Iron-catalyzed 1,4-addition of α-olefins to dienes

Article abstract of DOI:10.1021/ol802524r

Stereo-and Regiosetective 1,4-Addition A new intermolecular, stereo- and regioselective iron-catalyzed 1,4-addition of α-olefins to 1,3-dlenes using as low as 1 mol % of an iminopyridine-ferrous chloride complex was developed. Importantly, both double bon

Full text of DOI:10.1021/ol802524r

ORGANIC
LETTERS
2009
Vol. 11, No. 2
337-339
Iron-Catalyzed 1,4-Addition of r-Olefins
to Dienes
Benoˆıt Moreau, Jessica Y. Wu, and Tobias Ritter*
Department of Chemistry and Chemical Biology, HarVard UniVersity,
Cambridge, Massachusetts 02138
ritter@chemistry.harVard.edu
Received October 31, 2008
ABSTRACT
A new intermolecular, stereo- and regioselective iron-catalyzed 1,4-addition of r-olefins to 1,3-dienes using as low as 1 mol % of an
iminopyridine-ferrous chloride complex was developed. Importantly, both double bonds of the linear 1,4-diene addition products are obtained
with absolute stereocontrol.
Iron catalysis has the potential to form valuable carbon-carbon
bonds starting from simple starting materials such as hydro-
carbons.1 In this communication we present a functional-group-
tolerant, stereo- and regioselective iron-catalyzed 1,4-addition
reaction of R-olefins to 1,3-dienes (eq 1). Previously, in the
1960’s, Hata investigated the addition of butadiene and isoprene
to ethylene and propylene in an autoclave at >500 psi catalyzed
by an Fe(acac)3/Et3Al mixture.2 Using the same Fe(acac)3/Et3Al
mixture but in the presence of 2,2′-bipyridine, Takacs observed
formal [4 + 4] ene reactions with 1,3-dienes.3 The iron-diimine-
catalyzed dimerization of 1,3-dienes to afford cyclooctadienes
and vinyl cyclohexenes was developed by tom Dieck in the
1980′s.4 Within the past 5 years, Fu¨rstner has shown that a well-
defined anionic iron(0) complex, supported by a cyclopentadi-
enyl ligand, can catalyze intramolecular ene reactions,5 in-
tramolecular cycloadditions, and cycloisomerizations.6 In 2006,
Chirik demonstrated the intramolecular [2 + 2] cycloaddition
of 1,6-dienes catalyzed by a redox-active bisiminopyridine-iron
complex.7
We have investigated iminopyridine-ligated iron com-
plexes that provide access to linear 1,4-diene products that
cannot be obtained with tom Dieck’s or Takacs’ catalysts
or by any other hydrovinylation reaction reported to date.8
Our 1,4-addition reaction complements the functional-group-
tolerant cobalt-catalyzed 1,4-hydrovinylation reaction, pio-
neered by Hilt, which typically affords branched 1,4-
dienes.9Notable features of the carbon-carbon bond-forming
reaction presented herein include the regioselective introduc-
tion of prenyl and geranyl substituents, the stereospecific
formation of (E)-trisubstituted double bonds, and the func-
tionalization of unactivated commodity chemicals using a
simple low-valent iron catalyst.
The readily available iron(II) complex 1·FeCl2 shown in
eq 1 can be reduced in situ with activated magnesium metal
(3) (a) Takacs, J. M.; Anderson, L. G.; Madhavan, G. V. B.; Creswell,
M. W.; Seely, F. L.; Devroy, W. F. Organometallics 1986, 5, 2395. (b)
Takacs, J. M.; Anderson, L. G.; Madhavan, G. V. B.; Seely, F. L. Angew.
Chem., Int. Ed. 1987, 26, 1013. (c) Takacs, J. M.; Anderson, L. G.;
Newsome, P. W. J. Am. Chem. Soc. 1987, 109, 2542. (d) Takacs, J. M.;
Myoung, Y.-C.; Anderson, L. G. J. Org. Chem. 1994, 59, 6928. (e) Takacs,
J. M.; Newsome, P. W.; Kuehn, C.; Takusagawa, F. Tetrahedron 1990, 46,
5507.
(1) For recent reviews of iron catalysis, see: (a) Bolm, C.; Legros, J.;
Le Paih, J.; Zani, L. Chem. ReV. 2004, 104, 6217. (b) Enthaler, S.; Junge,
K.; Beller, M. Angew. Chem., Int. Ed. 2008, 47, 3317. (c) Correa, A.;
Mancheno, O. G.; Bolm, C. Chem. Soc. ReV. 2008, 37, 1108. (d) Sherry,
B. D.; Fu¨rstner, A. Acc. Chem. Res. 2008, 41, 1500.
(4) (a) tom Dieck, H.; Dietrich, J. Chem. Ber.-Recueil 1984, 117, 694.
(b) tom Dieck, H.; Dietrich, J. Angew. Chem., Int. Ed. Engl. 1985, 24, 781.
(5) Fu¨rstner, A.; Martin, R.; Majima, K. J. Am. Chem. Soc. 2005, 127,
12236.
(2) (a) Hata, G. J. Am. Chem. Soc. 1964, 86, 3903. (b) Hata, G.; Aoki,
D. J. Org. Chem. 1967, 32, 3754. (c) Hata, G.; Miyake, A. Bull. Chem.
Soc. Jpn. 1968, 41, 2762. For related publications, see: (d) Iwamoto, M.;
Yuguchi, S. J. Org. Chem. 1966, 31, 4290. (e) Iwamoto, M.; Yuguchi, S.
Bull. Chem. Soc. Jpn. 1966, 39, 2001.
(6) Fu¨rstner, A.; Majima, K.; Martin, R.; Krause, H.; Kattnig, E.;
Goddard, R.; Lehmann, C. W. J. Am. Chem. Soc. 2008, 130, 1992.
(7) Bouwkamp, M. W.; Bowman, A. C.; Lobkovsky, E.; Chirik, P. J.
J. Am. Chem. Soc. 2006, 128, 13340.
10.1021/ol802524r CCC: $40.75
Published on Web 12/18/2008
2009 American Chemical Society

