Æ 0.1. The H NMR spectra were recorded on 400 MHz instruments
(FT mode) for solutions in CDCl3 at 258C with TMS as internal reference.
The 13C NMR spectra were recorded on a 101 MHz instruments (FT mode)
for solutions in CDCl3 at 258C. The individual protons and carbon atoms
were assigned by using DEPT, COSY, NOESY, HSQC, and HMBC
techniques. The 31P NMR spectra were recorded at 162 MHz (FT mode) for
solutions in CDCl3 at 258C with H3PO4 as external reference. The IR
spectra were measured in dichloromethane or chloroform. The high-
resolution mass spectra were measured on a ZAB2-SEQ double-focusing
spectrometer (70 eV, 8 kV) with direct inlet and the lowest temperature
enabling evaporation; the accuracy was ꢁ5 ppm. Yields are given in
milligrams of isolated product, showing one spot on a chromatographic
plate and no impurities detectable in the NMR spectrum. 2,2'-Bis(diphe-
nylphosphino)diphenyl ether (dpePhos) was purchased from Strem. The
syntheses of 38 and 39 were carried out as described earlier.[6k]
1-Dimethylamino-8-naphthaleneboronic acid (6): nBuLi (22 mL of a 2.5M
solution in hexanes) was added to a solution of 1-(N,N-dimethylamino)-
naphthalene (4: 1.92 mL, 11.6mmol) in anhydrous diethyl ether (5 mL).
The yellow precipitate of the organolithium species 5 was observed after
approximately 18 24 h, and the reaction was complete within 2 3 days.
Aryllithium 5 thus generated was then added by means of a cannula to a
solution of trimethylborate (6.17 mL, 55.0 mmol) in THF (8 mL) cooled to
À788C and stirred at room temperature overnight. The reaction mixture
was then poured into 10% aqueous HCl and stirred at room temperature
Figure 5. Nonlinear effect of (R)-27 as catalyst in the Michael addition of
39 to methyl acrylate.
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Disubstituted Binaphthyls
4633 4648
for 2 h. The product was extracted with diethyl ether and sequentially
washed with 10% aqueous HCl, water, and brine, and dried over MgSO4.
Flash chromatography on silica gel (30 g) using petroleum ether as eluent
1.4 Hz, 1H), 7.74 (dd, J ˆ 8.2, 1.0 Hz, 1H), 7.84 (dd, J ˆ 8.2, 1.0 Hz, 1H),
8.41 (s, 1H).
1-Amino-8-bromonaphthalene (13):[30]
A solution of NaNO2 (6.70 g,
1
afforded pure, amorphous 6 (1.097 g, 44%). H NMR (400 MHz, CDCl3):
97.1 mmol, 1.02 equiv) in water (150 mL) was added to a solution of 1,8-
diaminonaphthalene (15.0 g, 94.8 mmol) in HCl (0.4m, 1.0 L) at À58C. The
mixture was then stirred at À58C for 2 h and at 108C for 18 h. The black
precipitate was filtered off, washed with water, dried at room temperature
for 1 h, and then dissolved in aqueous HBr (48%, 100 mL). Copper bronze
(4.0 g, 63 mmol), first activated by heating with flame for 10 min under
argon, was added to the resulting solution at 608C. The mixture was stirred
for 18 h, water (220 mL) was then added, and the mixture was heated to the
boiling point. The precipitate was filtered off with suction and boiled with
additional water. The combined filtrate was neutralized with ammonium
carbonate and extracted with dichloromethane (3 Â 40 mL); the extract
was dried with Na2SO4 and evaporated. Chromatography of the crude
product on silica gel (100 g) with toluene afforded 13 (5.66 g, 27%) as pink
crystals: m.p. 90 918C (toluene) and IR are in accord with the literature.[30]
1H NMR (400 MHz, CDCl3): d ˆ 5.14 (brs, 2H), 6.71 6.76 (m, 1H), 7.11
7.16 (m, 1H), 7.23 7.25 (m, 2H), 7.62 (dd, J ˆ 7.5, 1.2 Hz, 1H), 7.68 (dd, J ˆ
8.2, 1.2 Hz, 1H).
d ˆ 2.91 (s, 6H), 7.21 (d, J ˆ 7.3 Hz, 1H), 7.42 (t, J ˆ 7.7 Hz, 2H), 7.53 (t, J ˆ
7.3 Hz, 1H), 7.61 (dd, J ˆ 8.2, 0.9 Hz, 1H), 7.73 (d, J ˆ 8.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d ˆ 112.06 (d), 119.99 (s), 121.93 (d), 125.61 (d), 126.02
(d), 126.14 (d), 128.97 (d), 132.55 (s), 134.17 (s), 153.64 (s); 11B NMR
(acetone): d ˆ 10.56 (s).
1-Dimethylamino-8-(trimethyltin)naphthalene (7): The aryllithium 5 was
generated from 4 (0.96 mL, 5.84 mmol) and nBuLi (16.8 mL of 1.6M
solution in hexanes) in diethyl ether (5 mL) as described in the preparation
of 6. Trimethyltin chloride (28 mL of a 1.0m solution in hexanes) was added
at À788C, and the mixture was stirred at room temperature overnight. The
mixture was poured into water, extracted with diethyl ether and the
resulting solution was dried over MgSO4 and the solvent was evaporated.
Flash column chromatography on silica gel (20 g) using petroleum ether as
eluent afforded pure 7 (1.04 g, 53%). 1H NMR (400 MHz, CDCl3): d ˆ 0.26
(s, 9H), 2.66 (s, 6H), 7.32 (ddd, J ˆ 7.4, 1.3, 1.0 Hz, 1H), 7.50 7.42 (m, 2H),
7.66 (dd, J ˆ 8.0, 1.1 Hz, 1H), 7.79 (dd, J ˆ 7.7, 1.3 Hz, 2H); 13C NMR NMR
(100 MHz, CDCl3): d ˆ 10.9 (3q), 47.5 (2q), 115.9 (d), 125.5 (d), 125.6 (d),
125.7 (d), 128.3 (d), 134.3 (s), 134.8 (s), 135.8 (d), 138.7 (s), 153.0 (s).
1-Bromo-2-methoxynaphthalene (9):[26] A solution of bromine (12.9 mL,
0.25 mol) in acetic acid (100 mL) was added to a solution of 2-methoxy-
naphthalene (8: 39.5 g, 0.25 mol) in acetic acid (350 mL) over the period of
30 min. The mixture was stirred at room temperature for 30 min, the
resulting suspension was poured into water (1.5 L), and the precipitated
product was isolated with suction and washed with water. The crude
product was dried and crystallized from ethanol with charcoal to afford 9
(50.5 g, 85%) as colorless plates. M.p. 85 868C (in accordance with the
literature[26]); 1H NMR (400 MHz, CDCl3): d ˆ 4.03 (s, 3H), 7.28 (d, J ˆ
9.0 Hz, 1H), 7.37 7.42 (m, 1H), 7.54 7.59 (m, 1H), 7.76 7.84 (m, 2H),
8.20 8.24 (m, 1H).
2-Methoxy-1-naphthaleneboronic acid (10):[27] Magnesium (2.2 g,
91 mmol), activated by stirring for 24 h under argon was covered with
THF (30 mL) and then a solution of 9 (20 g, 84 mmol) in THF (150 mL)
was slowly added under argon. The formation of the Grignard reagent was
accompanied by spontaneous heating of the mixture to the boiling point.
After stirring for 30 min, the mixture was cooled to room temperature and
added by means of a cannula to a solution of (iPrO)3B (29 mL, 126 mmol,
1.5 equiv) in THF (40 mL) at À788C. The mixture was then stirred at
À788C for 1 h and at room temperature for 12 h. Water (30 mL) was then
added and the solvent was evaporated in vacuum. The residue was treated
with water (150 mL) and acidified with HCl (1m, 200 mL) to precipitate the
product. Dichloromethane (30 mL) was added and the resulting heteroge-
neous mixture was vigorously stirred for 10 min to dissolve 2-methoxy-
naphthalene, the undesired byproduct. The solid crude product was
isolated with suction and washed with CH2Cl2 (2 Â 10 mL). Crystallization
from aqueous ethanol (1:1, 60 mL) gave boronic acid 10 (11.5 g, 67%) as a
white solid: m.p. 140 1448C (literature[29] reports 143 58C). The IR
spectrum is in accordance with the literature data.[27] 1H NMR (400 MHz,
CDCl3): d ˆ 4.03 (s, 3H), 6.11 (s, 2H), 7.28 (d, J ˆ 9.2 Hz, 1H), 7.37 (ddd,
J ˆ 8.0, 6.7, 1.3 Hz, 1H), 7.51 (ddd, J ˆ 8.5, 6.9, 1.6 Hz, 1H), 7.78 (dm, J ˆ
8.2 Hz, 1H), 7.94 (d, J ˆ 9.0 Hz, 1H), 8.83 (dm, J ˆ 8.7 Hz, 1H).
1-Acetamido-8-bromonaphthalene (14):[31]
A mixture of 13 (3.10 g,
14 mmol), acetic anhydride (1.4 mL, 15 mmol, 1.07 equiv), and pyridine
(8 mL) was heated at 1008C for 1 h and then evaporated in vacuum. The
oily residue was treated with cold, diluted hydrochloric acid (50 mL), and
the resulting crystalline material was isolated with suction, washed with
water, and dried on the air. The crude product was recrystallized from 50%
aqueous acetic acid (8 mL) to furnish pure 14 (2.87 g, 80%) as colorless
crystals: m.p. 143 1448C agrees with the literature.[31] 1H NMR (400 MHz,
CDCl3): d ˆ 2.28 (s, 3H), 7.23 (t, J ˆ 8.0 Hz, 1H), 7.48 (t, J ˆ 7.8 Hz, 1H),
7.69 (d, J ˆ 8.0 Hz, 1H), 7.77 (d, J ˆ 7.8 Hz, 1H), 7.81 (d, J ˆ 8.0 Hz, 1H),
7.99 (d, J ˆ 7.8 Hz, 1H), 8.79 (brs, 1H); 13C NMR (100 MHz, CDCl3): d ˆ
24.83 (q), 115.73 (s), 124.56 (s), 124.82 (d), 125.91 (d), 126.29 (d), 127.00 (d),
129.57 (d), 131.98 (s), 133.68 (d), 136.57 (s), 168.36 (s); IR (CHCl3): nÄ ˆ 3438
À1
ˆ
À
(NH), 1690 (C O), 1530 (arom), 1490 (arom), 1272 (C N)cm
.
