An iron catalyzed regioselective oxidation of terminal alkenes to aldehydes

Article abstract of DOI:10.1039/c2cc32051g

Fe(BF₄)₂·6H₂O with pyridine-2,6-dicarboxylic acid and PhIO can efficiently catalyze the regioselective oxidation of terminal alkene derivatives to aldehydes under mild and benign reaction conditions.

Full text of DOI:10.1039/c2cc32051g

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COMMUNICATION
An iron catalyzed regioselective oxidation of terminal alkenes to
aldehydesw
Abhishek Dutta Chowdhury, Ritwika Ray and Goutam Kumar Lahiri*
Received 21st March 2012, Accepted 14th April 2012
DOI: 10.1039/c2cc32051g
Fe(BF4)2ꢀ6H2O with pyridine-2,6-dicarboxylic acid and PhIO can
efficiently catalyze the regioselective oxidation of terminal alkene
derivatives to aldehydes under mild and benign reaction conditions.
because of its low toxicity and increasing (high) price as well as
limited availability of palladium, rhodium or cobalt.9 Very
recently, we have developed a reliable and direct method for
iron catalyzed anti-Markovnikov acetal formation from styrene
derivatives.10 As a part of our ongoing research program of iron
catalyzed anti-Markovnikov regioselection process under mild
reaction conditions, the present communication highlights the
iron-catalyzed conversion of aromatic or aliphatic alkenes to
aldehydes with mechanistic insight (Scheme 1).
The regioselective functionalization of terminal alkenes and
alkynes is the most elementary reaction in organic synthesis as
it allows easy introduction of various hetero-atom(s) into the
existing molecular framework.1 Though the catalytic anti-
Markovnikov regioselective hydration of terminal alkynes to
aldehydes has gained considerable research interest over the
past decade,1a,2 the exclusive control of regioselectivity during
transition metal catalyzed functionalization of terminal
alkenes to aldehydes is emerging as a convenient approach
to synthesize aldehydes.3–5
The initial screening of suitable reaction conditions is
investigated in detail with styrene as a substrate. Fe(BF4)2ꢀ
6H2O (1) has been established to be much more selective
and efficient than other iron, ruthenium, copper and cobalt
salts in the presence of various commercially available ligands
and PhIO in CHCl3 at room temperature (Table 1). Similar
to our earlier observation, only dipic (dipic: pyridine-2,6-
dicarboxylic acid) is found to have excellent activity and
selectivity over other ligands in the presence of 1 and PhIO
as an oxidant (entries 14–20, Table 1).10 The electron rich
dianionic dipic ligand facilitates the in situ formation of the
active catalyst, i.e. high valent iron-oxo species, which in turn
exhibits the best activity (entry 20, Table 1). Consequently, the
analogous but monoanionic pic ligand (pic: pyridine-2-
carboxylic acid) renders only moderate activity (entry 18, Table 1).
The said catalytic system has initially been tested in different
solvents but reasonable activity is obtained only in chlorinated
solvents, and CHCl3 is found to be most effective (Table S1,
ESIw). Notably reasonable conversion has been achieved only
with PhIO among the large variety of oxidants (Table S2,
ESIw). In general, an in situ generated complex derived from 1
and dipic has led to significant activity and 2-phenylacetaldehyde
has been isolated in 92% yield (Table 1).
Direct oxidation of alkenes to the corresponding carbonyl
compounds is a widely employed chemical process due to their
immense utility as an intermediate or a synthon in targeted
organic synthesis.6 The well known palladium catalyzed Wacker
oxidation usually yields ketones i.e. Markovnikov products from
terminal alkenes,6 but the direct transformation of alkenes to
aldehydes is rather scarcely reported.3–5 A Wacker type catalyst
has also been shown to influence the anti-Markovnikov regio-
selectivity for alkene to aldehyde formation as a major product in
the presence of a directing group like heteroatom(s) which
facilitates the anti-Markovnikov regioselectivity via chelation
to palladium.4 However, exclusive anti-Markovnikov regio-
selectivity with broad substrate scope has recently been achieved
using iron and ruthenium porphyrin based catalysts through a
tandem epoxidation–isomerization (E–I) pathway.5
The exclusive anti-Markovnikov regioselectivity is known
to be achieved via stoichiometric multi-step hydroboration–
oxidation reaction.1 However the generation of a large amount
of non-recyclable waste from boron and peroxide makes this
process industrially undesirable. So, there is an urgent need to
develop an efficient method for synthesizing aldehydes from
terminal alkene functionalities.7,8 An immediate economical
and environmentally benign option is to use iron as a catalyst
The optimized reaction conditions facilitate the oxidation of
alkene derivatives, 2a–s, to the aldehydes (3a–s) using only
2 mol% 1 and dipic, PhIO as an oxidant and 3 A molecular
sieves in chloroform under an aerial atmosphere (Table 2). The
change of reaction conditions to an inert atmosphere does not
alter the yield and selectivity at all. Also, molecular sieves have
Department of Chemistry, Indian Institute of Technology Bombay,
Powai, Mumbai 400076, India. E-mail: lahiri@chem.iitb.ac.in;
Fax: +91-022-2572-3480
w Electronic supplementary information (ESI) available: Experimental
procedures, detailed characterizations, additional tables, figures and
schemes. See DOI: 10.1039/c2cc32051g
Scheme 1
c
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Chem. Commun., 2012, 48, 5497–5499 5497

