C2-Symmetric bicyclo[3.3.1]nona-2,6-diene and bicyclo[3.3.2]deca-2,6-diene: New chiral diene ligands based on the 1,5-cyclooctadiene framework

Article abstract of DOI:10.1016/j.tetasy.2005.02.022

As a new type of C₂-symmetric chiral diene ligands, which coordinate to a metal by their 1,5-cyclooctadiene framework, we prepared 2,6-disubstituted bicyclo[3.3.1]nona-2,6-diene (bnd*) and bicyclo[3.3.2]deca-2,6-diene (bdd*), and examined their catalytic activity and enantioselectivity for rhodium-catalyzed asymmetric 1,4-addition to α,β-unsaturated ketones and 1,2-addition to N-sulfonylimines. High enantioselectivity of the Ph-bnd* ligand was observed in the addition of phenylboroxine to N-tosylimine and N-4-nitrobenzenesulfonylimine of 4-chlorobenzaldehyde to give phenyl(4-chlorophenyl)methylamines in high enantiomeric excess (98-99% ee).

Full text of DOI:10.1016/j.tetasy.2005.02.022

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 1673–1679
C2-Symmetric bicyclo[3.3.1]nona-2,6-diene and
bicyclo[3.3.2]deca-2,6-diene: new chiral diene ligands
based on the 1,5-cyclooctadiene framework
Yusuke Otomaru, Asato Kina, Ryo Shintani and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Received 2 February 2005;accepted 18 February 2005
Available online 22 March 2005
Abstract—As a new type of C2-symmetric chiral diene ligands, which coordinate to a metal by their 1,5-cyclooctadiene framework,
we prepared 2,6-disubstituted bicyclo[3.3.1]nona-2,6-diene (bnd*) and bicyclo[3.3.2]deca-2,6-diene (bdd*), and examined their
catalytic activity and enantioselectivity for rhodium-catalyzed asymmetric 1,4-addition to a,b-unsaturated ketones and 1,2-addition
to N-sulfonylimines. High enantioselectivity of the Ph-bnd* ligand was observed in the addition of phenylboroxine to N-tosylimine
and N-4-nitrobenzenesulfonylimine of 4-chlorobenzaldehyde to give phenyl(4-chlorophenyl)methylamines in high enantiomeric
excess (98–99% ee).
ꢀ 2005 Published by Elsevier Ltd.
1,4-cyclohexadiene framework
1. Introduction
R
Ar R1
OMe
Chiral dienes, as a new type of chiral ligand, have been
gaining a prominent position in asymmetric reactions
catalyzed by late transition metal complexes.1 They have
been demonstrated to be highly effective especially in
rhodium-catalyzed aryl transfer reactions, where the
chiral diene–rhodium catalysts showed higher catalytic
activity and/or higher enantioselectivity than chiral
phosphine–rhodium catalysts. One common feature of
the chiral dienes reported to date is that they coordinate
to a metal with their 1,4-cyclohexadiene moiety (Fig. 1).
This common 1,4-cyclohexadiene framework is found in
2,5-dibenzylbicyclo[2.2.1]hepta-2,5-diene (Bn-nbd*),2,3
which we reported as the first example of diene ligands
in 2003, and in C2-symmetric 2,5-disubstituted bicy-
clo[2.2.2]octa-2,5-dienes (e.g., Bn-bod* and Ph-bod*)
which have been applied successfully to rhodium-cata-
lyzed asymmetric additions of arylboron reagents to
a,b-unsaturated ketones4 and N-tosylarylimines,5 and
asymmetric arylative cyclization of alkynals.6 Carreiraꢀs
C1-symmetric bicyclo[2.2.2]octa-2,5-dienes,7,8 which
were readily prepared from (ꢀ)-carvone, also have the
1,4-cyclohexadiene moiety as coordinating functional-
ity. Very recently, we reported the preparation of 2,6-
Bn-nbd* (R = CH2Ph)
OMe
R2
R
R
Carreira's dienes
Bn-bod* (R = CH2Ph)
Ph-bod* (R = Ph)
R
1,5-cyclooctadiene framework
Ph
Ph
Ph-bdd*
Ph-bnd*
Figure 1. Chiral dienes.
Ph
Ph
diphenylbicyclo[3.3.1]nona-2.6-diene (Ph-bnd*) and its
application to rhodium-catalyzed asymmetric arylation
of N-4-nitrobenzenesulfonylimines. This chiral diene is
different from other 1,4-cyclohexadiene-based dienes be-
cause it coordinates to a metal through its 1,5-cyclooct-
adiene framework.9 Herein we report in detail on the
new chiral dienes whose diene framework is 1,5-cyclo-
octadiene, that is, 2,6-disubstituted bicyclo[3.3.1]nona-
2,6-diene (bnd*) and its homologue bicyclo[3.3.2]deca-
2,6-diene (bdd*). Structural features of their rhodium
complexes and the results obtained for the rhodium-
catalyzed asymmetric phenylation reactions are also
described.