1,8-Dibromonaphthalene (15):[32] Solid NaNO2 (10.0 g, 0.145 mol,
2.3 equiv) was cautiously added to stirred concentrated H2SO4
a
(100 mL) at 08C. Then, a solution of 1,8-diaminonaphthalene (10.0 g,
63.2 mmol) in acetic acid (100 mL) was added at 08C over a period of 3 h
with vigorous stirring with a mechanical stirrer. The mixture was stirred at
08C for an additional 30 min and then slowly poured onto ice (200 g). Free
HNO2 was decomposed by adding a saturated aqueous solution of urea
(2.0 g). The resulting mixture was poured into a solution of CuBr (25.0 g,
0.174 mol) in aqueous HBr (48%, 375 mL) and stirred at room temper-
ature for 18 h. Toluene (150 mL) was then added and the solution was
filtered with suction and the black solid was washed with dichloromethane
and the filtrate was treated with water (1 L). The aqueous layer was
extracted with dichloromethane (2 Â 50 mL) and the combined extracts
were dried with Na2SO4 and evaporated in vacuum to produce crude 15.
Flash chromatography on silica gel (100 g) with toluene gave pure 15
(4.48 g, 25%) as yellow crystals: m.p. 104 1068C (toluene) and IR are in
accord with the literature.[32] 1H NMR (400 MHz, CDCl3): d ˆ 7.26 (dd, J ˆ
8.2, 7.6 Hz, 2H), 7.80 (dd, J ˆ 8.2, 1.2 Hz, 2H), 7.92 (dd, J ˆ 7.6, 1.2 Hz, 2H).
(Æ)-8-Acetamido-3'-methoxy-1,2'-binaphthyl (16): A solution of Na2CO3
(1.40 g) in water (6.5 mL), which was previously purged with argon for
10 min, was added to a solution of 14 (660 mg, 2.50 mmol), boronic acid 11
(505 mg, 2.50 mmol), and (Ph3P)4Pd (144 mg, 125 mmol, 5 mol%) in DME
(14 mL) under argon. The mixture was refluxed for 18 h and then the
solvent was evaporated in vacuum. Water (8 mL) was added to the residue
and the product was taken up into dichloromethane (2 Â 5 mL). The extract
was dried with Na2SO4 and evaporated. Chromatography of the crude
product on silica gel (50 g) with a petroleum ether/ethyl acetate mixture
(1:1) followed by crystallization from ethyl acetate afforded pure 16
(471 mg, 55%) as colorless crystals. M.p. 150 1518C; 1H NMR (400 MHz,
CDCl3): d ˆ 1.17 (s, 3H), 3.78 (s, 3H), 7.14 (brs, 1H), 7.25 (dd, J ˆ 6.7,
1.2 Hz, 1H), 7.40 7.46 (m, 1H), 7.48 7.56 (m, 4H), 7.76 7.88 (m, 5H), 7.92
(d, J ˆ 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d ˆ 23.50 (q), 55.72 (q),
105.16 (d), 122.77 (d), 124.55 (d), 124.95 (d), 125.66 (d), 125.93 (s), 126.40
(d), 126.55 (d), 126.93 (d), 127.64 (d), 128.41 (s), 129.14 (d), 129.27 (d),
130.00 (d), 133.05 (s), 133.08 (s), 134.23 (s), 134.27 (s), 134.88 (s), 155.65 (s),
2-Methoxy-3-naphthaleneboronic Acid (11):[29] A solution of n-butyllithi-
um (1.6m in hexanes, 15.6 mL, 25 mmol) was added to a solution of 9
(5.69 g, 24 mmol) in THF (30 mL) under argon at À788C. The mixture was
stirred at À788C for 2 h and then added by means of a cannula to a solution
of (iPrO)3B (8.3 mL, 36 mmol, 1.5 equiv) in THF (20 mL), cooled to
À788C. The resulting mixture was stirred at À788C for 1 h and then at
room temperature for 18 h. The mixture was then poured into HCl (1m,
250 mL) and vigorously stirred for 30 min. NaOH (5m, excess) was then
added and the mixture was extracted with dichloromethane (2 Â 50 mL).
The aqueous layer was acidified with Hcl (5m) and the product was
extracted into dichloromethane (3 Â 30 mL). The extract was washed with
water and dried with Na2SO4, and the solvent was evaporated in vacuum to
furnish crude product 15 (2.62 g, 54%) as light brown crystalline material
that was not further purified: m.p. 173 1748C (dichloromethane; liter-
ature[29] reports 153 1558C). The IR spectrum is in accordance with the
literature data.[29] 1H NMR (400 MHz, CDCl3): d ˆ 4.03 (s, 3H), 6.07 (s,
2H), 7.16 (s, 1H), 7.37 (ddd, J ˆ 8.2, 6.9, 1.3 Hz, 1H), 7.49 (ddd, J ˆ 8.2, 6.9,
ˆ
167.86 (s); IR (CHCl3): nÄ ˆ 3429 (NH), 1685 (C O), 1523 (arom), 1495
‡
(arom), 1255 cmÀ1 (C O); MS: m/z (%): 341 (74) [M ], 299 (18), 283 (12),
À
Chem. Eur. J. 2002, 8, No. 20
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0820-4641 $ 20.00+.50/0
4641

œ
œ
¬
œ
P. Kocovsky, S. Vyskocil, Y. N. Belokon et al.
FULL PAPER
268 (100), 267 (78), 254 (19), 43 (21); HRMS for C23H19NO2: calcd 341.1416;
found 341.1392. The small-scale enantiomeric separation was performed on a
Daicel Chiralpak AD column using a hexane-methanol-isopropyl alcohol
mixture (67:30:3); the retention times were 7.0 and 8.8 min.
Isolation of enantiopure (S)-(‡)-18: Solid K2CO3 (6.9 g, 50 mmol) and
methyl iodide (3.2 mL, 50 mmol) were added to a solution of (S)-(‡)-22
(1.81 g, 5 mmol) in acetone (25 mL), and the mixture was refluxed for 24 h.
The solvent was evaporated under the reduced pressure and the residue
was purified by chromatography on silica gel (50 g) with toluene as eluent
to give (S)-(‡)-18 (1.75 g, 97%) as a white powder. M.p. 160 1618C
(dichloromethane/hexane); [a]D ˆ ‡150.9 (c ˆ 1.0 in THF). Chiral chro-
matography on Daicel Chiralpak AD with a hexane/isopropyl alcohol
mixture (98:2) gave >99% ee for this product (tR ˆ 4.8 min, tS ˆ 5.8 min).
Crystallographic data for (S)-(‡)-18: C21H15BrO, Mr ˆ 362.03. Crystals
were obtained from a dichloromethane solution by slow diffusion of hexane
vapors at room temperature. Orthorhombic; space group P212121; a ˆ
14.6360(4), b ˆ 14.6340(3), c ˆ 14.9980(3) ä. Data were collected at
150(2) K on a Nonius KappaCCD diffractometer using MoKa radiation
(l ˆ 0.71073 ä), a graphite monochromator, and w scan mode at five
different crystal orientations up to 0.8106 ä resolution. A total of 47446
reflections were measured, from which 6311 were unique (Rint ˆ 0.071),
with 6078 observed data with I > 2s(I). The structure was solved by direct
methods (SIR92). All reflections were used in the structure refinement
based on F 2 by full-matrix least-squares technique (SHELXL97) with
hydrogen atoms calculated into theoretical positions, riding during refine-
ment on the respective pivot atom (418 parameters). The symmetry of the
lattice is close to tetragonal and crystals suffered by pseudomerohedric
twinning with twin matrix.
(Æ)-8-Bromo-3'-methoxy-1,2'-binaphthyl (17):
A solution of Na2CO3
(810 mg) in water (3.8 mL), which was previously purged with argon for
10 min, was added to a solution of 1,8-dibromonaphthalene 15 (418 mg,
1.46 mmol), boronic acid 11 (294 mg, 1.46 mmol), and (Ph3P)4Pd (84 mg,
73 mmol, 5 mol%) in DME (8.0 mL) under argon. The mixture was
refluxed for 18 h and then the solvent was evaporated in vacuum. Water
(5 mL) was added to the residue and the product was taken up into
dichloromethane (2 Â 3 mL). The extract was dried with Na2SO4 and
evaporated. Chromatography of the crude product on silica gel (50 g) with
a toluene/petroleum ether mixture (7:3) afforded pure 17 (359 mg, 68%).
