Photochemical Heck benzylation of styrenes catalyzed by Na[FeCp(CO)2]

Article abstract of DOI:10.1016/j.jorganchem.2014.12.033

Iron-catalyzed Heck coupling of benzyl chlorides and styrenes proceeds under photochemical conditions using the well-known anionic complex, [FeCp(CO)₂]^- (Fp^-), as a catalyst. The reaction likely proceeds through the established S_N2 mechanism for Fp^- alkylation, followed by styrene migratory insertion and β-hydride elimination steps that are enabled by photochemical CO dissociation.

Full text of DOI:10.1016/j.jorganchem.2014.12.033

Journal of Organometallic Chemistry 793 (2015) 171e174
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Photochemical Heck benzylation of styrenes catalyzed by
Na[FeCp(CO)2]
Greyson W. Waldhart, Neal P. Mankad*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Iron-catalyzed Heck coupling of benzyl chlorides and styrenes proceeds under photochemical conditions
using the well-known anionic complex, [FeCp(CO)2]- (Fpꢀ), as a catalyst. The reaction likely proceeds
through the established SN2 mechanism for Fpꢀ alkylation, followed by styrene migratory insertion and
Received 14 November 2014
Received in revised form
20 December 2014
Accepted 22 December 2014
Available online 30 December 2014
b
-hydride elimination steps that are enabled by photochemical CO dissociation.
© 2014 Elsevier B.V. All rights reserved.
This paper is dedicated in Memoriam to
Prof. A.E. Shilov and his inspiring contribu-
tions to organometallic chemistry.
Keywords:
Iron catalysis
Heck coupling
Photochemistry
Carbonecarbon coupling
CeH functionalization
Base metal catalysis
Introduction
driving force. A photocatalytic approach to this problem also has
been demonstrated [23]. The field of Fe-catalyzed coupling re-
actions is increasingly prolific [24e26] and has established the
ability to engage alkyl halide substrates as coupling partners
[27e32]. In this report, we disclose an Fe-catalyzed intermolecular
Heck benzylation of styrenes under photochemical conditions us-
ing the well-known anionic complex, [FeCp(CO)2]ꢀ (Fpꢀ).
The ability to catalyze transformations of CeH bonds to CeC and
CeX bonds has revolutionized synthesis [1e6,50]. Of the various
available technologies, the MizorokieHeck reaction (“Heck reac-
tion”) is among the most prolific in its utility for converting CeH
bonds to CeC bonds within complex organic structures [7]. While
Pd catalysts are ubiquitous for Heck arylations of alkenes, Pd-
catalyzed Heck alkylations are less common and have limited
scope. Alkyl halides pose several challenges as coupling partners in
traditional Pd catalysis: slow oxidative addition at Pd(0) [8,9], slow
Results and discussion
Recently, Yasuda et al. disclosed the stoichiometric arylation of
styrenes by Fp-Ar reagents at high temperatures (Fig. 1a) [33]. In
principle, this transformation could serve as the basis for a closed
catalytic cycle for Heck coupling (Fig. 1b) if only the aryliron(II)
bond could be installed by activation of an Ar-X reagent by Fpꢀ. In
practice, this is not possible because the SN2 pathway [34,35] for
oxidative addition by Fpꢀ is not compatible with aryl halides.
Indeed, arylation of Fpꢀ is itself known to require Pd catalysis [36].
Accordingly, attempts at either stoichiometric reactions of aryl
halides with Fpꢀ or catalytic arylation of styrene using Fpꢀ did not
result in detectable conversion in our hands.
alkene insertion into Pd(II)-alkyls [10], and unproductive b-hydride
elimination suppress productive alkene alkylation. For these rea-
sons, Heck-type alkylation of alkenes is an open problem in Pd
catalysis [8e17] and presents an opportunity for contributions from
alternative metals. Catalysts based on Ti [18], Co [19,20], and Ni
[21,22] have proven successful in this area, often requiring reactive
co-reagents such as Grignards or silyl triflates to provide a greater
* Corresponding author. Tel.: þ1 312 355 4990.
E-mail address: npm@uic.edu (N.P. Mankad).
http://dx.doi.org/10.1016/j.jorganchem.2014.12.033
0022-328X/© 2014 Elsevier B.V. All rights reserved.

