Activation and discovery of earth-abundant metal catalysts using sodium tert-butoxide

Article abstract of DOI:10.1038/nchem.2697

First-row, earth-abundant metals offer an inexpensive and sustainable alternative to precious-metal catalysts. As such, iron and cobalt catalysts have garnered interest as replacements for alkene and alkyne hydrofunctionalization reactions. However, these have required the use of air- and moisture-sensitive catalysts and reagents, limiting both adoption by the non-expert as well as applicability, particularly in industrial settings. Here, we report a simple method for the use of earth-abundant metal catalysts by general activation with sodium tert-butoxide. Using only robust air- and moisture-stable reagents and pre-catalysts, both known and, significantly, novel catalytic activities have been successfully achieved, covering hydrosilylation, hydroboration, hydrovinylation, hydrogenation and [2π+2π] alkene cycloaddition. This activation method allows for the easy use of earth-abundant metals, including iron, cobalt, nickel and manganese, and represents a generic platform for the discovery and application of non-precious metal catalysis.

Full text of DOI:10.1038/nchem.2697

ARTICLES
PUBLISHED ONLINE: 9 JANUARY 2017 | DOI: 10.1038/NCHEM.2697
Activation and discovery of earth-abundant metal
catalysts using sodium tert-butoxide
Jamie H. Docherty1, Jingying Peng1, Andrew P. Dominey2 and Stephen P. Thomas1
*
First-row, earth-abundant metals offer an inexpensive and sustainable alternative to precious-metal catalysts. As such,
iron and cobalt catalysts have garnered interest as replacements for alkene and alkyne hydrofunctionalization reactions.
However, these have required the use of air- and moisture-sensitive catalysts and reagents, limiting both adoption by the
non-expert as well as applicability, particularly in industrial settings. Here, we report a simple method for the use of earth-
abundant metal catalysts by general activation with sodium tert-butoxide. Using only robust air- and moisture-stable
reagents and pre-catalysts, both known and, significantly, novel catalytic activities have been successfully achieved,
covering hydrosilylation, hydroboration, hydrovinylation, hydrogenation and [2π+2π] alkene cycloaddition. This activation
method allows for the easy use of earth-abundant metals, including iron, cobalt, nickel and manganese, and represents a
generic platform for the discovery and application of non-precious metal catalysis.
arth-abundant metal catalysis is key to the sustainable future of reagents and pre-catalysts would be air- and moisture-stable solids
chemical synthesis and manufacturing. Despite this, precious- that are easily handled and applicable in large-scale processes,
E
metal catalysts remain the ‘go-to’ for both industry and academia. with minimal associated hazards. With this in mind, we questioned
Several reductive strategies have been developed to enable state-of- whether a non-organometallic reagent could serve as a pre-catalyst
the-art earth-abundant metal catalysis, but the majority of these activator, greatly simplifying low-oxidation-state non-precious-metal
rely on the use of air- and moisture-sensitive pre-catalysts (Fig. 1a, catalysis. This Article describes what promises to be a significant
upper)1–8 or reagents (Fig. 1a, lower)9–23, which are challenging to step along that road: the universal activation of first-row
handle, store and transport, thus hindering widespread adoption transition-metal pre-catalysts using sodium tert-butoxide
of these otherwise powerful methods. In the ideal scenario, all (NaOtBu, Fig. 1b).
a Generation of low-oxidation-state iron and cobalt catalysts
b General and simple pre-catalyst activation: a universal method
Feedstocks
Fe0 or CoI
Strong reductant
e.g. Na(Hg)
BPin
R2
Low-oxidation-state
pre-catalyst
R1
R2
R1
SiR3
R2
Isolate
H
R1
• Challenging synthesis
• Air/moisture sensitive
• Specialist equipment
FeII or CoII
H
(pre-catalyst)
H
H
H
M
R
In situ generated
low-oxidation-state
species
Organometallic
activator
FeII/CoII/MnII/NiII
(pre-catalyst)
Ar
+
H
• Pyrophoric reagents
• Pre-catalyst specific
Activator
H
RMgX
RLi
LiAlH4
NaBHEt3
Mg*
• Safe
• Easily handled
• Air/moisture stable
• Inexpensive
NaOtBu
Conventional (organometallic) reagents
Figure 1 | Activation strategies for iron and cobalt pre-catalysts. a, Typical routes to generate catalytically active iron(0) and cobalt(I) catalysts (upper).