M.p. 118 1198C (ethyl acetate/methanol); 1H NMR (400 MHz, CDCl3):
d ˆ 3.80 (s, 3H), 7.15 (s, 1H), 7.27 (dd, J ˆ 8.1, 7.3 Hz, 1H), 7.37 (ddd, J ˆ 8.1,
6.9, 1.2 Hz, 1H), 7.45 (dd, J ˆ 7.2, 1.5 Hz, 1H), 7.47 (ddd, J ˆ 8.2, 6.9, 1.4 Hz,
1H), 7.53 (dd, J ˆ 8.1, 7.0 Hz, 1H), 7.69 (s, 1H), 7.75 (dd, J ˆ 7.5, 1.4 Hz, 1H),
7.77 (dm, J ˆ 8.1 Hz, 1H), 7.81 (dm, J ˆ 8.1 Hz, 1H), 7.89 (dd, J ˆ 8.6,
1.4 Hz, 1H), 7.91 (dd, J ˆ 8.4, 1.5 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d ˆ 55.55 (q), 104.47 (d), 120.60 (s), 123.72 (d), 125.52 (d), 125.81 (d), 126.16
(d), 126.41 (d), 127.70 (d), 128.51 (s), 129.05 (d), 129.37 (d), 129.88 (d),
130.49 (s), 131.46 (d), 133.18 (d), 134.31 (s), 134.45 (s), 135.73 (s), 136.53 (s),
157.11 (s); IR (CHCl3): nÄ ˆ 1632 (arom), 1503 (arom), 1475 (arom), 1253
ꢀ
ꢁ
‡
‡
(C O), 1171 cmÀ1 (arom); MS: m/z (%): 364 (23) [M ] (81Br), 362 (23) [M ]
(79Br), 283 (78), 268 (100), 252 (46), 239 (53), 141.5 (18), 134 (41), 126 (16),
119.5 (44), 118.5 (17), 106.5 (11); HRMS for C21H1579BrO: calcd 362.0306;
found 362.0311. The small-scale enantiomeric separation was performed on
a Daicel Chiralpak AD column using a hexane-methanol-isopropyl alcohol
mixture (79:18:3); the retention times were 4.7 and 5.3 min.
À
h' 0 1 0 h
k' À1 0 0 k
l'
0 0 1 l
The correction for this effect was included into refinement, which yielded
fractional contribution of twin components 0.6991(8):0.3009. Absorption
correction (m ˆ 2.561 mmÀ1) was carried out, by using Gaussian methods
(Coppens, 1970): min/max transmission ˆ 0.558/0.753. The absolute struc-
ture was determined clearly since the absolute structure parameter is equal
0.000(9). Final R factors: R1 ˆ 0.030 for the observed data and 0.032 for all
data; wR2 ˆ 0.0765, S ˆ 0.925. The estimated error in the bond lengths for
non-hydrogen atoms is in the interval 0.004 to 0.007 ä.
(Æ)-8-Bromo-2'-methoxy-1,1'-binaphthyl (18):
A solution of Na2CO3
(3.2 g) in water (15 mL), which was previously purged with argon for
10 min, was added to a solution of 15 (2.0 g, 7.0 mmol), boronic acid 10
(1.41 g, 7.0 mmol), and [Pd(Ph3P)4] (290 mg, 0.25 mmol, 3.5 mol%) in
DME (32 mL) under argon. The mixture was refluxed for 24 h and then the
solvent was evaporated in vacuum. Water (40 mL) was added to the residue
and the product was taken up into dichloromethane (2 Â 10 mL). The
extract was dried with Na2SO4 and evaporated. Chromatography of the
crude product on silica gel (50 g) with a toluene-petroleum ether mixture
(1:1) afforded pure 18 (1.94 g, 76%) as yellow crystals. M.p. 121 1228C
(ethyl acetate/methanol); 1H NMR (400 MHz, CDCl3): d ˆ 3.80 (s, 3H),
7.08 (d, J ˆ 8.4 Hz, 1H), 7.24 (ddd, J ˆ 8.2, 6.9, 1.5 Hz, 1H), 7.28 (dd, J ˆ 8.4,
7.6 Hz, 1H), 7.31 (ddd, J ˆ 8.1, 6.7, 1.2 Hz, 1H), 7.35 (d, J ˆ 9.2 Hz, 1H), 7.42
(dd, J ˆ 7.0, 1.4 Hz, 1H), 7.59 (dd, J ˆ 8.2, 7.0 Hz, 1H), 7.69 (dd, J ˆ 7.5,
1.4 Hz, 1H), 7.84 (d, J ˆ 8.0 Hz, 1H), 7.93 (dd, J ˆ 8.2, 1.4 Hz, 1H), 7.95 (d,
J ˆ 9.0 Hz, 1H), 7.97 (dd, J ˆ 8.2, 1.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d ˆ 56.52 (q), 113.54 (d), 119.81 (s), 123.29 (d), 125.54 (d), 125.67
(s), 125.81 (d), 125.87 (d), 126.22 (d), 127.66 (d), 128.74 (s), 129.29 (3d),
130.75 (s), 131.98 (d), 133.39 (d), 134.19 (s), 135.04 (s), 136.04 (s), 154.54 (s);
(Æ)-8-Diphenylphosphino-2'-methoxy-1,1'-binaphthyl (19): Zinc powder
(130 mg, 2.0 mmol) was added to a solution of binaphthyl 18 (363 mg,
1.0 mmol), [NiCl2(dppe)] (26 mg, 50 mmol, 5 mol%), and chlorodiphenyl-
phosphine (285 mL, 1.5 mmol) in DMF (2 mL) under argon and the mixture
was heated at 1058C for 48 h. The mixture was cooled, water (10 mL)
added, and acidified with diluted hydrochloric acid. The product was
extracted with dichloromethane (2 Â 3 mL), and the organic phase was
dried with Na2SO4 and evaporated. The crude product was purified by
chromatography on silica gel (20 g) with a toluene/petroleum ether mixture
(1:1) to consecutively elute 21 (73 mg, 26%), 20 (17 mg, 6%), and 19
(150 mg, 32%) as the most polar compound. (Æ)-19 (a beige powder):
1H NMR (400 MHz, CDCl3): d ˆ 3.28 (s, 3H), 6.42 6.48 (m, 2H), 6.80
6.86 (m, 2H), 6.89 (dm, J ˆ 8.4 Hz, 1H), 6.91 6.96 (m, 2H), 7.00 7.05 (m,
2H), 7.07 (d, J ˆ 9.0 Hz, 1H), 7.10 (ddd, J ˆ 7.2, 4.0, 1.4 Hz, 1H), 7.14 7.21
(m, 4H), 7.33 (dd, J ˆ 7.0, 1.5 Hz, 1H), 7.35 (dd, J ˆ 8.1, 7.2 Hz, 1H), 7.58
(dd, J ˆ 8.2, 7.0 Hz, 1H), 7.75 (dm, J ˆ 8.1 Hz, 1H), 7.91 (d, J ˆ 9.0 Hz, 1H),
7.97 (dd, J ˆ 8.2, 1.5 Hz, 1H), 7.98 (dt, J ˆ 8.2, 1.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d ˆ 55.04 (q), 112.81 (d), 122.89 (d), 125.04 (d), 125.36
(d), 125.55 (d), 125.95 (d), 127.49 (2d), 127.69 (d), 127.77 (d, J(C,P) ˆ 6 Hz,
2d), 127.93 (d, J(C,P) ˆ 6 Hz), 128.78 (s), 129.28 (d), 129.54 (d), 130.89 (d),
131.46 (d), 133.04 (d, J(C,P) ˆ 21 Hz), 133.44 (d, J(C,P) ˆ 21 Hz), 134.71
135.10 (3s), 135.72 (s), 135.80 (s), 136.12 (d, J(C,P) ˆ 21 Hz), 136.93 (d),
139.19 (d, J(C,P) ˆ 18 Hz), 139.40 (d, J(C,P) ˆ 20 Hz), 154.81 (d, J(C,P) ˆ
6 Hz); 31P NMR (162 MHz, CDCl3): d ˆ À9.36 (s); IR (CCl4): nÄ ˆ 1623 and
ˆ
IR (CHCl3): nÄ ˆ 3015, 1623 (C C arom), 1595 (arom), 1510 (arom), 1274
‡
‡
(C O), 1085 cmÀ1 (arom); MS: m/z (%): 364 (21) [M ] (81Br), 362 (21) [M ]
(79Br), 283 (13), 268 (29), 252 (100), 239 (38); HRMS for C21H1579BrO: calcd
362.0306; found 362.0312. Crystallographic data for (Æ)-18: C21H15BrO,
Mr ˆ 362.03. Crystals were obtained from ethyl acetate by slow diffusion of
À
≈
methanol vapors at room temperature. System: triclinic; space group P1,
a ˆ 9.8350(2), b ˆ 15.2530(2), c ˆ 17.0760(3) ä, a ˆ 108.084(1)8, b ˆ
91.353(1)8, g ˆ 99.355(1)8. Data were collected at 105(2)K on a Nonius
KappaCCD diffractometer with MoKa radiation (l ˆ 0.71073 ä), a graphite
monochromator, and w scan mode at five different crystal orientations,
covering thus the entire reciprocal sphere up to 0.84 ä resolution. A
total of 34246 reflections were measured, from which 8418 were unique
(Rint ˆ 0.059), with 7525 observed data with I > 2s(I). The structure was
solved by direct methods (SIR92). All reflections were used in the
structure refinement based on F 2 by full-matrix least-squares
technique (SHELXL97). The hydrogen atoms were found on difference
Fourier map and refined isotropically. Absorption correction (m ˆ
2.576 mmÀ1) was carried on, using multiscan procedure (SORTAV): min/
ˆ
À
1594 (C C arom), 1510 and 1434 (arom), 1263 (C O); MS: m/z (%): 468
(5) [M ], 453 (7), 437 (100), 283 (4), 239 (3), 218.5 (3), 183 (2); HRMS for
‡
C33H25OP: calcd 468.1643; found 468.1651.
