A new tetratertiary phosphine ligand and its use in Pd-catalyzed allylic substitution

Article abstract of DOI:10.1021/jo001146j

A new tetraphosphine, the cis-cis-cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane (Tedicyp) 1 has been synthesized, characterized, and used in Pd-catalyzed allylic substitutions. The Tedicyp was easily prepared in seven steps from the commercially available himic anhydride. The structure of the complex Tedicyp-borane was determined by X-ray analysis. The tetraphosphine in combination with [Pd(η³-C₃H₅)Cl]₂ affords a very efficient catalyst for allylic substitution of several allylic acetates. Under mild conditions, very high turnover numbers and turnover frequencies have been obtained.

Full text of DOI:10.1021/jo001146j

J . Org. Chem. 2001, 66, 1633-1637
1633
A New Tetr a ter tia r y P h osp h in e Liga n d a n d Its Use in
P d -Ca ta lyzed Allylic Su bstitu tion
Doroth e´ e Laurenti, Marie Feuerstein, G e´ rard P e` pe, Henri Doucet, and Maurice Santelli*,†
‡
Laboratoire de Synth e` se Organique, UMR-CNRS 6009, Facult e´ de St-J e´ r oˆ me,
1
3397 Marseille Cedex 20, France
Received J uly 28, 2000
m.santelli@lso.u-3mrs.fr
A new tetraphosphine, the cis-cis-cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane (Te-
dicyp) 1 has been synthesized, characterized, and used in Pd-catalyzed allylic substitutions. The
Tedicyp was easily prepared in seven steps from the commercially available himic anhydride. The
structure of the complex Tedicyp-borane was determined by X-ray analysis. The tetraphosphine
3
in combination with [Pd(η -C
3
H
5
)Cl]
2
affords a very efficient catalyst for allylic substitution of several
allylic acetates. Under mild conditions, very high turnover numbers and turnover frequencies have
been obtained.
In tr od u ction
which four diphenylphosphino groups are stereospecifi-
cally bound to the same face of the cyclopentane ring.
P r ep a r a tion a n d Ch a r a cter iza tion of Ted icyp 1.
Tedicyp was prepared in seven steps from the com-
mercially available starting material himic anhydride 2
The transition-metal-mediated allylic substitution re-
action is known as an efficient synthetic tool for the
elaboration of carbon-carbon and carbon-heteroatom
bonds.1 In this area, the palladium-catalyzed allylic
as illustrated in Scheme 1. Reduction of the anhydride 2
2
alkylation constitutes the most useful reaction. The
6
with LiAlH
4
gave diol 3 in 74% yield. Treatment with
increasing importance of such transition metal-catalyzed
reactions has run parallel to the development of new
ligands, and diphosphine ligands have been widely used
for this purpose. Recently, extensive efforts have been
devoted to the design of new polypodal ligands.3 In
particular, transition-metal complexes of tripodal phos-
phines have begun to attract interest because of their
potential as catalysts in several homogeneous reactions.4
In contrast, tetraphosphine ligands have been poorly
exploited in homogeneous catalysis.5
methoxypropene afforded, in quantitative yield, the
tricyclic compound 4 which was submitted to ozonolysis
7
4
followed by reduction with NaBH to give 5 in 86% yield.
Exposure of 5 to water in tetrahydrofuran in the presence
8
of a strong acidic cation-exchange resin led to tetraol 6.
Treatment of 6 with an excess of tosyl chloride in pyridine
afforded the expected tetratosylate 7 in 60-65% yield
along with bicyclic ether 8 (20-25%).9 The desired
tetraphosphane Tedicyp 1 was prepared in excellent yield
10
employing established procedures. As 1 is air-sensitive
We wish to report here the preparation and the use in
palladium-catalyzed allylic substitution of the new tet-
rapodal phosphine ligand, cis-cis-cis-1,2,3,4-tetrakis-
and requires protection for handling and storage, borane
was added before workup. The Tedicyp-borane complex
9
was obtained in 82% yield. Deboronation was carried
(diphenylphosphinomethyl)cyclopentane or Tedicyp 1, in
11
out by treatment with diethylamine. When borane was
not added before workup, Tedicyp was partially oxidized
and, finally, the tetrakis phosphonoyl derivative 10 was
isolated in 66% yield.
†
To whom correspondence should be addressed.
Address X-ray correspondence to this author. E-mail: pepe@
‡
luminy.univ-mrs.fr.
1) (a) For reviews on allylic substitution reactions: (a) Hayashi, T.
