Cobalt-Catalyzed Hydroboration of Alkenes, Aldehydes, and Ketones

Article abstract of DOI:10.1021/acs.orglett.8b02775

An operationally convenient and general method for hydroboration of alkenes, aldehydes, and ketones employing Co(acac)₃ as a precatalyst is reported. The hydroboration of alkenes in the presence of HBpin, PPh₃, and NaO^tBu affords good to excellent yields with high Markovnikov selectivity with up to 97:3 branched/linear selectivity. Moreover, Co(acac)₃ could be used effectively to hydroborate aldehydes and ketones in the absence of additives under mild reaction conditions. Inter- and intramolecular chemoselective reduction of the aldehyde group took place over the ketone functional group.

Full text of DOI:10.1021/acs.orglett.8b02775

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Cobalt-Catalyzed Hydroboration of Alkenes, Aldehydes, and
Ketones
Sem Raj Tamang, Deepika Bedi, Sara Shafiei-Haghighi, Cecilia R. Smith, Christian Crawford,
and Michael Findlater*
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
S
* Supporting Information
ABSTRACT: An operationally convenient and general method for
hydroboration of alkenes, aldehydes, and ketones employing Co(acac)3 as
a precatalyst is reported. The hydroboration of alkenes in the presence of
HBpin, PPh3, and NaOtBu affords good to excellent yields with high
Markovnikov selectivity with up to 97:3 branched/linear selectivity.
Moreover, Co(acac)3 could be used effectively to hydroborate aldehydes
and ketones in the absence of additives under mild reaction conditions.
Inter- and intramolecular chemoselective reduction of the aldehyde group
took place over the ketone functional group.
rganic transformations catalyzed by Earth-abundant
transition metals have recently garnered attention due
Chirik,13a Huang,19 and Turculet.20 In each system, the
products favored anti-Markovnikov (linear) addition. In
2017, Thomas and co-workers reported a versatile cobalt(II)
catalytic system which yields Markovnikov (branched)
products while exhibiting a broad substrate scope and
tolerance of diverse steric and electronic effects; it should be
noted that anti-Markovnikov addition was the major product
for the aliphatic substrate.21 Prior to the work of Thomas, only
two examples of cobalt catalyzed Markovnikov addition were
known (Chirik15a and Hollis15c); however, only 1 example of
Markovnikov addition was reported. Therefore, there are still
opportunities to develop catalytic systems incorporating cobalt
that can generate secondary boronic esters with high yields and
regioselectivity.
O
to the increasing demand for inexpensive, efficient, atom-
economical, and environmentally benign synthetic methods.
The reduction of aldehydes and ketones to generate 1° and 2°
alcohols is an important reaction in the pharmaceutical
industry due to the inherent value of alcohols as building
blocks in the synthesis of bioactive molecules.1 There are
numerous literature examples of precious metals,2 main group
elements,3 rare earth metals,4 and alkali metals5 that are
capable of the effective and efficient reduction of carbonyl
compounds. Nevertheless, the demand for inexpensive
alternatives has resulted in the development of Earth-abundant
first-row transition-metal catalysis for such transformations
(Ni,6 Co,7 Cu,8 Fe,9a,7b,9b−d and Mn10).
Our group has a long-standing interest in base metal
catalysis,22 and more recently, we have focused on employing
commercially available metal salts in operationally convenient
transformations.23a,b,9b,23c,d Herein, we report cobalt-catalyzed
hydroboration of alkenes, aldehydes, and ketones by
commercially available Co(acac)3 (1) under mild reaction
conditions (Scheme 1). This simple precatalyst delivers (1) an
additive-free reduction of carbonyls into alcohols and (2) facile
regioselective hydroboration of alkenes in the presence of an
ancillary phosphine ligand and NaOtBu at room temperature.
Initially, we chose styrene (2a) as our model substrate and
ran catalytic hydroboration reactions employing HBpin in
THF with Co(acac)3 (1) for 24 h. Unsurprisingly, the reaction
yielded little to no product. However, we observed full
conversion of 2a in 4 h at room temperature after addition of
NaHBEt3 to 1 to generate a putative in situ “Co−H” catalytic
Boronic acid derivatives are key reaction intermediates that
have been used routinely to construct new bonds (C−C, C−N,
C−O, C−X). For example, the Suzuki−Miyaura cross-
coupling reaction utilizes boronic esters in C−C bond-forming
chemistry. Organoborates also serve as excellent surrogates
that can be modified into a variety of functional groups.