Isolation of enantiopure (S)-(‡)-19: Enantiopure 19 was prepared from
(S)-(‡)-18 (363 mg) in 32% yield by using the same procedure as that for
(Æ)-19. [a]D ˆ ‡23 (c ˆ 0.5 in CH2Cl2). Chromatography on Daicel
Chiralpak AD with a hexane/isopropyl alcohol mixture (98:2) showed
>99% ee for this product (tR ˆ 4.2 min, tS ˆ 4.6 min).
(Æ)-2-Methoxy-1,1'-binaphthyl (20): Compound 20 was obtained along
with 19 and 21 from the Ni0-catalyzed coupling of 18 with Ph2PCl. M.p.
107 1088C (aqueous MeOH) (ref. [35f] gives 107 1088C from aqueous
max transmission ˆ 0.415/0.598. Final
R
factors: R1 ˆ 0.0335 for the
observed data and 0.0397 for all data; wR2 ˆ 0.0900, S ˆ 0.993. The
estimated error in the bond lengths for non-hydrogen atoms is in the
interval 0.002 to 0.004 ä.
4642
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0820-4642 $ 20.00+.50/0
Chem. Eur. J. 2002, 8, No. 20

Disubstituted Binaphthyls
4633 4648
MeOH). The 1H NMR data were in agreement with the published
values.[35f] An authentic sample was prepared by Suzuki coupling of
1-naphthaleneboronic acid with 1-bromo-2-methoxynaphthalene.[35f]
Fourier map and refined isotropically (398 parameters). Absorption
correction (m ˆ 2.682mmÀ1) was carried out, using multiscans procedure
(SORTAV): min/max transmission ˆ 0.447/0.518. The absolute structure
was determined clearly, since the absolute structure parameter is equal
À0.009(6). Final R factors: R1 ˆ 0.030 for the observed data and 0.037 for
all data; wR2 ˆ 0.0657, S ˆ 1.050. The estimated error in the bond lengths
for non-hydrogen atoms is in the interval 0.003 to 0.006 ä.
1-Methoxyperylene (21): Compound 21 was obtained along with 19 and 20
from the Ni0-catalyzed coupling of 18 with Ph2PCl. M.p. 111 1138C
‡
(toluene, ref. [37] gives 1118C); MS: m/z (%): 282 (100) [M ], 268 (78), 239
(47), 141 (11), 119.5 (19); HRMS for C21H14O: calcd 282.1045; found
282.1053. Crystallographic data for 21: C21H14O, M ˆ 282.34. Crystals were
obtained from dichloromethane by a slow diffusion of hexane at room
temperature. Monoclinic; space group P21/c; a ˆ 18.2280(2), b ˆ
15.2280(3), c ˆ 10.2160(4) ä, b ˆ 104.4240(12)8. Data were collected at
150(2) K on a Nonius KappaCCD diffractometer with MoKa radiation (l ˆ
0.71073 ä), a graphite monochromator, and w scan mode at five different
crystal orientations up to 0.7696 ä resolution. A total of 43800 reflections
were measured, from which 6287 were unique (Rint ˆ 0.030), with 4753
observed data with I > 2s(I). The structure was solved by direct methods
(SIR92). All reflections were used in the structure refinement based on F 2
by full-matrix least-squares technique (SHELXL97), all hydrogen atoms
were found on difference Fourier map and refined isotropically (508
parameters). Absorption was neglected (m ˆ 0.082mmÀ1). Final R factors:
R1 ˆ 0.050 for the observed data and 0.075 for all data; wR2 ˆ 0.135, S ˆ
1.051. The estimated error in the bond lengths for non-hydrogen atoms is
0.002 ä.
(Æ)-8-Benzhydrylideneamino-2'-methoxy-1,1'-binaphthyl (23): Benzophe-
none imine[5l] (2.34 g, 2.17 mL, 13 mmol) was added to a suspension of 18
(3.62 g, 10 mmol), [Pd(dba)2] (229 mg, 0.5 mmol), 2,2'-bis(diphenylphos-
phino)diphenyl ether (268 mg, 0.5 mmol) and tBuONa (1.44 g, 15 mmol) in
dry toluene (50 mL) and the mixture was heated at 1008C for 24 h. The
solvent was evaporated in vacuum and the residue was purified by
chromatography on silica gel (50 g) with toluene as eluent to give 23 (4.49 g,
97%) as an amorphous solid: 1H NMR (400 MHz, CDCl3): d ˆ 3.66 (s, 3H),
6.01 (dd, J ˆ 7.4, 0.8 Hz, 1H), 6.72 6.76 (m, 3H), 6.95 7.02 (m, 4H), 7.04
7.12 (m, 3H), 7.15 7.18 (m, 2H), 7.21 7.30 (m, 5H), 7.52 7.58 (m, 3H), 7.91
(dd, J ˆ 8.4, 1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d ˆ 56.00 (q), 112.38
(d), 114.59 (d), 122.67 (d), 123.91 (d), 125.44 (d), 125.48 (d), 125.67 (d),
125.95 (d), 127.08 (2d), 127.32 (s), 127.48 (d), 127.69 (d), 128.11 (2d), 128.17
(s), 128.62 (s), 129.11 (d), 129.36 (d), 129.77 (d), 133.92 (s), 134.86 (s), 135.13
(s), 135.33 (s), 138.96 (s), 148.16 (s), 152.77 (s), 163.93 (s); IR (CCl4): nÄ ˆ
À1
ˆ
À
1622 and 1596 (C C arom), 1510, 1463 and 1446 (arom), 1261 cm (C O);
‡
MS: m/z (%): 463 (100) [M ], 432 (9), 320 (14), 282 (20), 281 (25), 268 (25),
(Æ)-8-Bromo-2'-hydroxy-1,1'-binaphthyl (22): Boron tribromide (15 mL,
1m solution in dichloromethane, 15 mmol) was added to a cooled solution
(08C) of 18 (3.62 g, 10 mmol) in dichloromethane (40 mL) and the solution
was slowly warmed to room temperature and stirred overnight. The
reaction was quenched by adding water (30 mL) and satd. NaHCO3
(10 mL), the dichloromethane phase was separated, and the water phase
was extracted with dichloromethane (2 Â 5 mL). The combined organic
extracts were dried with MgSO4 and evaporated in vacuum. The residue
was purified by chromatography on silica gel (50 g) with toluene as eluent
to give 22 (3.34 g, 96%). M.p. 145 1468C (toluene); 1H NMR (400 MHz,
CDCl3): d ˆ 4.77 (s, 1H), 6.95 (d, J ˆ 8.4 Hz, 1H), 7.21 7.35 (m, 4H), 7.54
(dd, J ˆ 6.8, 0.8 Hz, 1H), 7.64 (dd, J ˆ 7.6, 7.6 Hz, 1H), 7.75 (dd, J ˆ 7.6 Hz,
0.8 Hz, 1H), 7.82 (d, J ˆ 8.0 Hz, 1H), 7.86 (d, J ˆ 8.8 Hz, 1H), 7.96 (dd, J ˆ
8.0, 0.8 Hz, 1H), 8.05 (dd, J ˆ 8.4, 0.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d ˆ 117.30 (d), 119.44 (s), 121.65 (s), 123.15 (d), 124.90 (d), 126.37
(d), 126.40 (d), 126.60 (d), 127.83 (d), 128.64 (s), 129.39 (d), 129.70 (d),
130.81 (d), 130.86 (s), 131.22 (s), 133.29 (d), 134.21 (d), 135.06 (s), 136.43 (s),
150.74 (s); IR (CCl4): nÄ ˆ 3607 (OH), 3560 (OH associated to an aromatic
267 (16), 252 (20), 239 (20), 182 (11), 165 (13); HRMS for C34H25NO: calcd
463.1936; found 463.1929.
Isolation of enantiopure (S)-(À)-23: Enantiopure 23 was prepared from
(S)-(‡)-18 (3.62 g) in 97% yield by using the same procedure as that for
(Æ)-23. [a]D ˆ À603 (c ˆ 0.8 in THF). The enantiopurity was determined
after the transformation into (S)-(‡)-25 (>99% ee).
(Æ)-8-Benzhydrylideneamino-2'-hydroxy-1,1'-binaphthyl (24): Boron tri-
bromide (6 mL, 1m solution in dichloromethane, 6 mmol) was added to a
cooled solution (08C) of 23 (1.85 g, 4 mmol) in dichloromethane (20 mL).
