Markovnikov-Selective, Activator-Free Iron-Catalyzed Vinylarene Hydroboration

Article abstract of DOI:10.1021/acscatal.6b02281

Two series of structurally related alkoxy-tethered NHC iron(II) complexes have been developed as catalysts for the regioselective hydroboration of alkenes. Significantly, Markonikov-selective alkene hydroboration with HBpin has been controllably achieved using an iron catalyst (11 examples, 35-90% isolated yield) with up to 37:1 branched:linear selectivity. anti-Markovnikov-selective alkene hydroboration was also achieved using HBcat and modification of the ligand backbone (6 examples, 44-71% yields). In both cases, ligand design has enabled activator-free low-oxidation-state iron catalysis.

Full text of DOI:10.1021/acscatal.6b02281

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Letter
Markovnikov Selective, Activator-Free
Iron-Catalyzed Vinylarene Hydroboration
Alistair J. MacNair, Clément R. P. Millet, Gary S. Nichol, Alan Ironmonger, and Stephen P Thomas
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b02281 • Publication Date (Web): 22 Sep 2016
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ACS Catalysis
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Markovnikov Selective, Activator-Free Iron-Catalyzed Vinylarene
Hydroboration
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Alistair J. MacNair,a Clément R. P. Millet,a Gary S. Nichol,a,b Alan Ironmongerc and Stephen P.
Thomasa*
aEaStChem, School of Chemistry, University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh, EH9
3FJ. Eꢀmail: stephen.thomas@ed.ac.uk. bPlease direct enquiries regarding Xꢀray crystallography to G.S.Nicol@ed.ac.uk.
cResearch and Development, GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG1 2NY.
Supporting Information Placeholder
earth abundant metalꢀcatalyzed hydroboration reactions that proꢀ
ceeds with Markovnikov selectivity.25,26,27
ABSTRACT: Two series of structurally related alkoxyꢀtethered
NHC iron(II) complexes have been developed as catalysts for the
regioselective hydroboration of alkenes. Significantly, Markoniꢀ
kov selective alkene hydroboration with HBpin has been controlꢀ
lably achieved using an iron catalyst (11 examples 35ꢀ90% isolatꢀ
ed yield) with up to 37:1 branched:linear selectivity. antiꢀ
Markovnikov selective alkene hydroboration was also achieved
using HBcat and modification of the ligand backbone (6 examꢀ
ples, 44ꢀ71% yields). In both cases, ligand design has enabled
activatorꢀfree low oxidationꢀstate iron catalysis.
Scheme 1. The current state-of-the-art in metal-catalyzed
Keywords: iron, catalysis, hydroboration, Markovnikov se-
lectivity, NHC ligands
Boronic esters are ubiquitous in chemical synthesis due to the
vast number of bondꢀforming reactions able to selectivity transꢀ
form these stable reagents into a wideꢀrange of functionalities.1–4
The hydroboration of alkenes using boranes is a wellꢀestablished
method for the synthesis of alkyl boranes, which can be converted
to the benchꢀstable boronic esters in a straightforward manner.5,6
In contrast, the hydroboration of alkenes using boronic esters
leads directly to the alkyl boronic esters, but requires the use of a
precious metal catalyst, most commonly rhodium (Scheme 1).
alkene hydroboration reactions.
To this end, we sought to develop a Markovnikov selective
ironꢀcatalyzed hydroboration reaction. Ideally, this would be
achieved using operationally simple conditions: easily handled
reagents and without the need for an external activator. As part of
our continuing research efforts on the development of novel actiꢀ
vation modes for earth abundant metal preꢀcatalysts, and given
that alkoxyꢀtethered NHC ligands have been reported for the hyꢀ
drosilylation of carbonyl derivatives,28,29 we postulated that ligand
assistance could be used to enable both preꢀcatalyst and boronic
ester activation.