172
G.W. Waldhart, N.P. Mankad / Journal of Organometallic Chemistry 793 (2015) 171e174
Table 1
Optimization of reaction stoichiometry.a
Entry
PhCH2Cl
(equiv)
Styrene
(equiv)
NaOtBu
(equiv)
FpCH2Ph
(equiv)
Yield of 1b
1
2
3
4
5
6
7
8
1
2
1
1
1
1
1
1
1
1
1
1
1
2
6
10
1
1
1
6
6
1
1
1
1
1
2
1
1
0.1
0.1
0.1
0.1
0.1
0.1
0.05
0.25
0.25
0.2
0
34%
23%
53%
72%
62%
24%
4%
35%
89%
63%
0%
9
10
11
1.5
1.5
1.5
6
a
Selected data; full optimization in Supplementary Data.
b
Determined by 1H NMR integration relative to an internal standard.
migration was observed in most cases (Table 2). The two isomers
were not separable by standard column chromatography tech-
niques in the selected cases we attempted to purify, and so NMR
yields are presented here. In all cases, the corresponding Z-alkene
isomers either were not observed or were observed in trace (<1%)
amounts. Catalytic results were similar in the presence of several
different para substitutents (Table 2, Entries 1e8). The C(sp3)-Cl
bond of p-chlorobenzyl chloride is activated selectively over the
C(sp2)-Cl bond (Table 2, Entry 8) due to the SN2-like nature of
oxidative addition. On the other hand, Pd catalysts would activate
Fig. 1. (a) Stoichiometric Fe-mediated Heck arylation; (b) Fe-catalyzed Heck alkylation.
The steps of the catalytic cycle thought to require photochemical CO dissociation are
marked.
On the other hand, Fpꢀ is known to active alkyl halides readily
[37e39], and so we shifted our focus to catalytic alkylation of sty-
rene using Fpꢀ. Despite the long history of organoiron chemistry
using the Fp fragment [37e39], such catalysis has not been re-
ported previously. As an initial test reaction, we examined the
catalytic coupling of benzyl chloride and styrene, producing CeC
coupling product 1 (Table 1). We initially used air-stable FpCH2Ph
as a catalyst and pursued photochemical conditions due to the
instability of some of the hypothetical catalytic intermediates at
high temperatures. A series of tests indicated catalytic turnover was
indeed possible, with di-n-butyl ether being the optimal solvent
and NaOtBu the optimal base under UV irradiation with a 450-W
medium-pressure Hg arc lamp (see Supplementary Data for
optimization details). Addition of excess amounts of either benzyl
chloride (Table 1, Entry 2) or NaOtBu (Table 1, Entry 6) decreased
conversion to 1. Excess styrene increased conversion (Table 1, En-
tries 3e4), presumably because rapid interception of the FpCH2Ph
intermediate by styrene is necessary to outcompete side reactions
such as the well-known 1,1-migratory insertion of CO [39]. How-
ever, a small inhibitory effect was observed at high styrene loadings
(Table 1, Entry 5). The optimal ratio of benzyl chloride (1 equiv),
styrene (6 equiv), NaOtBu (1.5 equiv), and FpCH2Ph (0.25 equiv)
produced 1 in 89% conversion and was used for subsequent studies
(Table 1, Entry 9). No conversion to 1 was observed under these
conditions when the Fe complex was omitted or when Pd(OAc)2 or
Pd(PPh3)2Cl2 were used as catalysts in place of the Fe complex.
Under the optimized conditions, the E:Z ratio for 1 was >9.5:1. Use
of NaFp in place of FpCH2Ph resulted in only a slight decrease in
conversion to 1, and so NaFp was used as the catalyst in subsequent
studies. Other, less nucleophilic [38], metal carbonyl anions such as
[Mn(CO)5]ꢀ and [MCp(CO)3]ꢀ (M ¼ Cr, Mo, W) did not produce 1
under these conditions.
Table 2
Scope in benzyl chloride.
Entry
R
R0
Total yield of 2 and 3a
Ratio 2:3a
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
89%
48%
52%
51%
44%
92%
50%
50%
26%
0%
e
p-Me
p-OMe
p-Ph
p-CHCH2
p-CF3
p-F
3.4:1
1:0
1:0
n.d.b
1.2:1
2.3:1
2.1:1
2.5:1
e
p-Cl
p-Br
9
10
11
12
13
14
p-CN
p-SMe
p-CO2Me
o-Me
H
20%
28%
34%
42%
3.6:1
n.d.b
3.2:1
1:0
Several substituted benzyl chloride reagents were examined
using styrene as a coupling partner. In addition to the major Heck
coupling product (2), a minor product (3) resulting from alkene
a
Determined by 1H NMR integration relative to an internal standard.
Not determined due to peak overlap.
b