The solution was slowly warmed to room temperature and stirred
overnight. The reaction was quenched by adding water (20 mL) and satd
NaHCO3 (5 mL), the dichloromethane phase was separated and the water
phase was extracted with dichloromethane (2 Â 5 mL). The combined
organic extracts were dried with MgSO4 and evaporated in vacuum. The
residue was purified by chromatography on silica gel (20 g) with toluene as
eluent to give 24 (1.71 mg, 95%). M.p. 226 2298C (hexane/dichloro-
methane); 1H NMR (400 MHz, CDCl3): d ˆ 5.22 (brs, 1H), 6.15 (dd, J ˆ
7.3, 1.2 Hz, 1H), 6.78 (d, J ˆ 8.9 Hz, 1H), 6.80 6.87 (m, 4H), 7.02 7.26 (m,
10H), 7.30 (brt, J ˆ 7.3 Hz, 1H), 7.38 (dd, J ˆ 7.0, 1.4 Hz, 1H), 7.46 (m, 1H),
7.58 (dd, J ˆ 8.4, 1.2 Hz, 1H), 7.60 (dd, J ˆ 8.2, 7.0 Hz, 1H), 7.97 (dd, J ˆ 8.2,
1.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d ˆ 115.67 (d), 117.54 (d), 122.56
(d), 124.22 (d), 124.24 (s), 125.47 (d), 125.66 (d), 125.92 (d), 126.12 (d),
127.16 (2d), 127.53 (3d), 127.92 (d), 127.99 (s), 128.21 (d), 128.85 (s), 129.31
(2d), 129.51 (2d), 129.61 (d), 129.90 (d), 130.94 (s), 130.96 (d), 134.23 (s),
135.34 (s), 135.61 (2s), 138.72 (s), 147.65 (s), 149.88 (s), 164.91 (s); IR
À1
ˆ
p-orbital), 1623 and 1598 (C C arom), 1518 and 1469 cm (arom); MS:
‡
‡
m/z (%): 350 (36) [M ] (81Br), 348 (36) [M ] (79Br), 269 (100), 268 (53), 252
(44), 251 (30), 239 (56), 134 (9), 119.5 (16); HRMS for C20H1379BrO: calcd
348.0150; found 348.0156.
Resolution of (Æ)-22: Racemic 22 (3.5 g, 10 mmol) and (À)-N-benzylcin-
chonidinium chloride (2.1 g, 5 mmol) were dissolved in MeCN (50 mL) at
708C. The mixture was heated during an additional 5 h, during which
period a precipitate was formed. After cooling to room temperature, the
precipitate was filtered off, washed with cold MeCN (5 mL), and dried in to
give a white powder (3.5 g). The powder was suspended in dichloro-
methane (20 mL) and purified by chromatography on silica gel (50 g) with
dichloromethane as eluent to give (S)-(‡)-22 (1.5 g, 43%). M.p. 121
1238C (hexane/dichloromethane); [a]D ˆ ‡97.8 (c ˆ 0.5 in THF). Chroma-
tography on Daicel Chiralpak AD using a hexane-isopropyl alcohol
mixture (9:1) showed 99.4% ee for this product (tR ˆ 10.8 min, tS ˆ
12.2 min). The filtrate from the resolution process was evaporated under
the reduced pressure and worked up in a similar manner to give (R)-(À)-22
(1.9 g, 66%), which was of 84% ee. Crystallographic data for (S)-(‡)-22:
C20H13BrO, Mr ˆ 349.21. Crystals were obtained from dichloromethane by a
slow diffusion of hexane at room temperature. Tetragonal, space group P41;
a ˆ 8.7450(1), c ˆ 40.0620(6) ä. Data were collected at 150(2) K on a
Nonius KappaCCD diffractometer with MoKa radiation (l ˆ 0.71073 ä), a
graphite monochromator, and w scan mode at three different crystal
orientations up to 0.7696 ä resolution. A total of 15309 reflections were
measured, from which 6463 were unique (Rint ˆ 0.029), with 5858 observed
data having I > 2s(I). The structure was solved by direct methods (SIR92).
All reflections were used in the structure refinement based on F 2 by full-
matrix least-squares technique (SHELXL97) with hydrogen atoms calcu-
lated into theoretical positions, riding during refinement on the respective
pivot atom, except those of OH groups, which were found on difference
ˆ
(CCl4): nÄ ˆ 3545 (OH), 1621 and 1598 (C C arom), 1570, 1517 and
‡
1468 cmÀ1 (arom); MS: m/z (%): 449 (43) [M ], 268 (100), 239 (15); HRMS
for C33H23NO: calcd 449.1780; found 449.1781. Crystallographic data for
(Æ)-24: C33H23NO, M ˆ 449.18. Crystals (pale straw yellow) were obtained
from an acetonitrile at room temperature. Monoclinic; space group P21/c,
a ˆ 11.1055(1), b ˆ 11.6712(1), c ˆ 18.0627(1) ä, b ˆ 102.6753(3). Data
were collected at 100 K on an Bruker-Nonius KappaCCD diffractometer,
running under Nonius Collect software, and with graphite monochromated
X-radiation (l ˆ 0.71073 ä). A total of 35 scan sets were measured. The
low-angle scan sets were re-measured at one tenth the integration time to
record the intense low-angle data more accurately. For these short scan sets,
only those data with q < 158 were used in the merging process. Precise unit
cell dimensions were determined by post-refinement of the setting angles
of 97904 reflections with 2.9 < q < 41.158 data collection. The frame images
were integrated with Denzo-SMN[69] and the resultant raw intensity files
processed by using a locally modified version of DENZOX.[70] Data were
then sorted and merged using SORTAV[70] after application of a semi-
empirical absorption correction[71] to remove absorption anisotropy due to
the crystal and the mounting medium. The structure was solved by direct
methods (SHELXS-97).[72] All non-H atoms were allowed anisotropic
À
thermal motion. Aromatic C H hydrogen atoms were initially included at
À
calculated positions, with C H ˆ 0.96 ä, and were refined with a riding
Chem. Eur. J. 2002, 8, No. 20
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0820-4643 $ 20.00+.50/0
4643

œ
œ
¬
œ
P. Kocovsky, S. Vyskocil, Y. N. Belokon et al.
FULL PAPER
model and with Uiso set to 1.2 times that of the attached C atom. In the final
cycles of refinement, all these restraints were relaxed. The OH hydrogen
position was obtained from a difference map and was refined without
restraints. Refinement with SHELXL97[72] with full-matrix least-squares
0.8 in THF). Chiral chromatography on Daicel Chiralcel OD-H using a
hexane/isopropyl alcohol mixture (4:1) showed >99% ee for this product
(tS ˆ 8.0 min, tR ˆ 10.3 min).
Isolation of enantiopure (R)-(‡)-26: Enantiopure (R)-(‡)-26 was obtained
by enantiomeric enrichment of (R)-(‡)-26 as follows. (R)-(‡)-(25)
(285 mg, 1 mmol, 84% ee), prepared by using the same sequence as that
employed for its enantiomer [commencing with (R)-(À)-22 (84% ee)], was
dissolved in hot toluene (5 mL), and the solution was allowed to crystallize
overnight. The crystals were isolated by suction and dried to give (Æ)-(26)
(41 mg). The mother liquor containing (R)-(‡)-26 (244 mg), enriched in
94% ee, as revealed by chiral HPLC, was evaporated and the residue was
dissolved in dichloromethane (0.5 mL). The solution was over-layered with
hexane (3 mL) and set aside at room temperature overnight. The crystals
formed were collected to give of (R)-(‡)-26 (210 mg, 88%, >98% ee).
on F 2, all the unique data, and with the weighting scheme w ˆ [s(Fo)2
‡
(AP)2
‡
BP]À1, where P ˆ [Fo2/3‡2Fc2/3], A ˆ 0.0747, and B ˆ 0.1877,
converged to R1 ˆ 0.0421. In the final residual map, peaks of ꢀ0.7
0.5 eäÀ3 were observed at the mid-points of all the covalent bonds,
consistent with these being due to bonding density effects.
Isolation of enantiopure (S)-(À)-24: Enantiopure 24 was prepared from
(S)-(À)-23 (1.85 g) in 95% yield by using the same procedure as that for
(Æ)-23. M.p. 196 1998C (hexane/dichloromethane); [a]D ˆ À416 (c ˆ 0.6
in THF). The enantiopurity was determined after the transformation into
(S)-(‡)-25 (>99% ee).
(Æ)-8-Amino-2'-methoxy-1,1'-binaphthyl (25): A solution of 23 (2.3 g,
5 mmol) and conc HCl (1 mL, 10 mmol) in dichloromethane (30 mL) was
stirred at room temperature overnight; NaOH (20 mL of 1m water solution,
20 mmol) was then added, the dichloromethane phase was separated, and
the water phase was extracted with dichloromethane (2 Â 5 mL). The
combined organic extracts were dried with MgSO4 and evaporated in
vacuum. The residue was purified by chromatography on silica gel (50 g) by
using a 1:1 toluene/hexane mixture as eluent to give 25 (2.07 g, 92%). M.p.
(Æ)-8-Acetamido-2'-hydroxy-1,1'-binaphthyl (27): Racemic (Æ)-26
(285 mg, 1 mmol) was converted into racemic acetamide (Æ)-27 in the
same way as enantiopure (S)-(À)-26 was transformed into acetamide (S)-
(‡)-27; the procedure afforded (Æ)-27 (93%): m.p. 156 1588C (toluene).