Although high chemoselectivity, regioselectivity and enantioseꢀ
lectivity can be achieved using preciousꢀmetals,7–9 there is still
limited precedent for the direct generation of benchꢀstable pinacol
boronic esters by use of pinacol borane (HBpin),10–12 and precious
metals suffer from inherent toxicity, cost and sustainability conꢀ
cerns. To address these concerns, earth abundant metal species
have been developed as potential alternatives.13,14
Three aryloxyꢀfunctionalized imidazolinium salts were syntheꢀ
sized,30 along with two alkoxyꢀfunctionalized imidazolium salts
produced using a oneꢀpot protocol.31 These were deprotonated and
reacted with FeBr2 to give the five iron(II) complexes 1a-c and
2a, b, respectively (Scheme 2).32,33 It is worth noting at this point,
that even with ligand synthesis, these iron catalysts were prepared
in 2ꢀsteps and at considerably less cost than even commercially
available Wilkinson’s catalyst.34
A number of iron catalysts have been developed for the hyꢀ
droboration using HBpin, or formal hydroboration using B2Pin2
and an alkoxide, of alkene and alkynes to give the pinacol boronic
esters directly (Scheme 1).15–24 In all cases these hydroboration
reactions are either highly antiꢀMarkovnikov selective or give the
Markovnikov product as a mixture with the antiꢀMarkovnikov
product. Recently reported by Webster and coworkers, the highest
Markovnikov:antiꢀMarkovnikov selectivity ranges from 60:40 to
70:30 for styrene derivatives.23 Thus, there is a clear need for
Singleꢀcrystal Xꢀray analysis revealed that these bisꢀligated
complexes all adopted a similar distorted tetrahedral structure
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featuring an anchoring ironꢀcarbene bond and the potentially actiꢀ
vating group in the FeꢀO motif (see ESI for details).
Using 5 mol% of aryloxyꢀtethered NHCꢀFeII complex 1a the antiꢀ
1
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3
4
5
6
7
Markovnikov hydroboration product 4 was obtained, following
oxidation to give the linear alcohol 6a,10 in 81% yield. Interestingꢀ
ly, variation of the electronic character of the aryloxyꢀsubstituent
on the catalyst led to diminished hydroboration yields (see ESI for
further details). Alkoxyꢀtethered NHCꢀFeII complexes 2a, b were
considerably less active under these conditions (Entry 3, see ESI
for further details).
Scheme 2. Synthesis of novel Fe(II) complexes 1a-c and
2a,b. Molecular structure of 1a.
Initial testing of aryloxyꢀ and alkoxyꢀtethered NHCꢀFeII comꢀ
plexes 1a-c and 2a, b for alkene hydroboration using pinacolꢀ
borane (HBpin) resulted in alkene isomerization and hydrogenaꢀ
tion only (Table 1, entries 4 and 5, for full details see ESI). By
performing the hydroboration of styrene derivatives with HBpin
in the absence of solvent, mixtures of the secondary 5 and primary
4 alkylboronic ester products could be obtained (Entries 6ꢀ9, see
ESI for further details). Significantly, the Markovnikov
(branched) product was favored in all cases. Alkoxyꢀtethered
NHC complex 2a gave the best Markovnikov selectivity and yield
of the secondary hydroboration product 5 (Entries 7). Yields of
the secondary boronic ester 5 could be increased for aryloxyꢀ
tethered NHC complex 1a, but only by performing the reactions
in an excess of the styrene derivative (Entry 8). This was not necꢀ
essary for alkoxyꢀtethered NHC complex 2a which gave synthetiꢀ
cally useful isolated yields of the secondary boronic ester product
using 1.25 equivalents of HBpin (Entry 9). Further variation of
HBpin and catalyst loading gave no significant increase in yield
(see ESI for full details). Application of HBcat to the neat reaction
conditions using alkoxyꢀtethered complex 2a, led to formation of
the linear hydroboration product (Entries 10 and 11). These reacꢀ
tion mixtures were colorless and contained aggregates and the
product mixtures were indistinguishable from uncatalyzed control
reactions. This suggests that the alkoxyꢀtethered complex 2a is
decomposed by HBcat under these conditions, and that the backꢀ
ground, antiꢀMarkovnikov selective, reaction proceeds in this
case.
