?-Bound Phosphorus Heterocycles as Catalysts: Ring Opening of Epoxides with TMSCl in the Presence of a Phosphaferrocene

Full text of DOI:10.1021/jo970419g

4534
J . Org. Chem. 1997, 62, 4534-4535
Ta ble 1. Rin g Op en in g of Ep oxid es w ith TMSCl in th e
π-Bou n d P h osp h or u s Heter ocycles a s
P r esen ce of Ca ta lyst 1 (Eq 1)
Ca ta lysts: Rin g Op en in g of Ep oxid es w ith
TMSCl in th e P r esen ce of a
P h osp h a fer r ocen e
Christine E. Garrett and Gregory C. Fu*
Department of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139
Received March 6, 1997
We have recently begun to explore the reactivity of
heterocycles that are π-bound to transition metals, with
the goal of developing new families of chiral nucleophilic
catalysts and new classes of chiral ligands. To date, we
have focused our attention primarily on nitrogen hetero-
cycles, and we have demonstrated that π-bound pyrrole
and pyridine derivatives do indeed serve as effective
catalysts for a number of processes, including the acy-
lation of alcohols and the addition of ZnEt2 to aldehydes.1
In this report, we establish that π-bound phosphorus
heterocycles can also function as catalysts, specifically,
that phosphaferrocene 12 catalyzes the ring opening of
epoxides with TMSCl (eq 1).3
(Table 1, entry 5). For each substrate depicted in Table
1, no ring opening (<5% conversion) is observed in the
absence of catalyst 1 under otherwise identical condi-
tions.
On the basis of the differing ratios of regioisomers
produced in the phosphaferrocene-, PPh3-, and Bu4NCl-
catalyzed reactions of 1-dodecene oxide (eq 2), we specu-
late that a pentacoordinate 1‚TMSCl adduct6,7 may be a
reactive intermediate in the ring-opening process cata-
lyzed by the phosphaferrocene. We are pursuing studies
designed to test this hypothesis.
Phosphines serve as nucleophilic catalysts for a wide
array of reactions.4 We have determined that, like PPh3,5
phosphaferrocene 1 catalyzes the cleavage of epoxides
by TMSCl. Thus, treatment of an epoxide with 1.2 equiv
of TMSCl and 5 mol % of 1 in CH2Cl2 at room tempera-
ture, followed by deprotection of the resulting TMS ether
with acid, cleanly affords a chlorohydrin (eq 1; Table 1).
The reaction proceeds with inversion of configuration at
the carbon undergoing substitution (Table 1, entries
1-3). In the case of an unsymmetrical epoxide, displace-
ment occurs preferentially at the less hindered carbon
(Table 1, entry 4), barring an overriding electronic effect
In conclusion, we have presented the first examples of
a π-bound phosphorus heterocycle serving as a catalyst.
Future work will focus on the development of chiral
complexes for asymmetric catalysis.
Exp er im en ta l Section
Gen er a l Meth od s. 31P NMR chemical shifts are reported
in ppm downfield from H3PO4 (δ scale).
(1) (a) Ruble, J . C.; Fu, G. C. J . Org. Chem. 1996, 61, 7230-7231.
(b) Dosa, P. I.; Ruble, J . C.; Fu, G. C. J . Org. Chem. 1997, 62, 444-
445. (c) Ruble, J . C.; Latham, H. A.; Fu, G. C. J . Am. Chem. Soc. 1997,
119, 1492-1493.
(2) Roman, E.; Leiva, A. M.; Casasempere, M. A.; Charrier, C.;
Mathey, F.; Garland, M. T.; le Marouille, J .-Y. J . Organomet. Chem.
1986, 309, 323-332.
(3) For recent examples of enantioselective ring opening of epoxides,
see: (a) Nugent, W. A. J . Am. Chem. Soc. 1992, 114, 2768-2769. (b)
Martinez, L. E.; Leighton, J . L.; Carsten, D. H.; J acobsen, E. N. J .
Am. Chem. Soc. 1995, 117, 5897-5898. (c) Cole, B. M.; Shimizu, K.
D.; Krueger, C. A.; Harrity, J . P. A.; Snapper, M. L.; Hoveyda, A. H.
