Mild, efficient, and robust method for stereocomplementary iron-catalyzed cross-coupling using (E)- and (Z)-enol tosylates

Article abstract of DOI:10.1055/s-0030-1258131

Iron-catalyzed cross-coupling of Grignard reagents (RMgX) with (E)- and (Z)-enol tosylates proceeded smoothly to give a variety of the corresponding (E)- and (Z)-trisubstituted ,-unsaturated methyl esters (total 30 examples; 55-98% yield). The simple, mild, stereoretentive method utilized iron(III) chloride (FeCl₃), iron(III) acetylacetonate [Fe(acac)₃], and iron(III) tris(dibenzylmethane) [Fe(dbm). The (E)- and (Z)-enol tosylates were readily prepared by the reported stereocomplementary tosylation method from methyl -keto esters or -formyl esters. Methyl -formyl esters were obtained via a practical and robust TiCl₄-Et₃N-mediated -formylation of methyl esters with methyl formate.

Full text of DOI:10.1055/s-0030-1258131

LETTER
2087
Mild, Efficient, and Robust Method for Stereocomplementary Iron-Catalyzed
Cross-Coupling Using (E)- and (Z)-Enol Tosylates
I
ron-Catalyzed Cro
i
ss-Cou
r
pling U
o
(
E
)- and
s
(
Z
)-Enol
h
T
osylate
s
i Nishikado, Hidefumi Nakatsuji, Kanako Ueno, Ryohei Nagase, Yoo Tanabe*
Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan
Fax +81(79)5659077; E-mail: tanabe@kwansei.ac.jp
Received 3 May 2010
Negishi, Sonogashira, and Suzuki–Miyaura cross-cou-
Abstract: Iron-catalyzed cross-coupling of Grignard reagents
plings to give a number of b,b- or a,b-disubstituted (E)-
(RMgX) with (E)- and (Z)-enol tosylates proceeded smoothly to
and (Z)-a,b-unsaturated esters with high substrate gener-
give a variety of the corresponding (E)- and (Z)-trisubstituted a,b-
unsaturated methyl esters (total 30 examples; 55–98% yield). The
simple, mild, stereoretentive method utilized iron(III) chloride
(FeCl3), iron(III) acetylacetonate [Fe(acac)3], and iron(III)
tris(dibenzylmethane) [Fe(dbm)3]. The (E)- and (Z)-enol tosylates
were readily prepared by the reported stereocomplementary tosyla-
tion method from methyl b-keto esters or a-formyl esters. Methyl a-
formyl esters were obtained via a practical and robust TiCl4–Et3N-
mediated a-formylation of methyl esters with methyl formate.
ality (total 54 examples).7
The key issue of these two methods lies in the E- and Z-
stereocomplementary enol tosylations utilizing an effi-
cient TsCl-N-methylimidazole (NMI) scaffold8 and a ste-
reoretentive cross-coupling protocol using Pd catalysis.
As a novel extension, we present herein an efficient
FeCl3-, Fe(acac)3 [iron(III) acetylacetonate]-, or Fe(dbm)3
[(iron(III) tris(dibenzylmethane)]-catalyzed cross-cou-
pling using (E)- and (Z)-enol tosylates as outlined in
Scheme 1. The upper and lower figures depict the reaction
sequences starting from methyl b-keto esters and a-
formyl esters, respectively. Despite the usefulness of iron-
catalyzed cross-coupling, to our knowledge, there are no
methods with substrate generality for b-oxo enol sul-
fonate partners.
Key words: cross-coupling, iron, stereoselective synthesis, enol
tosylate, a,b-unsaturated ester
Various stereoretentive cross-coupling reactions using
(E)- and (Z)-vinyl halides and their derivatives have been
developed over the past decades for the synthesis of natu-
ral products and pharmaceuticals due to their advanta-
geous features, such as the wide range of possible
substrates and catalysts, mild reaction conditions, func-
tional compatibility, etc. Among a number of investiga-
tions, iron-catalyzed cross-couplings have recently
attracted considerable attention due to their low cost and
toxicity, and environmentally benign catalysis.1
The initial trial was guided by the methylation of a pair of
(E)- and (Z)-enol tosylates [(E)-1a and (Z)-1a]7a derived
from methyl 3-oxononadecanate using MeMgBr to give
respective (Z)-2a and (E)-2a a,b-unsaturated esters
(Table 1, entries 1, 2; notice: due to the sequence rule, a
reverse configuration of E and Z of 2a–g is indicated for
this stereoretentive reaction). Among several commer-
cially available Fe(III) salts screened, FeCl3 and Fe(dbm)3
afforded the best results under mild conditions (THF sol-
vent, 0–5 °C, 2 h).9 This simple and accessible, but suc-
cessful result prompted us to investigate the substrate
generality for the present cross-coupling reaction using
various (E)- and (Z)-enol tosylates [(E)-1 and (Z)-1] de-
rived from b-keto esters.
