Hydroboration of aldehydes, ketones and CO2under mild conditions mediated by iron(iii) salen complexes

Article abstract of DOI:10.1039/d1dt02092g

The hydroboration of aldehydes, ketones and CO₂is demonstrated using a cheap and air stable [Fe(salen)]₂-μ-oxo pre-catalyst with pinacolborane (HBpin) as the reductant under mild conditions. This catalyst system chemoselectively hydroborates aldehydes over ketones and ketones over alkenes. In addition, the [Fe(salen)₂]-μ-oxo pre-catalyst shows good efficacy at reducing “wet” CO₂with HBpin at room temperature.

Full text of DOI:10.1039/d1dt02092g

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Hydroboration of aldehydes, ketones and CO2
under mild conditions mediated by iron(III) salen
complexes†
Cite this: Dalton Trans., 2021, 50,
10696
Received 23rd June 2021,
Accepted 15th July 2021
Samantha Lau,
Ruth L. Webster
Cei B. Provis-Evans,
*
Alexander P. James and
DOI: 10.1039/d1dt02092g
rsc.li/dalton
The hydroboration of aldehydes, ketones and CO2 is demonstrated difficult but highly desired transformation is the asymmetric
using a cheap and air stable [Fe(salen)]2-µ-oxo pre-catalyst with hydroboration of ketones to achieve optically active secondary
pinacolborane (HBpin) as the reductant under mild conditions. alcohols,1 with only a handful of examples using iron com-
This catalyst system chemoselectively hydroborates aldehydes over plexes reported to date.23,30
ketones and ketones over alkenes. In addition, the [Fe(salen)2]-µ-
Beyond HB of carbonyl functionality of simple molecules,
oxo pre-catalyst shows good efficacy at reducing “wet” CO2 with there has been a paucity in reports of HB of CO2 mediated by
HBpin at room temperature.
iron complexes.31 In 2015, Sabo-Etienne, Bontemps and co-
workers32 reported high conversion and selectivity for the for-
mation of bis(boryl)acetal using 9-borabicyclo[3.3.1]-nonane
(9-BBN) as the borane source and [Fe(H)2(dmpe)2] (dmpe = 1,2-
bis(dimethylphosphino)ethane) as the catalyst.
Introduction
Continuing from our previous studies using a simple iron
salen complex (1a) to effect the hydrophosphination of
alkenes33,34 and the cyclotrimerization of alkynes,35 here we
report the hydroboration of both aldehydes and ketones with
good chemoselectivity observed for aldehydes over ketones.
Furthermore, we disclose modest rate of reduction of CO2 with
HBpin (Scheme 1).
Hydroboration (HB) of aldehydes and ketones is an efficient
route to access primary and secondary alcohols respectively
through the facile hydrolysis of organoborate intermediates
formed in these reactions.1–3 In recent years there has been a
focus on using earth abundant base metals, such as iron, to
catalyse hydrofunctionalisation reactions of unsaturated moi-
eties (alkenes, alkynes, nitriles)4–10 which have historically
been dominated by late transition metal complexes.11–17
Relative to noble metals, there are significantly fewer
reports on using iron complexes to mediate hydroboration of
aldehydes and ketones.18–24 Notably in 2017, Findlater and co-
workers reported the simple use of a Fe(acac)3/NaHBEt3 system
to hydroborate a range of aldehydes and ketones in moderate
to excellent yields in the presence of 10 mol% catalyst.25
Following on, Baker, Hein and co-workers demonstrated the
use of a [Fe(N2S2)]2 complex at 0.1 mol% catalyst loading to
hydroborate aldehydes selectively with TON ca. 5200 easily
achieved in one instance.26 In addition, the first case of an
iron(II) coordination polymer and heterogeneous Fe2O3 nano-
particles mediated hydroboration of these carbonyl moieties
have been reported by Zhang and co-workers27,28 and
Geetharani, Bose and co-workers29 respectively.
A more
Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
E-mail: r.l.webster@bath.ac.uk
†Electronic supplementary information (ESI) available: Synthetic methods, ana-
lysis data and NMR spectra. See DOI: 10.1039/d1dt02092g
Scheme 1 This work using [Fe(salen)]2-µ-oxo pre-catalyst in HB of
aldehydes, ketones and CO2.