(S)-(‡)-8-Acetimido-2'-hydroxy-1,1'-binaphthyl (27): Acetyl chloride
(214 mL, 3 mmol) was added to a solution of (S)-(À)-26 (285 mg, 1 mmol,
99% ee) in pyridine (5 mL), and the mixture was stirred at room
temperature overnight. The reaction was quenched by adding 5% HCl
(20 mL), the dichloromethane phase was separated and the water phase
was extracted with dichloromethane (2 Â 5 mL). The combined organic
extracts were dried with MgSO4 and evaporated in vacuum. The residue
was dissolved in dry methanol (20 mL), solid Na (20 mg) was added, and
the mixture was stirred at room temperature for 3 h. The reaction was
quenched by adding water (20 mL) and 5% HCl (10 mL) and the mixture
was extracted with dichloromethane (3 Â 10 mL). The combined organic
extracts were dried with MgSO4 and evaporated in vacuum. The residue
was purified by chromatography on silica gel (10 g) using toluene as eluent
to give (S)-(‡)-27 (307 mg, 94%). M.p. 213 2158C (toluene); [a]D ˆ ‡2.6
1
159 1608C (toluene); H NMR (400 MHz, CDCl3): d ˆ 3.82 (s, 3H), 6.53
(dd, J ˆ 7.4, 0.8 Hz, 1H), 7.12 (dd, J ˆ 7.0, 0.8 Hz, 1H), 7.22 7.38 (m, 5H),
7.41 (d, J ˆ 8.8 Hz, 1H), 7.48 (dd, J ˆ 8.0, 7.2 Hz, 1H), 7.82 7.88 (m, 2H),
7.96 (d, J ˆ 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): d ˆ 56.82 (q), 110.78
(d), 113.87 (d), 119.07 (d), 122.61 (s), 123.95 (d), 125.10 (d), 125.62 (d),
126.07 (s), 126.20 (d), 126.87 (d), 127.72 (d), 128.69 (s), 128.72 (d), 128.80
(d), 129.74 (d), 132.00 (s), 133.96 (s), 136.01 (s), 144.11 (s), 154.01 (s); IR
ˆ
(CCl4): nÄ ˆ 3484 and 3395 (NH2), 1618 and 1594 (C C arom), 1510 and 1460
‡
(arom), 1260 cmÀ1 (C O); MS: m/z (%): 299 (100) [M ], 268 (35), 267 (70),
À
239 (4), 133.5 (7); HRMS for C21H17NO: calcd 299.1310; found 299.1307.
1
Isolation of enantiopure (S)-(‡)-25: Enantiopure 25 was prepared from
(S)-(À)-23 (2.3 g) in 92% yield by using the same procedure as that for (Æ)-
25. M.p. 130 1338C (toluene); [a]D ˆ ‡86.2; (c ˆ 1 in THF). Chiral
chromatography on Daicel Chiralpak AD using a hexane/isopropyl alcohol
mixture (9:1) showed >99% ee for this product (tR ˆ 12.0 min, tS ˆ
16.6 min).
(c ˆ 1.0 in THF); H NMR (400 MHz, CDCl3): d ˆ 1.03 (s, 3H), 5.33 (brs,
1H), 7.09 (d, J ˆ 8.4 Hz, 1H), 7.22 (brs, 1H), 7.27 7.40 (m, 4H), 7.51 7.56
(m, 1H), 7.58 7.63 (m, 1H), 7.81 7.95 (m, 4H), 8.03 (dd, J ˆ 8.2, J ˆ 0.8 Hz,
1H); 13C NMR (100 MHz, CDCl3): d ˆ 23.28 (q), 117.94 (d), 121.35 (s),
122.63 (d), 124.23 (d), 124.65 (d), 125.77 (d), 125.81 (s), 126.42 (d), 126.59
(d), 127.70 (d), 127.73 (s), 128.06 (d), 128.80 (s), 130.28 (d), 130.81 (d),
131.87 (d), 133.10 (s), 133.44 (s), 135.84 (s), 150.65 (s), 168.25 (s); IR
(Æ)-8-Amino-2'-hydroxy-1,1'-binaphthyl (26) Method A: Boron tribromide
(6 mL, 1m solution in dichloromethane, 6 mmol) was added to a cooled
solution (08C) of 25 (1.20 g, 4 mmol) in dichloromethane (20 mL). The
solution was slowly warmed to room temperature and stirred overnight.
The reaction was quenched by adding water (20 mL) and satd NaHCO3
(5 mL), the dichloromethane phase was separated, and the water phase was
extracted with dichloromethane (2 Â 5 mL). The combined organic extracts
were dried with MgSO4 and evaporated in vacuum. The residue was
purified by chromatography on silica gel (20 g) with toluene as eluent to
give 26 (1.08 g, 95%). M.p. 153 1548C (toluene); 1H NMR (400 MHz,
CDCl3): d ˆ 3.70 (brs, 2H), 5.11 (s, 1H), 6.58 (dd, J ˆ 7.6, 1.2 Hz, 1H), 7.20
(dd, J ˆ 8.0, 0.8 Hz, 1H), 7.25 (dd, J ˆ 7.2, 1.2 Hz, 1H), 7.28 7.41 (m, 4H),
7.30 (d, J ˆ 8.8 Hz, 1H), 7.52 (dd, J ˆ 7.8, 7.2 Hz, 1H), 7.84 (dd, J ˆ 7.6,
1.2 Hz, 1H), 7.88 (d, J ˆ 8.8 Hz, 1H), 7.94 (dd, J ˆ 8.2, 1.2 Hz, 1H);
13C NMR (100 MHz, CDCl3): d ˆ 111.49 (d), 117.46 (d), 119.09 (d), 121.66
(s), 122.23 (s), 123.77 (d), 125.03 (d), 125.61 (d), 127.04 (2d), 127.95 (d),
128.63 (s), 128.74 (s), 130.01 (d), 130.14 (d), 130.43 (d), 133.56 (s), 136.48 (s),
143.98 (s), 150.62 (s); IR (CCl4): nÄ ˆ 3543 (OH), 3490 and 3398 (NH2), 1620
ˆ
ˆ
(CHCl3): nÄ ˆ 3530 (OH), 3405 (NH), 1688 (C O), 1619 and 1597 (C C
‡
arom), 1521 and 1428 cmÀ1 (arom); MS: m/z (%): 327 (65) [M ], 285 (49),
267 (100), 239 (10); HRMS for C22H17NO2: calcd 327.1259; found 327.1256.
(R)-(À)-8-Acetimido-2'-hydroxy-1,1'-binaphthyl (27): (R)-(‡)-26 (84% ee)
was acetylated using the same procedure as that employed for its
enantiomer to give the crude (R)-(À)-27 (327 mg, 1 mmol, 84% ee). The
latter material was dissolved in hot toluene (5 mL) and the solution was
allowed to crystallize overnight. The crystalline material was isolated by
suction and dried to give (R)-(À)-27 (247 mg, 90%). [a]D ˆ À2.5 (c ˆ 1.0 in
THF). Chiral chromatography on Daicel Chiralcel OD-H, with a hexane/
isopropyl alcohol mixture (4:1), showed >99% ee for this product (tR ˆ
7.7 min, tS ˆ 8.9 min).
(Æ)-8-Dimethylamino-2'-hydroxy-1,1'-binaphthyl (29): A solution of the
amino alcohol 26 (285 mg, 1 mmol) in THF (10 mL) and solid NaBH4
(530 mg, 14 mmol) were slowly added (simultaneously) to a solution of the
40% aqueous formaldehyde (2 mL 24 mmol) and a 20% aqueous H2SO4
(2 mL) in THF (10 mL) over a period of 15 min at RT. The reaction mixture
was stirred for an additional 15 min and then poured into a 2% aqueous
KOH (200 mL). The resulting suspension was extracted with ethyl acetate
(3 Â 50 mL), and the extract was dried with MgSO4 and evaporated. The
residue was purified by flash chromatography on silica gel (50 g) with
toluene to give the amino alcohol 29 (103 mg, 33%) as the faster moving
product and 30 (184 mg, 59%) as the slower moving product. M.p. 119
1208C (toluene); 1H NMR (400 MHz, CDCl3): d ˆ 1.71 (s, 3H), 2.22 (s,
3H), 5.07 (brs, 1H), 7.15 (dd, J ˆ 7.5, J ˆ 1.4 Hz, 1H), 7.17 7.19 (m, 2H),
7.23 7.26 (m, 1H), 7.26 (d, J ˆ 8.7 Hz, 1H), 7.44 7.50 (m, 2H), 7.59 (t, J ˆ
8.2 Hz, 1H), 7.72 (dd, J ˆ 8.1, J ˆ 1.3 Hz, 1H), 7.74 (d, J ˆ 8.7 Hz, 1H), 7.80
(td, J ˆ 7.9, 1.2 Hz, 1H), 7.98 (dd, J ˆ 8.1, 1.5 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d ˆ 45.02 (q), 45.10 (q), 116.90 (d), 118.63 (d), 122.56 (d), 124.46
(s), 124.95 (2d), 125.64 (d), 125.84 (d), 126.33 (d), 127.78 (d), 127.88 (d),
128.47 (s), 129.20 (s), 129.97 (d), 130.14 (s), 131.71 (d), 133.93 (s), 136.70 (s),
and 1599 (C C arom), 1516 and 1467 cmÀ1 (arom); MS: m/z (%): 285 (100)
ˆ
‡
[M ], 268 (35), 267 (30), 254 (6), 239 (6), 119.5 (3); HRMS for C20H15NO:
calcd 285.1154; found 285.1160.
Method B: A solution of 24 (449 mg, 1 mmol) and conc. HCl (0.2 mL,
2 mmol) in dichloromethane (10 mL) was stirred at room temperature
overnight; NaOH (2 mL of 1m water solution, 2 mmol) was then added, the
dichloromethane phase was separated, and the water phase was extracted
with dichloromethane (2 Â 2 mL). The combined organic extracts were
dried with MgSO4 and evaporated in vacuum. The residue was purified by
chromatography on silica gel (30 g) using a 1:1 toluene/hexane mixture as
eluent to give 26 (254 mg, 89%).