Traditionally, organoborates are accessed via synthetic
strategies such as hydroboration of alkenes or borylation of
olefins or alkanes. These reactions typically favor the formation
of the linear, anti-Markovnikov products and are well
documented with precious-metal catalysts (Rh, Ru, Ir),11
though there are examples of Earth-abundant transition metals
(Fe12 and Co13) that have been recently disclosed.
Selectivity for the branched Markovnikov products are
generally less frequently observed. Though progress has been
made, the number of reports of base metal (M = Fe,14 Co,15
Cu,16 Ni,17 and Mn18) catalyzed Markovnikov-selective alkene
hydroboration remains limited. Cobalt catalysts in hydro-
boration of alkenes have been studied by the groups of
Received: August 29, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02775
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
example, it has been proposed to activate HBpin directly and
subsequently serve as a hydride donor.7b
Scheme 1. Select Examples of Cobalt Catalysts in
Regioselective Hydroboration of Alkenes
Initial screening of the reaction with 1/NaOtBu/ L1 in a
1:1:1 ratio yielded 74% of the regioisomeric products with a
94:6 branched to linear ratio. Increasing L1 to 2 equiv yielded
90% of the hydroborated products without any erosion in the
observed regioselectivity. Control experiments showed that
productive catalysis was only observed when the combination
of catalyst, additive, and L1 was used. With these new reaction
conditions in hand, we decided to pursue catalytic hydro-
boration of alkenes with 1/NaOtBu/ L1 in 1:1:2 ratios
(Scheme 3). Under these reaction conditions, a wide scope
a
Scheme 3. Scope of Alkene Hydroboration
species. The GC−MS showed a mixture of products whereby
the formation of both Markovnikov and anti-Markovnikov
regioisomers (73:24 b/l, 52%) was observed. It should also be
noted that considerable amounts of ethylbenzene were also
formed. The screening of different cobalt salts with NaHBEt3
revealed that 1 was the most effective and efficient cobalt
source (Table S1). The combination of 1/NaHBEt3 showed
good results for several substrates that were screened (Scheme
S2). Appropriate control reactions determined that the
combination of both 1/ NaHBEt3 was catalyzing the reaction
(Table S1). Encouraged by these results, we were motivated to
develop reaction conditions that could further afford increased
regioselectivity and overall yield.
The screening of various neutral ancillary ligands showed
that PPh3 (L1) gave the best yield and regioselectivity; the ratio
of branched to linear regioisomer improved to 87:13, albeit in
similar yield (55%) (Scheme 2). Further optimization revealed
that 1/NaHBEt3/L1 in 1:1:3 ratio gave a yield of 88% with a
93:7 branched to linear ratio (Table S2). Although we were
able to obtain high selectivity with good yield, we were curious
about the role of NaOtBu as an alternative additive, as it is a
common and popular choice of additive in catalysis.7b For
a
1
Ratio of regioisomers determined by H NMR
Scheme 2. Initial Screening of Alkene Hydroboration with
Ligands
of substrates bearing electron-donating, electron-withdrawing,
halogen, and ester substituents was tolerated. Moreover, good
to excellent yields with high regioselectivity were observed.
The impact of steric crowding could be discerned employing
the substrates 2-methylstyrene (2d) and 2,4,6-trimethylstyrene
(2h). In the case of 2d, regioselectivity is degraded (4:1
Markovnikov/anti-Markovnikov), reaction time is lengthened,
and yield is diminished in comparison with parent styrene
(2a). Remarkably, in the case of 2h, regioselectivity was
completely reversed; a linear anti-Markovnikov product was
favored over the branched Markovnikov product (product
a
1
ratio was determined to be 4:1 by H NMR). Interestingly,
when 2,6-difluorostyrene (2i) was used as the substrate,
virtually no regioselectivity and a 44:56 branched to linear
product ratio was observed.
When 4-phenyl-1-butene (2m) was employed as substrate,
we were surprised to find that, in addition to diminished yield,
borylation occurred predominantly at the 4-position. This
product presumably arises from an isomerization process. In
addition to the borylation at the benzylic position, the minor
product was determined to be the species formed from
formation of the C−B bond at the terminal position (anti-
a
1
Yield and ratio of regioisomers determined by H NMR and GC−
MS.
B
DOI: 10.1021/acs.orglett.8b02775
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Markovnikov selectivity). Chirik and co-workers have
previously investigated isomerization of 4-phenyl-1-butene in
hydroboration chemistry using deuterium-labeling experi-
ments; the rate of C−B bond formation was observed to be
faster than isomerization as deuterium scrambling was not
observed due to the addition of DBpin exclusively at the β
position to the arene ring.15b Finally, the exclusive formation of
linear product was observed for the aliphatic substrate, 1-
hexene (2n).