Table 1. Iron-Catalyzed 1,4-Addition of Olefins to 1,3-Dienes
a Regioisomeric ratio as described (eq 2). b 1 mol % 1·FeCl2 used. c 20 mol % 2·FeCl2 used. d 10 mol % 2·FeCl2 used. e 5 mol % 1·FeCl2 used.
to catalyze carbon-carbon bond formation between styrene
and 2,3-dimethylbutadiene to afford 1,4-diene 3 in 94% yield
after 6 h at 23 °C. Control experiments showed that the
presence of iron, together with reducing agent and ligand,
is essential for productive catalysis. A 1:1 complex of ferrous
chloride and iminopyridine ligand10 (for X-ray, see Sup-
porting Information) is responsible for the exclusive forma-
tion of the intermolecular addition product 3, with no traces
of diene dimerization or subsequent observable double bond
isomerization. A selection of 18 other complexes derived
from bidentate nitrogenous ligands afforded the desired linear
1,4-diene 3 in less than 50% yield, provided significant
amounts of diene dimerization products as observed by tom
Dieck,4a or gave double bond isomerization to form a
conjugated 1,3-diene subsequent to addition (see Supporting
Information). As shown in Table 1, 2,3-dimethylbutadiene
can be added to electron-rich and -poor styrenes bearing
various functional groups such as ethers, an ester, and halides.
This practical procedure can be scaled to 100 mmol using 2
mol % of catalyst, 100 mL of solvent, and commercially
available styrene and isoprene (eq 2).
Although the reaction shown in eq 2 afforded 1,4-addition
product in 79% yield, two regioisomeric products were
obtained due to bond formation at either of the two different
olefin termini of isoprene. The regioselectivity in favor of
prenylation product 4a induced by ligand 1 was 86:14. The
introduction of a prenyl group upon 1,4-addition to isoprene
is synthetically useful,11 but control over regioselectivity is
challenging. To increase the regioselectivity, we evaluated
different iminopyridine ligands and found a strong depen-
dence of the regioselectivity on the ligand. The highest ratio
of 10:1 in favor of the desired linear 1,4-diene product was
observed with the trimethylsilyl-substituted ligand 2 (Table
1). Methyl substitution at the 6-position of the pyridyl ligand
(8) For hydrovinylation reactions of olefins, including 1,3-dienes, see:
(a) RajanBabu, T. V. Chem. ReV. 2003, 103, 2845. (b) Bogdanovi, B.;
Pauling, H.; Wilke, G.; Meister, B.; Henc, B. Angew. Chem., Int. Ed. 1972,
11, 1023. (c) Zhang, A. B.; RajanBabu, T. V. J. Am. Chem. Soc. 2006,
128, 54. (d) Shirakura, M.; Suginome, M. J. Am. Chem. Soc. 2008, 130,
5410. (e) Saha, B.; Smith, C. R.; RajanBabu, T. V. J. Am. Chem. Soc. 2008,
130, 9000.
(9) (a) Hilt, G.; du Mesnil, F. X.; Lu¨ers, S. Angew. Chem., Int. Ed. 2001,
40, 387. (b) Hilt, G.; Lu¨ers, S. Synthesis 2002, 609. (c) Hilt, G.; Lu¨ers, S.;
Schmidt, F. Synthesis 2004, 634. The functional-group-tolerant Co-catalyzed
1,4-hydrovinylation typically affords the branched 1,4-dienes; if acrylates
are used as enes, linear 1,4-diene products are observed, see ref 9c.
(10) Gibson, V. C.; O’Reilly, R. K.; Wass, D. F.; White, A. J. P.;
Williams, D. J. Dalton Trans. 2003, 2824. For a related review of
bisiminopyridine-iron complexes, see: (b) Gibson, V. C.; Redshaw, C.;
Solan, G. A. Chem. ReV. 2007, 107, 1745.
338
Org. Lett., Vol. 11, No. 2, 2009