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Table 1. Reaction optimization for the hydroboration of
1) NaN(SiMe3)2 (2 equiv.),
THF,
N
N
Mes
N
N
N
-20 °C to r.t., 30 min
Mes
2) FeBr2 (0.5 equiv.),
r.t., 18 h
FeII
O
O
HO
X
N
Mes
styrene derivativesa
N
N
O
N
N
O
R
R
Mes
Mes
N
aConditions: Boronic ester (equiv.), [Fe] (2.5 to 5.0 mol%) and
R
Fe
R
Fe
O
O
b
1
N
alkene (1 equiv.) in THF (0.5 M), r.t.. Yields determined by H
N
N
Mes
Mes
c
NMR relative to 1,3,5ꢀtrimethoxybenzene internal standard. Isoꢀ
1a
2a
R = H,
R = Bn
lated as the corresponding alcohols following oxidation with basic
i
1b R = OMe,
1c R = NO2,
2b R = Bu
Entry
[Fe]
R
HBOR2
(equiv.)
Yield (%)b
(mol%)
4
5
1c
2c
3c
none
PhCH2CH2
PhCH2CH2
PhCH2CH2
PhCH2CH2
4ꢀtBuꢀC6H4
4ꢀtBuꢀC6H4
4ꢀtBuꢀC6H4
4ꢀtBuꢀC6H4
4ꢀtBuꢀC6H4
4ꢀtBuꢀC6H4
PhCH2CH2
HBcat (1.5)
HBcat (1.5)
HBcat (1.5)
HBpin (2.0)
HBpin (2.0)
HBpin (2.0)
HBpin (2.0)
HBpin (1.0)
HBpin (1.25)
HBcat (1.25)
HBcat (1.25)
25
81
30
ꢀ
ꢀ
8
1a
1a (5.0)
2a (5.0)
1a (5.0)
1a (2.5)
1a (2.5)
2a (2.5)
1a (2.5)
2a (2.5)
2a (2.5)
2a (2.5)
ꢀ
50% probability ellipsoids; Hydrogen atoms and solvent moleꢀ
cules omitted for clarity; Grey = C, Blue = N, Red = O, Orange =
Fe. CCDC 1487368ꢀ1487371 contains the supplementary crystalꢀ
lographic data for complexes 1aꢀc and 2a.
4
ꢀ
5
6d
7d
8d,f
9d
10d
11d
ꢀ
6
5
26e
25e
67e
70e
ꢀ
3
Initial investigations into alkene hydroboration found success
using catecholborane (HBcat). HBcat is known to perform alkene
hydroboration at elevated temperatures, but the reaction proceeds
only very slowly at room temperature (Table 1, Entry 1).35,36 In
the presence of HBcat, complexes 1a-c were shown to be catalytiꢀ
cally active for the linear hydroboration of terminal alkenes in
THF at room temperature (Entry 2, see ESI for further details).
2
8
37e
65e
ꢀ
H2O2(aq). dConditions: neat. eConversions determined by integrals
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ACS Catalysis
1
tion of styrene derivatives using 2a.a,b
of benzylic product peaks in H NMR relative to the limiting reaꢀ
gent. f4ꢀtertꢀbutylstyrene (5 equiv.).
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aConditions: HBpin (1.25 equiv.) added in a single portion to 2a
(2.5 mol%), followed after ~15 s by alkene (1 equiv.), r.t., 4 h.