Analogous iron(II) and cobalt(II) complexes are bench-stable surrogates for these low-oxidation-state species, which are activated using external
organometallic reagents or reducing metals as in situ reductants (lower). b, Organometallic-free in situ pre-catalyst activation for olefin hydrofunctionalization
using first-row transition metals.
1EaStCHEM School of Chemistry, University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh EH9 3FJ, UK. 2GSK Medicines Research
Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. e-mail: stephen.thomas@ed.ac.uk
*
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Table 1 | Iron- and cobalt-catalysed hydroboration and hydrosilylation of alkenes.
H
H
or
BPin
B/Si
Si(OEt)3
B/Si
R
R
R
[M] (1 mol%)
or
H
NaOtBu (2 mol%)
+
HBPin or HSi(OEt)3
H
Myrcene
Linear
O
Branched
O
iPr
Ar
P(iPr)2
Br
N
P(R)2
N
N
N
N
N
N
N
N
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
M
M
Fe
Fe
Co
Co
Cl
N
Br
Cl
N
N
N
N
N
R = iPr-C6H3
or tBuCHMe
R
Ph
Ar
Ar
ArBIP)MCl2
Pre-catalyst
(RPNN)MCl2
Substrate
(RIP)FeCl2
(
iPrPNNH)FeBr2
[(S)-iPrIPO]CoCl2
(Terpy)CoCl2
(
Entry
Previously reported
Activator
This work
Yield (%)*
Yield (%)
Alkene hydroboration
1a
Na(Hg) (ref. 9)
NaBHEt3 (ref. 9)
EtMgBr (ref. 18)
NaBHEt3 (ref. 11)
Mg* (ref. 21)
NaBHEt3 (ref. 12)
Co(I)Me (ref. 5)
Co(I)Alkyl (ref. 6)
NaBHEt3 (ref. 16)
>98
47
90
90
92 (18:82)
>99
>98
87 (59:41)
85 (97% e.e.)
EtBIPFeCl2
1-Octene
>95
1b
2
3
4
5
6
7
EtBIPFeCl2
4-Ph-1-butene
1-Octene
Myrcene
1-Octene
1-Octene
1-Octene
α-Me-Styrene
91
87
tBuPNNFeCl2
iPrIPFeCl2
93† (20:80)
>95
iPrPNNCoCl2
MesBIPCoCl2
TerpyCoCl2
(S)-iPrIPOCoCl2
>95
>95 (93:7)
>95 (98% e.e.)
8
Alkene hydrosilylation
9
10
11
EtBIPFeCl2
1-Octene
1-Octene
Myrcene
Na(Hg) (ref. 27)
NaBHEt3 (ref. 14)
(1) ArLi,
>98
90
91 (95:5)
94‡
iPrPNNHFeBr2
5
tBuCHMeIPFeCl2
88§ (92:8)
(2) tBuCHMeIP (ref. 28)
12
13
14
TerpyCoCl2
EtBIPNiCl2
EtBIPMnBr2
1-Octene
1-Octene
1-Octene
−
−
−
−
−
−
68|| (93:7)
48||
60||,¶
*Reaction conditions: Alkene (0.4 mmol), HBPin (0.44 mmol) or HSi(OEt)3 (0.48 mmol), [Fe] (1 mol%), NaOtBu (2 mol%), THF (0.5 ml), 25 °C, 60 min. Yield determined by 1H NMR of the crude reaction
mixture using 1,3,5-trimethoxybenzene as an internal standard. Regioselectivities are reported in parentheses as a ratio of linear:branched isomers. †0.99 g product isolated. ‡8 mmol scale, neat. §1.06 g product
isolated. ||Using PhSiH3. ¶Using 2 mol% [Mn] and 4 mol% NaOtBu.
