Enantiopure 1-phosphanorbornadiene-2-carboxaldehydes

Article abstract of DOI:10.1016/S0957-4166(00)00443-2

The reaction of phenylpropargyl aldehyde diethyl acetal with 1-phenyl-3,4-dimethylphosphole at 140°C or 1,2,5-triphenylphosphole at 170°C leads, after deprotection, to the corresponding 1-phosphanorbornadiene-2-carboxaldehydes 3 and 4 in 88 and 45% yields

Full text of DOI:10.1016/S0957-4166(00)00443-2

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 4601–4608
Enantiopure 1-phosphanorbornadiene-2-carboxaldehydes
Ste`phane Lelie`vre, Franc¸ois Mercier, Louis Ricard and Franc¸ois Mathey*
Laboratoire He´te´roe´le´ments et Coordination UMR CNRS 7653, DCPH, Ecole Polytechnique,
91128 Palaiseau Cedex, France
Received 24 October 2000; accepted 8 November 2000
Abstract
The reaction of phenylpropargyl aldehyde diethyl acetal with 1-phenyl-3,4-dimethylphosphole at 140°C
or 1,2,5-triphenylphosphole at 170°C leads, after deprotection, to the corresponding 1-phosphanorborna-
diene-2-carboxaldehydes 3 and 4 in 88 and 45% yields, respectively. The resolution of 3 and 4 was carried
out by chromatography or fractional crystallization of the acetals derived from (S,S)-1,2-diphenylethane-
1,2-diol. The absolute configurations were established by X-ray analysis of one of these acetals or of a
2-bromomethyl derivative. © 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
The ready availability of 1-phosphanorbornadienes from 2H-phospholes and alkynes,1 com-
bined with their unusual geometry which incorporates a non-racemizable phosphorus at the
bridgehead of a strained bicyclic structure has led to an extensive investigation into their
potential as ligands in homogeneous catalysis. They have proven their worth in the rhodium(I)-
catalyzed hydrogenation of alkenes,2 hydroformylation of alkenes,3 asymmetric hydrogenation
of functional alkenes,4 and asymmetric isomerization of cyclic dienes.5 The bis(phosphine)
BIPNOR4,5 is currently under development by Rhodia SA, for use in asymmetric catalysis.
Furthermore, sulfonated (NORBOS)6 and phosphonated7 water-soluble 1-phosphanorbornadi-
enes have been synthesized and NORBOS has displayed exceptional activity in the biphasic
rhodium-catalyzed hydroformylation of propene.6 Even more recently, the use of oxazoline
derivatives in palladium-catalyzed asymmetric allylation and Heck reaction has been described.8
As a further development of this family of promising catalytic ligands, the investigation of
chelating species comprising a 1-phosphanorbornadiene unit and a coordinating side arm at the
a-position of the ring appeared as particularly desirable. In practice, a convenient access to these
mixed ligands required a straightforward synthesis of 1-phosphanorbornadiene-2-carboxalde-
hydes both as racemic and enantiopure species and this is the subject of this report.
* Corresponding author.
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00443-2

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2. Results and discussion
All our experiments have been performed with phospholes 1 and 2. These phospholes
equilibrate with the corresponding 2H-species around 140 and 170°C, respectively.1 At these
temperatures, a propargyl aldehyde unit has a limited lifetime. In addition, tertiary phosphines
are known to react via their lone pairs with activated alkynes.9 It was thus necessary to protect
and deactivate the aldehyde functionality by acetal formation (Scheme 1).
Scheme 1.
Fortunately, the [4+2] cycloaddition between the 2H-phospholes and the alkyne is completely
regioselective. The protecting group is removed by acidic treatment of the crude adducts. The
final yields are satisfactory in spite of the extreme reaction conditions. In their 1H and 13C NMR
3
spectra, the formyl groups appear as follows: 3 (CDCl3): lH 9.7, JHP=11.6 Hz; lC 191.0,
3
2
2JCP=16.7 Hz; 4 (CDCl3): lH 9.7, JHP=9.2 Hz; lC 190.3, JCP=16.5 Hz; The 31P couplings
confirm the a-substitution. The X-ray crystal structure analysis of 3 (Fig. 1) shows that the
carbonyl group is coplanar with the C5ꢀC6 double bond and lies in the same direction as the
P-lone pair. Otherwise, all the geometrical parameters of 3 are very close to those already
reported for the non-functional species (CHO replaced by Ph).1 The resolution of aldehydes 3
and 4 has been successfully carried out through acetalisation with (S,S)-1,2-diphenylethane-1,2-
diol.10 The resulting diastereomeric acetals 5a,b and 6a,b are easily separated, either by
chromatography on silica gel (for 5a and 5b) or by fractional crystallization (for 6a and 6b). The
deprotection is achieved as previously by acidic workup on silica gel in the presence of acetone
as solvent (Scheme 2).

