Design and synthesis of a C2-symmetric chiral 1,2-bis(diphenylphosphino)benzene ligand Via rhodium-catalyzed intramolecular [2+2+2] cycloaddition

Article abstract of DOI:10.3987/COM-12-S(N)30

The design and synthesis of a C₂-symmetric chiral 1,2-bis(diphenylphosphino)benzene ligand Via the rhodium-catalyzed intramolecular [2+2+2] cycloaddition followed by reduction are disclosed. This new chiral dppbz-type ligand could be employed for the rhodium-catalyzed asymmetric alkene hydrogenation.

Full text of DOI:10.3987/COM-12-S(N)30

HETEROCYCLES, Vol. 86, No. 1, 2012
139
HETEROCYCLES, Vol. 86, No. 1, 2012, pp. 139 - 146. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 9th June, 2012, Accepted, 20th July, 2012, Published online, 30th July, 2012
DOI: 10.3987/COM-12-S(N)30
DESIGN AND SYNTHESIS OF
A
C2-SYMMETRIC CHIRAL
1,2-BIS(DIPHENYLPHOSPHINO)BENZENE
LIGAND
INTRAMOLECULAR
VIA
RHODIUM-CATALYZED
CYCLOADDITION
[2+2+2]
Fumiya Mori,1 Keiichi Noguchi,2 and Ken Tanaka1,*
1
Department of Applied Chemistry, Graduate School of Engineering, Tokyo
University of Agriculture and Technology, Koganei, Tokyo184-8588ꢀ Japan
E-mail: tanaka-k@cc.tuat.ac.jp
2
Instrumentation Analysis Center, Tokyo University of Agriculture and
Technology, Koganei, Tokyo184-8588, Japan
Abstract
–
The design and synthesis of
ligand via
a
C2-symmetric chiral
1,2-bis(diphenylphosphino)benzene
the
rhodium-catalyzed
intramolecular [2+2+2] cycloaddition followed by reduction are disclosed. This
new chiral dppbz-type ligand could be employed for the rhodium-catalyzed
asymmetric alkene hydrogenation.
1,2-Bis(diphenylphosphino)benzene (dppbz) has been widely employed as a useful ligand for a number of
transition-metal-catalyzed reactions.1 As dppbz is an achiral ligand, asymmetric variants of
transition-metal-catalyzed reactions, in which the dppbz ligand is indispensable, cannot be developed.
Therefore, the design and synthesis of chiral dppbz-type ligands are important subjects.2 On the other
hand, the cationic rhodium(I)/biaryl bisphosphine complex-catalyzed [2+2+2] cycloadditions3–5 involving
phosphorus-substituted alkynes are useful methods for the synthesis of phosphorus-substituted
benzenes.6,7 In order to synthesize dppbz-type ligands, we attempted the reactions of terminal and internal
1,6-diynes 1a,b with bis(diphenylphosphinoyl)acetylene (2) in the presence of a cationic
rhodium(I)/rac-BINAP complex (10 mol %), while the expected 1,2-bis(diphenylphosphinoyl)benzenes
3a,b were not obtained at all even at the elevated temperature (80 °C) (Scheme 1).
Thus, we designed the intramolecular [2+2+2] cycloaddition of triyne diphosphine oxide 4a, which would
furnish tricyclic 1,2-bis(diphenylphosphinoyl)benzene 5a (Scheme 2). In this reaction, the use of chiral
propargyl alcohol-derived triyne diphosphine oxide 4b would furnish C2-symmetric chiral tricyclic
Dedicated to Professor Dr. Ei-ichi Negishi on the occasion of his 77th birthday.