*
Corresponding author. Tel.: +81 75 753 3983;fax: +81 75 753
3988;e-mail: thayashi@kuchem.kyoto-u.ac.jp
0957-4166/$ - see front matter ꢀ 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2005.02.022

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Y. Otomaru et al. / Tetrahedron: Asymmetry 16 (2005) 1673–1679
2. Results and discussion
Resolution of the C2-symmetric dienes dl-2a, b, and 5
thus obtained was efficiently carried out by use of a chi-
ral stationary phase column (Chiralcel OJ) of a prepar-
ative size to give both enantiomers of these dienes in an
enantiomerically pure form. The absolute configuration
of (ꢀ)-Tol-bnd* 2b was determined to be (S,S) by X-ray
crystal analysis of its rhodium complex (vide infra). The
other dienes, Ph-bnd* 2a and Ph-bdd* 5, were assigned
to be (ꢀ)-(S,S) and (ꢀ)-(R,R), respectively, by consider-
ation of the stereochemical reaction pathway2–5 in the
catalytic asymmetric phenylation reactions shown in
Schemes 2 and 3.
Scheme 1 shows the synthetic pathways to the enantio-
merically pure 2,6-disubstituted bicyclo[3.3.1]nona-2,6-
diene (bnd*) and bicyclo[3.3.2]deca-2,6-diene (bdd*).
Starting racemic diketone, bicyclo[3.3.1]nonane-2,6-
dione dl-1 was readily obtained through condensation
of dimethyl malonate with paraformaldehyde according
to the procedures reported by Schaefer.10 Phenyl-
ation of two carbonyl groups in diketone dl-1 with an
excess (2.6 equiv) of a phenylcerium reagent generated
from phenyllithium and cerium trichloride in THF gave
a quantitative yield of the diol, dehydration of which
with phosphorus oxychloride and pyridine gave racemic
2,6-diphenylbicyclo[3.3.1]nona-2,6-diene dl-2a (Ph-bnd)
in 95% yield (two steps). Alternatively, racemic 2,6-
disubstituted dienes 2 can be prepared by way of ditri-
flate dl-3, which is obtained by treatment of diketone 1
with lithium diisopropylamide (LDA) and N-(2-pyr-
idyl)triflimide. Thus, for example, palladium-catalyzed
Grignard cross-coupling of dl-3 with 4-methylphenyl-
magnesium bromide in ether in the presence of
PdCl2(dppf)11 provided 2,6-di(4-methylphenyl)bicyclo-
[3.3.1]nona-2,6-diene dl-2b (Tol-bnd). Another type of
2,6-disubstituted diene, 2,6-diphenylbicyclo[3.3.2]deca-
2,6-diene dl-5 (Ph-bdd), which is also expected to coor-
dinate to a metal with its 1,5-cyclooctadiene moiety,
was prepared, in a similar manner to Ph-bnd dl-2a, start-
ing with bicyclo[3.3.2]decane-2,6-dione dl-412 by the
addition of phenylcerium followed by dehydration of
the resulting diol.
O
O
[RhCl((R,R)-diene)]2
(3 mol% Rh)
+
PhB(OH)2
*
KOH (50 mol%)
Ph
dioxane/H2O (10/1)
6a-e
7a-e
O
O
O
O
O
6a
6b
6c
6d
6e
p-Tol
Ph
Ph
Ph
Ph
Ph
p-Tol
Ph
(R,R)-Ph-bod*
(R,R)-Ph-bnd* (R,R)-Tol-bnd* (R,R)-Ph-bdd*
2a
2b
5
Scheme 2.
SO2Ar
SO2Ar
HN
[RhCl((R,R)-diene)]2
(3 mol % Rh)
N
+ (PhBO)3
H
KOH/H2O
Ph
OH
1) PhLi/CeCl3
2) H2O
POCl3
pyridine
dioxane, 60 ˚C, 6 h
Cl
Cl
8a,b
8a: Ar =
8b: Ar =
Scheme 3.
HO
Ph
9a,b
O
Ar
Me
O
Ar
OTf
1) LDA
dl-2
dl-1
NO2
cat.PdCl2(dppf)
4-MeC6H4MgBr
2) Tf2NPy-2
TfO
63% yield
dl-3
Ar = Ph 2a: 95% yield (2 steps)
= 4-MeC6H4 2b: 76% yield
Ar
Ar
Treatment of the enantiomerically pure dienes (R,R)-2a,
b, and 5 with [RhCl(C2H4)2]2 in benzene at 50 ꢁC for
12 h gave high yields of the corresponding diene–rho-
resolution
+
dl-2
by chiral HPLC
(Chiralcel OJ)
Ar
Ar
(R,R)-(+)-Ph-bnd* 2a
(R,R)-(+)-Tol-bnd* 2b
(S,S)-(–)-Ph-bnd* 2a
(S,S)-(–)-Tol-bnd* 2b
1
dium complexes. Figure 2 shows the H NMR spectra
of Ph-bnd* 2a and its rhodium complex. On complex-
ation of 2a with rhodium, the olefinic proton H3 at
O
Ph
OH
Ph
5.97 ppm was largely shifted to
a higher field
1) PhLi/CeCl3
POCl3
(4.70 ppm). A lower field shift of the allylic protons H4
and a higher field shift of the protons H5 and H9 were
also observed on complexation. The chemical shifts
and coupling constants of [RhCl(Ph-bnd* 2a)]2 in 13C
NMR are shown in Figure 3. The couplings between
rhodium and carbons at the olefin and ipso position
on the phenyl group were observed by coordination to
the rhodium. These observations support the idea that
the chiral diene ligand 2a forms a stable chelating com-
plex with the rhodium.