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4603
,
Figure 1. Crystal structure of 3. Significant bond distances (A) and angles (°): PꢁC(1) 1.859(3), PꢁC(4) 1.843(3),
PꢁC(6) 1.852(3), C(1)ꢁC(2) 1.339(3), C(2)ꢁC(3) 1.542(4), C(3)ꢁC(4) 1.548(4), C(3)ꢁC(5) 1.555(4), C(5)ꢁC(6) 1.352(3),
C(6)ꢁC(7) 1.446(4), C(7)ꢁO 1.216(3); C(1)ꢁPꢁC(4) 86.6(1), C(1)ꢁPꢁC(6) 94.0(1), C(4)ꢁPꢁC(6) 85.9(1), PꢁC(4)ꢁC(3)
98.7(2), PꢁC(6)ꢁC(7) 122.3(2), C(6)ꢁC(7)ꢁO 124.4(2)
Scheme 2.
Two methods have been used for establishing the absolute configuration of these enantiomers.
The most straightforward involves the X-ray crystal structure analysis of 6a [Flack enantio-
pole=0.10 (18)] (Fig. 2). This shows that 4a has the (R)-configuration at phosphorus. Alterna-
tively, 3a was first reduced by LiAlH4 at low temperature, in order to avoid a reduction of the
conjugated CꢀC double bond, and the resulting alcohol 7a was reacted with bromine to give the
1-phosphanorbornadiene oxide 8a (Scheme 3).
The initial bromination takes place at the phosphorus of 7a; the resulting bromophosphonium
bromide shows a 31P resonance at +54 ppm. Then, the [P-Br]+Br- unit brominates the alcohol
function and is transformed into a PꢀO group. The absolute configuration of the final
2-bromomethyl-1-phosphanorbornadiene-1-oxide 8a is shown in Fig. 3. Hence 3a has the
(R)-configuration at phosphorus.

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Figure 2. Absolute configuration of 6a
Scheme 3.
The ready availability of the enantiopure 1-phosphanorbornadiene-2-carboxaldehydes 3a, 4a,
3b and 4b opens a pathway to a wide range of mixed chelating ligands containing an enantiomeri-
cally pure 1-phosphanorbornadiene unit. This possibility is currently being investigated.

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4605
Figure 3. Absolute configuration of 8a
3. Experimental
3.1. General
All reactions were carried out under argon by using standard techniques. Solvents were dried
under nitrogen by standard procedures, distilled before use and stored under argon. The
elemental analyses were performed by the Service microanalyse de Gif/Yvette, France. NMR
1
spectra were recorded on a Bruker AC 200 SY spectrometer operating at 200.13 MHz for H,
50.32 MHz for 13C and 81.01 MHz for 31P. Chemical shifts are expressed in parts per million
(ppm) downfield from external tetramethylsilane (1H and 13C) and 85% aqueous H3PO4 (31P).
3.2. Synthesis of 2,5-diphenyl-3,4-dimethyl-6-formyl-1-phosphanorborna-2,5-diene 3
A mixture of 9.4 g (50 mmol) of 3,4-dimethyl-1-phenylphosphole 111 and 10.2 g (50 mmol) of
phenylpropargyl aldehyde diethyl acetal was heated at 140°C for 4 h. After cooling to room
temperature, 40 ml of CH2Cl2, 12 g of silica gel and 4 ml of HCl (11N) were added to the brown
oil. The mixture was stirred for 15 min at room temperature. It was then filtered and the solvent
was evaporated in vacuo. The oily product was chromatographed on silica gel with CH2Cl2 as
the eluent. Crystals suitable for a crystal stucture determination were obtained from hexane.
Mp=112°C; 14.8 g; 87% yield. Anal. calcd for C21H19OP: C, 79.25; H, 6.01; P, 9.70. Found: C,
1
78.62; H, 6.14; P, 9.62. Mass spectrum: M+ (318, 10%); M+−C9H6O (188, 100%). H NMR
(CDCl3): l (ppm)=1.4 (s, 3H), 2.1 (s, 3H), 2.2 (m, 2H), 6.8–7.3 (m, 10H), 9.7 (d, J=9.2 Hz,
1H).13C NMR (CDCl3): l (ppm)=16.5, 20.4, 65.1, 73.6 (d, J=5.9 Hz), 191.0 (d, J=16.7 Hz).31P
(CDCl3) l (ppm)=−31.2.
3.3. Synthesis of 2,5,7,7’-tetraphenyl-6-formyl-1-phosphanorborna-2,5-diene 4
A mixture of 6.2 g (20 mmol) of 1,2,5-triphenylphosphole 2 and 4.1 g (20 mmol) of
phenylpropargyl aldehyde diethyl acetal was heated at 170°C for 8 days. After cooling to room
temperature, 20 ml of CH2Cl2, 6 g of silica gel and 2 ml of HCl (11N) were added to the brown