can invert the regioselectivity to 16:84 to afford 5a as the
major isomer (see Supporting Information). Substitution of
the 1,3-diene starting material with substituents larger than
methyl, such as that in the commodity chemical myrcene,
increased the regioselectivity to up to >20:1 (entry 10, 4i).
Using this procedure, the geranyl substituent can be intro-
duced regioselectively. A diene with branched substitution
coupling with styrene. We cannot yet rationalize the influence
of the catalyst on the regioselectivity that may be determined
during oxidative coupling. A π-σ rearrangement to form
the seven-membered η1-allyl ferracycle 9, in which the
phenyl substituent is pseudoequatorial, positions only one
ꢀ-hydride (Hz) syn to iron. Hence, ꢀ-hydride elimination can
only afford a single double bond isomer and delivers the
1,2-disubstituted E double bond as part of the iron(II) alkyl
hydride 10. Assuming that subsequent reductive elimination
proceeds without σ-π-σ rearrangement of 10, the new
trisubstituted double bond is formed with E geometry
stereospecifically. To substantiate the assumption that ste-
reospecific reductive elimination from 10 is faster than
isomerization, we designed two deuterium-labelingexperi-
ments. The deuterium atoms of ꢀ,ꢀ-dideuterostyrene and (E)-
ꢀ-deuterostyrene in the 1,4-addition reactions to isoprene
were observed exclusively at the positions indicated in 11
and 12, respectively, consistent with our mechanistic hy-
pothesis (eqs 3 and 4).
1
afforded a single regioisomer as determined by H NMR
(entry 11, 4j). Although the regioselectivity was increased
using ligand 2, higher catalyst loadings were required to
achieve full conversion of starting material.
The geometry of both double bonds of the 1,4-diene
products was controlled, and all addition products were
observed as single double bond isomers. Importantly, the
trisubstituted double bond that is generated upon 1,4-addition
is formed as its E-isomer exclusively (entries 9-11);
trisubstituted double bonds with three alkyl substituents are
otherwise difficult to form as E-isomers with high selectiv-
ity.12 The aliphatic R-olefin allylbenzene afforded a single
addition product after double bond transposition (entry 12,
4k). Addition of olefins to 1-substituted 1,3-dienes afforded
addition products, albeit in lower yields. Overall, the
iminopyridine iron complexes control stereo- and regiose-
lectivity and afford linear 1,4-diene addition products
selectively over potential dimerization, isomerization, or
branched products.
Although 1,4-addition reactions proceeded with aliphatic
R-olefins, product mixtures were generally observed. In
addition to the desired linear 1,4-dienes, branched 1,4-dienes9
and dienes resulting from double bond isomerization sub-
sequent to addition were detected. Therefore, the presented
addition reaction is currently limited to styrene derivatives
and selected aliphatic R-olefins (e.g., 4k, Table 1).
A mechanistic hypothesis that is consistent with our
experimental observations is detailed in Scheme 1. We
propose formation of iron(II) alkyl allyl complex 8 after
reduction13 of the Fe(II) complex 1·FeCl2 and oxidative
In conclusion, we have developed an intermolecular iron-
catalyzed 1,4-addition of R-olefins to 1,3-dienes using readily
available iminopyridine-ferrous chloride complexes. Im-
portantly, both regioselectivity and double bond geometry
of the addition products can be controlled. Furthermore,
synthetically useful products such as prenyl- and geranyl-
substituted molecules are synthesized from simple commod-
ity chemicals.
Acknowledgment. We thank Merck & Co. for unrestricted
support, FQRNT for a postgraduate fellowship for B.M.,
Novartis for a graduate fellowship for J.Y.W., Materia for a
gift of Grubbs catalyst, Dr. Douglas M. Ho (Harvard
University) for X-ray crystallographic analysis, and Rebecca
Loy and Stephan Zuend (Harvard University) for GC
analysis.
Scheme 1. Proposed Catalytic Cycle for 1,4-Addition to Dienes
Supporting Information Available: Detailed experimen-
tal procedures and spectroscopic data for all new compounds,
as well X-ray data in CIF format. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL802524R
(11) Isoprenoids Including Carotenoids and Steroids; Cane, D. E., Ed.;
ComprehensiVe Natural Products Chemistry; Barton, D., Nakanishi, K.,
Eds.; Elsevier: Oxford, 1999; Vol. 2.
(12) Yu, J. S.; Kleckley, T. S.; Wiemer, D. F. Org. Lett. 2005, 7, 4803.
(13) A related (1,2-diimine)iron(diene) complex was obtained similarly:
Bart, S. C.; Hawrelak, E. J.; Lobkowsky, E.; Chirik, P. J. Organometallics
2005, 24, 5518.
Org. Lett., Vol. 11, No. 2, 2009
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