Stereocontrolled preparation of (E)- and (Z)-a,b-unsatur-
ated esters is a major topic in organic synthesis, because
these compounds serve as useful structural scaffolds for
various (E)- and (Z)-stereodefined olefins. The stereose-
lective Horner–Wadsworth–Emmons reaction,2 dehydra-
tion of b-hydroxy esters,3 Michael reaction4 or
hydroxylation–alkylation using a-alkynyl esters5 are rep-
resentative methods.
Table 1 lists the successful results for preparing stereode-
fined b,b-disubstituted a,b-unsaturated esters [(Z)-2 and
(E)-2] and the salient features are as follows. (i) All exam-
ples examined produced good to excellent yield (18 exam-
ples; 55–98% yield) under identical conditions (THF
solvent, 0–5 °C, 2 h). (ii) Nearly complete stereoretention
was obtained for both E- and Z-substrates. (iii) With re-
gard to the yield, the FeCl3 catalyst worked best with (E)-
enol tosylates (E)-1, whereas the Fe(dbm)3 catalyst
worked best with (Z)-enol tosylates (Z)-1. (iv) Fe(acac)3
(acac = acetylacetonyl) with the NMP co-solvent method
by Cahiez’s group10 was effective for EtMgBr and
BuMgBr nucleophiles (entries 3, 5). (v) A terminal double
bond, chloro and ester functional groups were compatible
(entries 7–12). (vi) Slight E → Z isomerization occurred
Accordingly, there is a high demand for development of
efficient methods to improve stereo-, regio-, and
chemoselectivity and substrate generality. The (E)- and
(Z)-stereodefined enol sulfonates derived from b-keto and
a-formyl esters are promising stereoretentive cross-cou-
pling partners. Enol triflate analogues are popularly used
for this purpose,6 but they have two drawbacks, particular-
ly for process chemistry, instability, and high cost. We re-
cently reported a couple of practical stereocomplementary
preparations of various b-oxo ester enol p-toluene-
sulfonates (tosylates), followed by stereoretentive
SYNLETT 2010, No. 14, pp 2087–2092
x
x
.x
x
.2
0
1
0
Advanced online publication: 09.07.2010
DOI: 10.1055/s-0030-1258131; Art ID: U03410ST
© Georg Thieme Verlag Stuttgart · New York

2088
H. Nishikado et al.
LETTER
R3
OTs
TsCl, NMI,
Et3N
R3MgBr
(R1 > R3)
CO2Me
R1
R1
Fe(III) catalyst
O
CO2Me
OTs
(Z)
CO2Me
R1
R3
TsCl, NMI,
LiOH
CO2Me
(E)
CO2Me
R1
R1
R3
OTs
TsCl, NMI,
Et3N
R3MgBr
R2
R2
CO2Me
OTs
H
H
Fe(III) catalyst
O
CO2Me
CO2Me
(E)
H
R3
R2
TsCl, NMI,
LiOH
CO2Me
(Z)
CO2Me
H
H
R2
R2
(NMI = N-methylimidazole)
Scheme 1 Stereocomplementary preparation of (E)- and (Z)-a,b-unsaturated methyl esters utilizing iron-catalyzed cross-couplings of
R3MgBr with (E)- and (Z)-enol tosylates
in two cases (entries 14 and 17) and one considerable Z → reodefined a,b-disubstituted a,b-unsaturated esters [(E)-4
E isomerization unfortunately took place (entry 18).
and (Z)-4] and the salient features are as follows. (i) A lit-
tle contrary to the case using (E)-1 and (Z)-1, Fe(dbm)3 in-
stead of FeCl3 produced better result for both substrates
[(E)-3 and (Z)-3]. (ii) All reactions examined produced
moderate to excellent yield (12 examples; 58–98%) under
identical conditions (THF solvent, 0–5 °C, 2 h). (iii) The
reaction also proceeded with both nearly complete E- and
Z-stereoretention. (iv) It is noteworthy that the reaction
velocity was consistently higher than that using (E)-1 and
(Z)-1, whose tendency is apparently contrary to the report-
ed methods for Negishi, Sonogashira, and Suzuki–
Miyaura couplings.7 (v) In three cases, slight Z → E
isomerization occurred (entries 2, 6, and 12).