In Catalytic Asymmetric Synthesis, Ojima, I., Eds., VCH: New York,
993; p 325. (b) Pfaltz, A.; Lautens, M. Comprehensive Asymmetric
The stereochemical identity of 1 was verified by an
X-ray crystal structure determination of Tedicyp-borane
complex 9. The salient finding is the severe deviation
(
1
Catalysis II; J acobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer-
Verlag: Berlin-Heidelberg, 1999; p 833. (c) Consiglio, G.; Waymouth,
R. M. Chem. Rev. 1989, 89, 257-276.
s
from the idealized planar symmetry (C ). The boranato-
(
2) (a) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1989, 28, 1173-
(5) For tetrapodal ligands, see: (a) U. Nagel, U.; Kinzel, E.; Andrade,
J .; Prescher, G. Chem. Ber. 1986, 119, 3326-3343. (b) Khan, M. T. T.;
Paul, P.; Venkatasubramanian, K.; Purohit, S. J . Chem. Soc., Dalton
Trans. 1991, 3405-3412. (c) Schmidbaur, H.; St u¨ tzer, A.; Bissinger,
P. Z. Naturforsch. 1992, 47b, 640-644. (d) Mason, M. R.; Duff, C. M.;
Miller, L. L.; J acobson, R. A.; Verkade, J . G. Inorg. Chem. 1992, 31,
2746-2755. (e) Steewinkel, P.; Kolmshot, S.; Gossage, R. A.; Dani, P.;
Veldman, N.; Spek, A. L.; van Koten, G. Eur. J . Inorg. Chem. 1998,
477-483. (f) Bianchini, C.; Lee, H. M., Meli, A.; Oberhauser, W.; Vizza,
F.; Br u¨ ggeller, P.; Haid, R.; Langes, C. J . Chem. Soc., Chem. Commun.
2000, 777-778.
(6) Culberson, C. F.; Seward, J . H.; Wilder, P., J r. J . Am. Chem.
Soc. 1960, 82, 2541-2547.
(7) Mori, K.; Murata, N. Liebigs Ann. 1995, 2089-2092.
(8) B o¨ hme, H.; Seitz, G. Chem. Ber. 1968, 101, 1689-1693.
(9) Alder, K.; Roth, W. Chem. Ber. 1955, 88, 407.
1
192. (b) Tsuji, Palladium Reagents and Catalysis, Innovations in
Organic Synthesis; Wiley: New York, 1995. (c) Heumann, A.; R e´ glier,
M. Tetrahedron 1995, 51, 975-1015. (d) Trost, B. M.; Van Vranken,
D. L. Chem. Rev. 1996, 96, 395-422. (e) Trost, B. M. Acc. Chem. Res.
1
996, 29, 355-364. (f) Tonks, L.; Williams, J . M. J . J . Chem. Soc.,
Perkin Trans. 1 1998, 3637-3652. (g) J ohannsen, M.; J ørgensen, K.
A. Chem. Rev. 1998, 98, 1689-1708. (h) Hayashi, T. J . Organomet.
Chem. 1999, 576, 195-202. (i) Helmchen, G. J . Organomet. Chem.
1
999, 576, 203-214.
(
3) For a review on the polypodal diphenylphosphine ligands, see:
Laurenti, D.; Santelli, M. Org. Prep. Proc. Int. 1999, 31, 245-294.
4) (a) Ghilardi, C. A.; Midollini, S.; Sacconi, L. Inorg. Chem. 1975,
4, 1790-1795. (b) Cecconi, F.; Ghilardi, C. A.; Midollini, S.; Moneti,
S.; Orlandini, A.; Scapacci, G. J . Chem. Soc., Dalton Trans. 1989, 211-
16. (c) Bianchini C.; Meli, A.; Peruzzini, M.; Vizza, F.; Frediani, P.;
(
1
2
Ramirez, J . A. Organometallics 1990, 9, 226-240. (d) Gr e´ vin, J .; Kalck,
(10) B o¨ rner, A.; Ward, J .; Ruth, W.; Holz, J .; Kless, A.; Heller, D.;
Kagan, H. B. Tetrahedron 1994, 50, 10409-10430.
(11) Ohff, M.; Holz, J .; Quirmbach, M.; B o¨ rner, A. Synthesis 1998,
1391-1415.
P.; Dran, J . C.; Vaissermann, J .; Bianchini, C. Inorg. Chem. 1993, 32,
4
965-4967. (e) Seitz, T.; Asam, A.; Huttner, G.; Walter, O.; Zsolnai,
L. Z. Naturforsch. 1995, 50b, 1287-1306.
1
0.1021/jo001146j CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/31/2001

1
634 J . Org. Chem., Vol. 66, No. 5, 2001
Laurenti et al.
Sch em e 1a
Ch a r t 1
3 5 2
equiv of Tedicyp to 1 equiv of [PdCl(C H )] gave an
identical 31P NMR spectrum. Addition of 2 equiv of
3 5 2
Tedicyp to 0.5 equiv of [PdCl(C H )] led to a more
complicated spectrum. Mainly four signals of free phos-
phines at -16.9, -18.2, -19.3, and -20.9 ppm and some
broad peaks between 40 and 10 ppm were observed in
3
1
P NMR. In the first case, addition of 1 equiv of Tedicyp
to 0.5 equiv of Pd complex, the broad signals produced
at 19 and 25 ppm suggest that this complex is involved
in a succession of equilibriums due to a fast coordina-
tion-dissociation process of the four phosphines of the
ligand. The absence of peaks of free phosphines probably
comes from the equilibrium rate which seems to be of
the order of the NMR time scale. Similar results have
a
(
i)LiAlH4, THF, 65 °C, 3 h;(ii)MeC(OMe)CH2, cat. p-TsOH‚H2O,
rt, 2 h; (iii) O3-O2, CH2Cl2, -60 °C then NaBH4, EtOH, rt,
overnight; (iv) Amberlite IR-120(H), H2O-THF, 65 °C, 2 h; (v)
p-TsCl (1.5 equiv), pyridine, -20 °C, 5 h; (vi) ClPPh2-Li, THF,
rt, 5 h then BH3‚THF, THF, 0 °C, 1.5 h; (vii) Et2NH, 55-60 °C,
already been described, for example Pd(PPh
3 3
) is largely
dissociated, and the equilibrium rate is of the order of
1
0 h; (viii) ClPPh2 - Li, THF, rt, 5 h, then H2O2.
