Organocatalytic versus iron-assisted β-boration of electron-deficient olefins

Article abstract of DOI:10.1002/asia.201000826

Combo effects: The first example of an iron-mediated β-boration of activated olefins is reported. The origin and the benefits of the catalytic activity associated with the presence of iron have been questioned and carefully studied. The iron system has be

Full text of DOI:10.1002/asia.201000826

DOI: 10.1002/asia.201000826
Organocatalytic versus Iron-Assisted b-Boration of Electron-Deficient
Olefins
Amadeu Bonet, Cristina Sole, Henrik Gulyꢀs,* and Elena Fernꢀndez*[a]
In the light of current debates surrounding sustainable
and green chemistry, iron has now become an attractive al-
ternative to the most commonly used expensive noble
metals in a number of homogenous catalytic reactions, as it
is abundant, inexpensive, less toxic, and environmentally
more acceptable.[1] Despite the intense interest in the homo-
genous catalytic applications of iron complexes, the only
Scheme 1. b-boration model reaction of activated olefins.
À
known examples of iron-mediated C B bond formation are
the 1,4-hydroboration of 1,3-dienes to obtain linear (E)-g-
disubstituted allylboranes,[2] and the C H activation/boryla-
tion of furans and thiophenes catalyzed by a half-sandwich
iron N-heterocyclic carbene complex.[3] Consequently, we
became interested in exploring the benefits of iron in the b-
boration of electron-deficient olefins,[4] comparing it with
the known catalytic systems of copper[5] and nickel[6] com-
plexes, and in particular with the most recently developed
organocatalytic systems.[7] In this study, we focused on the b-
boration of a,b-unsaturated esters and imines, which are
highly versatile reactions to access polyfunctionalized mole-
cules.
The readily available iron(II) and iron
G
ACHTUNGTRENNUNG(acac)2
À
(acac=acetylacetonate), Fe(acac)3, FeCl2, and FeACHTUNGTRENNUNG
T
were selected as iron sources (2 mol% catalytic loading of
iron). However, none of these salts were able to promote
the b-boration reaction of 1a and 1b, even at 708C. Howev-
er, the addition of a base (Cs2CO3) to the reaction medium
favored the b-boration of ethylcrotonate (Table 1, entries 1–
4). The positive influence of base in this reaction was first
observed in the case of the CuCl/KOAc catalyst.[5a,b] The
catalytic system FeACHTUNRGTNEUNG(acac)2/PPh3 (Fe/PPh3 =1:2) was also in-
active, but the presence of the base, Cs2CO3, allowed the b-
boration of ethylcrotonate in quantitative conversions,
within 6 hours (Table 1, entries 5–8). Lowering the reaction
temperatures substantially diminished the reaction rate
(Table 1, entries 9 and 10). The catalytic activity observed
We started our study by exploring whether the addition of
iron salts has any positive influence on the b-boration of
a,b-unsaturated esters and imines with diboron reagents.
Therefore, we selected bis(pinacolato)diboron (B2pin2) as
the boron source, methanol as the proton source, ethylcroto-
nate 1a, and (E)-1-phenyl-N-(4-phenylbutan-2-ylidene)me-
thanamine 1b as the substrates for the model reactions
(Scheme 1).
for the FeACHTNUGTRNEN(UG acac)2/PPh3/Cs2CO3 system can be directly com-
pared with the corresponding PPh3/Cs2CO3 and Cs2CO3 cat-
alysts[7a] (Table 1, entries 8, 11, and 12). The base alone pro-
vides 45% conversion under the chosen catalytic conditions
(Table 1, entry 12). Combining the base with phosphine in-
creases the activity but the conversion is still moderate
(Table 1, entry 11). The addition of the iron salt to the PPh3/
Cs2CO3 system is strikingly beneficial; this results in com-
plete conversion (Table 1, entry 8).
[a] A. Bonet, C. Sole, Dr. H. Gulyꢀs, Dr. E. Fernꢀndez
Department Fꢁsica Quꢁmica i Inorgꢂnica
Faculty of Chemistry
University Rovira i Virgili
A similar trend has been observed for the b-boration of
(E)-1-phenyl-N-(4-phenylbutan-2-ylidene)methanamine 1b,
which to the best of our knowledge, has only been b-borated
with a copper catalyst modified with phosphine ligands.[8]
C/Marcel.lꢁ Domingo s/n (Spain)
Fax : (+34)977-559563
E-mail: mariaelena.fernandez@urv.cat
henrik.gulyas@urv.cat
Homepage: http://www.quimica.urv.cat/~tecat/catalytic_
organoborane_chemistry.php
While FeACHTUNTGRNE(UNG acac)2 did not show catalytic activity, its combina-
tion with Cs2CO3 resulted in 28% conversion (Table 2,
entry 1). The benefits of the addition of base were also ob-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201000826.