Angew. Chem., Int. Ed. Engl. 1996, 35, 1668-1671.
(4) For recent examples, see: (a) Vedejs, E.; Diver, S. T. J . Am.
Chem. Soc. 1993, 115, 3358-3359. (b) Trost, B. M.; Li, C.-J . J . Am.
Chem. Soc. 1994, 116, 10819-10820.
(5) Andrews, G. C.; Crawford, T. C.; Contillo, L. G., J r. Tetrahedron
Lett. 1981, 22, 3803-3806. PPh3 is more effective than 1 as a catalyst
for the ring opening of epoxides with TMSCl.
FeCl2 (Aldrich) was ground to a fine powder prior to use.
n-BuLi (1.6 M in hexanes; Strem), 2-chloroacetophenone (Ald-
rich), MgBr2‚Et2O (Aldrich), NaBH4 (Aldrich), naphthalene
(Aldrich), 1,2,3,4,5-pentamethylcyclopentadiene (Strem), PPh3
(Aldrich), and sodium (Aldrich) were used without further
purification. Chlorotrimethylsilane (Aldrich), cyclohexene oxide
(Aldrich), cyclopentene oxide (Aldrich), 1-dodecene oxide (Ald-
rich), and styrene oxide (Aldrich) were distilled prior to use. cis-
Stilbene oxide (Aldrich) was purified by flash chromatography.
(6) For leading references to π-bound phospholes that serve as σ
donors, see: Mathey, F. Coord. Chem. Rev. 1994, 137, 1-52.
(7) Nucleophilic activation of organosilicon compounds is
well-established: (a) Furin, G. G.; Vyazankina, O. A.; Gostevsky, B.
A.; Vyazankin, N. S. Tetrahedron 1988, 44, 2675-2749. (b) Holmes,
R. R. Chem. Rev. 1996, 96, 927-960.
S0022-3263(97)00419-2 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 13, 1997 4535
THF was distilled from sodium/benzophenone, CH2Cl2 was
distilled from CaH2, and CD2Cl2 was dried over alumina.
All reactions were carried out in oven-dried glassware with
magnetic stirring under an atmosphere of nitrogen or argon
using standard Schlenk or glovebox techniques.
P r ep a r a tion of Ca ta lyst 1. This procedure is nearly identi-
cal to that of Mathey.8 A solution of naphthalene (4.12 g, 32.1
mmol) in THF (15 mL) was added to a flask containing sodium
(0.781 g, 34.0 mmol) and 3,4-dimethyl-1-phenylphosphole9 (3.00
g, 16.0 mmol), resulting in a dark-red solution, which was stirred
at ∼30 °C for 3 h. The excess sodium was then removed, and
MgBr2‚Et2O (4.15 g, 16.1 mmol) was added. The resulting
yellow-brown slurry was stirred at ∼30 °C for 2 h.
Rin g op en in g of cyclop en ten e oxid e (Ta ble 1, en tr y 2):
run on 44 mg (0.52 mmol) of substrate; isolated 50 mg (80%) of
product; reaction time: 2 h.
tr a n s-2-Ch lor ocyclop en ta n ol: 1H NMR (300 MHz, CDCl3)
δ 1.50-1.65 (m, 1H), 1.75-1.85 (m, 3H), 2.10-2.35 (m, 2H), 2.37
(s, 1H), 3.95-4.25 (m, 1H), 4.20-4.30 (m, 1H); 13C NMR (75
MHz, CDCl3) δ 20.5, 31.2, 33.2, 65.6, 80.2; TLC (20% Et2O/
pentane; phosphomolybdic acid) Rf ) 0.20. Treatment of the
chlorohydrin with KOH regenerated cyclopentene oxide.
Rin g op en in g of cycloh exen e oxid e (Ta ble 1, en tr y 3):
run on 48 mg (0.50 mmol) of substrate; isolated 63 mg (94%) of
product; reaction time: 2 h.
tr a n s-2-Ch lor ocycloh exa n ol: 1H NMR (300 MHz, CDCl3)
δ 1.15-1.35 (m, 3H), 1.50-1.75 (m, 3H), 2.00-2.10 (m, 1H),
2.10-2.20 (m, 1H), 3.00 (br s, 1H), 3.40-3.50 (m, 1H), 3.65-
3.75 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 23.8, 25.4, 33.1, 35.0,
67.1, 75.0; TLC (20% Et2O/pentane; phosphomolybdic acid) Rf
) 0.30. Treatment of the chlorohydrin with pyridine regener-
ated cyclohexene oxide.