1
5
the NMR time scale even at low temperature.
Allylic Su bstitu tion s. Our aim was to obtain com-
plexes capable of very high turnover numbers in cataly-
sis. To evaluate the catalytic potential of Tedicyp, we
decided to investigate the palladium-catalyzed allylic
substitution of allyl acetate 11 with sodium dimethyl
malonate as a test reaction.
diphenylphosphanylmethyl groups were alternatively in
pseudoequatorial and pseudoaxial positions, displaying
a gear effect.12
Com p lexes Str u ctu r e. The chelate ring size has an
important effect on transition-metal-catalyzed reactions
1
3
particularly in palladium chemistry. We can expect a
great reactivity of the Pd-Tedicyp complex resulting
from the possibility for the metal atom to exchange ligand
in the way to increase “chelate effect”. According to the
tetrahedral structure of Pd(0) complexes,14 a tetradentate
ligand such as Tedicyp may exhibit six possible coordina-
tion modes, four built with two diphenylphosphino groups
Our first objective was to compare the catalysts
3
prepared with [Pd(η -C
3
H
5
)Cl]
2
associated with a mono-
3
phosphine (PPh ) or diphosphines such as 1,2-bis(diphe-
nylphosphino)ethane (dppe) or 1,4-bis(diphenylphosphino)-
butane (dppb) and our tetraphosphine 1. The addition of
sodium dimethyl malonate to allyl acetate in the presence
of 0.1% catalyst led to 93% conversion when PPh was
3
used as ligand and complete conversion with dppe, dppb,
(Chart 1, A-D) and two with three diphenylphosphino
groups (Chart 2, E, F ). Coordination modes of Tedicyp
to Pd(II) should be simpler, and only two phosphine
functions should be coordinated simultaneously. We tried
to get some information on the structure of this pal-
ladium-Tedicyp complex by 3 P NMR analysis. Addition
of 1 equiv of Tedicyp to 0.5 equiv of the dimer [PdCl-
or tedicyp (Table 1, entries 2-5). In the presence of 0.01%
catalyst, only 1% conversion was observed with PPh and
3
4
6
1
9-50% with dppe and dppb as ligands (Table 1, entries
-8). With Tedicyp, the conversion was complete (Table
1
, entry 9). A similar tendency was observed in the
presence of 0.001% catalyst, 16% conversion with dppe
and complete conversion with Tedicyp were obtained
3
1
(
C
3
H
5
)]
possesses two broad signals at 19 and 25 ppm (vs H
PO ). The characteristic signals of the free phosphine at
16.3 and -17.7 ppm were not observed. Addition of 1
2
gave a clean spectrum in P NMR which
3
-
(Table 1, entries 10 and 11). Finally, we tried to reach
4
the limits of Tedicyp-palladium complex for this reaction
and we obtained a conversion of 98% after 14 days in
the presence of 0.00001% catalyst (ratio substrate/
catalyst of 10 000 000) when the reaction was conducted
at 50 °C (Table 1, entry 14).
-
(12) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds;
J . Wiley & Sons: New York, 1994; pp 1160-1163.
(
13) Portnoy, M.; Milstein, D. Organometalics 1993, 12, 1655-1664.
(14) For a X-ray crystal structure determination of tetrakis(triph-
These results prompted us to investigate the allylation
of dimethyl malonate with substituted allyl acetates.
enylphosphine)palladium (tetrahedral coordination of the metal atom),
see: Andrianov, V. G.; Akhrem, I. S.; Chistovalova, N. M.; Truchkov,
Y. T. J . Struct. Chem. 1976, 17, 111-116. The structural analysis of
tris(triphenylphosphine)palladium presents a strongly distorted trigo-
nal pyramid, see: Sergienko, V. S.; Porai-Koshits, M. A. J . Struct.
Chem. 1987, 28, 548-552.
(15) (a) Amatore, C.; J utand, A.; Khalil, F.; M′Barki, M.; Mottier,
L. Organometallics 1993, 12, 3168-3178. (b) Amatore, C.; Broeker,
G.; J utand, A.; Khalil, F. J . Am. Chem. Soc. 1997, 119, 5176-5185.

Pd-Catalyzed Allylic Substitution
J . Org. Chem., Vol. 66, No. 5, 2001 1635
Ta ble 1. P d -Ca ta lyzed Allyl Aceta te Rea ction s w ith Sod iu m Dim eth yl Ma lon a tea
ratio
ligand/Pd
ratio
substrate/catalyst
reaction
time (h)
conversion
(%)
ratio
13/14
turnover
turnover
number
b
frequency (h-1)d
entry
ligand
1
2
3
4
5
6
7
8
9
0
1
2
3
4
-
-
2
2
2
1
4
2
2
1
2
1
1
1
1
1 000
1 000
1 000
1 000
1 000
10 000
10 000
10 000
10 000
3
3
3
3
3
3
3
3
3
24
24
19
60
340
0
93
100
100
100
1
50
49
100
16
99
-
0
310
333
333
333
0
PPh3
dppe
dppb
1
PPh3
dppe
dppb
1
dppe
1
1
1
1
4:1
930
1000
1000
1000
100
3.5:1
2.6:1
4.9:1
1:0
7.3:1
4.9:1
4.9:1
7.3:1
4.6:1
7.7:1
11.5:1
4.9:1
33
1666
1633
3333
830
5 000
4 900
10 000
16 000
99 000
740 000
5 600 000
9 800 000
1
1
1
1
1
100 000
100 000
1 000 000
10 000 000
10 000 000
12 000
39 000e
175 000e
190 000e
74
56
98
c
a
Allyl acetate 11, 1 equiv; dimethyl malonate 12, 2 equiv; sodium hydride, 2 equiv; THF; rt. b [ClPd(η -C3H5)]2. c 50 °C. d TOF calculated
3
e
between initial time and 3 h. Calculated after 19 h.