HO
Ph
2) H2O
pyridine
O
Ph
dl-4
dl-5
44% yield (2 steps)
Ph
Ph
resolution
+
by chiral HPLC
(Chiralcel OJ)
Ph
(R,R)-(–)-Ph-bdd* 5
Ph
(S,S)-(+)-Ph-bdd* 5
(R,R)-diene 2 or 5
[RhCl(C2H4)2]2
[RhCl((R,R)-diene (2 or 5))]2
benzene
50 ˚C, 12 h
The X-ray crystal structure of [RhCl((S,S)-Tol-bnd*
2b)]2 is shown in Figure 4. The steric difference between
Scheme 1.

Y. Otomaru et al. / Tetrahedron: Asymmetry 16 (2005) 1673–1679
1675
C1
Cβ'
Cα
Cα'
Cβ'
Rh
Cα
Cβ
C1
C1'
Cα'
Cβ
C1'
Rh
Rh-C1 = 3.13Å , Rh-Cα = 2.19Å , Rh-Cβ = 2.09 Å
∠
∠C1-Rh-C1' = 137º, ∠Cα-Rh-Cα' = 87º, Cβ-Rh-Cβ' = 103º
∠Cα-Cβ/Cα'-Cβ' = 23º, bite angle of the diene coordination = 89º
C1
Cα
Cβ
Cβ'
Cα'
Rh
Cα
Cβ'
C1'
C1
Rh
C1'
Figure 2. Comparison of the 1H NMR spectra (at 500 MHz in CDCl3)
of Ph-bnd* 2a (a) and its rhodium complex (b).
Rh-C1 = 3.05Å , Rh-Cα = 2.13 Å, Rh-Cβ = 2.10 Å
∠
∠
∠C1-Rh-C1' = 132º, Cα-Rh-Cα' = 81º, Cβ-Rh-Cβ' = 80º
∠
Cα-Cβ/Cα'-Cβ' = 1º, bite angle of the diene coordination = 72º
Figure 5. Selected bond distances and angles for [RhCl(Tol-bnd* 2b)]2
(upper) and [RhCl(Ph-bod*)]2 (lower).
72.7 ppm (d, JC-Rh = 11.4 Hz)
Ph
Rh
Cl
144.8 ppm (d, JC-Rh = 2.1 Hz)
86.2 ppm (d, JC-Rh = 14.5 Hz)
2
different to each other. This coordination manner is very
different from non-substituted cyclooctadiene complexes
such as [RhCl(cod)]2 where the diene coordination is
Figure 3. 13C NMR spectra (at 125 MHz in CDCl3) of [RhCl((R,R)-
Ph-bnd* 2a)]2.
13
parallel. The twisted coordination of bnd* is probably
caused by the torsion of the bridged backbone. Con-
versely, the 1,4-cyclohexadiene framework of the Ph-
bod* complex is highly symmetric, the two double
bonds coordinating to rhodium almost parallel (1ꢁ).
The bite angle of the diene coordination in [RhCl(Tol-
bnd*)]2 is 89ꢁ, much larger than that (72ꢁ) in the bod*
complex. The distance from rhodium to phenyl substitu-
˚
ent on the olefin of Tol-bnd* (Rh–C1 = 3.13 A) is
slightly longer than that of [RhCl(Ph-bod*)]2 (Rh–
˚
C1 = 3.05 A).
The rhodium complexes coordinated with the chelating
chiral dienes (R,R)-Ar-bnd* (Ar = Ph 2a and Tol 2b)
and (R,R)-Ph-bdd* 5 were examined for their catalytic
activity and enantioselectivity in the asymmetric 1,4-
addition14–16 of phenylboronic acid to a,b-unsaturated
ketones 6 (Scheme 2). As a general procedure, to a solu-
tion containing a phenylboronic acid and a chiral diene–
rhodium complex (3 mol%) in dioxane (1.0 mL) were
added enone 6 (0.30 mmol) and 1.5 M aqueous KOH
(0.10 mL), and the mixture stirred at 30–50 ꢁC for 1–
8 h. The 1,4-addition product 7 was isolated by a silica
gel chromatography after filtration through a pad of
silica gel. The results obtained are summarized in Table
1, which also contains the data reported using Ph-bod
for comparison.4 All the chiral diene complexes showed
high catalytic activity, but unfortunately the enantiose-
lectivity observed with Ar-bnd* 2a and b and Ph-bdd*
5 was lower than that with Ph-bod* for all the a,b-
unsaturated ketones examined. The enantioselectivity
of not lower than 90% was observed only for two
enones, 90% ee for cyclohexenone 6a with Ph-bdd* 5
Figure 4. ORTEP illustration of [RhCl((S,S)-Tol-bnd* 2b)]2 with
thermal ellipsoids drawn at the 50% probability level (shown as a
monomer for clarity).