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HETEROCYCLES, Vol. 86, No. 1, 2012
1,2-bis(diphenylphosphinoyl)benzene 5b (Scheme 2). In this Communication, we disclose the synthesis
of a new chiral 1,2-bis(diphenylphosphino)benzene ligand as well as achiral one via the
rhodium-catalyzed intramolecular [2+2+2] cycloaddition.
10 mol %
[Rh(cod)2]BF4/
rac-BINAP
R
R
P(O)Ph2
P(O)Ph2
P(O)Ph2
R
R
Z
Z
(CH2Cl)2, 80 °C
16 h
P(O)Ph2
1a (R = H)
1b (R = Me)
2
3a (R = H) / 0% yield
3b (R = Me) / 0% yield
Scheme 1. Rhodium-Catalyzed Reactions of 1,6-Diynes 1 with Bis(diphenylphosphinoyl)acetylene (2)
R
R
O
+
Rh(I) /
biaryl bisphsphine
catalyst
O
Ph (O)P
2
P(O)Ph
P(O)Ph
2
O
R
2
P(O)Ph
2
O
R
4a (R = H)
4b (R = Me)
5a (R = H, achiral)
5b (R = Me, chiral)
Scheme 2. Rhodium-Catalyzed [2+2+2] Cycloadditions of Triyne Diphosphine Oxides 4
Table 1. Optimization of Reaction Conditions for Rhodium-Catalyzed Intramolecular [2+2+2]
Cycoaddition of Triyne 4aa
10 mol %
O
Ph (O)P
2
[Rh(cod) ]BF /
2
ligand
4
P(O)Ph
P(O)Ph
O
2
2
CH Cl , rt
2
21 h
2
O
P(O)Ph
2
O
4a
5a
c
b
yield (%)
entry
ligand
conv (%)
d
1
BIPHEP
BINAP
80
94
93
91
100
100
100
100
2
3
4
H -BINAP
8
Segphos
a
b
[Rh(cod)2]BF4 (0.010 mmol), ligand (0.010 mmol), 4a (0.10 mmol), and solvent (2.0 mL) were used.
Determined by 1H NMR. c Isolated yield. d For 25 h.

HETEROCYCLES, Vol. 86, No. 1, 2012
141
O
O
O
PPh
PPh
PPh
PPh
PPh
PPh
PPh
2
2
2
2
2
2
2
PPh
2
O
BINAP
H -BINAP
8
Segphos
BIPHEP
Figure 1. Structures of Biaryl Bisphosphine Ligands
We first investigated the [2+2+2] cycloaddition of achiral triyne 4a (Table 1). Pleasingly, the desired
benzene 5a was obtained in good yield at room temperature by using a cationic rhodium(I)/BIPHEP
complex (entry 1). Screening of biaryl bisphosphine ligands (Figure 1, entries 1–4) revealed that the use
of BINAP furnished 5a in the highest yield (entry 2). Thus obtained diphosphine oxide 5a was reduced to
the corresponding diphosphine ligand 6a in moderate yield by treatment with HSiCl3 and Me2NC6H5
(Scheme 3).
O
O
O
O
HSiCl3
Me2NC6H5
P(O)Ph2
P(O)Ph2
PPh2
PPh2
xylene, 130 °C
5a
6a / 42%
Scheme 3. Reduction of Diphosphine Oxide 5a into Diphosphine 6a
Next, we examined the synthesis of chiral triyne diphosphine oxide 4b starting from commercially
available chiral propargylic alcohol (R)-7. Although the double etherification of dibromide 8 with racemic
(±)-7 leading to triyne 9 was first examined, complete decomposion of 8 was observed (Scheme 4).
Br
Me
Br
Me
OH
O
8, NaH
DMF, rt
O
(±)-7
Me
9 / 0% yield
(complete decomposion of 8)
Scheme 4. Reaction of Propargylic Alcohol (±)-7 with Dibromide 8