in very good yields.16 Addition to deuterated chiral
carveyl acetate 21 led to an equimolecular mixture of the
two isomers 22 and 23 (Table 2, entry 6).17
Sch em e 2
Addition to the anions of pentane-2,4-dione and ethyl
acetoacetate led mainly to the dialkylated products 26
and 29 in good yield in the presence of 0.1% catalyst
(Table 3, entries 1 and 2). The reaction of 2-carbomethox-
ycyclohexanone anion with allyl acetate occurred with
high turnover numbers (Table 3, entry 3).18 Finally the
use of Tedicyp-Pd complex provides a convenient access
to tertiary amines. Addition of dipropylamine 32 to allyl
1
9
acetate, led to the addition product 33 in good yield.
With a ratio substrate/catalyst of 300000 the conversion
was 84% after 90 h, and a turnover number of 680000
can be obtained with a ratio substrate/catalyst of 1000000
(Table 3, entries 5 and 6).
In conclusion, use of the complex Tedicyp-Pd obtained
3
by addition of [Pd(η -C
3
H
5
)Cl]
2
to Tedicyp 1 provides a
convenient catalyst for the allylic substitution reaction.
This catalyst is much more efficient than the complex
formed with triphenylphosphine ligand. This efficiency
probably comes from the presence of the four diphe-
nylphosphinoalkyl groups stereospecifically bound to the
same face of the cyclopentane ring which probably
increases the coordination of the ligand to the metal and
prevent precipitation of the catalyst. Such catalyst gives
-1
rates of ca. 6000 kg‚h of dimethyl allylmalonate 13 per
-
1
mol of palladium under mild conditions or 56 kg‚h of
3 per gram of palladium (in one batch, one mol of
1
catalyst affords the production of 1 685 tons of 13!). These
results represent an inexpensive, efficient, and environ-
mentally friendly synthesis. Further applications of the
ligand Tedicyp will be reported in due course.
When we used cinnamyl acetate 15 in the presence of
0
.1% catalyst (Table 2, entry 1), complete conversion was
observed, and a turnover number of 3400 was obtained
with 0.01 mol % catalyst (Table 2, entry 3). We noted a
good regioselectivity for the alkylation of cinnamyl
acetate in favor of the linear isomer. Lower turnover
numbers were observed in the course of the alkylation
of hindered E-3-acetoxy-1-phenyl-1-pentene 18 (Table 2,
entries 4 and 5). The major isomer 19 obtained for this
reaction corresponds to the addition to the carbon in
position 3; only 10% of the regioisomer 20 are observed.
Hayashi had reported that the alkylation of this sub-
strate by sodium dimethyl malonate in similar reaction
conditions and in the presence of tetrakis(triphenylphos-
phine)palladium(0) occurred in low yield (4%). In con-
trast, the use of the palladium-dppe system proceeded
Exp er im en ta l Section
Gen er a l. All reactions were run under argon in oven-dried
1
13
glassware. H (400 or 200 MHz) and C NMR (100 or 50 MHz)
spectra were recorded in CDCl solutions. Chemical shift (δ)
3
are reported in ppm relative to TMS. Flash chromatography
was performed on silica gel (230-400 mesh) and TLC on silica
gel.
(
16) Hayashi, T.; Yamamoto, A.; Hagihara, T. J . Org. Chem. 1986,
5
1
1
1, 723-727.
(17) Fiaud, J . C.; Malleron, J . L. Tetrahedron Lett. 1981, 22, 1399-
402.
(
18) Trost, B. M.; Radinov, R.; Grenzer, E. M. J . Am. Chem. Soc.
997, 119, 7879-7880.
(19) Trost, B. M.; Keinan, E. J . Org. Chem. 1979, 44, 3451-3457.

1
636 J . Org. Chem., Vol. 66, No. 5, 2001
Laurenti et al.
turnover number
Ta ble 2. P d -Ted icyp -Ca ta lyzed Allyla tion Rea ction s of Sod iu m Dim eth yl Ma lon a teb
a
allylic
ratio
reaction time (h) and conversion
turnover frequency
-
1 d
entry derivative substrate/catalyst
reaction temp. (°C)
(%)
ratio of product
(h
)
1
2
3
4
5
6
15
15
15
18
18
21
1 000
1 000
10 000
100
90, 25
15, 25
15, 25
20, 40
90, 55
24, 25
100
100
34
65
100
58
16:17 ) 9:1
16:17 ) 9:1
16:17 ) 9:1
19:20 ) 4.9:1
19:20 ) 9:1
22:23 ) 1:1
53
67
1 000
1 000
3 400
65
100
58
c
227
3.4
100
100
4.1e
2.4e
a
3
b
c
[
ClPd(η -C3H5)]2:Tedicyp ) 1:2 (mol/mol). Allyl derivative, 1 equiv; dimethyl malonate, 2 equiv; sodium hydride, 2 equiv; THF. 15,
d
1
2
equiv; dimethyl malonate, 5 equiv; sodium hydride, 4.5 equiv; THF. TOF calculated between initial time and 15 h. e Calculated after
4 h.