The ability of Co(acac)3 (1) to hydroborate alkenes under
mild conditions prompted us to explore the hydroboration of
aldehyde and ketones. The transition-metal-catalyzed hydro-
boration of carbonyls is now well-established, even with the
first-row metal elements;1−10 in most metal-catalyzed trans-
formations an additive of some kind is typically required. We
became interested in additive-free hydroboration catalyzed by
1. We initially selected 4-methoxybenzaldehyde (4a) as the
model substrate for our studies and carried out the reaction in
the absence of NaOtBu and phosphine ligand (unlike in the
alkene hydroboration). We were pleased to observe that within
24 h of stirring at room temperature >95% of 4a was
consumed; the reaction was monitored by 11B NMR. Further
optimization revealed that upon heating the reaction at 50 °C
100% conversion of 4a was observed within 4 h as determined
by 11B NMR and GC−MS. The control experiment in the
absence of 1 showed little to no activity (Table S3), suggesting
that 1 was catalyzing the reaction under mild and additive-free
reaction conditions.
inhibit product formation, although longer reaction times were
required to achieve satisfactory conversions. The hydro-
boration of trans-cinnamaldehyde (4i) afforded the α,β-
unsaturated 3-phenyl-2-propen-1-ol (5i) as the exclusive
product (>99% purity).24
The additive-free hydroboration method was also expanded
to ketones to afford quantitative yields of reduced boronate
ester products. Unsurprisingly, an examination of several
different ketone substrates demonstrated the generality of the
hydroboration protocol, as in most cases, yields of 2° alcohols
ranged from good to excellent (Scheme 4, 5k−q). Naturally
occurring molecules such as verbenone (5p), a terpene
commonly found in plants, showed limited reactivity,
presumably due to the presence of steric encumbrance.
Experiments designed to test for chemoselectivity were
carried out. In all cases, selectivity for aldehyde reduction over
ketone under equimolar addition of substrates and HBpin was
observed. The reaction mixtures of both 4-fluorobenzaldehyde
and 4-fluoroacetophenone were submitted to our optimized
1
conditions; analysis of the aliquots using H NMR revealed
that exclusive reduction of 4-fluorobenzaldehyde (91%) had
occurred (Scheme 5a). Selective hydroboration of aldehyde
a
Scheme 5. Chemoselective Hydroboration Reactions
Examination of several different aldehyde substrates
demonstrated the generality of the additive free hydroboration
protocol, as in all cases, good to excellent yields of 1° alcohol
(after work up) were obtained; electron-donating, electron-
withdrawing, halides, and aliphatic and alicyclic substrates were
all tolerated (Scheme 4, 5a−j). Moreover, introduction of
sterically encumbering groups in the substrate (4e,h) did not
a
Scheme 4. Scope of Carbonyl Hydroboration
a
1
Yields based on H NMR using mesitylene as the internal standard.
b
Yields in parentheses are after addition of second equivalent of
HBpin.
over ketone was also observed in an intramolecular fashion
employing, 3-acetylbenzaldehyde (6). 1H NMR analysis of the
reaction mixture showed the exclusive formation of 3-
acetylbenzyl alcohol (7) (Scheme 5b) (Figure S92).
The influence of substrate electronics was also examined by
means of a competition reaction employing electron-with-
drawing, electron-donating, and electron-neutral substrates.
The first competition reaction we carried out employed the
aldehydes: benzaldehyde (4b), 4-fluorobenzaldehyde (4c), and
a
1
Yields based on H NMR using mesitylene as the internal standard.
C
DOI: 10.1021/acs.orglett.8b02775
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
4-methoxybenzaldehyde (4a) (Scheme 5c). Analysis of the
reaction mixture after full consumption of 1 equiv of HBpin
showed approximately equal amounts of 4b and 4c were
consumed, whereas 4a remained unreacted. Subsequent
addition of a second equivalents of HBpin to the reaction
mixture showed further conversion of both 4b and 4c with 4a
present in significant unreacted quantities (Figure S93). From
these data, we surmise that the aldehydes react sufficiently
rapidly at the 1 h time point since similar amounts of both
electron-deficient and electron-neutral substrates have been
consumed. However, electron-rich substrates react at a
significantly slower rate. Similarly, the competition reaction
of the ketones showed analogous reactivity to that observed for
the aldehydes (Scheme 5c). Analysis of the reaction mixture
after addition of 1 equiv of HBpin showed that both 4-
fluoroacetophenone (4m) and acetophenone (4l) reacted,
while 4-methylacetophenone (4k) remained largely unreacted.