bIsolated yields following flash column chromatography. Converꢀ
sions in parentheses, and branched:linear ratios calculated from
relative integrals of starting material and product peaks in 1H
NMR, average of at least 2 runs. cProduct unstable on silica gel.37
The scope of the Markovnikov selective hydroboration reaction
was investigated using a range of electronically differentiated
styrene derivatives, alkoxyꢀtethered NHCꢀFeII 2a (2.5 mol%) and
HBpin (1.25 equivalents) (Table 2). Styrene proved to be an exꢀ
cellent substrate giving the secondary boronic ester 5a in 81%
isolated yield, and a 24:1 branched:linear ratio, significantly inꢀ
creased regioselectivity compared to those previously reported.23
Styrene derivatives bearing alkylꢀ and trialkylsilylꢀsubstituents
reacted in good yields (5bꢀ5d, 38ꢀ72%) and branched:linear selecꢀ
tivities (9:1 to 30:1). Alkyl substituents could also be tolerated in
the ortho position, with synthetically useful yields and
branched:linear selectivities achieved (5e). Styrene derivatives
bearing electronꢀdonating arylꢀsubstituents underwent successful
hydroboration in moderate to good yields (35ꢀ72%) and selectiviꢀ
ties (5:1 to 30:1) to give the branched boronic esters 5bꢀ5g. Styꢀ
rene derivatives bearing electronꢀwithdrawing arylꢀsubstituents
including fluoroꢀ and trifluoromethyl groups gave the secondary
alkylꢀboronic esters 5h-5k in good yields (48ꢀ90%) and excellent
branched:linear ratios (16:1 to 37:1). Using 4ꢀcyanostyrene resultꢀ
ed in only 7% of the alkene hydroboration product 5l, along with
a mixture of alkene and nitrile hydrogenation products. Alkylꢀ
alkenes, such as 4ꢀphenylꢀ1ꢀbutene gave no conversion to the
Markovnikov hydroboration product 5m under these conditions
with only starting material and a mixture of alkene isomerization
products recovered from these reactions. Styrene derivates bearꢀ
ing substituents at the αꢀ or βꢀ position, such as αꢀmethylstyrene,
βꢀmethylstyrene, and indene were all unreactive under the develꢀ
oped conditions.
The substrate scope of the hydroboration to give primary alkylꢀ
boronic esters was next investigated with aryloxyꢀtethered NHC
catalyst 1a (5 mol%), HBcat (1.5 equivalents) and various alkenes
(Table 3). Successful catalysis was achieved for terminal alkylꢀ
and arylꢀ alkenes to give the primary alcohol products 6a-6f, folꢀ
lowing oxidation with basic hydrogen peroxide. Alternatively, the
catecholꢀboronic esters could be transesterified with pinacol to
give the primary alkylꢀ boronic ester products 4a and 4b. Styrene
derivatives bearing both electronꢀwithdrawing and ꢀdonating
arene substituents gave the primary alcohol products in roughly
equal yields, albeit decreased from that obtained with alkylꢀ
substituted alkenes.
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Table 2. Iron-catalyzed Markovnikov selective hydrobora-
Table 3. Iron-catalyzed anti-Markovnikov selective hy-
droboration of terminal alkenes using 1a.a,b
aConditions: HBcat (1.5 equiv.) was added in a single portion to a
solution of 1a (5 mol%) and an alkene (1 equiv.) in THF (0.5 M),
r.t., 5 h. Then an aqueous H2O2/NaOH solution was added in a
single portion, 0 °C, 0.5 h. bIsolated yields following flash column
c
1
chromatography. Yield measured by H NMR of crude reaction
product relative to 1,3,5ꢀtrimethoxybenzene internal standard.
dInstead of oxidation, pinacol (1 equiv.) was added, r.t., 18 h.
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In order to gain insight into the mechanism of the alkene hyꢀ
Scheme 4: In situ reaction monitoring by ESI-MS.
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8
droboration with HBpin, deuterium labeling experiments were
performed. Catalytic hydroboration of d8ꢀstyrene with HBpin
gave the monoꢀprotioꢀboronic ester d8-5a exclusively with H inꢀ
corporation at the terminal methyl group (Scheme 3, a). When
DBpin was used for the hydroboration of styrene the monoꢀ
deuterated boronic ester d1-5a formed in a 3:1 mixture with the
fully protioꢀboronic ester 5a accompanied by deuteroꢀstyrene dn-
3a, (Scheme 3, b). This suggests that hydrometallation precedes
CꢀB bond formation. In addition, the returned deuteroꢀstyrene
showed deuterium at both alkene carbons suggesting βꢀhydride
elimination occurs following hydrometallation, as an alternative
to BꢀC bond formation. This βꢀhydride elimination accounts for
the formation of fully protioꢀboronic ester observed when using
DBpin.