Ta ble 3. P d -Ca ta lyzed Allyl Aceta te Rea ction s w ith Nu cleop h ilic Rea gen tsa
ratio
reaction time conversion
turnover frequency
-
1 e
entry nucleo. substrate/catalyst
(h)
(%)
ratio of product or product
(h
)
turnover number
b
50f
30
341
1100
6875
8125
1
2
3
4
5
6
24
27
30
32
32
32
1 000
1 000
10 000
20
40
48
90
90
100
100
100
99
84
68
26:25 ) 19:1
1 000
1 000
10 000
29 700
270 000
680 000
b
c
29:28 ) 24:1
31
33
33
33
d
d
d
30 000
300 000
1 000 000
136
a
3
b
c
[
ClPd(η -C3H5)]2:Tedicyp ) 1:2 (mol/mol). Allyl acetate, 1 equiv; 24 or 27, 2 equiv; sodium hydride, 2 equiv; THF; 25 °C. Allyl
acetate, 1 equiv; 30, 1.2 equiv; sodium hydride, 1 equiv; THF, 25 °C. Allyl acetate, 1 equiv; 32, 2 equiv, 25 °C. e TOF calculated between
d
initial time and 24 h. f Calculated after 24 h.
Ma ter ia l. endo,endo-Bis(hydroxymethyl)norborn-2-ene (3)
was prepared by a known procedure.
(4H, m), 1.84-1.74 (1H, m), 1.09-0.99 (1H, m); 13C NMR (50
MHz, DMSO-d ) δ 62.8 (t), 58.5 (t), 45.5 (d), 42.4 (d), 31.5 (t).
2
0
6
(
1R *,2S *,8R *,9S *)-5,5-D im e t h y l-4,6-d io x a t r ic y c lo -
(1R*,2R*,3S*,4S*)-1,2,3,4-Tet r a k is(((t olyl-4-su lfon yl)-
2
,8
21
22
[
7
(
7.2.1.0 ]d od ec-10-en e (4). To a solution of diol 3 (12 g,
7.9 mmol) in CH Cl (300 mL) were added 2-methoxypropene
14.7 mL, 156 mmol) and a catalytic amount of p-TsOH. After
stirring at room temperature for 2 h, some crystals of K CO
oxy)m eth yl)cyclop en ta n e (7). A solution of crude tetraol
2
2
6 (1.31 g, 6.9 mmol) in anhydrous pyridine (27.6 mL)(c ) 0.25
mmol/mL) was cooled to -20 °C. Tosyl chloride (7.9 g, 41.4
mmol) was added, and the mixture was stirred at -20 °C for
5 h. The mixture was poured on ice and acidified (pH ∼ 1) by
addition of diluted HCl followed by vigorous extraction with
2
3
were added, and the solution was stirred, filtered, and
concentrated in vacuo. The crude product was recrystallized
from petroleum ether yielding 4 (14.8 g, 76.3 mmol, 98%) as
CH
dried (MgSO
in Et O-CH
2 2
Cl . The combined organic layers were washed with brine,
1
white crystals: mp 45 °C; H NMR (200 MHz, CDCl
3
) δ 6.04
4
), and evaporated. The crude oil was crystallized
Cl , (1:2) to give white crystals: mp 145 °C, or
Cl )(3.38 g, 4.48 mmol,
) δ 7.72 (4H, d, J ) 8.3 Hz),
(
2H, t, J ) 1.7 Hz), 3.62 (2H, dd, J ) 13.0, 4.0 Hz), 3.31 (2H,
td, J ) 13.0, 11.1 Hz), 2.58 (4H, m), 1.42 (2H, t, J ) 1.7 Hz),
.27 (3H, s), 1.26 (3H, s); 13C NMR (50 MHz, CDCl
) δ 134.9
2
2
2
chromatographed on silica gel (CH
2
2
1
1
3
65%); H NMR (200 MHz, CDCl
3
(
(
d), 101.1 (s), 65.0 (t), 51.4 (t), 45.5 (d), 45.1 (d), 29.9 (q), 19.6
q).
7.70 (4H, d, J ) 8.3 Hz), 7.35 (4H, d, J ) 8.3 Hz), 7.34 (4H, d,
J ) 8.3 Hz), 4.05-3.85 (8H, m), 2.45 (6H, s), 2.44 (6H, s), 2.44-
1
3
(
1R*,7S*,8S*,10R*)-8,10-Bis(h yd r oxym et h yl)-4,4-d im -
2.35 (4H, m), 2.0-1.80 (1H, m), 1.05 (1H, m); C NMR (50
7
eth yl-3,5-d ioxa bicyclo[5.3.0]d eca n e (5). Ozone in oxygen
was bubbled through a solution of 4 (5.0 g, 25.8 mmol) in 300
3
MHz, CDCl ) δ 145.4 (s), 145.2 (s), 132.5 (s), 132.1 (s), 130.2
(d), 130.1 (d), 130.0 (d), 128.0 (d), 127.9 (d), 69.8 (t), 66.7 (t),
41.6 (d), 38.9 (d), 30.9 (t), 21.8 (q). Anal. Calcd for
mL of CH
MeOH/CH
remove the excess of ozone, followed by addition of a suspen-
sion of NaBH (3 g, 77.4 mmol) in EtOH (50 mL). The stirred
2
Cl
2
at -60 °C. The reaction was monitored by TLC
2
(
2
Cl
, 2/98). Then argon was purged through to
C
37
H
42
O
12
S
4
: C, 55.09; H, 5.21. Found: C, 54.79; H, 5.22.