Rin g op en in g of 1-d od ecen e oxid e (Ta ble 1, en tr y 4): run
on 91 mg (0.49 mmol) of substrate; isolated 110 mg (101%) of
product; reaction time: 6 h. 1H NMR revealed a 9.3:1.0 mixture
of secondary:primary alcohols.
Cp*Li was prepared by treating a solution of 1,2,3,4,5-
pentamethylcyclopentadiene (2.5 mL, 16 mmol) in THF (20 mL)
with n-BuLi (1.6 M in hexanes; 10.0 mL, 16 mmol), resulting in
a yellow solution and a large quantity of precipitate. This
mixture was added to a stirred slurry of FeCl2 (2.02 g, 16.0
mmol) in THF (5 mL). After completion of the addition, the
reaction was stirred for 1 h at ∼30 °C, resulting in a forest-
green solution containing a very fine precipitate. The 3,4-
dimethylphospholyl anion slurry (previous paragraph) was then
added, immediately providing a dark-brown mixture. The
reaction was stirred at ∼30 °C for 13.5 h and then refluxed for
1.5 h. After the mixture was cooled to room temperature, the
solvents were removed in vacuo, and the resulting brown residue
was extracted repeatedly with hexane. The washings were
filtered, and the solvent was removed in vacuo. The resulting
orange solid was sublimed (40 °C, 100 mTorr) and then chro-
matographed (adsorption alumina), affording an orange-yellow
solid that was identical by 1H, 13C, and 31P NMR with literature
data for complex 1.2
In d ep en d en t P r ep a r a tion of Rea ction P r od u cts. All
authentic products were prepared by the PPh3-catalyzed ring
opening of epoxides with TMSCl.5 The resulting TMS ethers
were cleaved by treatment with HCl (1 M in Et2O), and the
product alcohols were purified by flash chromatography and
characterized by 1H and 13C NMR.
Rep r esen ta tive P r oced u r e for Ta ble 1, In clu d in g Mon i-
t or in g t h e Ba ck gr ou n d R ea ct ion : R in g Op en in g of
1-Dod ecen e Oxid e. A solution was prepared of 1-dodecene
oxide (0.273 g, 1.48 mmol) and TMSCl (0.230 mL, 1.81 mmol)
in CD2Cl2 (4.52 mL). A portion of this stock solution was
transferred to a sealable NMR tube (background reaction), and
1.69 mL of the stock solution (0.49 mmol of epoxide, 0.60 mmol
of TMSCl) was transferred to a flask containing catalyst 1 (7.5
mg, 0.025 mmol). The resulting homogeneous orange solution
was then transferred to a sealable NMR tube. The two reactions
were followed by 1H NMR.
1-Ch lor od od eca n -2-ol: 1H NMR (300 MHz, CDCl3) δ 0.87
(t, J ) 7.0 Hz, 3H), 1.20-1.60 (m, 18H), 2.42 (br s, 1H), 3.47
(dd, J ) 7.0, 11.0 Hz, 1H), 3.61 (dd, J ) 3.3, 11.0 Hz, 1H), 3.78
(br s, 1H); 13C NMR (75 MHz, CDCl3) δ 14.1, 22.7, 25.6, 29.4,
29.5, 29.6, 31.9, 34.3, 50.5, 71.5; TLC (20% Et2O/pentane;
phosphomolybdic acid) Rf ) 0.35.
2-Ch lor od od eca n -1-ol: 1H NMR (300 MHz, CDCl3) δ 0.88
(t, J ) 6.5 Hz, 3H), 1.20-1.60 (m, 16H), 1.70-1.80 (m, 2H), 2.29
(br s, 1H), 3.60-3.70 (m, 1H), 3.75-3.85 (m, 1H), 3.95-4.05 (m,
1H); 13C NMR (75 MHz, CDCl3) δ 14.1, 22.7, 26.4, 29.1, 29.3,
29.5, 29.6, 31.9, 34.3, 65.4, 67.1; TLC (20% Et2O/pentane;
phosphomolybdic acid) Rf ) 0.25.