Addition of a second equivalent of HBpin showed further
reactivity of 4l and 4m with a large amount of unreacted 4k
(Figure S94).
stage, a more detailed study of the mechanism is currently
ongoing in our group.
In conclusion, we have shown that commercially available
Co(acac)3 can be used to effect operationally convenient and
regioselective hydroboration catalysis of both alkenes and
carbonyls. In particular, we have developed a general method
to catalyze regioselective Markovnikov hydroboration of
alkenes in good to excellent yields in the presence of PPh3
and NaOtBu. Moreover, Co(acac)3 was also employed in an
additive free hydroboration of aldehydes and ketones under
mild reaction conditions. Chemoselective experiments revealed
that the catalytic system was selective for aldehydes over
ketones.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b02775.
Experimental procedures, characterization data, and
GC−MS and NMR spectra for new compounds
(PDF)
To understand the reaction mechanism better, deuterium-
labeling experiments were performed. As expected, the
formation of an exclusively proteo-boronic ester was observed
when the hydroboration of styrene was performed in THF-d8
(Scheme 6a). Similarly, when styrene-d8 was used as the
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: michael.findlater@ttu.edu.
ORCID
Scheme 6. Deuterium-Labeling Experiments
Michael Findlater: 0000-0003-3738-4039
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The financial support of the Welch Foundation (Grant No. D-
1807) and the National Science Foundation (CHE-1554906)
is gratefully acknowledged.
REFERENCES
■
(1) (a) Cho, B. T. Recent development and improvement for boron
hydride-based catalytic asymmetric reduction of unsymmetrical
ketones. Chem. Soc. Rev. 2009, 38, 443−452. (b) Magano, J.;
Dunetz, J. R. Large-Scale Carbonyl Reductions in the Pharmaceutical
Industry. Org. Process Res. Dev. 2012, 16, 1156−1184. (c) Ito, J.-i.;
Nishiyama, H. Recent topics of transfer hydrogenation. Tetrahedron
Lett. 2014, 55, 3133−3146. (d) Chong, C. C.; Kinjo, R. Catalytic
Hydroboration of Carbonyl Derivatives, Imines, and Carbon Dioxide.
ACS Catal. 2015, 5, 3238−3259.
(2) (a) Koren-Selfridge, L.; Londino, H. N.; Vellucci, J. K.;
Simmons, B. J.; Casey, C. P.; Clark, T. B. A Boron-Substituted
Analogue of the Shvo Hydrogenation Catalyst: Catalytic Hydro-
boration of Aldehydes, Imines, and Ketones. Organometallics 2009,
28, 2085−2090. (b) Kaithal, A.; Chatterjee, B.; Gunanathan, C.
Ruthenium Catalyzed Selective Hydroboration of Carbonyl Com-
substrate, proton incorporation occurred solely at the terminal
methyl group (Scheme 6b). These data suggested that both H
and Bpin addition during the reaction originated from the
pinacolborane. A reaction with DBpin, which was synthesized
according to the procedure by Chavant et al.,25 showed a
1
́
pounds. Org. Lett. 2015, 17, 4790−4793. (c) Arevalo, R.; Vogels, C.
mixture of products. H NMR revealed the formation of both
́
M.; MacNeil, G. A.; Riera, L.; Perez, J.; Westcott, S. A. Rhenium-
the monodeuterated boronic ester and fully proteo-boronic
ester in a ratio of 89:11 (Scheme 6c and Figure S103). The
formation of the fully protio boronic ester warrants a further
discussion, as this implies that the mechanism includes
insertion of the alkene into the in situ generated active
cobalt-hydride species and β hydride elimination during the
transformation.14c,21 Alternatively, the H/D exchange observed
could also be due to the presence of residual water either in the
reaction or during the process of isolating the product. At this
catalysed hydroboration of aldehydes and aldimines. Dalton Trans
2017, 46, 7750−7757. (d) Newland, R. J.; Lynam, J. M.; Mansell, S.
M. Small bite-angle 2-phosphinophosphinine ligands enable rhodium-
catalysed hydroboration of carbonyls. Chem. Commun. 2018, 54,
5482−5485.