(1R*,2R*,4S*,5S*)-2,4-Bis(((tolyl-4-su lfon yl)oxy)m eth yl)-
7-oxa bicyclo[3.3.0]octa n e (8). This byproduct was isolated
4
solution was allowed to reach room-temperature overnight.
The reaction mixture was filtered on Celite and, after concen-
by chromatography of the reaction mixture (0.83 g, 1.72 mmol,
1
25%). Mp: 155 °C; H NMR (200 MHz, CDCl ) δ 7.72 (4H, dd,
3
tration, chromatographed on silica gel (MeOH-CH
2
Cl
2
, 5:95)
J ) 8.3 Hz), 7.32 (4H, d, J ) 8.3 Hz), 4.05-3.85 (4H, m), 3.48-
3.34 (4H, m), 2.72 (2H, br. s), 2.41 (6H, s), 2.40-2.27 (2H, m),
to give 5 (5.2 g, 22.6 mmol, 88%) as white crystals, mp 150
1
13
°
C; H NMR (200 MHz, CDCl
br. s), 1.79-1.62 (2H, m), 1.32 (6H, s); C NMR (50 MHz,
CDCl ) δ 102.1 (s), 63.1 (t), 60.8 (t), 45.1 (d), 42.8 (d), 29.7 (t),
4.7 (q), 24.5 (q).
1R*,2R*,3S*,4S*)-1,2,3,4-Tetr a k is(h yd r oxym eth yl)cy-
3
) δ 3.86-3.46 (8H, m), 2.27 (4H,
1.65 (1H, m), 1.16 (1H, m); C NMR (50 MHz, DMSO-d ) δ
6
1
3
144.8 (s), 132.4 (s), 129.7 (d), 127.6 (d), 70.0 (t), 68.3 (t), 44.3
(d), 40.5 (d), 30.9 (t), 21.4 (q). Anal. Calcd for C H O S : C,
3
2
3
28
7
2
2
57.50; H, 5.83. Found: C, 57.41; H, 5.85.
(
(1R *,2R *,3S *,4S *)-1,2,3,4-Te t r a k is((b or a n a t od ip h e -
n ylp h osp h a n yl)m eth yl)cyclop en ta n e (9). One piece of Li
(1 g, 0.14 atom.g) was hammer-wrought to give a foil which
was cut in narrow band and put in anhydrous THF (50 mL)
under argon. The suspension was stirred at 0 °C and chlo-
rodiphenylphosphine (10 mL, 55.7 mmol) was slowly added.
The mixture was then stirred at room temperature for 3 h to
give a solution of diphenylphosphide lithium (c ) 0.93 mmol/
mL). Tetratosylate 7 (1.0 g, 1.24 mmol) was added to THF (10
mL) under argon. The solution was stirred at 0 °C, and 21.5
mL of the solution of phosphide lithium was slowly added. The
8
clop en ta n e (6). To a solution of 5 (4.6 g, 20 mmol), water
20 mL), and THF (50 mL) under argon was added beads of
Amberlite IR-120 (1 g), the reaction mixture was refluxed for
h and then cooled to room temperature. After filtration, the
(
2
crude product was concentrated in vacuo. Toluene (25 mL) was
added and then removed by rotary evaporation. This operation
was repeated twice, and the crude product (oil) was used for
the following tosylation step. Purification for analysis was
2
accomplished by chromatography on silica gel (MeOH-CH -
1
Cl
2 6
, 1:3). H NMR (200 MHz, DMSO-d ) δ 4.55 (2H, t, J ) 4.8
Hz), 4.49 (2H, t, J ) 5.1 Hz), 3.52-3.25 (8H, m), 2.14-2.01
(
21) Torii, S.; Okumoto, H.; Ozaki, H.; Nakayasu, S.; Tadokoro, T.;
(
20) (a) Setzer, W. N.; Brown, L.; Yang, X.-j.; Thompson, M. A.;
Kotani, T. Tetrahedron Lett. 1992, 33, 3499-3502.
(22) Seitz, G.; Kr o¨ meke, G. Arch. Pharm. (Weinheim, Ger.) 1976,
309, 930-932.
Whitaker, K. W. J . Org. Chem. 1992, 57, 2812-2818. (b) Wu, H.-J .;
Chao, C.-S., Lin, C.-C. J . Org. Chem. 1998, 63, 7687-7693.

Pd-Catalyzed Allylic Substitution
J . Org. Chem., Vol. 66, No. 5, 2001 1637
solution was allowed to reach room temperature and stirred
for 5 h and then cooled to 0 °C. A solution of borane in THF (1
M, 28 mL, 28 mmol) was added. The reaction mixture was
(20 mg, 23.2 µmol). Anhydrous THF (10 mL) was added, and
then the solution was stirred at room temperature for 10 min.
3
1
Concentration of the catalyst solution was 2.32 µmol/mL.