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oil. The mixture was stirred for 15 min at room temperature then filtered and evaporated to
dryness in vacuo. The crude product was obtained as a white powder which was further purified
by chromatography on silica with CH2Cl2 as eluent. Crystals were obtained from hexane–tolu-
ene. Mp=234°C; 5.0 g; 45% yield. Mass spectrum m/z: M+ (442, 40%); M+−C18H14OP (165,
1
100%). H NMR (CDCl3): l (ppm)=5.4 (m, 1H), 7.6 (m, 21H), 9.7 (d, J=9.2 Hz, 1H). 13C
NMR (CDCl3): l (ppm)=71.6 (d, J=5.6 Hz), 88.2, 190.3 (d, J=16.5 Hz).31P (CDCl3) l
(ppm)=−0.3.
3.4. Synthesis and separation of the two diastereoisomers 5a and 5b
To a solution of 6.4 g (20 mmol) of 3 in 50 ml of toluene were added 4.3 g (20 mmol) of
(S,S)-1,2-diphenyl-1,2-ethanediol and 0.04 g of p-toluenesulfonic acid. The solution was then
refluxed for 3 h. Complete formation of the two diastereoisomers can be monitored by 31P
NMR. The solvent was removed in vacuo and the oily product was chromatographed through
silica gel (500 g) with hexane–CH2Cl2 (80:20) as solvent. 5a was eluted first and crystallized from
hexane. Mp=181°C; 4.5 g; 87% yield. [h]2D5=−69.3 (c=0.4 CHCl3). 5b was then eluted and
crystallized from pentane. Mp=116°C; 4.2 g; 80% yield. [h]2D5=−19 (c=1.0 CHCl3).
1
Compound 5a: H NMR (CDCl3): l (ppm)=1.4 (s, 3H), 2.0 (s, 3H), 2.3 (m, 2H), 4.7 (d,
J=8.0 Hz, 1H), 5.1 (d, J=8.0 Hz, 1H), 5.9 (d, J=8.7 Hz, 1H), 6.9–7.5 (m, 20H). 13C NMR
(CDCl3): l (ppm)=16.4, 21.0, 66.9, 71.8 (d, J=6.0 Hz), 86.1 (d, J=2.8 Hz), 87.6, 103.0 (d,
J=15.3 Hz).31P (CDCl3) l (ppm)=−22.9.
1
Compound 5b: H NMR (CDCl3): l (ppm)=1.5 (s, 3H), 2.2 (s, 3H), 2.3 (m, 2H), 5.0 (d,
J=8.0 Hz, 1H), 5.2 (d, J=8.0 Hz, 1H), 6.0 (d, J=9.0 Hz, 1H), 6.9–7.5 (m, 20H). 13C NMR
(CDCl3): l (ppm)=16.2, 20.9, 66.4, 71.8 (d, J=6.0 Hz), 83.8, 87.6, 102.6 (d, J=15.4 Hz).31P
(CDCl3) l (ppm)=−22.1.
3.5. Synthesis and separation of the two diastereoisomers 6a and 6b
To a solution of 4.4 g (10 mmol) of 4 in 50 ml of toluene were added 2.15 g (10 mmol) of
(S,S)-1,2-diphenylethanediol, 0.02 g of p-toluenesulfonic acid and the solution was heated at
50°C for 5 h. The solvent was removed in vacuo. Crystals of diastereoisomer 6a suitable for a
crystal stucture determination were obtained from hexane–toluene; 3.0 g; 45% yield. [h]2D5=
−119.6 (c=2.7 CDCl3). The diastereoisomer 6b was crystallized in hexane–CH2Cl2; 2.6 g; 40%
yield. [h]2D5=+241 (c=2.5 CDCl3).
Compound 6a: Anal. calcd for C45H35O2P: C, 84.61; H, 5.52; P, 4.85. Found: C, 84.41; H,
5.55; P, 5.1.1H NMR (CDCl3): l (ppm)=4.6 (d, J=8.1 Hz, 1H), 5.0 (d, J=8.1 Hz, 1H), 5.2 (m,
1H), 6.0 (d, J=9.7 Hz, 1H), 7–7.6 (m, 21H). 13C NMR (CDCl3): l (ppm)=70.1 (d, J=5.3 Hz),
86.0, 87.3, 87.8, 102.1 (d, J=15.6 Hz). 31P (CDCl3) l (ppm)=7.8
1
Compound 6b: H NMR (CDCl3): l (ppm)=4.6 (d, J=8.0 Hz, 1H), 5.1 (d, J=8.0 Hz, 1H),
5.2 (m, 1H), 6.0 (d, J=9.8 Hz, 1H), 7–7.6 (m, 21H). 13C NMR (CDCl3): l (ppm)=71.0 (d,
J=5.7 Hz), 86.8 (d, J=2.4 Hz), 88.1, 88.6, 102.7 (d, J=15.3 Hz). 31P (CDCl3) l (ppm)=6.7
3.6. Synthesis of the enantiomerically pure aldehydes 3a, 3b, 4a and 4b
A mixture of 6.0 g of silica gel, 20 ml of acetone and 2 ml of HCl (11N) was stirred at room
temperature for 10 min. Then a solution of 2.6 g (5 mmol) of 5a or 5b or (4 mmol) of 6a or 6b