a bulky 4-methylphenyl group and a small hydrogen on
the ligand is effectively dissecting the space in a C2-fash-
ion, thereby creating a very good chiral environment
around the rhodium. Figure 5 shows the structure of
the diene–rhodium moiety of this rhodium complex
coordinated with Tol-bnd* 2b and selected bond dis-
tances and angles around the rhodium atom. The data
reported for [RhCl(Ph-bod*)]24 are also shown for com-
parison. Two double bonds (Ca@Cb and Ca0@Cb0) of
bnd* coordinated to the rhodium are not parallel to
each other but twisted by 23ꢁ. As a result, the angles
\Ca–Rh–Ca0 (87ꢁ) and \Cb–Rh–Cb0 (103ꢁ) are very

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Y. Otomaru et al. / Tetrahedron: Asymmetry 16 (2005) 1673–1679
a
Table 1. Asymmetric 1,4-addition of phenylboronic acid to enones 6 catalyzed by [RhCl((R,R)-diene)]2
Entry
6
Diene
Temp (ꢁC)
Time (h)
Yield (%) of 7b
Eec (%)
1
6a
6a
6a
6a
6b
6b
6b
6c
6c
6c
6d
6d
6d
6e
6e
6e
Ph-bnd* 2a
Tol-bnd* 2b
Ph-bdd* 5
Ph-bod*
30
30
30
30
50
50
50
50
50
50
50
50
30
50
50
30
3
3
3
1
6
8
1
6
3
1
6
3
3
6
3
1
93 7a
97 7a
98 7a
97 7a
86 7b
98 7b
97 7b
83 7c
90 7c
95 7c
88 7d
86 7d
95 7d
86 7e
85 7e
90 7e
83 (R)
79 (R)
90 (R)
96 (R)
91 (R)
84 (R)
99 (R)
78 (R)
71 (R)
92 (R)
82 (R)
83 (R)
85 (R)
67 (S)
59 (S)
83 (S)
2
3
4d
5
Ph-bnd* 2a
Ph-bdd* 5
Ph-bod*
6
7d
8
Ph-bnd* 2a
Ph-bdd* 5
Ph-bod*
9
10d
11
12
13d
14
15
16d
Ph-bnd* 2a
Ph-bdd* 5
Ph-bod*
Ph-bnd* 2a
Ph-bdd* 5
Ph-bod*
a The reaction was carried out with enone 6a–e (0.30 mmol), phenylboronic acid (0.60 mmol), [RhCl((R,R)-diene)]2 (3 mol% Rh, diene = 2a,b, or 5),
and 1.5 M aq KOH (0.10 mL) in dioxane (1.0 mL).
b Isolated yield after silica gel chromatography.
c Determined by HPLC analysis with chiral stationary phase columns: Chiralcel OD-H for 7a, c–e;OB-H for 7b.
d Reported in Ref. 4.
(entry 3) and 91% ee for cyclopentenone 6b with Ph-
bnd* 2a (entry 5). In the phenylation of enones 6c and
d, the enantioselectivity was around 80% ee with both
of the newly prepared dienes, bdd* and bnd*.
3. Conclusions
As a new type of C2-symmetric chiral diene ligands, we
prepared 2,6-disubstituted bicyclo[3.3.1]nona-2,6-diene
(bnd*) and bicyclo[3.3.2]deca-2,6-diene (bdd*), which
coordinate to a metal by their 1,5-cyclooctadiene frame-
work. Although their enantioselectivity in the rhodium-
catalyzed asymmetric 1,4-addition to a,b-unsaturated
ketones was not as high as that of bicyclo[2.2.2]octa-
2,5-diene (bod*) ligands which we previously reported,4
one of the bnd* ligand showed the highest enantioselec-
tivity in the asymmetric addition of a phenylboron
reagent to N-sulfonylimines.