P
poured on ice and extracted with CH
combined organic layers were washed with brine, dried
MgSO ), and evaporated. The crude oil was chromatographed
2
Cl
2
(3 × 200 mL). The
NMR (162 MHz, CDCl ) δ 25 (w ) 80 Hz), 19.4 (w ) 110 Hz).
3
Gen er a l P r oced u r e for th e Allylic Alk yla tion Rea c-
tion . To a solution of catalyst in anhydrous THF in a Schlenk
tube under argon atmosphere was added allylic acetate. The
solution was stirred at room temperature for 10 mn, and the
nucleophilic reagent was added. The progress of the reaction
was monitored by GC. The mixture was submitted to the usual
workup.
(
4
on silica gel (AcOEt-PE, 1:4) to give white crystals (0.93 g,
1
1
7
2
1
3
.0 mmol, 82%): mp 149 °C; H NMR (400 MHz, CDCl ) δ
.74-7.59 (16H, m), 7.48-7.38 (16H, m), 7.35-7.28 (8H, m),
.45 (2H, m), 2.14 (4H, m), 2.00 (2H, m), 1.76 (4H, dt, J )
1
3
2.5, 10.2 Hz), 1.27 (2H, m), 1.21-0.5 (12H, m); C NMR (50
1 1
MHz, CDCl
9
3
) δ 133.0 (d, | J |P,C ) 9.0 Hz), 132.7 (d, | J |P,C
)
Dim eth yl Allylm a lon a te (13) a n d Dim eth yl Dia llylm a -
lon a te (14). To 1 mL of a solution of Pd-Tedicyp catalyst (C
1
1
.0 Hz), 132.55 (d, | J |P,C ) 9.0 Hz), 132.4 (d, | J |P,C ) 10.0
2
3
-3
Hz), 131.7 (d, | J |P,C ) 16.0 Hz), 131.3 (br. s), 129.3 (d, | J |P,C
) 2.32 10 µmol/mL) in anhydrous THF was added allyl
1
1
)
10.0 Hz), 129.1 (d, | J |P,C ) 10.0 Hz), 129.0 (d, | J |P,C ) 10.0
acetate 11 (2.5 mL, 23.2 mmol), and the mixture was stirred
at room temperature for 10 min. In an other Schlenk tube
under argon atmosphere, dimethylmalonate 12 (5.32 mL, 46.4
mmol) was added dropwise to a solution of NaH (1.11 g, 46.2
mmol), in anhydrous THF (100 mL), and the mixture was
stirred at room temperature for 30 min.. The resulting anion
was transferred to the solution of catalyst. The mixture was
stirred at 55 °C during 14 days. Diethyl ether (200 mL) and
water (20 mL) were added. After extraction with diethyl ether,
1
Hz), 128.7 (d, | J |P,C ) 10.0 Hz), 43.2 (d, br. s), 37.1 (t), 36.2
1
1
(
d, br.s), 29.2 (t, br. d, | J |P,C ) 34.1 Hz), 21.9 (t, | J |P,C ) 35.1
31
3
Hz); P NMR (162 MHz, CDCl
) δ 16.7, 15.4.
(
1R*,2R*,3S*,4S*)-1,2,3,4-Tetr a k is((d ip h en ylp h osp h a -
n yl)m eth yl)cyclop en ta n e (1). Borane-phosphine 9 (1 g, 1
mmol) was added to anhydrous diethylamine and the solution
was heated at 55-60 °C for 10 h. The amine was removed in
vacuo. This operation was repeated twice. The crude product
was chromatographed on silica gel (Et
white crystals (0.90 g, 0.98 mmol, 98%), mp 79 °C. The white
crystals are not air stable and were stored under argon. H
2
O-PE, 1:20) to give
the combined organic layers were dried (MgSO ), and evapo-
4
rated. The product was purified by chromatography on silica
1
gel (Et O-PE, 5:95) to give 13 and 14 (ratio 13/14, 4.9:1) in
2
1
NMR (400 MHz, THF-d
m), 2.38-1.72 (10H, m), 1.25 (2H, m); C NMR (100 MHz,
8
) δ 7.71-7.23 (40H, m) 2.91-2.52 (2H,
95% yield (3.94 g, 22.1 mmol). 13, H NMR (200 MHz, CDCl )
3
1
3
δ 5.71 (1H, ddt, J ) 17.0, 10.1, 6.8 Hz), 5.08 (1H, dd, J ) 17.0,
1
1
THF-d
8
) δ 141.6 (s, | J |P,C ) 15.1 Hz), 141.1 (s, | J |P,C ) 14.1
1.6 Hz), 5.02 (1H, dd, J ) 10.1, 1.6 Hz), 3.68 (6H, s), 3.41 (1H,
1
1
13
Hz), 140.0 (s, | J |P,C ) 15.0 Hz), 139.4 (s, | J |P,C ) 16.0 Hz),
t, J ) 7.5 Hz), 2.59 (2H, dd, J ) 7.5, 6.8 Hz); C NMR (50
1
1
34.6 (d, |J |P,C ) 20.1 Hz), 134.5 (d, |J |P,C ) 19.1 Hz), 133.5 (d,
MHz, CDCl ) δ 169.9, 133.9, 117.7, 52.6, 51.4, 32.9. 14,
H
3
|
J |P,C ) 17.0 Hz), 133.3 (d, |J |P,C ) 18.0 Hz), 129.6 (d, |J |P,C
)