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borate products can be converted to their primary alcohol by
quenching the reaction with minimal MeOH and then removal
Results and discussion
Optimisation of reaction conditions using 4-methyl- of the iron through a silica plug with methylene chloride as
benzaldehyde as the model substrate shows proficiency of the the eluent.
catalyst system to hydroborate the substrate using aromatic sol-
The homogeneity of the HB of aldehydes was tested.
vents (benzene, toluene) and polar solvents (dimethyl- Complementary results from parallel PMe3 and Hg dropping
formamide, methylene chloride, tetrahydrofuran). Acetonitrile test suggest the reaction is homogenous in nature (see ESI†).
was chosen due to higher solubility of 1a and ease of monitor-
Hydroboration of ketones requires a higher temperature
ing the reactions in CD3CN. Furthermore, HBpin was found to and longer reaction time. Standard substrate, acetophenone,
be much more active than catecholborane (HBcat) under com- gives 3a in good spectroscopic yield on 0.25 mmol scale and
parable conditions (see ESI†). The reactions are carried out 58% (0.59 g) isolated yield of 1-phenyl ethan-1-ol when the
with 1 mol% catalyst loading at room temperature and 60 °C reaction is scaled by over 30 times (to 8.3 mmol). Good yields
for aldehyde and ketone substrates respectively. Control reac- are obtained with electron withdrawing groups (3d–f) in the
tions without any 1a show lower conversion for benzaldehyde para position with lower conversions found for electron donat-
(58%) and acetophenone (<5%) under similar reaction con- ing groups (3b, 3g) in the same position. The conversions of
ditions (Fig. 1 and Fig. 2).
the ketones are comparable to the recent literature on iron
Excellent yields are achieved across all the aldehydes tested mediated HB of ketones (vide supra). Aliphatic products 3i and
with almost full conversion to the organoborate product 3j are formed in excellent spectroscopic yield. Competitive
observed spectroscopically. Electronic effects para to the benz- alkene HB is not observed, for example 3k is produced in low
aldehyde do not influence yields and the system is proficient spectroscopic yield but the alkene is unreacted, while we attri-
for both aryl and alkyl aldehydes. 4-Hydroxybenzaldehyde bute the modest yield of 3m to the volatility of the starting
requires a second equivalent of HBpin due to competing reac- material. Unfortunately, our catalyst system is unable to hydro-
tivity of the hydroxyl group with the reducing reagent (2f). borate esters or tertiary amides, with less than 5% conversion
Chemoselectivity is demonstrated with the alkene functionality of starting material observed for the ester substrates; ethyl ben-
left intact for cinnamaldehyde and only the mono hydrobora- zoate, vinyl benzoate, methyl 2-bromobenzoate, methyl
tion product observed (2h) by NMR spectroscopy. The organo- formate, and the amide substrates; N,N-diisopropylbenzamide,
N-(tert-butyl)-N-isopropyl-3,5-bis(trifluoromethyl)benzamide
and, N-(tert-butyl)-N-ethyl-4-methylbenzamide respectively,
even at 80 °C with higher equivalents of HBpin used (Fig. 2).
Fig. 1 Substrate scope for HB of aldehydes. All reactions were per-
formed using 0.25 mmol aldehyde and 0.30 mmol HBpin in CD3CN
(500 µL) unless stated otherwise. Spectroscopic yields reported using
1,2-dichloroethane as the internal standard. a2.4 equiv. of HBpin
required for doubly reduced product. bPercentage conversion deter-
mined by loss of CHO signal due to 1,2-dichloroethane signal overlap-
ping with characteristic methylene peak from reduction.
Fig. 2 Substrate scope for HB of ketones. All reactions were performed
using 0.25 mmol ketone and 0.30 mmol HBpin in CD3CN (500 µL)
unless stated otherwise. Spectroscopic yields reported using 1,2-
dichloroethane as the internal standard.
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The chemoselectivity of the catalyst system was further
investigated; intermolecular competition reactions show the
catalytic system selectively hydroborates aldehydes over
ketones and ketones over alkenes (Scheme 2a–c). Due to the
high conversions across all benzaldehyde derivatives with
different electronic properties in the para position, a qualitat-
ive intermolecular competition reaction using 4-bromobenz-
aldehyde, benzaldehyde and 4-methoxybenzaldehyde was set
up (Scheme 2d). The calculated spectroscopic conversions
show faster reaction with electron withdrawing substituent –Br
at the para position relative to electron donating substituent
–OMe.
To further interrogate the limits of this catalytic system, the
HB of acetophenone derivatives using the chiral iron salen
complex 1b under the same reaction conditions was carried
out to probe if enantioinduction36 can be conferred to the
product (Fig. 3, top). The reactions of the substrates are visibly
faster; good to excellent conversions are achieved within 2 h at
60 °C compared to 24 h using 1a. Unfortunately, no enantio-
induction is observed in the organoborate products after work-
up to the secondary alcohols and reacting these with the chiral
auxiliary (R)-Mosher’s acid37 to form the corresponding dia-
stereoisomeric ester product.38
Fig. 3 (Top) HB of acetophenone derivatives mediated by 1b, unfortu-
nately no enantioinduction was induced to the organoborate product.