Next, we turned our attention on the reaction using (E)-
and (Z)-enol tosylates [(E)-3 and (Z)-3] derived from
methyl a-formyl esters. As described in our earlier re-
port,7b a-formylation of various esters using TiCl4–
HCO2Me reagent (a kind of Ti-Claisen condensation) is
efficient due to its higher yield, accessibility, and repro-
ducibility, compared with the traditional method using
base reagents (NaOR, NaH, etc.).11 Utilizing this Ti-
Claisen condensation and subsequent stereocomplemen-
tary enol tosylation, various stereodefined enol tosylates
[(E)-3 and (Z)-3] were prepared.7b
With these substrates [(E)-3 and (Z)-3] in our hands, the
present iron-catalyzed cross-coupling protocol was ap-
plied. Table 2 lists the successful results for preparing ste-
Table 1 Stereocomplementary Iron-Catalyzed Cross-Coupling of (E)-and (Z)-Enol Tosylates 1 Derived from Methyl b-Keto Esters
R3MgBr
R3
OTs
TsCl, NMI,
Et3N
cat. FeCl3
R1
R1
THF, 0–5 °C, 2 h
O
CO2Me
(Z)-2
CO2Me
CO2Me
(E)-1
R1
R3MgBr
R3
OTs
TsCl, NMI,
LiOH
cat. Fe(dmb)3
CO2Me
CO2Me
R1
R1
THF, 0–5 °C, 2 h
(Z)-1
(E)-2
Entry
Enol tosylate
R3
Product
Yield (%)a
Me
1
2
(E)-1a
(Z)-1a
(Z)-2a
(E)-2a
94
98
Me
CO2Me
7
Et
3
4
(E)-1a
(Z)-1a
(Z)-2b
(E)-2b
78b
76
Et
CO2Me
CO2Me
7
Bu
5
6
(E)-1a
(Z)-1a
(Z)-2c
(E)-2c
67, 81b
71
Bu
7
Synlett 2010, No. 14, 2087–2092 © Thieme Stuttgart · New York

LETTER
Iron-Catalyzed Cross-Coupling Using (E)- and (Z)-Enol Tosylates
2089
Table 1 Stereocomplementary Iron-Catalyzed Cross-Coupling of (E)-and (Z)-Enol Tosylates 1 Derived from Methyl b-Keto Esters
(continued)
R3MgBr
R3
OTs
TsCl, NMI,
Et3N
cat. FeCl3
R1
R1
THF, 0–5 °C, 2 h
O
CO2Me
(Z)-2
CO2Me
CO2Me
(E)-1
R1
R3MgBr
R3
OTs
TsCl, NMI,
LiOH
cat. Fe(dmb)3
CO2Me
CO2Me
R1
R1
THF, 0–5 °C, 2 h
(Z)-1
(E)-2
Entry
Enol tosylate
R3
Product
Yield (%)a
Me
7
8
(E)-1b
(Z)-1b
(Z)-2d
(E)-2d
94
82
Me
CO2Me
7
Me
9
10
(E)-1c
(Z)-1c
(Z)-2e
(E)-2e
71
88
Me
Me
Me
CO2Me
Me
Cl
11
12
(E)-1d
(Z)-1d
(Z)-2f
(E)-2f
90
88
CO2Me
MeO2C
13
14
(E)-1e
(Z)-1e
Me
(Z)-2g
(E)-2g
72
94c
CO2Me
CO2Me
Me
15
16
(E)-1f
(Z)-1f
(Z)-2h
(E)-2h
53, 94d
95
Me
Ph
55e
68f
Ph
17
18
(E)-1g
(Z)-1g
(E)-2i
(Z)-2i
CO2Me
Me
a Isolated.
b Fe(acac)3 was used instead of FeCl3 with 1.0 equiv of N-methylpyrrolidone (NMP) as co-solvent.
c E/Z = 89:11.
d Fe(dbm)3 was used instead of FeCl3.
e E/Z = 87:13.
f E/Z = 77:23.
