Iron-catalyzed Doyle-Kirmse reaction of allyl sulfides with (trimethylsilyl)diazomethane

Article abstract of DOI:10.1021/ol005740r

(formula presented) Iron salts efficiently catalyze the Doyle-Kirmse reaction of allyl sulfides with (trimethylsilyl)diazomethane and ethyl diazoacetate in dichloroethane at 83°C. Competitive dimerization is less of a problem with (trimethylsilyl)diazomet

Full text of DOI:10.1021/ol005740r

ORGANIC
LETTERS
2000
Vol. 2, No. 9
1303-1305
Iron-Catalyzed Doyle−Kirmse Reaction
of Allyl Sulfides with
(Trimethylsilyl)diazomethane
David S. Carter and David L. Van Vranken*
Department of Chemistry, UniVersity of California, IrVine, California 92697-2025
dlVanVra@uci.edu
Received February 29, 2000
ABSTRACT
Iron salts efficiently catalyze the Doyle−Kirmse reaction of allyl sulfides with (trimethylsilyl)diazomethane and ethyl diazoacetate in dichloroethane
at 83 °C. Competitive dimerization is less of a problem with (trimethylsilyl)diazomethane than with ethyl diazoacetate. Good results are obtained
using only 1.5 equiv of (trimethylsilyl)diazomethane, even without slow addition. Phosphine ligands affect the kinetics, but not the
diastereoselectivity. Dppe and BINAP lead to higher yields than dppp, but no enantioselection was detected with R-(+)-BINAP.
Iron is one of the premier transition metals for biological
catalysis, but in organic synthesis iron plays a diminutive
role relative to metals such as palladium, rhodium, and
ruthenium, especially for carbon-carbon bond forming
reactions. The most common homogeneous iron catalysts
have undesirable properties. For example, iron porphyrins1
are difficult to modify, while cyclopentadienyl iron com-
plexes2 are often unstable when exposed to air. Recently,
simple iron catalyst precursors have found application in
carbon-carbon bond forming reactions, for example, the
Fe(acac)3-catalyzed coupling of Grignard reagents and vinyl
halides.3
iron-catalyzed process is unknown. The recently reported
iron-catalyzed nitrene transfer to sulfides and sulfoxides is
an essential precedent for the corresponding Doyle-Kirmse
reaction.5 The following work demonstrates the efficacy of
simple iron complexes as catalyst precursors for the Doyle-
Kirmse reaction of allyl sulfides. When the Doyle-Kirmse
Scheme 1
The Doyle-Kirmse reaction of allyl sulfides and diazo
compounds is a powerful method for C-C bond formation,
presumably involving metal carbenoid intermediates.4 A
variety of metals catalyze the Doyle-Kirmse reaction,
notably rhodium, copper, and cobalt, but the corresponding
reaction was carried out using commercially available
dppeFeCl2, the reaction was found to proceed efficiently with
(trimethylsilyl)diazomethane (TMSD) but not with ethyl
diazoacetate (Scheme 1). This is the first example of iron
catalysis of the Doyle-Kirmse reaction.
(1) Wolf, J. R.; Hamaker, C. G.; Djukic, J. P.; Kodadek, T.; Woo, L. K.
J. Am. Chem. Soc. 1995, 117, 9194.
(2) Mahmood, S. J.; Saha, A. K.; Hossain, M. M. Tetrahedron 1998,
54, 349.
(3) Cahiez, G.; Avedissian, H. Synthesis 1998, 1199.
(4) (a)Kirmse, W.; Kapps, M. Chem. Ber. 1968, 101, 994. (b) Doyle,
M. P.; Griffin, J. H.; Chinn, M. S.; van Leusen, D. J. Org. Chem. 1984, 49,
1917. (c) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds: From Cyclopropanes to
Ylides; John Wiley&Sons: New York, 1998. (d) Aggarwal, V. K.; Ferrara,
M.; Hainz, R.; Spey, S. E. Tetrahedron Lett. 1999, 40, 8923. (e) Carter, D.
S.; Van Vranken, D. L. Tetrahedron Lett. 1999, 40, 1617. (f) Cagle, P. C.;
Arif, A. M.; Gladysz, J. A. J. Am. Chem. Soc. 1994, 117, 11730. (g) Meyer,
O.; Cagle, P. C.; Weickhardt, K.; Vichard, D.; Gladysz, J. A. Pure Appl.
Chem. 1996, 68, 79.
(5) Bach, T.; Korber, C. Tetrahedron Lett. 1998, 39, 5015.
10.1021/ol005740r CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/31/2000