In an effort to discover a practical pre-catalyst activation method, reduction of the iron(II) precursor9. NaOtBu activation of the
we first targeted iron-catalysed hydroboration, as there are estab- bench-stable iron(II) pre-catalyst EtBIPFeCl2 gave the linear alkyl-
lished benchmarks using both a state-of-the-art isolated ‘iron(0)’ boronic ester product in excellent yield (>95%), with complete
catalyst9 and an organometallic activation method18. After testing control of regioselectivity and, importantly, equalling the reactivity
several reagent classes, metal alkoxide salts proved to be exception- of the isolated iron(0) manifold (Table 1, entry 1a) and surpassing
ally efficient activators (see Supplementary Table 1). An important that using an organometallic reagent (Table 1, entry 1b). Ethyl
series of control reactions established that the combination of an magnesium bromide (EtMgBr) has also been used for the in situ
iron(II) pre-catalyst and sodium tert-butoxide was necessary for activation of the iron(II) pre-catalyst EtBIPFeCl2 (ref. 18).
any catalytic activity. Stoichiometric quantities of alkoxide salt Activation using NaOtBu again gave equal reactivity to the
have been used previously to activate bis(pinacolato)diboron organometallic activator, with excellent yield and regioselectivity
[B2(Pin)2] and transfer B(Pin) to iron(II) chloride, but not to achieved in the hydroboration of 4-phenyl-1-butene (Table 1,
trigger low-oxidation-state catalysis or a general reductive catalysis entry 2). Huang has reported the catalytic activity of an iron(II)
platform19. From a practicality perspective it is key to note that pincer complex, tBuPNNFeCl2, in combination with NaBHEt3 as
these reactions were conducted using reagents as supplied from the activator for the anti-Markovnikov hydroboration of alkenes11.
commercial vendors, without purification, even after extended Using this iron(II) pre-catalyst and NaOtBu, in place of NaBHEt3,
storage in air, and using a single straightforward activation protocol. again gave the linear alkylboronic ester in excellent yield, with
exclusive regioselectivity and equal reactivity to that using
Results and discussion
NaBHEt3 (87%, Table 1, entry 3). Ritter has previously used
The generality of any synthetic protocol is essential for widespread (imino)pyridine iron(II) dichloride pre-catalysts for the 1,4-hydro-
adoption. It was therefore important to assess whether the NaOtBu boration of 1,3-dienes using activated magnesium as the activator22.
activation could be applied to a range of pre-catalyst classes We further exemplified our activation method by successful
(Table 1). Chirik has reported the use of iron(0) bis(imino)pyridine application to six (imino)pyridine iron(II) chloride pre-catalysts
complexes as catalysts for the hydroboration of alkenes, where the (see Supplementary Table 3). Using NaOtBu, the pre-catalyst
key iron(0) species is prepared by sodium–mercury amalgam iPrIPFeCl2, loading could be reduced to 1 mol% (from 4 mol%),
2
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ARTICLES
HBPin
or
H
H
[Fe] or [Co] (1 mol%)
R1
+
or
BPin
SiH2Ph
R
NaOtBu (2 mol%)
25 °C, 1 h
R
R
PhSiH3
1a–1k
2a–2k
O
O
H
BPin
O
O
H
O
S
BPin
2
N
BPin
BPin
HN
MeO
PhN
H
2
8
H
BPin
H
2a [Co] >95% (70%)
2b [Co] 90% (80%)
2d [Co] >95% (70%)
2e [Co] 70%
2c [Co] 72% (50%)*
H
H
H
H
H
BPin
BPin
BPin
BPin
BPin
AcO
Cl
Br
2g [Co]† >95% (90%)
2i [Co]† 75% (68%)
2f [Co] >95% (88%)
2h [Co] 82% (80%)
2j [Fe] 78% (60%)
H
H
H
H
SiH2Ph
BPin
F3C
SiH2Ph
SiH2Ph
F
SiH2Ph
H
H2N
2k [Fe] 71% (68%)
2l [Fe] 94% (85%)
2m [Fe] >95% (89%)
2n [Fe] >95% (88%)
2o [Fe] 71% (69%)
H
H
Iron/cobalt
n-C6H13
SiH2Ph
stereodivergence
n-C6H13
SiH2Ph
2p [Fe] >95% (95%)
(99:1, Z/E)
• Iron = Z-selective
• Cobalt = E-selective
2q [Co] >95% (75%)
(11:89, Z/E)
Figure 2 | Iron- and cobalt-catalysed hydroboration and hydrosilylation using NaOtBu as a pre-catalyst activator. Iron- and cobalt-catalyst substrate
scope for alkene and alkyne hydroboration (2a–2k) and hydrosilylation (2l–2q). Yields determined by 1H NMR of the crude reaction mixture using
1,3,5-trimethoxybenzene as an internal standard and isolated yields are reported in parentheses. Pre-catalyst used: [Fe] = EtBIPFeCl2, [Co] = MesBIPCoCl2,
[Co]† = iPrPNNCoCl2. *Yield of isolated product following oxidative work-up.