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Table 2 Iron catalyzed oxidation of alkene functionalitiesa
Table 1 Catalytic oxidation of styrene to aldehydesa
Entry
Catalystb
Conversion (%)
Yieldc (%)
1
2
3
4
5
6
7
8
RuCl3ꢀxH2O/dipic
Ru(acac)3/dipic
[Ru(p-cym)2Cl2]2/dipic
Ru(trpy)Cl3/dipic
Ru3(CO)12/dipic
o1
o1
51
0
0
0
0
0
46
o1
Fe2O3/dipic
10
26
0
CoCl2ꢀ6H2O/dipic
Co(acac)2(H2O)2/dipic
FeCl3ꢀ6H2O/dipic
FeCl3ꢀ6H2O/dppf
FeCl2/dipic
o1
o1
45
o1
25
o5
52
o1
12
16
6
35
65
5
60
10
75
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Fe(acac)3/dipic
Fe(OAc)2/dipic
Fe(BF4)2ꢀ6H2O
o1
Fe(BF4)2ꢀ6H2O/dppf
Fe(BF4)2ꢀ6H2O/en
Fe(BF4)2ꢀ6H2O/dppe
Fe(BF4)2ꢀ6H2O/pic
Fe(BF4)2ꢀ6H2O/trpy
Fe(BF4)2ꢀ6H2O (1)/dipic
Fe(ClO4)2ꢀ6H2O/dipic
Cu(ClO4)2ꢀ6H2O/dipic
Cu(BF4)2ꢀ6H2O/dipic
25
21
17
65
27
100
100
100
100
51
9
92d
70
42
61
a
Reaction conditions: 2 mol% catalyst, 2 mol% L, styrene, 1.5 equiv.
PhIO in 4 mL CHCl3, 3 A molecular sieves, RT, 20 h. See ESI for
b
details. dipic = pyridine-2,6-dicarboxylic acid, trpy = 2,20:60,200-
terpyridine, dppf = 1,10-bis(diphenylphosphino) ferrocene, en =
ethylenediamine, dppe = 1,2-bis(diphenylphosphino)ethane, pic =
pyridine-2-carboxylic acid, acac = acetylacetonate, p-cym = p-cymene
c
or 4-isopropyltoluene. Determined by GC using n-dodecane as an
d
internal standard. Isolated yield.
shown a prominent effect on conversion.10 Epoxides have not
been detected at all at the end of the reaction. Interestingly,
completely regioselective Markovnikov ethyl ketone is formed
from both (Z)/(E)-b-methyl styrene (2e–2f). Such entirely
reversal of regioselectivity from substrates like 2e or 2f has
been reported earlier, which provides the necessary justification
about the mechanism; especially the nature of the intermediate
(vide infra).3a,11 Unlike mono- and di-substituted alkenes, products
from the tri-substituted alkenes (1-phenylcyclohexene, 2l)
undergo alkyl migration during isomerization; indicating the
existence of the E–I mechanism.5c Furthermore, under similar
optimized reaction conditions, various aliphatic alkenes (2o–s)
have been screened to give aldehydes (3o–s) but at an elevated
temperature (60 1C) using 2 equiv. of PhIO (Table 2). The very
poor conversion (o10%) from substrates like 2-allylphenol or
eugenol is probably due to the chelating nature of the hydroxyl
group with iron. Remarkably, unlike earlier observations,5 the
present catalytic protocol functions smoothly in the absence
of either base or silver additives. In essence, both terminal
aromatic and aliphatic alkenes can be regioselectively oxidized
to aldehydes when 1 is used as a catalyst under optimized
reaction conditions.
a
A tentative mechanism is depicted in Scheme 2. Interaction
of the active iron-oxo species (1a) with the terminal alkenes via
a side-on approach leads to the formation of aldehydes by
following the two alternate pathways: (a) the tandem E–I
mechanism (path a, Scheme 2) and (b) a pinacol like rearrange-
ment (path b, Scheme 2).5,12 Initially, 1a catalyzes the oxida-
tion of alkenes to epoxides followed by isomerization to
Reaction conditions: 2 mol% 1, 2 mol% dipic, substrate, 1.5 equiv.
PhIO in 4 mL CHCl3, 3 A molecular sieves, RT, 20 h. See ESI for
b
details. Isolated yields are given. NMR yield. Markovnikov ketone
c
d
from (Z)-b-methyl styrene (2e). Markovnikov ketone from (E)-b-methyl
styrene (2f). Small amount of benzaldehyde is also obtained.
e
f
g
Isomerized product from 1-phenylcyclohexene (2l). 2 equiv. of
PhIO, 60 1C, 48 h, the rest is unreacted alkene.
c
5498 Chem. Commun., 2012, 48, 5497–5499
