Bis(imino)pyridine iron complexes for aldehyde and ketone hydrosilylation

Article abstract of DOI:10.1021/ol800906b

(Chemical Equation Presented) Bis(imino)pyridine iron dinitrogen and dialkyl complexes are well-defined precatalysts for the chemo- and regioselective reduction of aldehydes and ketones. Efficient carbonyl hydrosilylation is observed at low (0.1-1.0 mol %) catalyst loadings and with 2 equiv of either PhSiH₃ or Ph₂SiH₂, representing one of the most active iron-catalyzed carbonyl reductions reported to date.

Full text of DOI:10.1021/ol800906b

ORGANIC
LETTERS
2008
Vol. 10, No. 13
2789-2792
Bis(imino)pyridine Iron Complexes for
Aldehyde and Ketone Hydrosilylation
Aaron M. Tondreau, Emil Lobkovsky, and Paul J. Chirik*
Department of Chemistry and Chemical Biology, Baker Laboratory,
Cornell UniVersity, Ithaca, New York 14853
pc92@cornell.edu
Received April 19, 2008
ABSTRACT
Bis(imino)pyridine iron dinitrogen and dialkyl complexes are well-defined precatalysts for the chemo- and regioselective reduction of aldehydes
and ketones. Efficient carbonyl hydrosilylation is observed at low (0.1-1.0 mol %) catalyst loadings and with 2 equiv of either PhSiH3 or
Ph2SiH2, representing one of the most active iron-catalyzed carbonyl reductions reported to date.
The metal-catalyzed reduction of carbonyl compounds to
alcohols by hydrogenation, hydrosilylation, or transfer
hydrogenation has emerged as a powerful method in organic
synthesis and has found application in the commercial
production of fine chemicals, perfumes, and pharmaceuti-
cals.1 Precious metal catalysts, particularly those containing
Rh(I) and Ru(II), are seminal and widely used examples.1,2
The cost of the these metals, coupled with concerns about
disposal and removal of trace metal residues, have motivated
the search for base metal alternatives. Highly active and
selective Ti,3 Cu,4 and organocatalytic methods5 have
become state of the art.
of organic carbonyl compounds has recently emerged as an
area of intense investigation. Transfer hydrogenation7 and
direct H2 addition reactions8 have been reported by Beller
and Casey. For Si-H addition, Nishiyama described that
Fe(OAc)2, in combination with various N-donor ligands and
(EtO)3SiH, is effective for ketone hydrosilylation at 65 °C
in THF.9 Beller has since modified this protocol to
Fe(OAc)2-phosphine mixtures with excess PMHS (poly-
(methylhydrosiloxane)) as the reductant.10 Introduction of
chiral phosphines produced high enantiomeric excesses for
selected, hindered substrates.10b More well-defined iron
precatalysts have also been described by Morris11 and, more
recently, Nikonov.12 The latter example, [(η5-C5H5) Fe(PR3)-
(CH3CN)2]2+, operates efficiently at ambient temperature
although the substrate scope has yet to be reported. Here
The high natural abundance, low cost, environmental
capability, and biological importance of iron inspire efforts
to expand its use in catalysis.6 The iron-catalyzed reduction
(1) (a) Nishiyama, H. Transition Metals for Organic Synthesis; Beller,
M., Bolm, C., Eds.; Wiley-VCH: Weinheim, 2004. (b) Ohkuma, T.; Noyori,
R. In ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: Berlin, 1999. (c) Ikariya, T.; Blacker, J.
Acc. Chem. Res. 2007, 40, 1300.
(6) (a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. ReV. 2004,
104, 6217. (b) Fu¨rstner, A.; Martin, R. Chem. Lett. 2005, 624. (c) Enthaler,
S.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2008, 47, 3317.
(7) Enthaler, S.; Hagemann, B.; Erre, G.; Junge, K.; Beller, M. Chem.
Asian J. 2006, 1, 598.
(2) Nishiyama, H.; Itoh, K. Asymmetric Hydrosilylation and Related
Reactions. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley VCH:
(8) Casey, C. P.; Guan, H. J. Am. Chem. Soc. 2007, 129, 5816.
(9) Nishiyama, H.; Furuta, A. Chem. Commun. 2007, 760.
(10) (a) Shaikh, N. S.; Junge, K.; Beller, M. Org. Lett. 2007, 9, 5429.
(b) Shaikh, N. S.; Enthaler, S.; Junge, K.; Beller, M. Angew. Chem. Int.
Ed. 2008, 47, 2497.
New York, 2000
.
(3) Yun, J.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 5640.
(4) (a) Lipshutz, B. H.; Noson, K.; Chrisman, W.; Lower, A. J. Am.
Chem. Soc. 2003, 125, 8779. (b) Lipshutz, B. H.; Frieman, B. A. Angew.
Chem., Int. Ed. 2005, 44, 6345.
(11) Sui-Seng, C.; Freutel, F.; Lough, A. J.; Morris, R. H. Angew. Chem.,
Int. Ed. 2008, 47, 940.
(5) Ouellet, S. G.; Walji, A. M.; MacMillan, D. W. C. Acc. Chem. Res.
2007, 40, 1327.
(12) Gutsulyak, D. V.; Kuzmina, L. G.; Howard, J. A. K.; Vyboish-
chikov, S. F.; Nikonov, G. I. J. Am. Chem. Soc. 2008, 130, 3732.
10.1021/ol800906b CCC: $40.75
Published on Web 06/07/2008
2008 American Chemical Society