and the 1,4-hydroboration products of myrcene, a naturally industry consumes approximately 5.6 metric tonnes of platinum
occurring terpene, could be synthesized in high yield (93%), on annually26. As a consequence, several new earth-abundant metal
gram-scale and with equal regioselectivity to that previously catalysts have emerged for alkene hydrosilylation20,27,28
.
reported (Table 1, entry 4).
We began by testing the catalytic activity of a range of iron(II)
With the successful activation of over ten iron pre-catalysts, we pre-catalysts, in combination with 1-octene and silanes that were
were curious as to whether the NaOtBu activation could be compatible with previous methods involving organometallic activa-
applied to other earth-abundant metals24. Chirik has shown that tors20. We quickly found success. A range of bis(imino)pyridine
MesBIPCo(I)Me is a highly efficient pre-catalyst for alkene hydro- iron(II) pre-catalysts, BIPFeCl2, with varying steric environments,
boration5, and Huang similarly reported the hydroboration of were compatible (see Supplementary Table 6), and we could use
alkenes using a cobalt(II)-pincer complex, iPrPNNCoCl2, in combi- EtBIPFeCl2 to catalyse the hydrosilylation of 1-octene with triethoxy-
nation with NaBHEt3 as the activator12. Remarkably, NaOtBu suc- silane to give the silylated product in excellent yield (94%) with
cessfully facilitated pre-catalyst activation for both structurally exclusive linear regioselectivity (Table 1, entry 9). Again, both the
unique cobalt(II) pre-catalysts, iPrPNNCoCl2 and MesBIPCoCl2, to high yield and regioselectivity matched that of the analogous
give the alkyl boronic ester in equal yield to that reported previously state-of-the-art Fe(0) complex27. The catalyst scope for alkene
(>95%) and with complete control of regioselectivity in both cases hydrosilylation was assessed by application of the activation
(Table 1, entries 5 and 6). Significantly, the activation method was method to a selection of pre-catalysts with literature-established
extended to the activation of an enantiopure C1-symmetric imino- low-oxidation-state catalytic activity (Table 1, entries 9–11). Ritter
pyridine-oxazoline cobalt(II) pre-catalyst iPrIPOCoCl2, which reported the iron-catalysed 1,4-hydrosilylation of 1,3-dienes using
enabled the hydroboration of α-methylstyrene in excellent yield an (imino)pyridine iron(0) species that was formed by a ligand-
(95%) and enantioselectivity (98% e.e., Table 1, entry 8), once again induced reductive elimination (C2sp–Cs2p, bond forming) from a
equalling the reported reactivity using an organometallic activator16. sensitive aryl-ligated iron(II) complex28. We therefore applied our
Having successfully developed a practical activation method for novel activation method to the analogous (imino)pyridine iron(II)
alkene hydroboration using different ligand structures and metals, dichloride pre-catalysts (see Supplementary Table 4). Using NaOtBu,
we decided to investigate the generality of this method with the 1,4-hydrosilylation of myrcene was achieved on a gram scale in
respect to other reaction classes. Alkene hydrosilylation is one of high yield (88%) and with equal regioselectivity to that previously
the largest industrial processes currently in operation25. reported (Table 1, entry 11).
