M. Lenze et al. / Tetrahedron Letters 51 (2010) 2855–2858
2857
in 48–83% yields (Table 2). The catalytic performance of complexes
4a and 4c were comparable, but complex 4a was used for further
studies, as its ligand 1a is synthetically more easily accessed than
the other ligands.
A variety of aromatic substitution patterns in the aldehyde is
compatible with the catalyst. The catalysts loads were 3% and the
turnover frequencies ranged from 64 to 106 hꢀ1. The new iron
indenyl complexes are thus highly active in the title reaction.
Nishiyama recently revealed that 8 mol % of the rhenium complex
Re(CO)5Br catalyzes the conversion of the silyl enol ether 6 and
aromatic aldehydes to the corresponding aldol products (1 h,
80 °C, 50–80% isolated yields).16 Mukaiyama reported that
10 mol % of an InCl3ꢂAgClO4 mixture is catalytically active in the
reaction between 6 and benzaldehyde (2 h, ꢀ78 °C, 96% isolated
yield).17 Reetz described the cationic complex [Fe(Cp)(dppe)(CO)]+
as a catalyst in the reaction between 6 and benzaldehyde after
photolytic activation (2.5 mol % catalyst, 20 h, ꢀ20 °C, 77%,
dppe = diphenylphosphinoethane).18 The catalytic activity of the
new indenyl complexes 4 described herein is, thus, comparable
to other transition metal complexes that catalyze the reactions
shown in Table 2.
The complex 4b was isolated in high diastereomeric purity (1H,
31P NMR). The Mukaiyama aldol reaction in Table 2 produces chiral
aldol products 7. We anticipated that the chiral complex 4b could
be catalytically active in enantioselective formation of the prod-
ucts. However, essentially no enantiomeric excess was observed
for the reaction of benzaldehyde with 1-(tert-butyldimethylsilyl-
oxy)-1-methoxyethene 6 (Table 2, entry 1).
Table 1
Initial Screening of Iron catalyzed Mukaiyama aldol reactions
catalyst
In conclusion, the present study shows for the first time the cat-
alytic activity of new iron indenyl PHOX complexes of the general
t-BuMe2SiO
O
OMe
O
OMe
conditions
rt
OSiMe2t-Bu
formula [Fe(g
5-Ind)(CO)(PHOX)]+ in the Mukaiyama aldol reaction
+
R
H
R
of 1-(tert-butyldimethylsilyloxy)-1-methoxyethene and a variety
of aromatic aldehydes to give the corresponding aldol products
in 48–83% isolated yields. The new complexes show high activity,
as the reaction proceeds at room temperature within 15 min. The
substitution of a Cp ligand by an indenyl ligand enhanced the cat-
alytic activity in the [Fe(L)(CO)(PHOX)]+ system. Ligand and metal
complex modifications to improve catalytic activity for other silane
substrates and to obtain enantiomeric excesses are currently
underway.
7
5
6
Entry
Aldehyde
Catalyst
Conditionsa
Yieldb (%)
1
2
3
4
5
6
7
8
R = Ph
R = Ph
R = Ph
R = Ph
R = CH3(CH2)4
2-Ethylbutanal
Acetophenone
Acetophenone
2a
2a
3
CH3CN, 25 min
CH3CN, 3 h
CH3CN, 15 min
CH3CN, 15 min
CH3CN, 5 h
CH3CN, 5 h
CH3CN, 20 min
CH3CN, 5 h
3
61
89
90
48
0d
5
4ac
4a
4a
4a
4a
50
Acknowledgments
a
Conditions: The aldehyde (0.377 mmol) was dissolved in the solvent (1.0 mL).
The catalyst (0.011 mmol) was added, followed by 1-(tert-butyldimethylsilyloxy)-
1-methoxyethene (0.377 mmol). After the time indicated, the reaction mixture was
filtered through a short pad of silica gel and analyzed by GC/MS. All reactions were
carried out at room temperature.
We thank the University of Missouri-St. Louis for support. Fund-
ing from the National Science Foundation for the purchase of the
NMR spectrometer (CHE-9974801), for the ApexII diffractometer
(MRI, CHE-0420497), and the purchase of the mass spectrometer
(CHE-9708640) is acknowledged.
b
Determined by GC/MS.
Complexes 4b and 4c showed comparable activity.
c
d
No aldol product was obtained, but unidentified side products were observed,
presumably due to elimination reactions.