we describe the application of readily accessible bis(imi-
no)pyridine iron dialkyl compounds that are active precata-
lysts for the hydrosilylation of aldehydes and ketones at low
catalyst loadings. These compounds are tolerant of many
functional groups and are some of the most active iron-based
reduction catalysts reported.
cyclohexyl-substituted bis(imino)pyridine iron alkyl complex,
2-R2, is also paramagnetic with a solution magnetic moment
consistent with an S ) 2 ground state. The solid-state
structure (Figure 2) was determined by X-ray diffraction and
The bis(imino)pyridine iron bis(dintrogen) complex,
(iPrPDI)Fe(N2)2 (1-(N2)2), has proven to be an effective
precursor for the catalytic hydrogenation and hydrosilylation
of unactivated13 and functionalized alkenes.14 Seeking to
extend the scope of this chemistry into aldehyde and ketone
reductions, the hydrosilylation of p-tolualdehyde and ac-
etophenone with Ph2SiH2 was initially examined. Both sub-
strates were quantitatively converted to PhCHROSiH2Ph in
less than 1 h with 1 mol % of 1-(N2)2 at 23 °C in a pentane
solution. Hydrolysis with NaOH quantitatively produced the
corresponding alcohol.
These initial results prompted exploration of different iron
precatalysts. Because analogues of 1-(N2)2 with various
bis(imino)pyridine ligands have thus far eluded isolation,
dialkyliron compounds were targeted. Ca´mpora and co-
workers have described a straightforward method for the
synthesis of bis(imino)pyridine iron dialkyl compounds by
substitution of the pyridine ligands in (py)2Fe(CH2SiMe3)2
with the appropriate chelate.15 This method has been
exploited by our laboratory as an alternative, high yielding
route to 1-R2 (R ) CH2SiMe3) and other related bis(imi-
no)pyridine iron dialkyls.16
Figure 2. Molecular structure of 2-R2 at 30% probability ellipsoids.
establishes a distorted trigonal bipyramidal iron center where
the two alkyl carbons and the pyridine nitrogen define the
equatorial plane. The sum of these angles is 360.00(21)°.
The imine nitrogens are axial and deviate from linearity due
to the constraints of the chelate.
The two iron dialkyls, 1-R2 and 2-R2, were assayed for
the catalytic hydrosilylation of aldehydes and ketones at 23
°C (Table 1). Standard conditions involved stirring a 0.40
M toluene solution of substrate with either 1.0 (1-R2) or 0.1
(2-R2) mol % of iron in the presence of 2 equiv of Ph2SiH2.
One equivalent of silane is also effective. The arylated
bis(imino)pyridine iron dialkyl, 1-R2, required a higher
catalyst loading (1 mol %) to achieve the same level of
productivity as 2-R2. This difference is likely due to the