Principally, these reactions are carried out using well-established
platinum catalysts, and it is estimated that the global silicone both iron(II) and cobalt(II) pre-catalysts, then the activation of a wide
We recognized that if NaOtBu could be used for the activation of
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range of traditionally synthetically challenging catalyst systems may
also be possible. Specifically, our activation method could be used to
discover novel catalytic reaction manifolds. Remarkably, we observed
noteworthy reactivity from the outset. The cobalt complex
TerpyCoCl2, derived from the widely available terpyridine ligand,
showed good hydrosilylation activity (Table 1, entry 12). To our sur-
prise, we were unable to find literature precedent for hydrosilylation
activity using any analogous terpyridine–cobalt complex. We next
targeted nickel(II) and manganese(II) pre-catalysts, as there are
very limited examples of alkene hydrofunctionalization reactions
with these metals29–31. Formation of EtBIPNiCl2 and EtBIPMnCl2,
followed by application of our NaOtBu activation method, led to
the discovery of two entirely novel catalytic manifolds (Table 1,
entries 13 and 14). In both cases, successful hydrosilylation to
give the anti-Markovnikov silane product was achieved with com-
plete regiocontrol in good yields. To the best of our knowledge,
these are the first examples of a manganese-catalysed alkene hydro-
silylation using a manganese(II) pre-catalyst and of hydrosilylation
using a bis(imino)pyridine nickel species. These results illustrate
the efficacy of the NaOtBu activation method, not for only the sim-
plification of established methodologies, but also for the discovery of
new catalytic processes.
[
EtBIPFe0(N2)]2
(200 ppm Fe)
97% (GC-yield)
Ref. 27
n-C6H13
H
Si(OEt)3
+
n-C6H13
HSi(OEt)3
EtBIPFeIICl2
(94 ppm Fe)
NaOtBu (430 ppm)
94% (>2 g isolated)
Ar
N
Ar
Cl
Cl
N
N
N
Ar
N
N
Fe
Fe
N
N
N
N
N
N
Et
Et
Fe
N
Et
Et
N
N
Importantly, we were able to apply the NaOtBu activation to both
iron and cobalt pre-catalysts for the hydroboration and hydrosilyla-
tion of a series of functionalized substrates without detriment to cat-
alyst activity (Fig. 2). Carbonyl functionalities including ester 1a,
Ar
[
EtBIPFe0(N2)]2
EtBIPFeIICl2
ketone 1b and indole-containing ketone 1c underwent chemoselec- Figure 3 | Gram-scale hydrosilylation using a ppm quantity of iron
tive alkene hydroboration using MesBIPCoCl2. Sulfonamide 1d pre-catalyst. Well-defined low-oxidation-state iron catalysts have been used
reacted efficiently without S–N bond cleavage or reduction, and at ppm loadings for alkene hydrosilylation in excellent yield, although these
aldimine 1e was well tolerated using these catalyst activation con- are air/moisture-sensitive and synthetically challenging. Here, we demonstrate
ditions. Styrene 1f and derivatives bearing potentially sensitive the applicability and efficacy of the NaOtBu activation for large-scale
acetoxy- 1g, chloro- 1h and even bromo-substituents 1i reacted effi- application, matching catalytic efficiency of isolated iron(0) species.