Chem. Asian J. 2011, 6, 1011 – 1014
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1011

COMMUNICATION
Table 1. Influence of iron on catalytic b-boration of ethylcrotonate.[a]
AHCTUNRTGEG(NNNU cod)2 (cod= cycloocta-l,5-
diene),[11] under the standard
conditions of the iron-mediated
reactions. In these reactions,
NaOtBu was used as a base in
the stock solutions because of
its high solubility in tetrahydro-
furan (THF; Table 3, entries 1–
3, 9, and 10). In subsequent ex-
periments, we gradually de-
creased the concentration of
the “in situ” formed, base-acti-
vated copper and nickel com-
Entry
Iron system
Fe(acac)2
FeCl2
Fe(OMe)2
(acac)3
(acac)2
(acac)2
(acac)2
(acac)2
(acac)2
(acac)2
Cs2CO3 [mol%]
PPh3 [mol%]
T [8C]
t [h]
Conv. [%][b]
1
2
3
4
5
6
7
8
U
3
3
3
3
3
–
–
–
–
4
4
4
4
4
4
4
–
70
70
70
70
70
70
70
70
45
25
70
70
6/24
6
6
6
6/24
6
6
6
6
6
42/80
60
15
56
26/99
73
87
99
54
21
G
Fe
Fe
Fe
Fe
Fe
Fe
Fe
E
N
R
6
N
12
15
15
15
15
15
T
9
R
10
11
12
C
–
–
6
6
54
45
[a] Standard conditions: ethylcrotonate/bis(pinacolato)diboron/Fe complex=0.5:0.55:0.01. Fe/PPh3 =1:2.
Cs2CO3: mol% with respect to the substrate, MeOH: (2.5 mol%). Solvent: THF (2 mL). [b] Determined by
G.C.
plexes from 5ꢄ10À3
m
to 5ꢄ
and
10À6 m.
Both CuCl
CuOTf·4CH3CN form consider-
ably more active catalysts than
served in the Fe
G
(acac)2 when applied in the same concentration, 5ꢄ10À3
FeACHTUNRGTNEGNU m
sired b-borated product in quantitative yield (Table 2, en-
tries 2–4). Importantly, the PPh3/Cs2CO3 organocatalytic
system was not able to promote the b-boration of the imine
substrate (Table 2, entry 5).
(Table 2, entries 1–3). The higher activity is even more obvi-
ous when the catalyst concentration is decreased by one
magnitude, to 5ꢄ10À4 m (S/Cu=500), and the substrate is
still quantitatively converted into the product (Table 2,
entry 4). Further decreasing the concentration of the copper
Recent evidence about the role of metal impurities in
“iron-mediated” reactions[9] prompted us to carefully exam-
complex, the conversion quickly diminishes: at 5ꢄ10À5
m
copper concentration only 5%
of the product can be observed,
and at 5ꢄ10À6 m concentration,
the substrate remains intact.
Under the optimized conditions
for the iron-mediated b-bora-
tion reactions, nickel complexes
are much less active than the
copper catalysts (Table 2, en-
tries 9 and 10). Both NiCl2 and
Table 2. Influence of iron on catalytic b-boration of (E)-1-phenyl-N-(4-phenylbutan-2-ylidene)methanamine.[a]
Entry
Iron system
Cs2CO3 [mol%]
PPh3 [mol%]
T [8C]
t [h]
Conversion [%][b]
1
2
3
4
5
Fe
Fe
Fe
Fe
N
15
3
9
15
15
–
4
4
4
4
70
70
70
70
70
6
6
6
6
6
28
32
74
99
–
–
[a] Standard conditions: (E)-1-phenyl-N-(4-phenylbutan-2-ylidene)methanamine/bis(pinacolato)diboron/Fe
complex=0.5:0.55:0:01. Fe/PPh3 =1:2. Cs2CO3: mol% with respect to the substrate, MeOH: (2.5 mol%). Sol-
1
vent: THF (2.5 mL). [b] Determined by H NMR spectroscopy.
Ni
ACHTUNGRTEN(NUNG cod)2 provided incomplete
conversions when applied in the
ine the possible effect of traces of transition metals in our
iron precursors. As a matter of fact, the Fe(acac)2 catalyst
concentration of the iron precursor, and decreasing the con-
centration by one magnitude resulted in complete inactivity.