Reactions of the antiꢀMarkovnikov selective catalyst 1a with
HBcat showed cleavage of HꢀB bond to give an adduct bearing a
borylated ligand (1a·Bcat m/z = 733.26). The analogous reaction
with HBpin lead to no such borylation product being observed.
However when the Markovnikov selective catalyst 2a was used,
HBpin was cleaved and borylated complexes 2a·Bpin and
2a·(Bpin)2 (m/z = 821.39 and 948.48 respectively) were observed.
The alkoxyꢀtethered complex 2a, when treated with HBcat, gave
only products of ligand dissociation and complex decomposition.
This is in keeping with the results above, which indicted that 2a is
not a stable catalyst for hydroboration with HBcat.
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That the reaction conditions effectively catalyze the isomerizaꢀ
tion of terminal alkylꢀsubstituted alkenes (vide supra) strongly
implies that the reaction proceeds by alkene hydrometallation by
an ironꢀhydride complex. The observed borylated iron complexes
1a·Bcat, 2a·Bpin (Scheme 4) are presumably derived from the
corresponding ironꢀhydride complexes 7a and 8a respectively on
ionization. We propose that the alkoxyꢀtethered ligand is more
able to activate Bpin, promoting the formation of the required
ironꢀhydride species and in contrast to the analogous reaction with
HBcat which only leads to catalysts decomposition. The low acꢀ
tivity of 1a in the hydroboration of alkenes with HBpin is preꢀ
sumably due to the low reactivity of this ligand towards the actiꢀ
vation of HBpin. It is not clear whether these reactions proceed by
a single catalytic ironꢀhydride species or an ensemble thereof.
Scheme 3. Deuterium labeling studies of Marknovnikov
selective alkene hydroboration. Isolated yields following
The regioselectivity of the Markovnikov selective hydroboraꢀ
tion of styrene derivatives with HBpin and alkoxyꢀtethered comꢀ
plex 2a can be rationalized by the formation a stabilized benzylꢀ
iron intermediate following hydrometallation. For the antiꢀ
Markovnikov selective hydroboration reactions with the more
electrophilic HBcat, where catalyst decomposition is observed, a
Lewis acid/base promoted,40 or radical hydrogenꢀatom transfer41
reactions cannot be ruled out. However, we also cannot exclude
the formation of a kinetically favored terminal alkylꢀiron intermeꢀ
diate when using HBcat. Further mechanistic investigations, in
order to investigate the regioselectivity switch, and allow refineꢀ
ment of the catalyst design and expansion of the reaction scope,
are still ongoing.
flash column chromatography.
Reaction monitoring by 11B NMR provided no evidence of any
boron containing species other than the product and HBpin in the
reaction mixtures. Oxidation of the branched hydroboration prodꢀ
uct, followed by chiral HPLC analysis revealed no enantioenꢀ
richment of the secondary alcohol products, despite the enantioenꢀ
riched ligand (see ESI for details).
To further probe the mechanism, and given the lack of any enꢀ
antioselectivity, the catalytic hydroboration of styrene with HBpin
was performed in the presence of radical inhibitors TEMPO and
galvinoxyl free radical. In both cases, increased loading of radical
inhibitor was needed to considerably attenuate catalytic activity
(see ESI for details). The formation of neither alkylꢀTEMPO nor
alkylꢀgalvinoxyl adducts were observed. Diminished yields in the
presence of free radical additives may simply be due to reactions
between the additive and the iron catalyst.38,39
In summary we have developed a series of novel Fe(II) cataꢀ
lysts bearing alkoxyꢀtethered NHC ligands that are catalytically
active for the hydroboration of terminal alkenes with controlled
and switchable regioselectivity. Alkoxyꢀtethered NHCꢀFeII comꢀ
plex 2a is the first reported iron catalyst that is effective for the
Markovnikov (branched) selective hydroboration of styrene deꢀ
rivatives using HBpin. Additionally, aryloxyꢀtethered NHCꢀFeII
complex 1a has been shown to be an effective catalyst for the
antiꢀMarkovnikov (linear) selective hydroboration of terminal
alkenes using HBcat. Mechanistic investigations suggest that the
innovative ligand design facilitates a ligandꢀassisted catalyst actiꢀ
vation. The proposed catalytically active hydride species enable
ironꢀcatalyzed hydroboration reactions to proceed in short reacꢀ
tion times at ambient temperatures and, most significantly, in the
absence of any external activator.