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in 10 ml of acetone was added dropwise and the mixture was stirred for 2 h. Neutralisation was
accomplished with NaOH (30%), the solution was filtered and the aldehyde was extracted with
CH2Cl2. The organic phase was dried over magnesium sulfate, filtered and the solvent was
removed in vacuo. After crystallization, a pure aldehyde was obtained.
3a [h]2D5=−133 (c=0.55, CDCl3)
3b [h]2D5=+133 (c=0.5, CDCl3)
4a [h]2D5=+90 (c=0.4, CDCl3)
4b [h]2D5=−90 (c=0.4, CDCl3)
3.7. Reduction of 2,5-diphenyl-3,4-dimethyl-6-formyl-1-phosphanorborna-2,5-diene 3a
To a solution of 1.27 g (4 mmol) of phosphanorbornadiene aldehyde 3a in 10 ml of THF were
added at −20°C 228 mg (6 mmol) of lithium aluminium hydride in one portion. After stirring
for 10 min, the reaction mixture was quenched with a small piece of ice. The product was
isolated via classical extractive workup which afforded 1.22 g of 7a (95% yield) as a colourless
1
oil. Mass spectrum m/z: M+, (320, 10%); M+−C9H8O (188, 100%). H NMR (CDCl3): l
(ppm)=1.35 (s, 3H), 1.7 (s, 1H), 2.0 (m, 2H), 2.1 (s, 3H), 4.3 (m, 2H), 6.9–7.5 (m, 10H). 13C
NMR (CDCl3): l (ppm)=16.4, 21.4, 62.0 (d, J=19.3 Hz), 66.9, 71.6 (d, J=5.8 Hz). 31P (CDCl3)
l (ppm)=−19.5.
3.8. Synthesis of 2,5-diphenyl-3,4-dimethyl-6-bromomethyl-1-phosphanorborna-2,5-diene 1-oxide
8a
A solution of 0.16 ml of Br2 (3.1 mmol) in 10 ml of CH2Cl2 was added dropwise slowly to a
solution of 1.0 g of 7a (3.1 mmol) in 100 ml of CH2Cl2. The mixture was stirred for 30 min at
room temperature. Bromination can be monitored by 31P NMR. At the end of the reaction, the
excess of Br2 was destroyed with a solution of sodium thiosulfate. The bromophosphine oxide
was extracted with CH2Cl2, dried with magnesium sulfate and the solvent evaporated in vacuo.
Crystals of 8a suitable for a crystal stucture determination were obtained from toluene at −20°C;
830 mg; 67% yield. [h]2D5=−125 (c=0.95 AcOEt). Mass spectrum m/z: M+ (400, 18%); M+−
1
C9H7Br (204, 100%). H NMR (CDCl3): l (ppm)=1.4 (s, 3H), 2.1 (d, J=2.8 Hz, 3H), 2.6 (m,
2H), 4.1 (dd, J=22.3 Hz and J=12.5 Hz, 1H), 4.4 (pt, J=8.8 Hz, 1H), 6.9–7.5 (m, 10H). 13C
NMR (CDCl3): l (ppm)=15.7 (d, J=14.2 Hz), 19.1 (d, J=18.2 Hz), 25.5 (d, J=8.2 Hz), 49.7
(d, J=26.0 Hz), 68.0 (d, J=68.0 Hz). 31P (CDCl3) l (ppm)=45.5.
Acknowledgements
This work has been funded by Rhodia SA. One of us (S.L.) thanks Rhodia SA for financial
support.
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