Table 2 Stereocomplementary Iron-Catalyzed Cross-Coupling of (E)-and (Z)-Enol Tosylates 3 Derived from Methyl a-Formyl Esters
R3MgBr
R3
OTs
TsCl, NMI,
Et3N
R2
cat. FeCl3
R2
H
H
H
THF, 0–5 °C, 2 h
O
CO2Me
CO2Me
(E)-3
CO2Me
(E)-4
H
R3MgBr
R3
OTs
R2
TsCl, NMI,
LiOH
cat. FeCl3
CO2Me
CO2Me
H
THF, 0–5 °C, 2 h
R2
R2
(Z)-3
(Z)-4
Entry
Enol tosylate
R3
Product
Yield (%)a
CO2Me
Me
1
2
(E)-3a
(Z)-3a
(E)-4a
(Z)-4a
94
Me
Bu
Bu
93b
Oct
3
4
(E)-3a
(Z)-3b
(E)-4b
(Z)-4b
83c
83c
CO2Me
Bu
Oct
5
6
(E)-3c
(Z)-3c
(E)-4c
(Z)-4c
82c
CO2Bu
Bu
58c,d
Synlett 2010, No. 14, 2087–2092 © Thieme Stuttgart · New York

2090
H. Nishikado et al.
LETTER
Table 2 Stereocomplementary Iron-Catalyzed Cross-Coupling of (E)-and (Z)-Enol Tosylates 3 Derived from Methyl a-Formyl Esters
(continued)
R3MgBr
R3
OTs
TsCl, NMI,
Et3N
R2
cat. FeCl3
R2
H
H
H
THF, 0–5 °C, 2 h
O
CO2Me
CO2Me
(E)-3
CO2Me
(E)-4
H
R3MgBr
R3
OTs
R2
TsCl, NMI,
LiOH
cat. FeCl3
CO2Me
CO2Me
H
THF, 0–5 °C, 2 h
R2
R2
(Z)-3
(Z)-4
Entry
Enol tosylate
R3
Product
Yield (%)a
CO2Me
Me
7
8
(E)-3d
(Z)-3d
(E)-4d
(Z)-4d
88
81
Me
6
CO2Me
Me
9
10
(E)-3e
(Z)-3e
(E)-4e
(Z)-4e
68
69
Me
Me
Cl
CO2Me
11
12
(E)-3f
(Z)-3f
(E)-4f
(Z)-4f
98
Me
80e
Ph
a Isolated.
b E/Z = 5:95.
c BuMgBr used: 2 equiv.
d E/Z = 8:92.
e E/Z = 9:91.
ganic phase was washed with brine, dried (Na2SO4), and concentrat-
ed. The residue was purified by column chromatography on SiO2
(hexane–EtOAc = 5:1) to give the desired ester (4.59 g, 81%).
In conclusion, we developed a stereocomplementary
method for iron-catalyzed cross-coupling using (E)- and
(Z)-stereodefined enol tosylates. The present simple,
mild, robust, and totally efficient method will open a new
avenue for the synthesis of a wide range of stereodefined
(E)- and (Z)-a,b-unsaturated esters.
1
Pale yellow oil. H NMR (300 MHz, CDCl3): d = 0.88 (3 H, t,
J = 7.6 Hz), 1.13–1.36 (12 H, m), 1.37–1.47 (2 H, m), 2.47 (3 H, s),
2.68 (2 H, t, J = 7.6 Hz), 3.69 (3 H, s), 5.80 (1 H, s), 7.33–7.40 (2
H, m), 7.79–7.85 (2 H, m). 13C NMR (75 MHz, CDCl3): d = 14.0,
21.6, 22.6, 26.3, 28.9, 29.2 (2 C), 29.3, 31.3, 31.8, 51.4, 109.1,
128.1, 129.9, 132.9, 145.7, 165.7, 166.3. IR (neat): 2928, 2857,
1727, 1599, 1437, 1364, 1194, 1181cm–1. ESI-HRMS: m/z calcd for
C20H30O5S [M + Na+]: 405.1712; found: 405.1713.
NMR spectra were recorded on a JEOL DELTA 300 spectrometer,
1
operating at 300 MHz for H NMR and 75 MHz for 13C NMR.