Rin g op en in g of styr en e oxid e (Ta ble 1, en tr y 5): run
on 60 mg (0.50 mmol) of substrate; isolated 69 mg (88%) of
product; reaction time:0.1 h. 1H NMR revealed a 1.0:2.7 mixture
of secondary:primary alcohols. The identity of the secondary
alcohol was confirmed by comparison with 2-chloro-1-phenyl-
ethan-1-ol prepared by reduction of 2-chloroacetophenone with
NaBH4.
2-Ch lor o-1-p h en yleth a n ol: 1H NMR (300 MHz, CDCl3) δ
2.74 (br s, 1H), 3.66 (dd, J ) 8.7, 11.2 Hz, 1H), 3.76 (dd, J ) 3.6,
11.4 Hz, 1H), 4.91 (dd, J ) 3.5, 8.6 Hz, 1H), 7.30-7.40 (m, 5H);
13C NMR (75 MHz, CDCl3) δ 51.0, 74.2, 126.2, 128.6, 128.8,
140.0; TLC (20% Et2O/pentane; phosphomolybdic acid) Rf ) 0.40.
2-Ch lor o-2-p h en yleth a n ol: 1H NMR (300 MHz, CDCl3) δ
2.34 (br s, 1H), 3.85-3.95 (m, 2H), 4.99 (t, J ) 6.6, 1H), 7.35-
7.45 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 64.8, 67.9, 127.5,
128.8, 128.9, 137.9; TLC (20% Et2O/pentane; phosphomolybdic
acid) Rf ) 0.30.
After 6 h, 1H NMR showed that the catalyzed reaction was
complete and that the background reaction had not proceeded
(<5% conversion). For the catalyzed reaction, the solvent was
removed in vacuo, and the TMS ether was treated with HCl (1
M in Et2O) for 1 h at rt. The resulting chlorohydrins were
purified by flash chromatography (20% Et2O/pentane), yielding
110 mg (101%) of a 9.3:1 mixture of secondary:primary alcohols.
Note: A control experiment (no catalyst 1) was conducted for
each substrate illustrated in Table 1.
Ack n ow led gm en t. Support has been provided by
the American Cancer Society, the Camille and Henry
Dreyfus Foundation, the National Science Foundation
(predoctoral fellowship to C.E.G.; Young Investigator
Award to G.C.F., with funding from Procter & Gamble,
Glaxo Wellcome, Bristol-Myers Squibb, Eli Lilly, Merck,
Pfizer, Rohm & Haas, Pharmacia & Upjohn, and Du-
Pont), and the Research Corporation. Acknowledgment
is made to the donors of the Petroleum Research Fund,
administered by the ACS, for partial support of this
research.
Rin g op en in g of cis-stilben e oxid e (Ta ble 1, en tr y 1):
run on 99 mg (0.50 mmol) of substrate; isolated 112 mg (96%)
of product; reaction time: 100 h.
(R*,R*)-2-Ch lor o-1,2-d ip h en yleth a n -1-ol: 1H NMR (300
MHz, CDCl3) δ 3.27 (br s, 1H), 4.98 (d, J ) 8.2 Hz, 1H), 5.05 (d,
J ) 8.2 Hz, 1H), 7.10-7.30 (m, 10H); 13C NMR (75 MHz, CDCl3)
δ 70.5, 78.7, 127.0, 128.0, 128.1, 128.3, 128.5, 137.7, 138.8; TLC
(10% Et2O/pentane; phosphomolybdic acid) Rf ) 0.20. Treat-
ment of the chlorohydrin with pyridine regenerated cis-stilbene
oxide (95% isomeric purity).
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra of
the reaction products (5 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
(8) (a) de Lauzon, G.; Deschamps, B.; Fischer, J .; Mathey, F.;
Mitschler, A. J . Am. Chem. Soc. 1980, 102, 994-1000. (b) Nief, F.;
Mathey, F.; Ricard, L.; Robert, F. Organometallics 1988, 7, 921-926.
(9) Breque, A.; Mathey, F.; Savignac, P. Synthesis 1981, 983-985.
J O970419G