Isolation of enantiopure (S)-(À)-26: Enantiopure (S)-(À)-26 was prepared
from (S)-(‡)-25 (1.20 g) in 95% yield by using the same procedure as that
for (Æ)-25. M.p. 140 1418C (dichloromethane/hexane); [a]D ˆ À25.9 (c ˆ
4644
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0820-4644 $ 20.00+.50/0
Chem. Eur. J. 2002, 8, No. 20

Disubstituted Binaphthyls
4633 4648
ˆ
149.06 (s), 151.83 (s); IR (CCl4): nÄ ˆ 3551 (OH), 1621 and 1598 (C C arom),
1688C (ethyl acetate); 1H NMR (400 MHz, CDCl3): d ˆ 6.97 7.02 (m, 1H),
7.32 7.49 (m, 6H), 7.65 (dd, J ˆ 8.2, 0.9 Hz, 1H), 7.69 (d, J ˆ 8.1 Hz, 1H),
7.79 (d, J ˆ 8.1 Hz, 1H), 7.86 (dd, J ˆ 7.3, 1.1 Hz, 1H), 8.28 (s, 1H); 13C NMR
(100 MHz, CDCl3): d ˆ 108.52 (d), 112.24 (d), 115.66 (d), 120.10 (d), 120.71
(s), 121.28 (s), 121.92 (d), 124.81 (d), 126.46 (s), 126.52 (d), 126.70 (d),
126.84 (d), 127.18 (d), 127.23 (d), 128.03 (d), 130.33 (s), 134.49 (s), 134.78 (s),
‡
1576, 1517, and 1468 cmÀ1 (arom); MS: m/z (%): 313 (80) [M ], 268 (100),
265 (42), 239 (28); HRMS for C22H19NO: calcd 313.1467; found 313.1466.
Compound (Æ)-30: Compound (Æ)-30 was obtained as the major (polar)
product along with 29 (vide supra) as an amorphous solid. 1H NMR
(400 MHz, CDCl3): d ˆ 2.98 (s, 3H; CH3), 3.34 (d, J ˆ 11.6 Hz, 1H; CHH),
3.55 (d, J ˆ 11.6 Hz, 1H; CHH), 6.27 (d, J ˆ 9.8 Hz, 1H; 3'-H), 6.69 (dd, J ˆ
7.6, 1.2 Hz, 1H; 7-H), 6.78 (dd, J ˆ 7.2, 1.2 Hz, 1H; 2-H), 6.90 (dm, J ˆ
7.8 Hz, 1H; 8'-H), 7.21 (td, J ˆ 7.8, 1.5 Hz, 1H; 7'-H), 7.30 (td, J ˆ 7.5, 1.2 Hz,
1H; 6'-H), 7.34 (dd, J ˆ 8.2, 7.2 Hz, 1H; 3-H), 7.34 (dd, J ˆ 8.2, 1.2 Hz, 1H;
5-H), 7.41 (dd, J ˆ 7.5, 1.5 Hz, 1H; 5'-H), 7.44 (dd, J ˆ 8.1, 7.6 Hz, 1H; 6-H),
7.58 (brd, J ˆ 9.9 Hz, 1H; 4'-H), 7.75 (dd, J ˆ 8.2, 1.2 Hz, 1H; 4-H);
13C NMR (100 MHz, CDCl3): d ˆ 39.61 (q, CH3), 58.47 (s, C-1'), 61.80 (t,
CH2), 105.06 (d, C-7), 117.54 (d, C-5), 123.39 (s, C-9), 123.88 (d, C-2), 124.39
(d, C-3'), 125.77 (d, C-3), 126.42 (d, C-6), 127.29 (d, C-6'), 127.37 (d, C-4),
129.17 (s, C-10'), 129.48 (d, C-5'), 129.85 (d, C-7'), 129.96 (d, C-8'), 134.09 (s,
C-1 or C-10), 134.18 (s, C-1 or C-10), 143.86 (s, C-9'), 144.08 (s, C-8), 144.72
ˆ
149.94 (s), 150.51 (s); IR (CHCl3): nÄ ˆ 3016 (d), 1628 (C C arom), 1450
‡
(arom), 1402 (arom), 1276 cmÀ1 (C O); MS: m/z (%): 268 (100) [M ], 239
À
(17), 237 (7), 134 (19), 119.5 (10); HRMS for C20H12O: calcd 268.0888;
found 268.0881.
7H-Dibenzo[b,kl]acridine (37): A solution of 34 (150 mg, 0.46 mmol) in a
mixture of amyl alcohol (6.0 mL) and hydrazine hydrate (80%, 4.0 mL)
was stirred under reflux for 40 h and then evaporated under reduced
pressure. The crude product was purified by chromatography on silica gel
(15 g) with a 1:1 ethyl acetate/petroleum ether mixture as eluent to afford
37 as brown crystals (96 mg, 78%): m.p. 210 2128C (toluene); 1H NMR
(400 MHz, CDCl3): d ˆ 6.46 (dd, J ˆ 7.2, 1.0 Hz, 1H), 6.85 (brs, 1H), 6.94 (s,
1H), 7.10 (d, J ˆ 8.2 Hz, 1H), 7.18 7.25 (m, 2H), 7.31 7.36 (m, 1H), 7.39
7.44 (m, 1H), 7.50 7.56 (m, 2H), 7.72 (d, J ˆ 8.2 Hz, 1H), 7.83 (d, J ˆ 7.3 Hz,
1H), 8.26 (s, 1H); 13C NMR (100 MHz, CDCl3): d ˆ 103.96 (d), 108.22 (d),
115.25 (d), 116.84 (d), 122.22 (d), 122.33 (s), 123.45 (d), 125.52 (d), 125.76
(d), 126.84 (d), 127.19 (d), 127.28 (d), 128.22 (d), 129.38 (s), 129.98 (s),
134.74 (s), 135.61 (s), 137.05 (s), 137.99 (s); IR (CHCl3): nÄ ˆ 3411 (NH), 1633
ˆ
ˆ
(d, C-4'), 200.33 (s, C-2'). IR (CCl4): nÄ ˆ 1666 (C O), 1621 and 1592 (C C
arom), 1566, 1514, and 1482 cmÀ1 (arom); MS: m/z (%): 311 (100) [M ],
‡
296 (22), 268 (31), 266 (19), 253 (14), 239 (11), 86 (40); HRMS for
C22H17NO: calcd 311.1310; found 311.1310.
(Æ)-8-Acetamido-3'-hydroxy-1,2'-binaphthyl (34): Boron tribromide (1m in
dichloromethane, 1.5 mL, 1.50 mmol) was added to a solution of 16
(341 mg, 1.0 mmol) in dichloromethane (4 mL) at 08C, and the mixture was
stirred for 18 h at room temperature and then poured into water. Saturated
NaHCO3 was then added, and the product was extracted into ethyl acetate
(2 Â 3 mL). The combined organic extracts were dried over Na2SO4 and
concentrated under reduced pressure, and the residue was purified by
chromatography on silica gel (20 g), with a 1:1 ethyl acetate/dichloro-
methane mixture as eluent to produce 34 as a white solid (301 mg, 92%).
M.p. 208 2118C (decomp); 1H NMR (400 MHz, CDCl3): d ˆ 1.13 (s, 3H),
6.30 (brs, 1H), 7.17 (brs, 1H), 7.32 7.41 (m, 3H), 7.44 7.56 (m, 3H), 7.69
7.84 (m, 5H), 7.95 (dd, J ˆ 8.3, 1.5 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d ˆ 23.32 (q), 110.03 (d), 123.94 (d), 124.28 (d), 125.30 (d), 125.95 (s), 126.03
(d), 126.21 (d), 126.86 (d), 127.12 (d), 127.65 (d), 128.44 (s), 128.87 (d),
130.08 (d), 130.99 (d), 131.36 (s), 132.50 (s), 132.75 (s), 134.55 (s), 135.25 (s),
À1
ˆ
(C C arom), 1587 (arom), 1478 (arom), 1463 cm (arom); MS: m/z (%):
‡
267 (100) [M ], 266 (27), 264 (10), 239 (5), 135 (21), 133 (11), 132.5 (14);
HRMS for C20H13N: calcd 267.1048; found 267.1043.
Asymmetric Michael addition of complex 39 to methyl acrylates: Sodium
hydride (0.096 g, 2.4 mmol) was added to a solution of (R)-27 (0.118 g,
0.36 mmol) in CH2Cl2, first thoroughly purged with Ar, and the mixture
was stirred at room temperature for 3 min under argon. Complex 39 (1.00 g,
2.4 mmol) was then added while stirring, followed 5 min later by methyl
acrylate or methyl methacrylate (13.7 mmol), and the reaction mixture was
agitated for an additional 5 min [the course of the reaction was monitored
by TLC (CHCl3/Me2CO 5:1)]. The reaction mixture was then quenched
with aqueous acetic acid and the product was extracted into chloroform.
The organic layer was separated and an aliquot was used to check the ee of
the glutamic acid (Table 5). The remainder of the organic layer was
evaporated and the residue was purified by chromatography on a silica gel
column with a CHCl3/Et2O/AcOH mixture (3:1:1). The catalyst (R)-27 was
recovered from the first fraction and recrystallized from benzene (60%).
The fraction containing 41 was decomposed with a 1:1 mixture of MeOH
and conc. HCl by refluxing for 5 min (until the red color of the solution had
disappeared). The resulting solution was evaporated, water was added to
the residue, and the insoluble hydrochloride of 38 was removed by
filtration. The pH of the filtrate was brought to 8 with aqueous NH3, the
solution was extracted with CHCl3, and the aqueous solution was desalted
À
151.85 (s), 168.99 (s); IR (CHCl3): nÄ ˆ 3547 (OH), 3426 (NH), 1684 (C O),
1518, 1495 (arom), 1262 cmÀ1 (C O); MS: m/z (%): 327 (26) [M ], 285 (16),
‡
À
284 (12), 268 (95), 267 (100), 254 (12), 239 (10), 43 (24); HRMS for
C22H17NO2: calcd 327.1259; found 327.1244.