We have reported that the rhodium complexes of the
diene ligands are much more active and enantioselective
than those of the phosphorus ligands for the addition
of arylboroxines to N-tosylimines5 and N-4-nitro-
benzenesulfonylimines.9 The chiral dienes, Ph-bnd* 2a,
Ph-bdd* 5, and Ph-bod*, were examined for their ability
in the rhodium-catalyzed asymmetric addition of
phenylboroxine to N-tosylimine 8a and N-4-nitro-
benzenesulfonylimine 8b of 4-chlorobenzaldehyde giving
diarylmethylamines 9 (Scheme 3). Ph-bnd* 2a showed
the highest enantioselectivity for both 8a (99% ee) and
8b (98% ee) (entries 1 and 4 in Table 2). The enantio-
selectivity of Ph-bod* is as high as that of Ph-bnd* 2a
for the phenylation of N-tosylimine 8a, but it is not so
high for N-4-nitrobenzenesulfonylimine 8b (entries 3
and 6). Ph-bdd* 5 is also an enantioselective ligand
for the phenylation of imines, although its enantio-
selectivity is a little lower than Ph-bnd* 2a (entries 2
and 5).
4. Experimental
4.1. General
All anaerobic and moisture-sensitive manipulations
were carried out with standard Schlenk techniques
under predried nitrogen or glovebox techniques under
prepurified argon. NMR spectra were recorded at
500 MHz for 1H, and 125 MHz for 13C. Chemical shifts
a
Table 2. Asymmetric addition of phenylboroxine to imines 8 catalyzed by [RhCl((R,R)-diene)]2
Entry
Ar
Diene
Yield (%) of 9b
% Eec (%)
1
4-MeC6H4 8a
Ph-bnd* 2a
Ph-bdd* 5
Ph-bod*
95 9a
88 9a
96 9a
96 9b
99 9b
96 9b
99 (S)
94 (S)
98 (S)
98 (S)
90 (S)
89 (S)
2
3d
4e
5
4-NO2C6H4 8b
Ph-bnd* 2a
Ph-bdd* 5
Ph-bod*
6e
a The reaction was carried out in dioxane (1.0 mL) at 60 ꢁC for 6 h with imine 8 (0.10 mmol) and 1.2 equiv of phenylboroxine in the presence of
20 mol% KOH, 1 equiv (with respect to boron) of H2O, and 3 mol% Rh of [RhCl((R,R)-diene (2a or 5))]2.
b Isolated yield after silica gel chromatography.
c Determined by HPLC analysis with a chiral stationary phase column (Chiralcel OD-H).
d Reported in Ref. 5.
e Reported in Ref. 9.

Y. Otomaru et al. / Tetrahedron: Asymmetry 16 (2005) 1673–1679
1677
are reported in d ppm referenced to an internal SiMe4
residue was purified by recrystallization (THF/hexane)
to give 179 mg (87% yield) of [RhCl((R,R)-Ph-bnd*
2a)]2. H NMR (CDCl3): d 1.28 (s, 4H), 2.24 (s, 4H),
2.29 (d, J = 15.1 Hz, 4H), 3.50 (dt, J = 15.1 and
3.7 Hz, 4H), 4.70 (d, J = 2.9 Hz, 4H), 7.22–7.29 (m,
12H), 7.50 (d, J = 7.2 Hz, 8H). 13C{1H} NMR (CDCl3):
d 32.9, 34.6, 41.5, 72.7 (d, J = 11.4 Hz), 86.2 (d,
1
standard for H NMR and chloroform-d (d 77.05) for
13C NMR. Chiralcel OJ (2 cmB · 25 cm) was used for
the separation of enantiomers of diene ligands 2 and 5.
1
4.2. Materials
J = 14.5 Hz), 126.5, 126.6, 127.8, 144.8 (d, J = 2.1 Hz).
½aŠ ¼ ꢀ998 (c 0.06, CHCl3).
THF, benzene, and dioxane were distilled from sodium
benzophenone-ketyl under nitrogen. Racemic bicyclo-
[3.3.1]nonane-2,6-dione 1,10 racemic bicyclo[3.3.2]dec-
ane-2,6-dione 4,12 [RhCl(C2H4)2]2,17 and PdCl2(dppf)11
were prepared according to the reported procedures.