Traditionally, the Doyle-Kirmse reaction is run with an
excess of sulfide and slow addition of the diazo compound
to favor path a over path b (Scheme 2), but in a recent
Table 1. Catalysis of the Doyle-Kirmse Reaction by Fe Salts
Scheme 2
entry
catalyst
product, %
start. mtrl, %
a
1
2
3
4
5
6
7
8
FeCl2
11
84
65
0
82
74
0
79
0
23
nd
0
0
nd
0
FeBr2
FeI2
Fe(OAc)2
FeCl3
FeBr3
Fe(acac)3
Fe(acac)3
a
83
a 4.5 equiv of TMSD.
While it is possible that the reactions in Table 1 proceed via
Fe(III) intermediates, a more likely scenario is that the ferric
salts are reduced to catalytically active ferrous species.
For the cinnamyl substrates 3a and 4a, diastereoselection
was modest.6 However, diastereoselection offers the op-
portunity to address the role of ligand and metal in the [2,3]
rearrangement process. If the ligand affects the rate of the
reaction, then it is probably involved in the catalytic cycle;
if the ligand affects the diastereoselectivity, then it is probably
involved in the rearrangement step of the catalytic cycle.
As the phosphine ligand is varied, or even omitted, the
diastereoselection does not change markedly (Table 3). Thus,
advance Aggarwal and co-workers have shown that slow
addition is unnecessary for efficient rhodium-catalyzed
Doyle-Kirmse reaction with (trimethylsilyl)diazomethane.4d
These conditions are possible with TMSD for two reasons:
first, the rhodium (trimethylsilyl)carbenoid is less electro-
philic than the corresponding carboxyethylcarbenoid, second,
the bulkier trimethylsilyl group slows addition of TMSD to
the carbenoid.
Following this precedent, the Doyle-Kirmse reaction was
carried out with dppeFeCl2 by stirring 4.5 equiv of TMSD
with the allyl sulfide 1 in refluxing dichloroethane for 2 h.
The yield for this reaction (85%) was comparable to the yield
obtained with slow addition (Scheme 1). Further studies of
reaction stoichiometry demonstrated that the large excess of
TMSD is unnecessary. Even better results (90% yield) were
obtained with 1.5 equiv of the diazo compound.
Table 2. Substituent Effects on Reactivity
A variety of Fe(II) and Fe(III) salts were explored as
catalyst precursors. While 2,6-di-tert-butylpyridine has a
beneficial effect on the CuOTf-catalyzed Doyle-Kirmse
reaction, it was found to be unnecessary for the iron-catalyzed
process. Ferrous chloride, ferrous bromide, and ferrous iodide
all catalyzed the Doyle-Kirmse reaction (Table 1, entries
1-3). The reaction appears to be slower with ferrous iodide,
but when the reaction time is extended from 2 to 5 h the
yield of [2,3] product 1b goes up to 77% and the amount of
recovered starting material drops to 17%. The insolubility
of ferrous chloride in dichloroethane makes it difficult to
assess the effect of halide because the ferrous salt did not
dissolve until the TMSD was added and the reaction was
heated. Halide ligands seem to be important for the Fe(II)-
catalyzed process, since with ferrous iodide catalyst the
reaction was still incomplete after 8 h (77% product, 17%
-
starting material). Both Fe(OAc)2 and [(H2O)6Fe]2+‚2BF4
gave no product, even with 4.5 equiv of TMSD.
it seems unlikely that the phosphine ligand is involved in
the step that determines diastereoselection. This result is
surprising because Aggarwal has shown convincingly that
the diastereomeric ratio observed in the Doyle-Kirmse
reaction of substrate 4a using rhodium dimer catalysts is
ligand dependent. Rh2(OAc)4 leads to 90:10 diastereomeric
ratio whereas Rh2(5S-MEPY)4 leads to a 49:51 diastereo-
Fe(III) salts were also effective catalyst precursors (Table
1). The requirement for halides seemed to be required by
the failure of Fe(acac)3 to catalyze the reaction, but surpris-
ingly Fe(acac)3 gave an 83% yield of homoallyl sulfide 1b
when the stoichiometry of TMSD was raised to 4.5 equiv.
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Org. Lett., Vol. 2, No. 9, 2000