ciently to give the expected products 2f–2i in high yields and
without detrimental side reactions, such as dehalogenation. (OtBu)2). In this scenario, however, it was difficult to propose an
Additionally, the iron pre-catalyst EtBIPFeCl2 could be used for effective activation mechanism based on a reductive elimination
the hydroboration of internal alkyne 1j to give (Z)-alkenylboronic event. Nonetheless, we did postulate that β-methyl-scission could
ester 2j in good yield. Furthermore, alkene hydrosilylation using potentially occur (to generate a metal–methyl complex and
the same catalyst, EtBIPFeCl2, was successful for a number of func- acetone)32. To assess the propensity for the formation of metal
tionalized alkenes, tolerating trifluormethyl- 1l, fluoro- 1m and free tert-butoxide species, we performed stoichiometric reactions
amine 1o groups. We were also able to use our activation method to between both EtBIPFeCl2 and MesBIPCoCl2, and NaOtBu (that is,
discover the switchable stereoselective hydrosilylation of 1-octyne to 2:1 alkoxide:pre-catalyst). The resulting mixtures were analysed by
give the (Z)- or (E)-alkenylsilane, 2p and 2q, simply by exchanging 1H NMR spectroscopy to determine if a new species had been
the metal from Co to Fe, respectively. This wide functional group generated. When mixing the iron catalyst EtBIPFeCl2 and sodium
tolerance, even on base-sensitive substrates, demonstrates the exten- tert-butoxide in d8-THF, we observed ligand de-metallation and
sive applicability of this activation method and one that should aid formation of a catalytically inactive mixture, as had been observed
the general progression of base-metal catalysis.
previously33. The cobalt complex MesBIPCoCl2 showed only slight
Isolated low oxidation-state formal iron(0) complexes have been ligand de-metallation, but formed neither the alkoxide complex
shown to offer catalytic activity that surpasses that of conventional nor a catalytically active species.
platinium catalysts for alkene hydrosilylation27. Therefore, it was
Given that the reaction between pre-catalyst and NaOtBu led to
important to assess the effectiveness of our activation method for catalytically incompetent mixtures, we postulated that the NaOtBu
the generation of active catalysts in industrially relevant situations. activation may proceed by reaction of the alkoxide with the
We targeted the hydrosilylation of 1-octene with triethoxysilane, a boronic ester or silane to form a hypervalent ‘ate’ species. Once
commercially relevant silane, as there was a comparable example formed, these intermediate ‘ate’ complexes could then serve as
for this using an analogous ‘iron(0)’ complex. Using NaOtBu and hydride donors, which would facilitate the formation of metal-
EtBIPFeCl2, we were able to achieve equal reactivity to the state- hydrides and allow for a dihydrogen reductive elimination event.
of-the-art Fe(0) complex, {[EtBIPFe(N2)]2(µ2-N2)}, with even To investigate this activation mode, we first conducted stoichio-
lower catalyst loadings than have previously been reported (Fig. 3). metric reactions between alkoxide and pinacolborane, which
To understand the mode of catalyst activation using NaOtBu, we revealed a classic disproportionation by 11B NMR analysis to
carried out a series of mechanistic investigations. Initially, we recog- boron ‘ate’ complex 3, borane and borohydride34. We were able to
nized that the activation of these metal pre-catalysts using classical confirm the reductive power of complex 3 by synthesis of an analo-
organometallic activators relied on the formation of metal-hydride gous ‘ate’ species in the absence of borane or borohydride (see
or metal-alkyl intermediates that subsequently participated in a Supplementary Section 13). Similarly, reaction of phenylsilane
reductive elimination event to generate a low-oxidation-state (PhSiH3) with NaOtBu resulted in the observation of a penta-
active catalyst. In the NaOtBu activation process, the potential coordinate silicon ‘ate’ species 4 by 29Si NMR spectroscopy.
salt-metathesis with metal dichloride could lead to the generation Addition of either of these mixtures of ‘ate’ complex to an iron
of a metal bis-tert-butoxide complex (for example, EtBIPFe pre-catalyst, EtBIPFeCl2, resulted in the formation a mixture of
4
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11B = 4.7 ppm
OtBu
a Proposed activation pathway
δ
HBPin
B
O
Ar
H
N
O
N
Cl
Cl
3
Fe
N
NaOtBu
Fe
In situ generated
reducing species
Et
Et
Catalytically
active
Ph
H
PhSiH3
EtBIPFeCl2
(0.5 equiv.)