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HETEROCYCLES, Vol. 86, No. 1, 2012
Therefore, the stepwise etherification was examined as shown in Scheme 5. The etherification of bromide
108 with (R)-7 (98% ee) followed by desilylation afforded diyne (R)-11 in good yield. Bromination of
(R)-11 furnished bromide (R)-12 in good yield. The second etherification of (R)-12 with (R)-7 also
proceeded to give the desired triyne (R,R)-9 in high yield. The subsequent copper(I)-catalyzed double
diphenylphosphination9 followed by oxidation with H2O2 furnished chiral triyne diphosphine oxide
(R,R)-(+)-4b in high yield. In order to optimize the [2+2+2] cycloaddition step, the reaction of
diastereomeric mixture of triyne 4b, prepared from racemic propargylic alcohol (±)-7, was examined by
using various biaryl bisphosphine ligands (Table 2). Among the ligands examined (Figure 1, entries 1–4),
the use of BIPHEP furnished the desired benzene 5b with the highest selectivity at room temperature for
16 h, although 4b was still remained in 24% (entry 1). Pleasingly, when the reaction of chiral triyne
(R,R)-(+)-4b was conducted at room temperature for 24 h, complete conversion of 4b was observed to
give (R,R)-(+)-5b in good yield (Scheme 5). Thus obtained diphosphine oxide (R,R)-(+)-5b could be
reduced to the corresponding diphosphine (R,R)-(+)-6b (98% ee) by treatment with HSiCl3 and iPr2NH,
although the product yield was low.
OTBS
Br
10
1) 10 (1.05 equiv)
NaH (1.2 equiv)
OH
Me
DMF, rt
CBr , PPh
4 3
O
2) TBAF, THF, rt
CH Cl , 0 °C–rt
2 2
OH
Me
(R)-7 (98% ee)
(R)-11 / 64% (2 steps)
Me
1) 20 mol % CuI
(R)-7 (98% ee)
Br
ClPAr (2.5 equiv)
(1 equiv)
2
O
Et N, toluene, rt
NaH (1.2 equiv)
3
O
DMF, rt
2) H O , rt
2 2
O
Me
Me
(R)-12 / 75%
(1.05 equiv)
(R,R)-9 / 81% from (R)-7
Me
Me
O
20 mol %
O
Ph (O)P
2
[Rh(cod) ]BF /
2
4
P(X)Ph
P(X)Ph
2
BIPHEP
(CH Cl) , rt
2
2
O
2
24 h
P(O)Ph
2
O
Me
Me
(R,R)-(+)-4b / 77%
(R,R)-(+)-5b (X = O) / 68%
(R,R)-(+)-6b (X = –) / 26%
(98% ee)
HSiCl , iPr NH
xylene, 120 °C
3
2
Scheme 5. Synthesis of C2-Symmetric Chiral 1,2-Bis(diphenylphosphino)benzene Ligand (R,R)-(+)-6b
Starting from Commercially Available Chiral Propargylic Alcohol (R)-7

HETEROCYCLES, Vol. 86, No. 1, 2012
143
Table 2. Optimization of Reaction Conditions for Rhodium-Catalyzed Intramolecular [2+2+2]
Cycoaddition of Triyne 4ba
Me
Me
20 mol %
[Rh(cod) ]BF /
O
Ph (O)P
2
2
ligand
4
P(O)Ph
P(O)Ph
O
2
(CH Cl) , rt
2
16 h
2
O
2
P(O)Ph
2
O
Me
Me
4b
5b (d.r. = 1:1)
c
b
yield (%)
entry
ligand
conv (%)
1
2
3
4
BIPHEP
Segphos
BINAP
55
32
22
0
76
71
100
15
H -BINAP
8
a
[Rh(cod)2]BF4 (0.0060 mmol), ligand (0.0060 mmol), 4b (0.030 mmol), and (CH2Cl)2 (2.0 mL) were
used. b Determined by 1H NMR. c Isolated yield.
The ORTEP diagrams of [Rh(cod)((+)-6b)]SbF6 are shown in Figure 2.10 In the front view, four phenyl
groups on the phosphorus atoms are distorted C2-symmetrically due to steric repulsions between the
methyl and phenyl groups. However, in the side view, four phenyl groups on the phosphorus atoms are
not distorted presumably due to the high rigidity of the ligand backbone.
Figure 2. ORTEP diagram of [Rh(cod)((+)-6b)]SbF6 with ellipsoids at 20% probability (left: front view,
right: side view): cod and SbF6 anion are omitted for clarity.
In order to evaluate a potential applicability of the chiral diphosphine ligand (R,R)-6b (98% ee), its
application to the rhodium-catalyzed asymmetric hydrogenation of alkenes was examined briefly (Table