(Bottom) HB of benzaldehyde (0.25 mmol) and HBpin (0.30 mmol) in
CD3CN (500 µL) mediated by 1c.
The different reactivity observed between 1a and 1b on the
HB of ketones may allude to the mechanism involved in these
reactions. The varying modes of activation that 1a can undergo
have been investigated previously by our group showing poten- ment, or alternatively can simply be reduced down to 1c, an
tial to form a twisted Fe salen complex containing ‘Bpin’ frag- Fe(II) air and moisture sensitive analogue of 1a.34,35 Reacting
benzaldehyde with 2 mol% 1c, results in 92% conversion to 2a
at room temperature after 2 h which is comparable to the
efficacy of 1a (Fig. 3, bottom). This data would suggest the
mechanism of the HB of carbonyls is likely to undergo a
reduction with HBpin to generate the active species 1c that
participates in the catalytic cycle. The empirical observation
that 1b is a more active pre-catalyst than 1a could be due to
the greater electron density on the iron centre from the tert-
butyl groups on the phenolate arms as well as the cyclohexyl
backbone of the ligand for a faster reduction to the active Fe(II)
species. Further detailed study is necessary to determine
whether 1c undergoes further activation (i.e. twisting) to gene-
rate an on-cycle species, or whether 1c is a discrete on-cycle
catalyst in its own right.
We next examined the reduction of CO2 using 1a as the pre-
catalyst.‡ The advantage of using boranes for CO2 reduction
circumvents harsher reaction conditions normally associated
when using dihydrogen gas as the reductant by exploiting the
more reactive B–H bond.39–43 Due to the insolubility of bis
(pinacolato)diborane (BOB) formed during the reaction in
CD3CN, a 1 : 1 mixture of CD3CN : C6D6 is used for the follow-
ing studies. Furthermore, “wet” CO2 generated from dry ice/
toluene mixture, and without passing through a drying
column, is added directly to the reaction vessel. Modest con-
sumption of HBpin is achieved after 7 days at room tempera-
ture, with formation of the formoxy (4), acetal (5), methoxy (6)
derivatives of HBpin, and undesired BOB confirmed by 1H and
11B NMR spectroscopy.44 Repeating the reaction at 60 °C
Scheme 2 Competition HB reactions:
selectivity between benzaldehyde and acetophenone,
molecular chemoselectivity between benzaldehyde and styrene, c –
intermolecular chemoselectivity between acetophenone and styrene
a
–
intermolecular chemo-
inter-
b
–
and
d – intermolecular competition of electronic effects para to
benzaldehyde.
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Table 1 Reduction of CO2 with boranes
Notes and references
‡CO2 reactions performed in a standard J. Young NMR tube. Estimated theore-
tical maximum amount of CO2 in reaction vessel at 1 atm and 25 °C was calcu-
lated to be 0.08 mmol.
[Fe]
Borane
4
5
6
COa + H2 + R2BOBR2
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shows similar conversions to 4, 5, and 6 but with a higher
yield of BOB (see ESI†). Although the rate of the reaction is
slow and conversions modest, the use of “wet” CO2 demon-
strates the air and moisture stability of 1a in this catalytic
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from gas cylinder shows similar reactivity and confirmed no
detrimental effect in using “wet” CO2.
Alternative borane sources 9-BBN and HBcat were also
tested but perform poorly in the reaction; differing from
trends observed in the reported literature.31,32,45 Furthermore,
no advantageous improvement to reduction of CO2 is observed
using 1b as the pre-catalyst. However, the potential to optimise
the ligand design of these [Fe(salen)]2-µ-oxo complexes pro-
vides an attractive opportunity to improve the rate of CO2
reduction but is beyond the scope of this study (Table 1).
Conclusions
The hydroboration of aldehydes and ketones was achieved
using an air and moisture stable [Fe(salen)]2-µ-oxo (1a) pre-
catalyst. The catalyst system was chemoselective for aldehyde
over ketone substrates. Unfortunately, the chemistry could
not be expanded to induce enantioinduction using a chiral
pre-catalyst, 1b. However, the reduction of CO2 using
boranes was investigated with 1a tolerating “wet” CO2,
formed from a dry ice/toluene mixture. Although the rate of
conversion was slow and conversions modest for the
reduction of CO2, future work on ligand design provides an
attractive opportunity to improve the reaction whilst still
benefitting from the air and moisture stability of these
[Fe(salen)]2-µ-oxo complexes.
Conflicts of interest
There are no conflicts to declare.
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