20
D
4.5. 2,6-Bis(trifluoromethanesulfonyloxy)bicyclo[3.3.1]-
nona-2,6-diene 3
LDA was generated by the dropwise addition of a
1.59 M solution of n-BuLi (7.1 mL, 13 mmol) in hexane
to a solution of diisopropylamine (1.6 mL, 11 mmol)
in 20 mL of THF at 0 ꢁC. This solution was stirred
for an additional 10 min before a solution of bicy-
clo[3.3.1]nonan-2,6-dione dl-1 (610 mg, 4.0 mmol) in
17 mL of THF was slowly added at ꢀ78 ꢁC. The result-
ing mixture was stirred at ꢀ78 ꢁC for an additional
4.3. (1R,5R)-2,6-Diphenylbicyclo[3.3.1]nona-2,6-diene
(R,R)-2a
CeCl3Æ7H2O (969 mg, 2.6 mmol) was heated in vacuo at
140 ꢁC for 2 h and cooled. THF (10 mL) was added and
the suspension stirred for 1 h. To this suspension was
added at ꢀ78 ꢁC, phenyllithium in cyclohexane/Et2O
(2.5 mL, 1.05 M, 2.6 mmol) with stirring. After stirring
was continued for 1 h, racemic bicyclo[3.3.1]nonane-
2,6-dione (dl-1, 152 mg, 1.0 mmol) in THF (2.0 mL)
was added, and the reaction mixture stirred at ꢀ78 ꢁC
for 6 h. Water was added to quench the reaction and
the organic solvent removed in vacuo. The aqueous
layer was extracted with ethyl acetate three times. The
combined organic layers were dried over magnesium sul-
fate. Removal of the solvent gave the crude diol. To the
crude diol were added pyridine (1.0 mL) and POCl3
(927 mg, 6.0 mmol) at room temperature, and the mix-
ture was heated to reflux for 12 h. After being cooled
to room temperature, the reaction mixture was
quenched with water, and extracted with Et2O. The
combined organic layers were washed with 2 M NaOH
and water, and then dried over magnesium sulfate. Re-
moval of the solvent gave the crude product, which
was purified by preparative TLC (silica gel, hexane/
Et2O = 5/1) to give 259 mg (95% yield for two steps)
of racemic 2,6-diphenylbicyclo[3.3.1]nona-2,6-diene dl-
hour, before
a solution of N-(2-pyridyl)triflimide
(4.0 g, 11 mmol) in 20 mL of THF was slowly added
at ꢀ78 ꢁC. This mixture was warmed to room tempera-
ture while being stirred for 41 h. Ice water was added to
quench the reaction and the organic solvent removed
under reduced pressure. The aqueous layer was ex-
tracted with Et2O three times. The combined organic
layers were washed with 10% NaOH and then dried over
magnesium sulfate. Removal of the solvent gave the
crude product, which was chromatographed on silica
gel (ethyl acetate/hexane = 1/10) to give 1.0 g (63% yield)
1
of ditriflate 3. H NMR (CDCl3): d 1.99 (t, J = 3.1 Hz,
2H), 2.42 (m, 4H), 2.76 (br, 2H), 5.77 (dd, J = 5.2 and
2.5 Hz, 2H). 13C{1H} NMR (CDCl3): d 28.0, 29.3,
30.9, 116.0, 118.5 (q, J = 319 Hz), 149.8. Anal. Calcd
for C11H10F6O6S2: C, 31.73;H, 2.42. Found: C, 31.72;
H, 2.33.
4.6. (1R,5R)-2,6-Di-(4-methylphenyl)bicyclo[3.3.1]nona-
2,6-diene 2b
1
2a. H NMR (CDCl3): d 2.00 (t, J = 3.1 Hz, 2H), 2.08
(dd, J = 18.1 and 5.1 Hz, 2H), 2.47 (dm, J = 18.1 Hz,
2H), 3.10–3.14 (m, 2H), 5.97 (dd, J = 5.1 and 2.4 Hz,
2H), 7.23 (t, J = 7.4 Hz, 2H), 7.32 (t, J = 7.4 Hz, 4H),
7.41 (d, J = 7.4 Hz, 4H). 13C{1H} NMR (CDCl3): d
29.2, 29.8, 31.7, 122.6, 125.8, 126.6, 128.2, 140.2,
141.4. Anal. Calcd for C21H20: C, 92.60;H, 7.40. Found:
C, 92.47;H, 7.52. Enantiomerically pure (1 R,5R)-2,6-
diphenylbicyclo[3.3.1]nona-2,6-diene (R,R)-2a was ob-
tained by separation of the racemic diene on Chiralcel
To a mixture of ditriflate 3 (416 mg, 1.00 mmol) and
PdCl2(dppf) (14.8 mg, 20 lmol) in 3.0 mL of Et2O was
added 4-methylphenylmagnesium bromide (2.1 mL,
1.4 M, 3.0 mmol) in Et2O at room temperature, and
the reaction mixture heated to reflux overnight. After
being cooled to room temperature, the reaction mixture
was quenched with water, and extracted with Et2O. The
combined organic layers were dried over magnesium sul-
fate and the solvent removed under reduced pressure.
The residue was chromatographed on silica gel (ethyl
acetate/hexane = 1/10) to give 227 mg (76% yield) of
racemic 2,6-di(4-methylphenyl)bicyclo[3.3.1]nona-2,6-
OJ column with hexane/2-propanol = 2/1, flow =
20
D
12 mL/min, wavelength = 254 nm. ½aŠ ¼ þ39 (c 0.58,
CHCl3).