H
Si
H
OtBu
4
δ
29Si = –96.2 ppm
b Hydrosilylation using M'DM: a 'non-activating' silane
d Diene [2π+2π] cycloaddition
M'DM unable to activate
pre-catalyst
EtBIPFeCl2 (1 mol%)
NaOtBu (2 mol%)
H
BnN
BnN
Pre-catalyst
(5 mol%)
No reaction
4 (10 mol%)
n-C6H13
H
H
+
SiMe(Me3SiO)2
n-C6H13
iPrBIPFeCl2 84%
iPrBIPCoCl2 93%
Pre-catalyst and yield:
(Me3SiO)2MeSiH
(M'DM)
(1.1 equiv.)
EtBIPFeCl2 (1 mol%)
e 1,4-Hydrovinylation enabled by NaOtBu activation
4 (2 mol%)
Pre-catalyst
activated by 4
H
88% (78% isolated)
Ph
c Alkene hydrogenation
[Fe] (4 mol%)
90:10 L:B
in all reactions
+
H
Activator
Pre-catalyst
(1 mol%)
(8 mol%)
H
H
Ph
Ph
4 (2 mol%)
Ph
78% (70%) using PhSiH3
75% using HBPin
H2 (10 bar)
N
85% using 4
tBuPNNFeCl2 82%
iPrPNNCoCl2 87%
MesBIPFeCl2 80%
MesBIPCoCl2 86%
Cl
Pre-catalyst and yield:
Fe
Cl
N
Pre-catalyst activators
NaOtBu
+
PhSiH3 or HBPin
Ph
SiMe3
BnTMSIPFeCl2
or 4
Figure 4 | Mechanistic proposal for alkoxide pre-catalyst activation and insight-driven application. a, Proposed pre-catalyst activation pathway, by
formation of boron ‘ate’ species 3 or silicon ‘ate’ 4. b, Alkene hydrosilylation using M’DM enabled by pre-catalyst reduction using silicon ‘ate’ 4. Note that
the alkoxide/M’DM fusion does not alone activate the pre-catalyst (EtBIPFeCl2). c, Alkene hydrogenation by in situ generated active catalysts using silicon
‘ate’ 4. d, Alkene [2π+2π] cycloaddition, previously accessed using a low-oxidation-state pre-catalysts, enabled by in situ formation of active species using
silicon ‘ate’ 4. e, 1,4-Hydrovinylation of myrcene, using an iminopyridine-iron pre-catalyst activated by sub-stoichiometric quantities of either (1) phenylsilane
or pinacolborane and sodium tert-butoxide or (2) using a solution of 4.
paramagnetic iron species that demonstrated high catalytic activity complex 4, or (3) substoichiometric quantities of silane or borane
(Fig. 4a, see Supplementary Information for experimental details). and NaOtBu could potentially be used as general pre-catalyst activa-
When (Me3SiO)2MeSiH, M’DM, was reacted with NaOtBu and an tors to enable reactions outwith hydroboration and hydrosilylation.
iron pre-catalyst, EtBIPFeCl2, no activation occurred, and thus cata- Therefore, we sought reactions that did not use borane or silane
lytic hydrosilylation was unsuccessful using this substrate. However, starting materials to unambiguously validate the role of the alkoxide
when a pre-formed mixture of silicon ‘ate’ complex 4 was added to in pre-catalyst activation. Specifically we targeted hydrogenation2,17
,
the reaction of 1-octene with M’DM with EtBIPFeCl2 as pre-catalyst, alkene [2π+2π] cycloaddition35,36 and hydrovinylation21 reactions in
catalyst activity was recovered, demonstrating the role of ‘ate’ an effort to demonstrate general accessibility to low-oxidation-state
complex 4 in activating the pre-catalyst (Fig. 4e).