other transition metals such as Pd(+2) and Ru(+2) are
known to bind to dialkyl sulfides with high affinity.7
Some ligands can diminish the catalyst efficiency. For
example, when dppp is added to the reaction, 33% starting
material remains after 2 h. When the Woerpel-Evans bis-
oxazoline (BOX) ligand is added, the reaction is completely
shut down and no reaction is observed. These results suggest
that dppp and bis-oxazolines bind to and deactivate the
catalyst.
When ferrous bromide was premixed with dppe, the
Doyle-Kirmse reaction continuously generated product over
about 90 min following higher order kinetics. In contrast,
when the reaction was carried out with FeBr2 in the absence
of phosphine there was an induction period of about 30 min
during which time virtually no product was formed. After
this induction period, a rapid reaction began and the starting
material was fully consumed within the next 30 min. Thus,
a highly reactive catalyst species is involved in the absence
of phosphine ligands.
In conclusion, this work represents the first example of a
Doyle-Kirmse reaction catalyzed by iron salts. The reaction
proceeds in refluxing dichloroethane with 1.5 equiv of
(trimethylsilyl)diazomethane without slow addition of the
diazo compound. The halide ligand has little influence on
the reaction, and the diastereoselectivity is relatively insensi-
tive to the presence of phosphine ligands. Currently, the role
of phosphine ligands, if any, is uncertain.
Table 3. Effects of Ligands on the Fe-Catalyzed
Doyle-Kirmse Reaction
entry
ligand
dppe
Ph3P
(R)-BINAP
dppp
product, %
dra
1
2
3
4
5
93
88
92
37
87
80:20
85:15
83:17
80:20
80:20
none
a dr ) diastereomeric ratio.
meric ratio.4d There are two plausible explanations for the
insensitivity of diastereomeric ratio (Table 3) with phosphine
ligand. Either iron is bound to sulfide substrate in preference
to the phosphine or the iron is not bound to sulfide or
phosphine. The former explanation seems plausible since
(6) To a flame dried round-bottom flask equipped with a magnetic stir-
bar was added FeCl2dppe (0.018 g, 0.03 mmol) under argon. Sulfide 3a
(0.152 g, 0.67 mmol) was dissolved in 6.7 mL of 1,2-dichloroethane and
introduced via syringe. The mixture was allowed to stir 10 min. (Trimeth-
ylsilyl)diazomethane (0.50 mL, 2.0 M in hexanes, 1.01 mmol) was
introduced via syringe. The mixture was warmed to reflux. After 2 h the
solution was cooled, filtered through Celite, and concentrated in vacuo to
give a brown oil. The crude mixture was purified via preparative thin-layer
chromatography (hexanes) to afford 3b (0.196 g, 94%, dr: 83:17) as a clear
oil. 3b: 1H NMR, major diastereomer (500 MHz, CDCl3,) δ 7.27-7.24
(m, 2H), 7.21-7.17 (m, 2H), 7.14-7.09 (m, 1H), 7.09-7.05 (m, 2H), 7.04-
7.00 (m, 1H), 6.98-6.96 (m, 2H), 6.31 (ddd, J ) 17.0, 10.2, 9.1 Hz, 1H),
5.15-5.09 (m, 2H), 3.79 (dd, J ) 9.1, 5.1 Hz, 1H), 2.74 (d, J ) 5.1 Hz,
1H), 0.07 (s, 9H); 13C NMR, major diastereomer (125 MHz, CDCl3) δ
144.0, 139.8, 138.8, 129.4, 128.3, 128.2, 128.1, 126.5, 125.4, 116.3, 51.6,
43.2, -1.6; HRMS(EI) Calcd for C19H24SSi [M]+ 312.1368, Found:
312.1362. Anal. Calcd for C19H24SSi: C, 73.02; H, 7.74. Found: C, 73.27;
H, 7.74.
Acknowledgment. This work is supported by the Na-
tional Science Foundation (CHE-9623903) with additional
support from the Glaxo-Wellcome Chemistry Scholars
program, Eli Lilly, and Dupont.
OL005740R
(7) (a) Albe´niz, A. C.; Casado, A. L.; Espinet, P. Inorg. Chem. 1999,
38, 2510. (b) Kuehn, C. G.; Taube, H. J. Am. Chem. Soc. 1976, 98, 689.
Org. Lett., Vol. 2, No. 9, 2000
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