1
diene (dl-2b). H NMR (CDCl3): d 1.97 (t, J = 3.1 Hz,
4.4. Preparation of [RhCl((R,R)-Ph-bnd* 2a)]2
2H), 2.05 (dd, J = 18.3 and 5.0 Hz, 2H), 2.33 (s, 6H),
2.44 (dd, J = 18.3 and 5.3 Hz, 2H), 3.08 (br, 2H), 5.92
(dd, J = 5.0 and 2.4 Hz, 2H), 7.12 (d, J = 8.1 Hz, 4H),
7.30 (d, J = 8.1 Hz, 4H). 13C{1H} NMR (CDCl3):
d 21.0, 29.3, 29.8, 31.7, 121.8, 125.7, 129.0, 136.2,
138.6, 139.9. Anal. Calcd for C23H24: C, 91.95;H,
8.05. Found: C, 91.75;H, 8.15. Enantiomerically pure
(1R,5R)-2,6-di(4-methylphenyl)bicyclo[3.3.1]nona-2,6-diene
A suspension of [RhCl(C2H4)2]2 (117 mg, 0.60 mmol
Rh) and (1R,5R)-2,6-diphenylbicyclo[3.3.1]nona-2,6-
diene (R,R)-2a (136 mg, 0.50 mmol) in 15 mL of benzene
was stirred at 50 ꢁC for 12 h. After being cooled to room
temperature, the reaction mixture was filtered and the
filtrate was concentrated under reduced pressure. The

1678
Y. Otomaru et al. / Tetrahedron: Asymmetry 16 (2005) 1673–1679
(R,R)-2b was obtained by separation of the racemic
diene on Chiralcel OJ column with hexane/2-propanol =
C22H22: C, 92.26;H, 7.74. Found: C, 91.98;H, 7.92.
Enantiomerically pure (1R,5R)-2,6-diphenylbicyclo-
[3.3.2]deca-2,6-diene (R,R)-5 was obtained by separation
of the racemic diene on Chiralcel OJ column with hex-
20
D
9/1, flow = 18 mL/min, wavelength = 254 nm. ½aŠ
¼
þ43 (c 0.25, CHCl3).
ane/2-propanol = 2/1, flow = 8 mL/min, wavelength =
20
D
254 nm. ½aŠ ¼ ꢀ67 (c 0.34, CHCl3).
4.7. Preparation of [RhCl((R,R)-Tol-bnd* 2b)]2
In a similar manner to the preparation of [RhCl((R,R)-
Ph-bnd* 2a)]2, treatment of (R,R)-Tol-bnd 2b (47.9 mg,
0.16 mmol) with [RhCl(C2H4)2]2 (31.1 mg, 0.16 mmol
Rh) in benzene at 50 ꢁC for 12 h gave a quantitative
yield of [RhCl((R,R)-Tol-bnd* 2b)]2. 1H NMR (CDCl3):
d 1.25 (br, 4H), 2.21 (br, 4H), 2.25 (d, J = 15.0 Hz, 4H),
2.29 (s, 12H), 3.42 (d, J = 15.0 Hz, 4H), 4.69 (br, 4H),
7.05 (d, J = 8.0 Hz, 8H), 7.37 (d, J = 8.0 Hz, 8H).
13C{1H} NMR (CDCl3): d 21.2, 32.9, 34.5, 41.2, 71.9
(d, J = 11.4 Hz), 86.0 (d, J = 13.9 Hz), 126.3, 128.5,
4.10. Preparation of [RhCl((R,R)-Ph-bdd* 5)]2
In a similar manner to the preparation of [RhCl((R,R)-
Ph-bnd* 2a)]2, treatment of (R,R)-Ph-bdd 5 (140 mg,
0.49 mmol) with [RhCl(C2H4)2]2 (114 mg, 0.59 mmol
Rh) in benzene at 50 ꢁC for 12 h gave a quantitative
1
yield of [RhCl((R,R)-Ph-bdd* 5)]2. H NMR (CDCl3):
d 1.37–1.48 (m, 4H), 1.70–1.79 (m, 4H), 2.47 (d,
J = 15.6 Hz, 4H), 2.93 (t, J = 7.4 Hz, 4H), 3.64 (ddd,
J = 14.8, 8.1, and 6.7 Hz, 4H), 4.38 (d, J = 5.5 Hz,
4H), 7.20–7.24 (m, 12H), 7.44–7.54 (m, 8H). 13C{1H}
136.2, 141.6. Anal. Calcd for C46H48Cl2Rh2: C, 62.96;
20
D
H, 5.51. Found: C, 63.26;H, 5.80. ½aŠ ¼ ꢀ907 (c
NMR (CDCl3):
J = 11.9 Hz), 93.2 (d, J = 14.4 Hz), 126.2, 126.5, 127.5,
d
27.4, 39.4, 45.8, 73.4 (d,
0.19, CHCl3).
20
D
149.2 (d, J = 1.6 Hz). ½aŠ ¼ ꢀ286 (c 0.06, CHCl3).
4.8. X-ray crystal structure of [RhCl((R,R)-Tol-bnd*
2b)]2
4.11. Rhodium-catalyzed asymmetric 1,4-addition of
phenylboronic acid to enones
A
yellow prism crystal (0.60 · 0.30 · 0.10 mm) of
C46H44Cl2Rh2 was obtained by solvent evaporation
from dichloromethane solution at room temperature.