G.W. Waldhart, N.P. Mankad / Journal of Organometallic Chemistry 793 (2015) 171e174
173
both positions unselectively, and we have been unable to identify
previous examples of p-chlorobenzyl chloride engaging in Pd-
catalyzed cross coupling of any sort. Such catalytic selectivity
orthogonal to Pd has been observed with other non-traditional
elements [19e23,28,29,31]. Coordinating groups in the para posi-
tion such as CN, SMe, and CO2Me prevented catalytic turnover
(Table 2, Entries 10e12). Sterically hindered ortho-methylbenzyl
chloride also did not submit to efficient catalysis (Table 2, Entry 13),
Fig. 2. Catalytic results for the coupling of disubstituted styrenes shown with benzyl
chloride. Reaction conditions were as in Tables 2e3 Yields were determined by 1H
NMR integration relative to an internal standard.
although
a-methylbenzyl chloride performed reasonably well
(Table 2, Entry 14) compared to other less hindered substrates.
Benzyl fluoride (0%), benzyl bromide (11%), cyclohexyl chloride
(0%), and neo-pentyl chloride (0%) all performed much worse than
benzyl chloride itself. Benzyl tosylate reacted with the base under
these conditions to form PhCH2OtBu.
Similar experiments were carried out with substituted styrenes
using benzyl chloride as a coupling partner. Although p-methyl-
styrene performed equally well as styrene itself (Table 3, Entries
1e2), other para substituents were not well tolerated (Table 3,
Entries 3e6). Here, once again, aryl-halide linkages were tolerated
and remained intact under these conditions (Table 3, Entry 7):
product 4 produced from p-bromostyrene has not been constructed
by Heck coupling before, to our knowledge. Less activated alkenes
such as vinyltrimethylsilane, t-butylethylene, and cyclopentene did
not undergo coupling under these conditions.
Furthermore, a mechanism involving benzyl radical transfer would
be unlikely to discriminate to such a large extent between the cis-
and trans- b-methylstyrene isomers (Fig. 2). We also note that the
coupling of benzyl chloride and styrene was inhibited by the pres-
ence of either CO (1 atm, 25% conversion) or pyridine (0.5 equiv, 45%
conversion; 6.0 equiv, 30% conversion), consistent with CO dissoci-
ation being involved in the catalytic pathway. Although conversion
was affected adversely by radical traps such as 1,4-cyclohexadiene
(1 equiv, 62% conversion) and 9,10-dihydroanthracene (1 equiv,
30% conversion), this inhibition is consistent with any pathway
proceeding through FpH due to its instability towards H-atom do-
nors [46]. Nonetheless, Fe-R homolysis may represent an unpro-
ductive pathway competing with productive Heck coupling in this
system. For example, when analyzing the crude reaction mixture
from one of the low-yielding catalytic reactions (Table 2, Entry 2),
we found that all of the benzyl chloride substrate had been
consumed even though the corresponding bibenzyl was not
detected and the Heck coupling product was formed in only 48%
yield. These observations indicate that some of the unaccounted
mass balance results from non-productive decomposition of the
benzyl chloride partner under these conditions, possibly through
formation and subsequent decomposition of the benzyl radical.
Coupling reactions of disubstituted styrenes with benzyl chlo-
ride also were examined (Fig. 2). No conversion to products was
observed with
observed with cis-
were obtained with trans-
a
-methylstyrene, and only trace conversion was
-methylstyrene. However, exemplary results
-methylstyrene (83%).
b
b
Regarding the mechanism of catalysis, we favor a classical Heck-
type mechanism (Fig. 1b) in which the role of the UV light is to
induce CO dissociation and reveal unsaturated intermediates
necessary for insertion/elimination processes. This proposal stands
opposed to a radical mechanism in which the role of the UV light
would be to induce Fe-R homolysis, followed by R$ trapping by the
styrene [40]. In related half-sandwich metal carbonyl complexes,
ultrafast infrared studies have established that UV irradiation in-
Conclusions
In conclusion, the first Fe-catalyzed Heck alkylation of alkenes is
reported here. The method is not of preparative use at this time due
to modest yields and alkene isomerization, and studies towards
overcoming these obstacles are underway in our laboratory.
Nonetheless, these initial results highlight a promising strategy for
developing methods that convert CeH bonds to CeC bonds using
earth-abundant metal catalysts.
duces CO dissociation to yield unsaturated intermediates with ms
lifetimes sufficiently long to coordinate exogenous ligands (here, the
styrene) [41], and similar conclusions were reached for the photo-
chemistry of FpBR2 complexes [42e45]. Alkylation of Fpꢀ is known
to proceed through
a two-electron, SN2 pathway [34,35].
Table 3
Scope in styrene.
Experimental section
General considerations
Unless otherwise specified, all reactions and manipulations
were performed under purified N2 in an MBraun glovebox or using
standard Schlenk techniques. Glassware was oven-dried prior to
use. Tetrahydrofuran, toluene, pentane, diethyl ether, acetonitrile,
methylene chloride, heptane, dioxane and triethylamine were
sparged with argon and dried using a Glass Contour Solvent System
built by Pure Process Technology, LLC. Acetone, hexanes, methanol
and ethanol were purified by distillation according to standard
procedures. All other solvents were purified by repeated freeze-
epumpethaw cycles followed by prolonged storage over activated,
3 Å molecular sieves. Photolysis was conducted using a 450 W
Hanovia mercury arc lamp in an immersion well filled with circu-
lating water, and samples were placed approximately 0.75 inches
from the lamp. NMR spectra were recorded at ambient temperature
using Bruker Avance DPX-400, Bruker Avance DRX-500 and Bruker
Avance-II 800 MHz spectrometers with a delay time of 5 s and a
Entry
R
Total yield of 4 and 5a
Ratio 4:5a
1
2
3
4
5
6
7
H
89%
88%
26%
0%
34%
31%
45%
e
Me
OMe
Ph
F
Cl
Br
2.4:1
2.2:1
e
1.7:1
1.2:1
1:0
Determined by 1H NMR integration relative to an internal standard.
pulse time of 3.0 m
s. 1H NMR chemical shifts and integration values
a