catalyst manifolds. Initially, we used 4 as an in situ activator for a
Given that we could access an active catalyst using 4, we instinc- selection of iron and cobalt pre-catalysts, which enabled alkene
tively realized that either (1) boron ‘ate’ complex 3, (2) silicon ‘ate’ hydrogenation in high yield (Fig. 4c). Similarly, iPrBIPFeCl2 and
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NATURE CHEMISTRY DOI: 10.1038/NCHEM.2697
ARTICLES
iPrBIPCoCl2 could be activated using 4 to catalyse the intramolecular
[2π+2π] cycloaddition reaction, which was previously only reported
using isolated low-oxidation-state (Fe0 and CoI) pre-catalysts
(Fig. 4d). Finally, the hydrovinylation reaction of myrcene with
styrene using the in situ generated catalyst, from BnTMSIPFeCl2, pro-
duced the anticipated 1,4-functionalized products when using either
substoichiometric HBPin or PhSiH3 and NaOtBu, or pre-formed 4, in
excellent yields and with identical regioselectivity in every case, sugges-
tive of a commonly generated active species (Fig. 4e).
16. Zhang, L., Zuo, Z., Wan, X. & Huang, Z. Cobalt-catalyzed enantioselective
hydroboration of 1,1-disubstituted aryl alkenes. J. Am. Chem. Soc. 136,
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Conclusion
In summary, an easily handled, air- and moisture-stable alkoxide
salt (NaOtBu) has been used for the activation of a wide range of
non-precious-metal pre-catalysts. State-of-the-art low-oxidation-
state iron- and cobalt-catalysed manifolds, previously only accessi-
ble using strict air/moisture-free techniques, were realized in the
simplest manner and opened to the non-expert. Notably, using
the NaOtBu activation approach, novel cobalt(II)-, manganese(II)-
and nickel(II)-catalysed alkene hydrofunctionalization reactions
were discovered. Mechanistic investigations show that NaOtBu
acts as a masked reducing agent, by forming an ‘ate’ species with
HBPin or silanes that then serves as a pre-catalyst activator. The
simplicity and generality of this method provides a platform for
the development and exploitation of non-precious-metal catalysis.
22. Wu, J. Y., Moreau, B. & Ritter, T. Iron-catalyzed 1,4-hydroboration of 1,3-dienes.
J. Am. Chem. Soc. 131, 12915–12917 (2009).
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Received 18 March 2016; accepted 15 November 2016;
published online 9 January 2017
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Acknowledgements
S.P.T. acknowledges the University of Edinburgh for a Chancellor’s Fellowship and the
Royal Society for a University Research Fellowship. J.H.D. and S.P.T. acknowledge
GlaxoSmithKline and the EPSRC (EP/M506515/1) for a PhD studentship. J.P.
acknowledges the China Scholarship Council for a studentship. The authors thank
Z. Huang for provision of the iminopyridine oxazoline ligand.
Author contributions
J.H.D. and S.P.T. conceived and discovered the NaOtBu activation. J.H.D. and J.P.
conducted the experimental work. S.P.T. and A.P.D. provided advice for the investigations.
J.H.D. and S.P.T. prepared the manuscript.
12. Zhang, L., Zuo, Z., Leng, X. & Huang, Z. A cobalt-catalyzed alkene
hydroboration with pinacolborane. Angew. Chem. Int. Ed. 53, 2696–2700 (2014).
13. Chen, J., Xi, T., Xiang, R., Cheng, B., Guo, J. & Lu, Z. Asymmetric cobalt
catalysts for hydroboration of 1,1-disubstituted alkenes. Org. Chem. Front. 1,
1306–1309 (2014).
14. Peng, D. et al. Phosphinite-iminopyridine iron catalysts for chemoselective
alkene hydrosilylation. J. Am. Chem. Soc. 135, 19154–19166 (2013).
15. Chen, J., Xi, T. & Lu, Z. Iminopyridine oxazoline iron catalyst for asymmetric
hydroboration of 1,1-disubstituted aryl alkenes. Org. Lett. 16, 6452–6455 (2014).
Additional information
Supplementary information and chemical compound information are available in the
online version of the paper. Reprints and permissions information is available online at
www.nature.com/reprints. Correspondence and requests for materials should be addressed
to S.P.T.
Competing financial interests
The authors declare no competing financial interests.
6
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