AHCTUNGTRENNUNG
precursor received from Sigma–Aldrich (99.95%) reported-
ly contains copper and nickel impurities in 6.1 and 43.0 ppm
concentrations, respectively. Phosphine complexes of copper
and nickel are well-known catalysts for b-boration of acti-
vated olefins.[5,6] No other metals, known to be active in b-
boration of a,b-unsaturated carbonyl compounds, such as
platinum, rhodium, and palladium were listed in the quality
certificate of the product. Under standard reaction condi-
tions, the concentration of the iron system is approximately
5ꢄ10À3 m (Table 1, foot note). Considering the heavy metal
impurities reported by the provider, the catalytic system
might contain “in situ” formed copper/phosphine, nickel/
phosphine complexes in 1.2ꢄ10À7 m and 9.2ꢄ10À7 m concen-
trations, respectively. To estimate the contribution of the im-
purities to the overall catalytic activity, we monitored the
conversion as the function of the phosphine-complex con-
centration for both copper and nickel. As a comparison, we
performed reactions using CuCl and CuOTf·4CH3CN[10] as
transition-metal precursors, as well as with NiCl2 and Ni-
Considering the high purity of the FeACTHNGUTRENU(NG acac)2 precursor
(99.95%), and the activity versus concentration profiles of
Table 3. Conversions in b-boration of ethylcrotonate with bis(pinacola-
to)diboron as the function of the concentration of copper and nickel, typ-
ical heavy metal impurities of the FeACTHNUTRGNEUNG
(acac)2 precursor.[a]
Entry
Precursor
Concentration [moldmÀ3
]
Conversion [%][b]
1
2
3
4
5
6
7
8
Fe(acac)2
CuCl
N
5ꢄ10À3
5ꢄ10À3
45
99
99
99
28
17
5
CuOTf·4CH3CN
CuOTf·4CH3CN
CuOTf·4CH3CN
CuOTf·4CH3CN
CuOTf·4CH3CN
CuOTf·4CH3CN
NiCl2
5ꢄ10À3
5ꢄ10À4
2.5ꢄ10À4
1.25ꢄ10À4
5ꢄ10À5
5ꢄ10À6
0
9
10
11
5ꢄ10À3
53
51
0
Ni
Ni
U
5ꢄ10À3
5ꢄ(10À4–10À6
)
[a] Standard conditions: ethylcrotonate=0.5 mmol, bis(pinacolato)dibor-
on=0.55 mmol, metal/PPh3/NaOtBu=1:2:5, T=708C, t=6 h. MeOH
(2.5 mol%). Solvent: THF (2 mL). [b] Determined by G.C.
1012
www.chemasianj.org
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2011, 6, 1011 – 1014

b-Boration of Electron-Deficient Olefins
the copper and nickel catalysts, one can conclude that the
heavy metal impurities cannot contribute to the overall ac-
tivity in the iron-mediated b-boration reactions.
Next, the scope of the iron-mediated b-boration was ex-
plored by using a,b-unsaturated esters, ketones, and imines
3-en-2-ylidene)aniline and (E)-N-((E)-4-phenylbut-3-en-2-
ylidene)butan-1-amine, nicely demonstrates the benefits of
the iron salt (Table 4, entries 9 and 11). In these cases, the
organocatalytic system alone cannot promote the boron-
conjugate addition to the a,b-unsaturated imines (Table 4,
entries 10 and 12).