Chemical shifts (d, ppm) in CDCl3 were reported downfield from
TMS (d = 0) or CHCl3 (d = 7.26 ppm) for 1H NMR. For 13C NMR,
chemical shifts were reported in the scale relative to CDCl3 (d =
77.00 ppm) as an internal reference. IR spectra were recorded on a
JASCO FT/IR-5300 spectrometer.
(Z)-Methyl 3-(p-Toluenesulfonyloxy)-2-dodecenate [(Z)-1a]
(Scheme 3)
OTs
O
TsCl, NMI, LiOH
(E)-Methyl 3-(p-Toluenesulfonyloxy)-2-dodecenoate [(E)-1a]
(Scheme 2)
CO2Me
CO2Me
C6H5Cl, 0–5 °C, 1 h,
20–25 °C, 2 h
7
7
(Z)-1a
OTs
O
TsCl, NMI, Et3N
Scheme 3
CO2Me
C6H5Cl, 0–5 °C,
20–25 °C, 2 h
7
7
CO2Me
TsCl (4.28 g, 22.5 mmol) in chlorobenzene (15 mL) was added
dropwise to a stirred suspension of 3-oxododecanoate (3.42 g, 15
mmol), NMI (1.85 g, 22.5 mmol), and LiOH powder (commercially
available, anhyd; 539 mg, 22.5 mmol) in chlorobenzene (20 mL) at
0–5 °C under an Ar atmosphere, and the mixture was stirred at the
same temperature for 1 h, followed by being stirred at 20–25 °C for
1 h. A similar workup for preparing (E)-1a, the residue was purified
by column chromatography on SiO2 (hexane–EtOAc = 25:1 to 5:1)
to give the desired ester (4.11 g, 72%).
(E)-1a
Scheme 2
TsCl (4.28 g, 22.5 mmol) in chlorobenzene (15 mL) was added
dropwise to a stirred solution of methyl 3-oxododecanoate (3.42 g,
15 mmol), NMI (1.85 g, 22.5 mmol), and Et3N (2.28 g, 22.5 mmol)
in chlorobenzene (15 mL) at 0–5 °C under an Ar atmosphere, and
the mixture was stirred at 20–25 °C for 2 h. H2O was added to the
mixture, which was extracted twice with EtOAc. The combined or-
1
Pale yellow oil. H NMR (300 MHz, CDCl3): d = 0.88 (3 H, t,
J = 7.2 Hz), 1.15–1.35 (12 H, m), 1.41–1.55 (2 H, m), 2.37 (2 H, t,
Synlett 2010, No. 14, 2087–2092 © Thieme Stuttgart · New York

LETTER
Iron-Catalyzed Cross-Coupling Using (E)- and (Z)-Enol Tosylates
2091
J = 7.2 Hz), 2.46 (3 H, s), 3.59 (3 H, s), 5.53 (1 H, s), 7.32–7.40 (2
H, m), 7.87–7.93 (2 H, m). 13C NMR (75 MHz, CDCl3): d = 14.0,
21.6, 22.6, 26.1, 28.6, 29.1, 29.1, 29.3, 31.7, 35.1, 51.3, 109.9,
128.3, 129.6, 133.5, 145.2, 160.2, 163.4.
THF (1.0 mL) at 0–5 °C under an Ar atomosphere, and the mixture
was stirred for 2 h. A workup similar to that for the preparation of
(Z)-2a–g gave the desired product.
General Procedure for Preparing Z-a-Substituted a,b-Unsatur-
ated Esters (Z)-4a–f (Scheme 7)
(E)- and (Z)-1b–g7a and (E)- and (Z)-3a–f are known compounds.7b
General Procedure for Preparing (Z)- or (E)-b-Substituted
a,b-Unsaturated Esters [(Z)-2a–g (R3 = Me, Et, Bu) or (E)-2h
(R3 = Ph)] (Scheme 4)
R3MgX (1.2 equiv),
FeCl3 (0.05 equiv)
R3
OTs
CO2Me
CO2Me
R3MgX (1.2 equiv),
FeCl3 (0.05 equiv)
H
H
THF, 0–5 °C, 2 h
R3
OTs
R2
R2
(Z)-3
R1
R1
THF, 0–5 °C, 2 h
(Z)-4
CO2Me
CO2Me
Scheme 7
(E)-1
(Z)-2a–g
(E)-2h
1 M R3MgX (1.20 mmol in THF) was added to a stirred solution of
a (Z)-enol tosylate (1.00 mmol) and FeCl3 (8 mg, 0.05 mmol) in
THF (1.0 mL) at 0–5 °C under an Ar atomosphere, and the mixture
was stirred for 2 h. A workup similar to that for the preparation of
(Z)-2a–g using (E)-2 gave the desired products.