NMR (200 MHz, CDCl ) δ 5.65 (2H, ddt, J ) 17.0, 10.1, 6.8
Hz), 5.08 (2H, dd, J ) 17.0, 1.6 Hz), 5.02 (2H, dd, J ) 10.1,
1.6 Hz), 3.68 (6H, s), 2.65 (4H, d, J ) 6.8 Hz).
3
2
1
4.0 Hz), 129.3-129.0, 128.9 (d, |J |P,C ) 15.0), 45.4 (t, | J |P,C
2
2
)
8.6 Hz), 45.2 (d, | J |P,C ) 8.7 Hz), 40.4 (t, | J |P,C ) 8.75 Hz),
2
2
4
0.3 (t, | J |P,C ) 9.2 Hz), 39.1 (d, | J |P,C ) 13.3 Hz), 33.2 (d,
Met h yl 3-E t h yl-2-m et h oxyca r b on yl-5-p h en yl-4-p en -
ten oa te (19) a n d Meth yl 2-Meth oxyca r bon yl-3-p h en yl-
1
1
31
|
J |P,C ) 10 Hz), 26.5 (t, | J |P,C ) 12.9 Hz); P NMR (162 MHz,
THF-d ) δ -16.3, -17.7.
1R*,2R*,3S*,4S*)-1,2,3,4-Tet r a k is((d ip h en ylp h osp h i-
1
8
4-h ep ten oa te (20). Inseparable mixture. 19: H NMR (400
(
MHz, CDCl ) δ 7.35-7.15 (5H, m), 6.45 (1H, d, J ) 15.7 Hz),
3
n oyl)m eth yl)cyclop en ta n e (10). Procedure as in the syn-
thesis of 9 with the exception that borane solution was not
6.00 (1H, dd, J ) 15.7, 9.6 Hz), 3.70 (3H, s) 3.65 (3H, s), 3.49
(1H, d, J ) 4.0 Hz) ), 2.87 (1H, dtd, J ) 9.6, 9.4, 4.0 Hz), 1.3
2
added. To the crude material in THF was added excess H
2
O
2
.
(2H, dq, J ) 9.4, 7.3 Hz), 0.9 (3H, t, J ) 7.3 Hz); 13C NMR (50
The mixture was stirred at room temperature for 4 days. After
usual workup, 10 was purified by chromatography on silica
MHz, CDCl ) δ 168.7, 137.1, 134.8, 129.4, 128.5, 127.4, 126.3,
3
1
56.9, 52.5, 52.3, 45.3, 25.9, 11.8. 20: H NMR (400 MHz, CDCl3)
gel (MeOH-CH
2
Cl
2
, 5:95)(0.76 g, 0.82 mmol, 66%). White
δ 5.6-5.5 (2H, m), 4.0-3.8 (2H, m), the other signals are
1
crystals, mp 165 °C; H NMR (400 MHz, CDCl
3
) δ 7.79-7.62
masked by those of compound 19. Anal. Calcd for C H O :
1
6
20
4
(
16H, m), 7.50-7.35 (16H, m), 7.32-7.28 (8H, m), 2.85 (2H,
C, 69.55; H, 7.30. Found: C, 70.02; H, 7.18.
br t, J ) 12.9 Hz), 2.28 (4H, d, J ) 11.9 Hz), 2.26-2.15 (2H,
m), 2.10-2.05 (2H, m), 1.88 (2H, br q, J ) 12.9 Hz), 1.60 (1H,
Ack n ow led gm en t. We thank Dr. R. Faure for his
assistance in NMR measurements. D.L. and M.F. are
grateful to the Minist e` re de l′Education Nationale, de
la Recherche et de la Technologie, for a grant.
1
3
dt, J ) 13.8, 7.5 Hz), 1.36 (1H, dt, J ) 13.8, 10.2 Hz); C NMR
1
1
(
100 MHz, CDCl
3
) δ 134.3 (| J |P,C ) 13.0 Hz), 133.3 (| J |P,C
,
1
1
m), 131.94 (| J |P,C ) 5 Hz), 131.62 (| J |P,C ) 5 Hz), 131.27-
2
1
31.0 (m), 129.0-128.6 (m), 41.9 (d, | J |P,C ) 10.0 Hz), 38.0
1
1
(t), 35.2 (d), 33.0 (t, | J |P,C ) 69.9 Hz), 27.1 (t, | J |P,C ) 70.0
31
3
Hz); P NMR (162 MHz, CDCl ) δ 32.2; HRMS calcd for
Su p p or tin g In for m a tion Ava ila ble: Crystal structure
refinement data for compound 9 including tables of atomic
coordinates, thermal parameters, and bond lengths and angles,
and the labeled structure. 31P NMR spectra for 1. This material
is available free of charge via the Internet at http://pubs.acs.org.
C
C
57
H
H
54
O
O
4
P
P
4
926.2972, found 926.2965. Anal. Calcd for
: C, 73.86; H, 5.87. Found: C, 73.54; H, 5.82.
57
54
4
4
P r ep a r a tion of th e P d -Ted icyp Ca ta lyst. An oven-dried
0-mL Schlenk tube, equipped with a magnetic stirring bar,
a serum cap, and a stopcock under argon atmosphere, was
4
3
charged with [Pd(η -C
3
H
5
)Cl]
2
(4.2 mg, 11.6 µmol) and Tedicyp
J O001146J