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In conclusion, an efficient and reliable catalytic protocol has
been developed for anti-Markovnikov oxidation to aldehydes
from terminal alkene functionalities under mild reaction condi-
tions. The present catalytic system functions well at room
temperature in most cases with the abundant, cheap, benign
and simple iron-catalyst, which is currently considered as an ideal
option to replace any precious metal in homogeneous catalysis.9
Both the tandem epoxidation–isomerization and pinacol like
rearrangement are found to be operational in the present
catalytic process. Further improvement of the present catalytic
protocol with respect to the effective use of more benign
oxidants and non-chlorinated solvents is in progress.
The financial support received from DST, CSIR (fellowship
to A.D.C.) and UGC (fellowship to R.R.), New Delhi, India,
is gratefully acknowledged.
Scheme 2
aldehydes by 1.5 The formation of epoxides during the course
of the reaction has also been established (Fig. S1, ESIw).
1H and 13C NMR spectra of a control reaction with styrene
as a model substrate at a lesser reaction time reveal the
existence of the final product, 2-phenylacetaldehyde, inter-
mediary styrene oxide and unreacted styrene (Fig. S2–S3,
ESIw). Moreover, the direct treatment of styrene oxide with
2 mol% of 1 and dipic in CHCl3 at RT for 6 h affords 3a in
99% yield. Hence, under identical reaction conditions 1 is the
active catalyst for isomerization, which indeed supports the
proposed E–I mechanism (path a, Scheme 2).5 Subsequently,
3a can also be produced directly via a pinacol like rearrange-
ment from the cationic intermediate (1b) as postulated earlier
by Groves and Collman et al. (path b, Scheme 2 and Scheme S1,
ESIw).12 Such an intermediate may also be imagined to arrive
from metallaoxetene via Fe–Ca bond cleavage (Scheme S2,
ESIw).12 The cis Cb–H bond is eventually aligned for the
requisite rearrangement or migration to 2-phenylacetaldehyde
due to conformational preference of the cyclic four-membered
ring of metallaoxetene which finally results in the carbon–
oxygen double bond as well as subsequent cleavage of the
Fe–Ca bond.12b This in turn provides indirect justification in
favor of the completely opposite regioselectivity from 2e or 2f.
Either greater stabilization of the carbocation at the benzylic
over allylic position or the relatively stable Fe–Cb bond due to
benzylic resonance presumably influences such reversal of
regioselectivity (Scheme S3, ESIw).11,12 Benzylic resonance
facilitates Cb–H to coordinate to iron to form a s-agostic
structure (sCa–H serves as an electron donor and high
lying s*Ca–H acts as a p-acceptor), which accounts for the
Markovnikov product formation.1a,11 Additionally, treatment
of styrene with PhIO and HCO2H and its subsequent reaction
with K2CO3 under similar catalytic conditions give 2-phenyl-
acetaldehyde and 1-phenylethane-1,2-diol (via ring opening of
epoxide), implying the simultaneous existence of both
pathways.5c However, the influential role of strong Lewis
Notes and references
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ꢁ
acidic iron and BF4 cannot be excluded.13 Nevertheless, a
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similar conversion even in the presence of a radical scavenger
and absolute retention of the strained four membered ring of
a-pinene essentially rule out the alternate possibility of a
radical intermediate in the present case.14
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unreacted 2e or 2f.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 5497–5499 5499