Scheme 4
1 M R3MgX (1.20 mmol in THF) was added to a stirred solution of
an (E)-enol tosylate (1; 1.00 mmol) and FeCl3 (8 mg, 0.05 mmol) in
THF (1.0 mL) at 0–5 °C under an Ar atmosphere, and the mixture
was stirred for 2 h. H2O was added to the mixture, which was fil-
tered using Celite®. The resultant mixture was extracted twice with
EtOAc, and the organic phase was washed with brine, dried
(Na2SO4), and concentrated to give the residue, which was purified
by column chromatography on SiO2 (hexane–EtOAc = 100:1 to
25:1) to give the desired product.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
This research was partially supported by Grant-in-Aids for Scienti-
fic Research on Basic Areas (B) ‘18350056’, Priority Areas (A)
‘17035087’ and ‘18037068’, and Exploratory Research ‘17655045’
from the Ministry of Education, Culture, Sports, Science and Tech-
nology (MEXT).
General Procedure for Preparing (E)- or (Z)-b-Substituted
a,b-Unsaturated Esters [(E)-2a–g (R3 = Me, Et, Bu) or (Z)-2h
(R3 = Ph)] (Scheme 5)
R3MgX (1.2 equiv),
Fe(dbm)3 (0.05 equiv)
R3
OTs
References and Notes
CO2Me
CO2Me
R1
(E)-2a–g
R1
(Z)-1
THF, 0–5 °C, 2 h
(1) Recent books: (a) Iron Catalysis in Organic Chemistry;
Plietker, B., Ed.; Wiley-VCH: Weinheim, 2008.
(Z)-2h
(b) Nakamura, M.; Ito, S. In Modern Arylation Methods;
Ackermann, L., Ed.; Wiley-VCH: Weinheim, 2009, 155.
Recent reviews: (c) Fürstner, A.; Leitner, A. Angew. Chem.
Int. Ed. 2002, 41, 609. (d) Bolm, C.; Legros, J.; Paih, J. L.;
Zani, L. Chem. Rev. 2004, 104, 6217. (e) Shinokubo, H.;
Oshima, K. Eur. J. Org. Chem. 2004, 2081. (f)Fürstner,A.;
Martin, R. Chem. Lett. 2005, 34, 624. (g) Bauer, E. B. Curr.
Org. Chem. 2008, 12, 1341 . A recent iron-catalyzed cross-
coupling of zinc reagents with alkyl tosylates: (h) Ito, S.;
Fujiwara, Y.; Nakamura, E.; Nakamura, M. Org. Lett. 2009,
11, 4306; and relevant references cited therein.
Scheme 5
1 M R3MgX (1.20 mmol in THF) was added to a stirred solution of
a (Z)-enol tosylate (1; 1.00 mmol) and Fe(dbm)3 (18 mg, 0.05
mmol) in THF (1.0 mL) at 0–5 °C under an Ar atmosphere, and the
mixture was stirred for 2 h. A workup similar to that for the prepa-
ration of (Z)-2a–g gave the desired product.
General Procedure for Preparing (E)-a-Substituted a,b-Unsat-
urated Esters (E)-4a–f (Scheme 6)
(2) (a) Wothers, P.; Greeves, N.; Warren, S.; Clayden, J.
Organic Chemistry; Oxford: New York, 2001, 817.
(b) Smith, M. B.; March, J. Advanced Organic Chemistry,
6th ed.; Wiley: New York, 2007, 1375.
(3) For examples: (a) Zimmerman, H. E.; Ahramjian, L. J. Am.
Chem. Soc. 1959, 81, 2086. (b) Sai, H.; Ohmizu, H.
Tetrahedron Lett. 1999, 40, 5019. (c) Feuillet, F. J. P.;
Robinson, D. E. J.; Bull, S. D. Chem. Commun. 2003, 2184.