Having proposed that the alkoxyꢀtethered NHC ligands could
act in conjunction with the FeII center to activate the boronic esꢀ
ters, investigation into the identity of the catalytic intermediates
was paramount. ESIꢀMS was used to directly probe the reaction
mixtures of both the antiꢀMarkovnikovꢀ and Markovnikov selecꢀ
tive hydroboration of styrene 3g (Scheme 4).
ASSOCIATED CONTENT
Supporting Information
Experimental procedures and compound characterization data
including crystallographic data for compounds 1a, 1b, 1c and 2a
in cif format. This material is available free of charge via the Inꢀ
ternet at http://pubs.acs.org.
AUTHOR INFORMATION
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Corresponding Author
ACS Catalysis
(20) Chen, J.; Xi, T.; Lu, Z. Org. Lett. 2014, 16, 6452–6455.
(21) Tseng, K.ꢀN. T.; Kampf, J. W.; Szymczak, N. K. ACS Catal. 2015,
5, 411–415.
(22) GilbertꢀWilson, R.; Chu, W.ꢀY.; Rauchfuss, T. B. Inorg. Chem.
2015, 54, 5596–5603.
(23) EspinalꢀViguri, M.; Woof, C. R.; Webster, R. L. Chem. – Eur. J.
2016, 22, 11605ꢀ11608.
(24) Liu, Y.; Zhou, Y.; Wang, H.; Qu, J. RSC Adv., 2015, 5, 73705ꢀ
73713.
(25) Noh, D; Chea, H; Ju, J; Yun, J. Angew. Chem. Int. Ed. 2009, 48,
6062ꢀ6064.
(26) Reilly, S. W.; Webster, C. E.; Hollis, T. K.; Valle, H. U. Dalton
Trans. 2016, 45, 2823ꢀ2828.
1
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stephen.thomas@ed.ac.uk
3
4
ACKNOWLEDGMENT
AJM and SPT thank GlaxoSmithKline and the University of Edꢀ
inburgh for the provision of a studentship (AJM). SPT thanks the
Royal Society for a University Research Fellowship. We also
thank both the NMR and Mass Spectrometry services at the Uniꢀ
versity of Edinburgh.
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60
(27) Scheuermann, M. L.; Johnson, E. J.; Chirik, P. J. Org. Lett. 2015,
17, 2716ꢀ2719.
(28) Buitrago, E.; Tinnis, F.; Adolfsson, H. Adv. Synth. Catal. 2012,
354, 217–222.
(29) Volkov, A.; Buitrago, E.; Adolfsson, H. Eur. J. Org. Chem. 2013,
2013, 2066–2070.
(30) Waltman, A. W.; Grubbs, R. H. Organometallics 2004, 23, 3105–
3107.
(31) JahierꢀDiallo, C.; Morin, M. S. T.; Queval, P.; Rouen, M.; Artur,
I.; Querard, P.; Toupet, L.; Crévisy, C.; Baslé, O.; Mauduit, M.
Chem. – Eur. J. 2015, 21, 993–997.
(32) Chen, M.ꢀZ.; Sun, H.ꢀM.; Li, W.ꢀF.; Wang, Z.ꢀG.; Shen, Q.;
Zhang, Y. J. Organomet. Chem. 2006, 691, 2489–2494.
(33) Wang, Y.; Sun, H.; Tao, X.; Shen, Q.; Zhang, Y. Chin. Sci. Bull.
2007, 52, 3193–3199.
REFERENCES
(1)
(2)
Brown, H. C. Organic Synthesis Via Boranes; John Wiley & Sons
Inc: New York, 1975.
Ramachandran, P. V.; Brown, H. C. Organoboranes for Syntheꢀ
ses; ACS Symposium Series; American Chemical Society, 2001;
Vol. 783.