144
HETEROCYCLES, Vol. 86, No. 1, 2012
3). For comparison purpose, the same reactions were conducted using (S)-BINAP and (S,S)-Chiraphos,
possessing the distorted backbone, as a ligand under the same reaction conditions. In the hydrogenation of
sterically less demanding !-substituted acrylates 13a,b, the ee values using (R,R)-6b (entries 1 and 4)
were significantly lower than those using (S)-BINAP7d and (S,S)-Chiraphos (entries 2, 3, 5, and 6). On the
contrary, in the hydrogenation of sterically demanding !,"-disubstituted acrylamide 13c, the conversion
and/or ee value using (R,R)-6b (entry 7) were markedly higher than those using (S)-BINAP and
(S,S)-Chiraphos (entries 8 and 9). Although there remains room for improvement in the enantioselectivity,
these results would demonstrate the potential utility of the new C2-symmetric chiral dppbz-type ligand for
asymmetric catalyses.
Table 3. Rhodium-Catalyzed Asymmetric Hydrogenation of Alkenes 13a–c Using (R,R)-6b, (S)-BINAP,
and (S,S)-Chiraphosa
5 mol % [Rh(cod) ]BF /
2
4
O
O
ligand
3
3
R
R
(CH Cl) , H (1 atm)
2
2
rt,16 h
2
1
2
1
2
R
R
R
R
13
14
Me
O
Me
Me
PPh
PPh
PPh
PPh
2
2
PPh
PPh
2
2
2
2
O
Me
(R,R)-6b
(S,S)-Chiraphos
(S)-BINAP
1
2
3
b
14 / ee (%)
(R)-14a / 7
entry
13
R
R
R
ligand
conv (%)
c
1
2
3
4
5
6
7
8
9
13a
13a
13a
13b
13b
13b
13c
13c
13c
H
NHAc
NHAc
NHAc
OMe
(R,R)-6b
(S)-BINAP
100
100
d
(R)-14a / 25
(R)-14a / 82
(R)-14b / 32
H
OMe
OMe
OMe
OMe
OMe
H
(S,S)-Chiraphos
100
100
100
100
100
62
c
H
CH CO Me
(R,R)-6b
2
2
d
(S)-14b / 76
(S)-14b / 82
(–)-14c / 52
(+)-14c / 29
(+)-14c / 9
H
CH CO Me
2
(S)-BINAP
2
H
CH CO Me
2
(S,S)-Chiraphos
2
c
Me
Me
Me
Me
Me
Me
NPh
NPh
NPh
(R,R)-6b
2
2
2
(S)-BINAP
(S,S)-Chiraphos
100
a [Rh(nbd)2]BF4 (0.0033 mmol), ligand (0.0033 mmol), 13a–c (0.065 mmol), and (CH2Cl)2 (1.0 mL) were
used. b Determined by 1H NMR. c 98% ee. d Data reported in reference 7d.

HETEROCYCLES, Vol. 86, No. 1, 2012
145
In conclusion, we have disclosed the design and synthesis of a C2-symmetric chiral
1,2-bis(diphenylphosphino)benzene ligand via the rhodium-catalyzed intramolecular [2+2+2]
cycloaddition. This new chiral dppbz-type ligand could be employed for the rhodium-catalyzed
asymmetric alkene hydrogenation. Future work will focus on further tuning of chiral ligand structures and
their application to asymmetric catalyses.
ACKNOWLEDGEMENTS
This work was supported partly by a Grant-in-Aid for Scientific Research (No. 20675002) from MEXT,
Japan. We thank Takasago International Corporation for the gift of chiral propargylic alcohol (R)-7, and
Umicore for generous support in supplying of a rhodium complex.
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