(d) Mani, N. S.; Mapes, C. M.; Wu, J.; Deng, X.; Jones,
T. K. J. Org. Chem. 2006, 71, 5039.
R3MgX (1.2 equiv),
FeCl3 (0.05 equiv)
R3
OTs
R2
R2
H
H
THF, 0–5 °C, 2 h
CO2Me
CO2Me
(E)-3
(E)-4
Scheme 6
(4) Ref. 2b, p. 1501.
(5) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. J. Am.
Chem. Soc. 2001, 123, 9918.
1 M R3MgX (1.20 mmol in THF) was added to a stirred solution of
an (E)-enol tosylate (1.00 mmol) and FeCl3 (8 mg, 0.05 mmol) in
Synlett 2010, No. 14, 2087–2092 © Thieme Stuttgart · New York

2092
H. Nishikado et al.
LETTER
Tanabe, Y. Org. Lett. 2006, 8, 5215. (e) Nakatsuji, H.;
Morita, J.; Misaki, T.; Tanabe, Y. Adv. Synth. Catal. 2006,
348, 2057. (f) Nakatsuji, H.; Morimoto, M.; Misaki, T.;
Tanabe, Y. Tetrahedron 2007, 50, 12071.
(6) For examples: (a) Scheiper, B.; Bonnekessel, M.; Krause,
H.; Fürstner, A. J. Org. Chem. 2004, 69, 3943.
(b) Babinski, D.; Soltani, O.; Frantz, D. E. Org. Lett. 2008,
10, 2901. (c) Specklin, S.; Bertus, P.; Weibel, J. M.; Pale, P.
J. Org. Chem. 2008, 73, 7845. (d) Maity, P.; Lepore, S. D.
J. Org. Chem. 2009, 74, 158 . Alkenyl and dienyl
phospahates: (e) Cahiez, G.; Gager, O.; Habiak, V. Synthesis
2008, 2636. (f) Cahiez, G.; Habiak, V.; Gager, O. Org. Lett.
2008, 10, 2389. Recent alkenyl pivalates: (g) Li, B.-J.; Xu,
L.; Wu, Z.-H.; Guan, B.-T.; Sun, C.-L.; Wang, B.-Q.; Shi,
Z.-J. J. Am. Chem. Soc. 2009, 131, 14656.
(9) In the absence of Fe(III) catalysts, the major side reaction
was an addition to the ester moiety and the desired coupling
products were not obtained. The basic reactivity order of the
Fe(III) catalysts is as follows: Fe(dbm)3 > Fe(acac)3 with
NMP > Fe(acac)3 > FeCl3. Due to the accessibility and
cheapness, the choice order was FeCl3, Fe(acac)3, and
Fe(dbm)3; For (E)-1, (E)-3, and (Z)-3, FeCl3 sufficiently
worked well, whereas reactive Fe(dbm)3 was required for
(Z)-1.
(10) (a) Cahiez, G.; Avedissaian, H. Synthesis 1998, 1199.
(b) Cahiez, G.; Marquais, S. Pure Appl. Chem. 1996, 68, 53.
(11) Yields of the traditional basic method range from 0 to 50%.
Reexamination of NaH-promoted a-formylation using an
aliphatic simple esters, Me(CH2)4CO2Me, in our hands,
however, was not reproducible under identical conditions.
These strongly basic and heterogeneous conditions might be
troublesome.
(7) (a) Nakatsuji, H.; Ueno, K.; Misaki, T.; Tanabe, Y. Org.
Lett. 2008, 10, 2131. (b) Nakatsuji, H.; Nishikado, H.;
Ueno, K.; Tanabe, Y. Org. Lett. 2009, 11, 4258.
(8) (a) Wakasugi, K.; Iida, A.; Misaki, T.; Nishii, Y.; Tanabe, Y.
Adv. Synth. Catal. 2003, 345, 1209. (b) Yasukochi, H.;
Atago, T.; Tanaka, A.; Yoshida, E.; Kakehi, A.; Nishii, Y.;
Tanabe, Y. Org. Biomol. Chem. 2008, 6, 540. Utilization of
relevant reactive ammonium intermediates between RCOCl
and NMI: (c) Misaki, T.; Nagase, R.; Matsumoto, K.;
Tanabe, Y. J. Am. Chem. Soc. 2005, 127, 2854. (d) Iida, A.;
Nakazawa, S.; Okabayashi, T.; Horii, A.; Misaki, T.;
Synlett 2010, No. 14, 2087–2092 © Thieme Stuttgart · New York