Crystallographic data for [RhCl((S,S)-Tol-bnd* 2b)]2
(at ꢀ150 1 ꢁC). F.W. = 873.57, monoclinic, C2 (#5),
The reaction conditions and results are summarized
in Table 1. A typical experimental procedure (entry 1
in Table 1) is shown below: To a solution of
[RhCl((R,R)-Ph-bnd* 2a)]2 (3.7 mg, 9.0 lmol Rh) and
phenylboronic acid (73.2 mg, 0.60 mmol) in 1.0 mL of
dioxane was added 2-cyclohexenone 6a (28.8 mg,
0.30 mmol) and aqueous KOH (0.10 mL, 1.5 M,
0.15 mmol). After stirring at 30 ꢁC for 3 h, the mixture
was passed through a short silica gel column (eluent:
diethyl ether). Evaporation of the solvent followed by
preparative TLC (silica gel, hexane/ethyl acetate = 3/1)
gave 48.7 mg (93% yield) of (R)-7a in 83% ee. Products
7 obtained by the rhodium-catalyzed asymmetric 1,4-
addition were fully characterized by comparison of their
spectral and analytical data with those reported in the
literature.15a
˚
a = 28.87(2), b = 6.787(4), c = 12.232(9) A, b =
113.30(3)ꢁ, V = 2201(2) A , Z = 2, qcalcd = 1.32 g/cm3,
3
˚
2hmax = 55.0ꢁ, F0 0 0 = 880, l(Mo-Ka) = 9.0 cmꢀ1
. A
total of 2726 reflections were collected. The final R values
were R = 0.043 (I > 2h(I)), R = 0.044, Rw = 0.015 (all
data). The maximum and minimum peaks on the final
difference Fourier map corresponded to 2.87 and
ꢀ
3
˚
ꢀ2.99 e /A , respectively. CCDC-262190 contains the
supplementary crystallographic data for this paper. This
data can be obtained free of charge via www.ccdc.cam.
ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12 Union Road Cam-
bridge CB21EZ, UK;fax: (+44)1223-336-033;or
e-mail: deposit@ccdc.cam.ac.uk).
4.12. Rhodium-catalyzed asymmetric phenylation of
imines with phenylboroxine
4.9. (1R,5R)-2,6-Diphenylbicyclo[3.3.2]deca-2,6-diene
(R,R)-5
The reaction conditions and results are summarized in
Table 2. A typical experimental procedure is shown
below: To a solution of [RhCl((R,R)-Ph-bnd* 2a)]2
(1.2 mg, 1.5 lmol, 3 mol% Rh) in 1,4-dioxane
(0.30 mL) was added aqueous KOH (6.5 lL, 3.1 M,
20 mol% KOH, H2O: 1 equiv to boron) at room temper-
ature and the solution was stirred for 5 min. This solu-
tion containing the catalyst was added to a solution of
N-(4-chlorophenyl)methylidene-4-methybenzenesulfon-
amide 8a (29.4 mg, 0.10 mmol) and phenylboroxine
(37.4 mg, 0.12 mmol) in 1,4-dioxane (0.50 mL) at the
same temperature. After being stirred at 60 ꢁC for 6 h,
the mixture was passed through a short silica gel column
(pretreated with methanol, eluent: ethyl acetate). Evap-
oration of the solvent followed by silica gel chromato-
graphy (hexane/ethyl acetate = 2/1) gave 35.5 mg (95%
yield) of (S)-9a5,9 which is 99% ee.
In a similar manner to the preparation of (R,R)-2a,
racemic bicyclo[3.3.2]decane-2,6-dione dl-4 (445 mg,
2.7 mmol) was treated with a phenylcerium reagent gen-
erated from phenyllithium in cyclohexane/Et2O (7.8 mL,
0.90 M, 7.0 mmol) and cerium trichloride (1.73 g,
7.0 mmol) in THF followed by dehydration of the
resulting diol with phosphoryl chloride (1.5 mL,
16 mmol) in pyridine gave 44% yield of racemic 2,6-
diphenylbicyclo[3.3.2]deca-2,6-diene dl-5. 1H NMR
(CDCl3): d 1.97–2.08 (m, 2H), 2.22–2.31 (m, 2H), 2.37
(dt, J = 18.0 and 6.7 Hz, 2H), 2.56 (d, J = 18.0 Hz,
2H), 3.09 (t, J = 5.8 Hz, 2H), 5.78 (dd, J = 7.8 and
1.2 Hz, 2H), 7.18–7.23 (m, 2H), 7.25–7.33 (m 8H).
13C{1H} NMR (CDCl3): d 32.0, 32.2, 41.6, 126.5,
126.7, 127.1, 128.1, 145.1, 146.2. Anal. Calcd for

Y. Otomaru et al. / Tetrahedron: Asymmetry 16 (2005) 1673–1679
1679
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Acknowledgements
Support has been provided in part by a Grant-in-Aid for
Scientific Research, the Ministry of Education, Culture,
Sports, Science and Technology, Japan (21 COE on
Kyoto University Alliance for Chemistry).
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