greater moisture sensitivity of this specific iron dialkyl. The
For example, addition of the cyclohexyl-substituted bis-
(imino)pyridine to (py)2Fe(CH2SiMe3)2 furnished the desired
iron dialkyl compound, 2-R2, as deep purple, air- and
moisture-sensitive crystals in 83% yield (Figure 1). Notably,
1
progress of the reaction was monitored by GC or H NMR
spectroscopy by analysis of either the silyl ether or the
corresponding alcohol after treatment with NaOH.
PhSiH3 was also effective for carbonyl hydrosilylation
although the reactions were often exothermic and yielded
products from multiple silane additions. These reactions also
produced large amounts of dimer and oligomers derived from
dehydrogenative coupling of the silane. Importantly, basic
hydrolysis of the product mixtures obtained from these
procedures cleanly yielded the desired alcohol. More hin-
dered silanes such as Et3SiH or PMHS produced no turnover
even upon heating to 65 °C. The observed silane selectivity
with the bis(imino)pyridine iron compounds is opposite to
that described for Fe(OAc)2-promoted aldehyde and ketone
hydrosilylations where tertiary silanes are most effective.9,10
Importantly, all of the iron compounds reported in this study
are active catalysts for both aldehyde and ketone reduction
at 23 °C without the need for an activator and with only 2
equiv of silane.
Figure 1. Bis(imino)pyridine iron precatalysts.
the ligand exchange procedure allowed straightforward
isolation of alkyl- rather than aryl-substituted bis(imino)py-
ridine iron dialkyl complexes. Attempts to prepare 2-R2 from
direct alkylation of 2-Cl2 with LiCH2SiMe3 also provided
the desired product, albeit in lower yield and purity.
Paramagnetic 1-R2 has been previously reported and fully
characterized, including by X-ray crystallography.17,18 The
(13) Bart, S. C.; Lobkovsky, E.; Chirik, P. J. J. Am. Chem. Soc. 2004,
126, 13794.
(14) Trovitch, R. J.; Lobkovsky, E.; Bill, E.; Chirik, P. J. Organome-
tallics 2008, 27, 1470.
´
(15) Ca´mpora, J.; Naz, A. M.; Palma, P.; Alvarez, E.; Reyes, M. L.
Iron-catalyzed hydrosilylation with 1-R2 and 2-R2 exhibits
a broad functional group tolerance. Substituted acetophe-
Organometallics 2005, 24, 4878.
(16) Ferna´ndez, I.; Trovitch, R. J.; Lobkovsky, E.; Chirik, P. J.
Organometallics 2008, 27, 109.
(17) Bouwkamp, M. W.; Bart, S. C.; Hawrelak, E. J.; Trovitch, R. J.;
(18) Scott, J.; Gambarotta, S.; Korobkov, I.; Budzelaar, P. H. M. J. Am.
Lobkovsky, E.; Chirik, P. J. Chem. Commun. 2005, 3406
.
Chem. Soc. 2005, 127, 13019.
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Org. Lett., Vol. 10, No. 13, 2008