(Æ)-8-Amino-3'-hydroxy-1,2'-binaphthyl (35): Trichlorosilane (0.75 mL,
7.2 mmol) was added to
a mixture of 34 (200 mg, 0.61 mmol) and
triethylamine (1.7 mL, 12 mmol) in xylene (14 mL) at 08C, and the mixture
was stirred at 1208C for 15 h. After being cooled to room temperature, the
mixture was diluted with ethyl acetate (10 mL) and quenched with a small
amount of saturated NaHCO3. The resulting suspension was filtered
through Celite, and the solid was washed with ethyl acetate (3 Â 10 mL).
The combined organic extracts were dried over Na2SO4 and concentrated
under reduced pressure. The crude product was purified by chromatog-
raphy on silica gel (20 g) with a toluene-ethyl acetate mixture (9:1) to
furnish 35 as a white solid (30 mg, 16%). M.p. 192 1938C (ethyl acetate);
1H NMR (400 MHz, CDCl3): d ˆ 6.67 (dd, J ˆ 7.4, 1.4 Hz, 1H), 7.27 7.35
(m, 2H), 7.36 7.41 (m, 3H), 7.46 7.52 (m, 3H), 7.77 7.84 (m, 2H), 7.90
(dd, J ˆ 8.2, 1.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d ˆ 110.24 (d),
111.85 (d), 119.42 (d), 121.37 (s), 124.20 (d), 125.22 (d), 126.54 (d), 126.78
(d), 127.08 (d), 127.80 (d), 128.39 (s), 128.88 (d), 129.57 (d), 130.24 (d),
131.17 (s), 132.39 (s), 134.81 (s), 136.02 (s), 143.71 (s), 151.56 (s); IR
‡
on Dowex 50 in its H form to give glutamic acid 43. For yields and ee, see
Table 5. The ee was determined by chiral GLC (Chirasil-Val phase).
Acknowledgement
We thank the EPSRC for grant No GR/J69219, EPSRC and GSK for a
œ
CASE award to S.C.L., GACR for grants No 203/01/D051, 203/00/0601,
203/00/0632, and 203/99/M037, GAUK for grant No 243/20B CH, Ministry
of Education of the Czech Republic for the project MSM 113100001,
œ
NATO for a fellowship (administered by the Royal Society) to S.V., ISTC
(CHCl3): nÄ ˆ 3549 (OH), 3496 (NH), 3402 (NH), 1597 (arom), 1500 (arom),
for grant A-356, and the University of Glasgow for additional support. We
1449 (arom), 1263 cmÀ1 (C O); MS: m/z (%): 285 (9) [M ], 267 (100), 264
‡
ˆ
œ
also thank Dr. Zdenek Havlas for consultations regarding the quantum
(10), 239 (5), 133.5 (16), 132.5 (11); HRMS for C20H15NO: calcd 285.1154;
found 285.1162. The small-scale enantiomeric separation was performed on
a Daicel Chiralpak AD column using a hexane-methanol-isopropyl alcohol
mixture (77:20:3); the retention times were 11.0 and 14.1 min.
chemistry calculations and Dr. Nikolai S. Ikonnikov for GLC enantiomeric
analysis of glutamic acid and its derivatives.
Dibenzo[b,kl]xanthene (36): A solution of 34 (80 mg, 0.24 mmol) in a
mixture of ethanol (1.6 mL) and aqueous HCl (10%, 0.5 mL) was stirred
under reflux for 16 h and then concentrated under reduced pressure. Water
and saturated NaHCO3 were added to the residue and the product was
extracted into dichloromethane (2 Â 2 mL). Combined organic extracts
were dried over Na2SO4 and concentrated under reduced pressure and the
residue was purified by chromatography on silica gel (10 g) with toluene as
eluent to produce 36 as a bright yellow solid (33 mg, 50%). M.p. 167
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¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0820-4645 $ 20.00+.50/0
4645

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œ
¬
œ
P. Kocovsky, S. Vyskocil, Y. N. Belokon et al.
FULL PAPER
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Vyskocil, P. Kocovsky, Chem. Eur. J. 2002, 8, 4443.
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œ
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¬
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œ
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œ
œ
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œ
œ
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œ
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[8] a) S. Vyskocil, M. Smrcina, V. Hanus, J. Polasek, P. Kocovsky, J. Org.
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œ
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Chem. 1998, 63, 7738; b) S. Vyskocil, M. Smrcina, P. Kocovsky,
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œ
À
œ
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[23] For a recent study on the intramolecular N B interaction, forming a
œ
¬
œ
¬
œ
CÌsarova, J. Sejbal, I. Tislerova, M. Smrcina, G. C. Lloyd-Jones, S. C.
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4646
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0947-6539/02/0820-4646 $ 20.00+.50/0
Chem. Eur. J. 2002, 8, No. 20

Disubstituted Binaphthyls
4633 4648
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[28] Note that the corresponding organolithium would be unsuitable to
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3-naphthyllithium, which, as the less sterically hindered species, reacts
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Tetrahedron: Asymmetry 1995, 6, 2123; d) S. Vyskocil, M. Smrcina, M.
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[33] Lowering the catalyst load to 2 mol% promoted the formation of the
reduction product 20 (ꢀ20%) at the expense of the desired derivative
18 (ꢀ20%). Similar effects were observed when stronger base, such
as, Ba(OH)2 or tBuONa, were employed instead of K2CO3, or when
the content of water in the reaction medium was lowered to 10%; in
this last case, 2,2'-dimethoxy-1,1'-binaphthyl was isolated as the major
product (ꢀ30%). With other catalysts, such as [Pd2(dba)3], [{Pd(al-
lyl)Cl}2], or [Pd(AcO)2], the reduction product 20 dominated the
product mixture. Finally, the temperature also proved important since
at 50 708C, formation of the reduction product 20 and of 2,2'-
dimethoxy-1,1'-binaphthyl was promoted at the expense of 18.
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œ
¬
Farrugia, P. Kocovsky, J. Org. Chem. 2001, 66, 1351; resolution with
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been performed by using the STQN method. Second derivative
calculations established the nature of stationary point (one negative
eigenvalue). The reaction path was confirmed by IRC calcula-
tions.
[56] Preliminary X-ray data indicate that the chiral axis in the 1,2'-isomer
17 is rather longer (1.570 ä) than that in 18 (1.496 ä). This structural
feature is apparently reflected in the lower barriers to racemization of
16, 17, and 35 (Tables 3 and 4).
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with a position of the naphthalene unit close to C(5') (i.e., between
C29 and C15 in Figure 2), observed by high-resolution X-ray
crystallography. Details of this study and further confirmation of this
interaction provided by quantum chemistry calculations will be
published elsewhere.
À
[36] a) For a related insertion of Pd into the aromatic C H bond, see, for
¬
example: B. MartÌn-Matute, C. Mateo, D. J. Cardenas, A. M. Echa-
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À608C. Around ca. À508C, minimal broadening of the individual
signals was observed, suggesting that the coalescent temperature will
lay well below the reach of the instrument.
[59] The crystallographically suitable crystals were obtained from a CH2Cl2
solution by a slow diffusion of hexane.
[60] Interestingly, the X-ray crystallography of (S)-(‡)-18 (Figure S4,
Supporting Information) revealed the presence of two molecules in
the cell, which differ slightly from each other. Thus, for instance, the
dihedral angle about the chiral axis in the two molecules (C2-C1-C1'-
C2') differs by 7.98, being 77.68 and 69.78, respectively. Interestingly,
this angle in the case of racemic ( Æ )-18 is 89.78.
[61] No racemization had occurred during these transformations, as
revealed by chiral HPLC (note that racemates were available for
comparison).
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¬
[44] N. M. Brunkan, P. S. White, M. R. Gagne, J. Am. Chem. Soc. 1998, 120,
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œ
[47] M. Smrcina, Ph.D. Thesis, Charles University, Prague (Czech Repub-
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¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0820-4647 $ 20.00+.50/0
4647

œ
œ
¬
œ
P. Kocovsky, S. Vyskocil, Y. N. Belokon et al.
FULL PAPER
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[66] The previously observed 99% ee for the alkylation of 39 with
ArCH2Br[6k] indicates that racemization of the monoalkylated prod-
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[67] Preliminary crystallographic data show the complex 39 to be
essentially flat with minor Ni puckering.
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¬
¬
M. T. GarcÌa-Lopez, R. Gonzalez-Muniz, J. Org. Chem. 2001, 66, 3538;
for the factors governing the a-carbon acidity of glycine derivatives,
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[64] In preliminary experiments, we have found (S)-iso-NOBIN [(S)-(À)-
26] slightly less effective in alkylation of 39, giving (S)-phenyl alanine
87% ee under the same conditions (solid NaOH, RT, 13 min, 40%):
œ
œ
œ
¬
Y. N. Belokon, S. R. Harutyunyan, S. Vyskocil, P. Kocovsky, unpub-
lished results.
[65] The formamide analogue of acetamide 1i catalyzed the formation of
41 (RT, 6 min; 65%) but gave a practically racemic product (compare
Received: January 22, 2002
Revised: March 25, 2002 [F3814]
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Chem. Eur. J. 2002, 8, No. 20