as substrates. The FeACHTNUGTRENNUG(acac)2/PPh3/Cs2CO3 system quantita-
tively converted isobutyl crotonate into the corresponding
b-borated product, within 6 hours at 708C in tetrahydrofur-
an (Table 4, entry 1), despite the steric hindrance imparted
by the isobutyl moiety. This is in sharp contrast to the mod-
erate conversion (51%) obtained with the corresponding or-
In order to gain deeper insight into the role of iron in the
b-boration reactions, we have explored two possibilities:
a) an iron complex activates the diboron reagent, thus form-
[12]
À
ing Fe B bonds (by oxidative addition
or transmetalla-
tion), and this promotes the boron-addition to the electron-
deficient olefins in its inner coordination sphere; b) the sub-
strate is activated by the iron salt through a Lewis acid–base
interaction between the metal and the carbonyl or imino
group, which polarizes the conjugated p-electron system of
the substrate and facilitates the boron-addition. Towards
this end, we first conducted NMR studies with: a) 1 equiva-
ganocatalytic system, that is, in the absence of FeACHTNUTRGNEUNG(acac)2
(Table 4, entry 2). The b-boration of acyclic a,b-unsaturated
ketones, trans-4-hexen-3-one and trans-3-nonen-2-one,
reached complete conversion with both the PPh3/Cs2CO3 or-
ganocatalytic system and the iron-assisted system (Table 4,
entries 3–6). However, complete conversion of cyclohexe-
none required the presence of the Fe(II) salt (Table 4, en-
tries 7 and 8). Remarkably, the complete conversion of the
b-boration of 1-azadienes, such as (E)-N-((E)-4-phenylbut-
lent of Fe
ACHTUNGTRNE(NUNG acac)2 and 1 equivalent of B2pin2, b) 1 equivalent
of Fe(acac)2, 1 equivalent of B2pin2, and 1 equivalent of
AHCTUNGTRENNUNG
NaOtBu, c) 1 equivalent of B2pin2 and 1 equivalent of
NaOtBu. We have observed
that the diboron reagent is only
affected by the base, independ-
ently of the presence or ab-
Table 4. Influence of iron on catalytic b-boration of electron-deficient olefins with bis(pinacolato)diboron.[a]
Entry
Iron
Cs2CO3 [mol%] PPh3 [mol%]
Substrate
Product
Conversion [%][b]
[Yield] [%][c]
system
sence of FeACHTUNRGTNE(NUG acac)2. In order to
study possible interactions be-
tween the iron precursors and
the substrates, we performed
ESI-MS+ analyses of solutions
1
2
Fe
N
15
15
4
4
99
[90%]
51[d]
of FeACHTNUTGRENNUG(acac)2 and FeACHTUNTGERN(NUGN acac)3 in
3
4
5
6
Fe
Fe
G
15
15
15
15
4
4
4
4
99
99
93
98
ACHTUNGTRENNUNG
the presence of the two model
substrates 1a and 1b. In the
case of the combinations [Fe-
ACHTUNGTRENNUNG
A
ACHTUNGTERN(NUNG acac)2]/1b, and
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
7
8
Fe
G
15
15
4
4
91
43
[82%][c]
ACHTUNGTRENNUNG
sponding adducts with 1a and
1b are oxidized under the con-
ditions of the ESI-MS+ analy-
sis, which leads to the observa-
tion of the corresponding [Fe-
N
(acac)2]+-1a, and
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
9
Fe
Fe
G
15
15
15
15
4
4
4
4
99
0
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
(acac)3 +Na]+ by ESI-
10
11
12
MS+. To act as a Lewis acid it
needs to lose a ligand, in ac-
cordance with the observation
of the [Fe
The analogous [Fe
99
0
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
chalcone adduct has also been
observed in the FeCl3/acac-cata-
lyzed Friedel–Crafts alkylation
of indoles.[13]
[a] Standard conditions: ethylcrotonate/bis(pinacolato)diboron/Fe complex=0.5:0.55:0.01. Fe/PPh3 =1:2.
Cs2CO3: mol% with respect to the substrate, MeOH: (5 mol%). Solvent: THF (2.5 mL), T=708C, t=6 h.
[b] Determined by G.C. and H NMR spectroscopy. [c] Isolated yield. [d] Ref. [9].
1
Chem. Asian J. 2011, 6, 1011 – 1014
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1013

E. Fernꢀndez, H. Gulyꢀs et al.
COMMUNICATION
Acknowledgements
We
thank
MEC
for
funding
(CTQ2010-16226 and Consolider-In-
genio 2010 CSD2006-0003).
Keywords: b-boration
·
electron-deficient olefins · iron ·
lewis acids · organocatalysis
[1] B. Plietker in Iron Catalysis in
Organic Synthesis Wiley-VCH,
Weinheim, Germany, 2008.
[2] J. Y. Wu, B. Moreau, T. Ritter, J.
Scheme 2. Iron-mediated b-boration reaction of activated olefins.
Am. Chem. Soc. 2009, 131, 12915.
[3] T. Hatanaka, Y. Ohki, K. Tatsu-
mi, Chem. Asian J. 2010, 5, 1657.
Based on these experimental results, we suggest a preacti-
vation of the substrates by the Lewis acidic Fe(II) and Fe-
ACHTUNGTRENNUNG(III) salts (Scheme 2), as it has been proposed for the iron-
[4] a) J. A. Schiffner, K. Mꢅther, M. Oestreich, Angew. Chem. 2010,
122, 1214; Angew. Chem. Int. Ed. 2010, 49, 1194; b) V. Lillo, A.
Bonet, E. Fernꢀndez, Dalton Trans. 2009, 2899; c) T. B. Marder, J.