2-R2 followed by analysis of the resulting silyl ether by GC
(eq 1). Overall, the relative rate of ketone hydrosilylation
increases with electron-withdrawing groups in the para
position,19,20 where the most electron-deficient substrates,
p-CF3 and p-H, are reduced the most rapidly while those
with electron-donating groups, p-NMe2 and p-tBu, are the
most sluggish. While electron-withdrawing groups are known
to slow Ru transfer hydrogenation catalysts, a trend similar
to that reported here has been observed by Morris and co-
workers with ferrous dications.11
Table 1. Catalytic Hydrosilylation of Aldehydes and Ketones
with 1-R2 and 2-R2 and Ph2SiH2 (Percent Conversions Are
Reported)
The iron-catalyzed hydrosilylation of R,ꢀ-unsaturated
ketones was also examined (Figure 3). Previous work from
Figure 3. Hydrosilylation of R,ꢀ-unsaturated ketones with 2-R2.
our laboratory has established that addition of this class of
substrates to 1-(N2)2 results in immediate decomposition of
the iron compound.14 Thus, iron dialkyl compounds were
explored as alternatives. Hydrosilylation of cyclohexenone
or isophorone with Ph2SiH2 in the presence of 0.1 mol % of
2-R2 occurred smoothly over the course of 12 h at 23 °C.
The corresponding alcohols, with no evidence for alkene
reduction, were obtained exclusively following basic hy-
drolysis. Replacing the secondary silane with the more
reactive PhSiH3 also resulted in complete conversion to
product with exclusive selectivity.
Iron-catalyzed hydrosilylation of chalcone or benzylidene
acetone with 2 equiv of PhSiH3 and 0.1 mol % of 2-R2
resulted in predominantly 1,2-addition (carbonyl) reduction
with detectable amounts of 1,4-addition products (Figure 3).
The selectivities exhibited by 2-R2 are superior to those
observed with the Shvo-type iron hydrogenation catalyst
reported by Casey where mixtures of the product from 1,2-
addition and complete reduction were observed.8
a 1 mol % of 1-R2. b 0.1 mol % of 2-R2.
nones, with the exception of 3,5- and 2,4-disubstituted
examples (entries 6 and 7), are quantitatively reduced in 3 h.
Alkyl-substituted ketones are more sluggish (entries 9-11),
although longer reaction times, typically 12 h, produced
complete conversion with little evidence for catalyst decom-
position. The iron-catalyzed hydrosilylation reactions were
easily adapted to preparative scale. For example, the 2-R2-
catalyzed reduction of acetophenone on a 0.600 g scale
yielded 97% of isolated silyl ether and 90% of 1-phenyle-
thanol.
Deuterium-labeling studies were also performed to confirm
the selectivity for 1,2-addition. Deuterosilylation of cyclo-
Because many of the substituted acetophenones were
completely converted after 3 h, competition experiments were
conducted to delineate substituent effects. Each experiment
involved hydrosilylation of an equimolar mixture of the two
substrates with 0.5 equiv of Ph2SiH2 (1 equiv of ketone 1/1
equiv of ketone 2/0.5 equiv of Ph2SiH2) using 0.1 mol % of
(19) Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic
Chemistry; University Science Books: Sausalito, CA, 2006; p 446
(20) (a) Hansch, C.; Leo, A.; Taft, R. W. Chem. ReV. 1991, 91, 165.
(b) Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noyori, R. J. Am.
.
Chem. Soc. 1995, 117, 7562
.
Org. Lett., Vol. 10, No. 13, 2008
2791

hexenone with PhSiD3 and 2-R2 produced a single peak in
the 2H NMR spectrum corresponding to the alcohol methine
position following basic hydrolysis. In contrast, deuterosi-
lylation of chalcone in the presence of 0.1 mol % of 2-R2
and PhSiD3 confirmed the 7:1 ratio of 1,2- versus 1,4-addition
of the silane as deuteration was observed both in the methine
(1,2) and benzylic positions.
high activities at 23 °C. Further investigations into the scope,
mechanism, and enantioselectivity of these reactions are a
continuing area of investigation in our laboratory.
Acknowledgment. We thank the Packard Foundation for
financial support.
Supporting Information Available: Complete experi-
mental procedures and full characterization data including
the crystallographic data for 2-R2. This material is available
free of charge via the Internet at http://pubs.acs.org.
In summary, readily accessed bis(imino)pyridine iron
dialkyl complexes are efficient precatalysts for the hydrosi-
lylation of aldehydes and ketones using PhSiH3 and Ph2SiH2.
This method exhibits broad functional group tolerance and
OL800906B
2792
Org. Lett., Vol. 10, No. 13, 2008