174
G.W. Waldhart, N.P. Mankad / Journal of Organometallic Chemistry 793 (2015) 171e174
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were referenced to an internal standard (mesitylene). Na
[Fe(CO)2(
5-C5H5)] [46], K[Fe(CO)2( 5-C5H5)] [47], [Fe(CH2C6H5)
(CO)2(
5-C5H5)] [48], and benzyl fluoride [49], were prepared using
a literature procedures. Unless otherwise indicated, all other
chemicals were purchased from commercial sources and used
without further purification.
h
h
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General procedure for catalytic reactions
In a nitrogen filled glovebox, catalyst (~10 mg) was dissolved in
solvent (1 mL). Base, benzyl chloride, and styrene were added to the
solution according the stoichiometry described in the data tables or
in the text, and then the reaction solution was quantitatively
transferred to either a J-Young NMR tube or an airtight NMR tube
with screw cap seal. The NMR tube was taken out of the glovebox
and placed approximately 0.75 inches away from the condenser of a
450 W mercury arc UV lamp. After 16 h, the NMR tube was trans-
ferred back into the glovebox, and the reaction mixture was filtered
through a small plug of silica gel. Multiple aliquots of diethyl ether
were used to wash the silica gel plug. Volatiles were removed under
vacuum until an oil or solid remained. This residue was dissolved in
CDCl3, and mesitylene was added as an internal standard. Yields
and isomeric ratios were determined by integrating the 1H NMR
resonance for the benzylic protons of the product(s) relative to the
internal standard. In the 1H NMR spectra shown as Supplementary
Data for the product mixtures, the chemical shifts and integral
values for the benzylic protons and the internal standard peaks are
shown. Yields are reported as averages of three independent runs.
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Acknowledgments
Funding was provided by the UIC Department of Chemistry
(start-up funds), the UIC Campus Research Board (Pilot Grant), and
the NSF (CHE-1362294). Dr. Benjamin Ramirez assisted with NMR
spectroscopy.
Appendix A. Supplementary data
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Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2014.12.033.
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