Organomet. Chem. 2008, 34, 46; d) L. Dang, Z. Lin, T. B. Marder,
Organometallics 2008, 27, 4443.
[5] a) K. Takahashi, T. Isiyama, N. Miyaura, Chem. Lett. 2000, 982;
b) K. Takahashi, T. Isiyama, N. Miyaura, J. Organomet. Chem. 2001,
625, 47; c) H. Ito, H. Yamanaka, J. Tateiwa, A. Hosomi, Tetrahedron
Lett. 2000, 41, 6821; d) S. Mun, J.-E Lee, J. Yun, Org. Lett. 2006, 8,
4887.
[6] K. Hirano, H. Yorimitsu, K. Oshima, Org. Lett. 2007, 9, 5031.
[7] a) A. Bonet, H. Gulyꢀs, E. Fernꢀndez, Angew. Chem. 2010, 122,
5256; Angew. Chem. Int. Ed. 2010, 49, 5130; b) B. List, L. Ratjen,
Synfacts Contributors 2010, 9, 1072; c) K.-S. Lee, A. R. Zhugralin,
A. H. Hoveyda, J. Am. Chem. Soc. 2009, 131, 7253.
catalyzed Michael additions and other conjugate addition
reactions.[14] The boron nucleophile is generated upon the
interaction of the bis(pinacolato)diboron and the organoca-
talyst.[7a] Thus, the reaction is facilitated by two catalytic sys-
tems, which function independently. The synergetic effect of
the transition-metal and the PPh3/Cs2CO3 catalytic system is
particularly striking in the case of the imine substrates. Nei-
ther the iron salt nor the PPh3/Cs2CO3 system alone can ac-
tivate these substrates, however, their combination leads to
complete conversions.
[8] C. Sole, E. Fernꢀndez, Chem. Asian J. 2009, 4, 1790.
[9] a) S. L. Buchwald, C. Bolm, Angew. Chem. 2009, 121, 5694; Angew.
Chem. Int. Ed. 2009, 48, 5586; b) P.-F. Larsson, A. Correa, M. Carril,
P.-O. Norrby, C. Bolm, Angew. Chem. 2009, 121, 5801; Angew.
Chem. Int. Ed. 2009, 48, 5691.
Experimental Section
Experimental procedure for the iron-mediated b-boration of a,b-unsatu-
rated esters, ketones, and imines with bis(pinacolato)diboron. The iron
precursor (0.01 mmol) and PPh3 (0.02 mmol of phosphorus) were placed
in a Schlenk tube, and dissolved in THF (2 mL) under argon. The suspen-
sion was stirred for 10 min and Cs2CO3 (0.075 mmol, 15 mol%) was
added. Afterwards, the substrate (0.5 mmol) and bis(pinacolato)diboron
(0.55 mmol) were added. Finally, MeOH (100 mL, 2.5 mol%) was added,
and the mixture was allowed to stir for 6h at 708C. The reaction mixture
was cooled to room temperature. An aliquot (0.2 mL) was taken from
the solution. It was diluted with CH2Cl2 (1 mL) and analyzed by G.C. to
determine conversion. After G.C. analysis, the same aliquot was gently
concentrated on a rotary evaporator at room temperature, and analyzed
by 1H NMR spectroscopy to confirm the conversion previously observed
by G.C.. In each case, both methods indicated that one single product
was formed from the substrate. The differences in the conversions ob-
tained with the two methods are within 5% in most cases.
[10] In general, CuCl is the most commonly used precursor in copper-
mediated b-borylation reactions. CuOTf is a convenient alternative
for this study, because of its high solubility in a wide range of organ-
ic solvents, it is an ideal copper(I) precursor to prepare stock solu-
tions.
[11] Both nickel(II) and nickel(0) complexes have been found to be
active in b-borylation of activated olefins. Due to their high solubili-
ty in THF, NiACHTNUTRGNENG(U cod)2 could conveniently be used to prepare stock sol-
utions for this study.
[12] X. He, J. F. Hartwig, Organometallics 1996, 15, 400.
[13] Z.-Y. Jiang, J.-R. Wu, L. Li, X.-H. Chen, G.-Q. Lai, J.-X. Jiang, Y.
Lu, L.-W. Xu, Cent. Eur. J. Chem. 2010, 8, 669.
[14] C. Bolm, J. Legros, J. Le Paih, L. Zani, Chem. Rev. 2004, 104, 6217.
Received: November 19, 2010
Published online: February 14, 2011
1014
www.chemasianj.org
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2011, 6, 1011 – 1014