(3)
Boronic Acids: Preparation and Applications in Organic Syntheꢀ
sis, Medicine and Materials, 2nd Completely Revised Edition, 2
Volume Set edition.; Hall, D. G., Ed.; Wiley VCH: Weinheim,
2011.
(4)
(5)
Doucet, H. Eur. J. Org. Chem. 2008, 2008, 2013–2030.
Brown, H. C.; Ramachandran, P. V. In Reductions in Organic
Synthesis; ACS Symposium Series; American Chemical Society,
1996; Vol. 641, pp 1–30.
(34) Costs for complex 2a break down as follows: ligand approximateꢀ
ly £10/mmol; iron(II) bromide approximately £1/mmol;
(6)
Zaidlewicz, M.; Wolan, A.; Budny, M. In Comprehensive Organic
Synthesis II (Second Edition); Elsevier: Amsterdam, 2014; pp
877–963.
Na(SiMe3)2 (1.0
M in THF) approximately £0.50/mmol; complex
synthesis (85% yield) approximately £14/mmol. Cost for Wilꢀ
kinson’s catalyst: approximately £70/mmol.
(7)
(8)
(9)
Burgess, K.; Ohlmeyer, M. J. Chem. Rev. 1991, 91, 1179–1191.
Beletskaya, I.; Pelter, A. Tetrahedron 1997, 53, 4957–5026.
Crudden, C. M.; Edwards, D. Eur. J. Org. Chem. 2003, 24, 4695–
4712.
(35) Brown, H. C.; Gupta, S. K. J. Am. Chem. Soc. 1971, 93, 1816–
1818.
(36) Brown, H. C.; Gupta, S. K. J. Am. Chem. Soc. 1975, 97, 5249–
5255.
(37) Jones, A. S.; Paliga, J. F.; Greenhalgh, M. D.; Quibell, J. M.;
Steven, A.; Thomas, S. P. Org. Lett. 2014, 16, 5964–5967.
(38) Albéniz, A. C.; Espinet, P.; LópezꢀFernández, R.; Sen, A. J. Am.
Chem. Soc. 2002, 124, 11278–11279.
(39) Du, X.; Zhang, Y.; Peng, D.; Huang, Z. Angew. Chem. Int. Ed.
2016, 55, 6671–6675.
(10) Crudden, C. M.; Hleba, Y. B.; Chen, A. C. J. Am. Chem. Soc.
2004, 126, 9200–9201.
(11) Carroll, A.ꢀM.; O’Sullivan, T. P.; Guiry, P. J. Adv. Synth. Catal.
2005, 347, 609–631.
(12) Edwards, D. R.; Hleba, Y. B.; Lata, C. J.; Calhoun, L. A.; Crudꢀ
den, C. M. Angew. Chem. Int. Ed. 2007, 46, 7799–7802.
(13) Bauer, I.; Knölker, H.ꢀJ. Chem. Rev. 2015, 115, 3170–3387.
(14) Greenhalgh, M. D.; Thomas, S. P. ChemCatChem 2014, 6, 1520–
1522.
(15) Obligacion, J. V.; Chirik, P. J. Org. Lett. 2013, 15, 2680–2683.
(16) Zheng, J.; Sortais, J.ꢀB.; Darcel, C. ChemCatChem 2014, 6, 763–
766.
(17) Zhang, L.; Huang, Z. Synlett 2013, 24, 1745–1747.
(18) Zhang, L.; Peng, D.; Leng, X.; Huang, Z. Angew. Chem. Int. Ed.
2013, 52, 3676–3680.
(19) Greenhalgh, M. D.; Thomas, S. P. Chem. Commun. 2013, 49,
11230–11232.
(40) Garrett, C. E.; Fu, G. C. J. Org. Chem. 1996, 61, 6671–6675.
(41) Villa, M.; Jacobi von Wangelin, A. Angew. Chem. Int. Ed. 2015,
54, 11906ꢀ11908 and the references contained therein.
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switchable Markovnikov or anti-Markovnikov selective hydroboration
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H
B(OR)2
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Mes
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