Supplementary data
Table 2
Crystallographic data (excluding structure factors) for the struc-
ture in this paper has been deposited with the Cambridge Crystal-
lographic Data Centre as supplementary publication CCDC 766377.
Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: +44-(0)1223-
336033 or e-mail: deposit@ccdc.cam.ac.uk). Experimental details,
characterization data and 1H and 13C NMR spectra for ligand 1c,
all new complexes and for the catalysis products in Table 2; exper-
imental details and crystallographic data for the X-ray determina-
tion of 4a are available. Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/
Iron catalyzed Mukaiyama aldol reaction
cat. 4aa
R1
O
t-BuMe2SiO
OMe
O
R1
R2
R3
OMe
CH3CN
R2
R3
H
+
rt, 15 min
R4
OSiMe2t-Bu
R4
5
6
7
c
Entry
Aldehyde
R1 = R2 = R3 = R4 = H, a
Yieldb (%)
TOF/hꢀ1
1
2
3
4
5
6
7
8
9
74d
59
62
78
70
83
76
64
70
79
48
54
98
78
80
101
91
104
101
86
93
106
64
R
R
R
R
1 = R2 = R4 = H, R3 = NO2, b
1 = OMe, R2 = R3 = R4 = H, c
2 = OMe, R1 = R3 = R4 = H, d
3 = OMe, R1 = R2 = R4 = H, e
R1 = Cl, R2 = R3 = R4 = h, f
References and notes
R
R
R
R
R
3 = CH3, R1 = R2 = R4 = H, g
1 = R3 = R4 = CH3, R2 = H, h
1 = CH3, R2 = R3 = R4 = H, i
2 = CH3, R1 = R3 = R4 = H, k
1 = R2 = R4 = H, R3 = Et, I
1. (a) Czaplik, W. M.; Mayer, M.; Cvengroš, J.; Jacobi von Wangelin, A.
ChemSusChem 2009, 2, 396; (b) Fürstner, A. Angew. Chem., Int. Ed. 2009, 48,
1364; (c) Bauer, E. B. Curr. Org. Chem. 2008, 12, 1341; (d) Enthaler, S.; Junge, K.;
Beller, M. Angew. Chem., Int. Ed. 2008, 47, 3317; (e) Correra, A.; Garcia
Mancheño, O.; Bolm, C. Chem. Soc. Rev. 2008, 37, 1108; (f) Sherry, B. D.;
Fürstner, A. Acc. Chem. Res. 2008, 41, 1500; (g) Gaillard, S.; Renaud, J.-L.
ChemSusChem 2008, 1, 505; (h) Díaz Díaz, D.; Miranda, P. O.; Padròn, J. I.;
Martín, V. S. Curr. Org. Chem. 2006, 10, 457; (i) Bolm, C.; Legros, J.; Le Paih, J.;
Zani, L. Chem. Rev. 2004, 104, 6217; (k) Costas, M.; Mehn, M. P.; Jensen, M. P.;
Que, L., Jr. Chem. Rev. 2004, 104, 939.
10
11
12
Butyraldehyde, m
71
a
Conditions: The aldehyde 5 (0.377 mmol) was dissolved in CH3CN (1.0 mL). The
catalyst 4a (0.011 mmol) was added, followed by 1-(tert-butyldimethylsilyloxy)-1-
methoxyethene (6, 0.377 mmol). After 15 min at rt, the solvent was removed and
the products were isolated by column chromatography.
b
Isolated yields after column chromatography.
Turnover frequency determined from isolated yields: number of moles (prod-
2. Garrett, C. E.; Prasad, K. Adv. Synth. Catal. 2004, 346, 889.
c
3. (a) Gelalcha, F. G.; Anilkumar, G.; Tse, M. K.; Brückner, A.; Beller, M. Chem. Eur. J.
2008, 14, 7687; (b) Nakanishia, M.; Bolm, C. Adv. Synth. Catal. 2007, 349, 861;
(c) Casey, C. P.; Guan, H. J. Am. Chem. Soc. 2009, 131, 2499; (d) Czaplik, W. M.;
Mayer, M.; Jacobi von Wangelin, A. Angew. Chem., Int. Ed. 2009, 48, 607; (e)
uct) over (number of moles (catalyst) times reaction time).
d
Employment of the chiral catalyst 4b resulted in essentially no enantiomeric
excess for this reaction, as determined by chiral GC.