̈
(3) (a) Arrowsmith, M.; Hadlington, T. J.; Hill, M. S.; Kociok-Kohn,
G. Magnesium-catalysed hydroboration of aldehydes and ketones.
Chem. Commun. 2012, 48, 4567−4569. (b) Hadlington, T. J.;
Hermann, M.; Frenking, G.; Jones, C. Low Coordinate Germanium-
D
DOI: 10.1021/acs.orglett.8b02775
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(II) and Tin(II) Hydride Complexes: Efficient Catalysts for the
Hydroboration of Carbonyl Compounds. J. Am. Chem. Soc. 2014, 136,
3028−3031. (c) Chong, C. C.; Hirao, H.; Kinjo, R. Metal-Free σ-
Bond Metathesis in 1,3,2-Diazaphospholene-Catalyzed Hydrobora-
tion of Carbonyl Compounds. Angew. Chem., Int. Ed. 2015, 54, 190−
194. (d) Yang, Z.; Zhong, M.; Ma, X.; De, S.; Anusha, C.;
Parameswaran, P.; Roesky, H. W. An Aluminum Hydride That
Functions like a Transition-Metal Catalyst. Angew. Chem., Int. Ed.
2015, 54, 10225−10229. (e) Jakhar, V. K.; Barman, M. K.;
Nembenna, S. Aluminum Monohydride Catalyzed Selective Hydro-
boration of Carbonyl Compounds. Org. Lett. 2016, 18, 4710−4713.
(f) Schneider, J.; Sindlinger, C. P.; Freitag, S. M.; Schubert, H.;
Wesemann, L. Diverse Activation Modes in the Hydroboration of
Aldehydes and Ketones with Germanium, Tin, and Lead Lewis Pairs.
Angew. Chem., Int. Ed. 2017, 56, 333−337. (g) Pollard, V. A.; Orr, S.
A.; McLellan, R.; Kennedy, A. R.; Hevia, E.; Mulvey, R. E. Lithium
diamidodihydridoaluminates: bimetallic cooperativity in catalytic
hydroboration and metallation applications. Chem. Commun. 2018,
54, 1233−1236.
(4) (a) Chen, S.; Yan, D.; Xue, M.; Hong, Y.; Yao, Y.; Shen, Q.
Tris(cyclopentadienyl)lanthanide Complexes as Catalysts for Hydro-
boration Reaction toward Aldehydes and Ketones. Org. Lett. 2017, 19,
3382−3385. (b) Weidner, V. L.; Barger, C. J.; Delferro, M.; Lohr, T.
L.; Marks, T. J. Rapid, Mild, and Selective Ketone and Aldehyde
Hydroboration/Reduction Mediated by a Simple Lanthanide
Catalyst. ACS Catal. 2017, 7, 1244−1247. (c) Wang, W.; Shen, X.;
Zhao, F.; Jiang, H.; Yao, W.; Pullarkat, S. A.; Xu, L.; Ma, M.
Ytterbium-Catalyzed Hydroboration of Aldehydes and Ketones. J.
Org. Chem. 2018, 83, 69−74. (d) Yan, D.; Dai, P.; Chen, S.; Xue, M.;
Yao, Y.; Shen, Q.; Bao, X. Highly efficient hydroboration of carbonyl
compounds catalyzed by tris(methylcyclopentadienyl)lanthanide
complexes. Org. Biomol. Chem. 2018, 16, 2787−2791.
(5) (a) Query, I. P.; Squier, P. A.; Larson, E. M.; Isley, N. A.; Clark,
T. B. Alkoxide-Catalyzed Reduction of Ketones with Pinacolborane. J.
Org. Chem. 2011, 76, 6452−6456. (b) Mukherjee, D.; Osseili, H.;
Spaniol, T. P.; Okuda, J. Alkali Metal Hydridotriphenylborates
[(L)M][HBPh3] (M = Li, Na, K): Chemoselective Catalysts for
Carbonyl and CO2 Hydroboration. J. Am. Chem. Soc. 2016, 138,
10790−10793. (c) Osseili, H.; Mukherjee, D.; Spaniol, T. P.; Okuda,
J. Ligand Influence on Carbonyl Hydroboration Catalysis by Alkali
Metal Hydridotriphenylborates [(L)M][HBPh3] (M = Li, Na, K).
Chem. - Eur. J. 2017, 23, 14292−14298. (d) Osseili, H.; Mukherjee,
D.; Beckerle, K.; Spaniol, T. P.; Okuda, J. Me6TREN-Supported
Alkali Metal Hydridotriphenylborates [(L)M][HBPh3] (M = Li, Na,
K): Synthesis, Structure, and Reactivity. Organometallics 2017, 36,
3029−3034. (e) Wu, Y.; Shan, C.; Ying, J.; Su, J.; Zhu, J.; Liu, L. L.;
Zhao, Y. Catalytic hydroboration of aldehydes, ketones, alkynes and
alkenes initiated by NaOH. Green Chem. 2017, 19, 4169−4175.
(6) King, A. E.; Stieber, S. C. E.; Henson, N. J.; Kozimor, S. A.;
Scott, B. L.; Smythe, N. C.; Sutton, A. D.; Gordon, J. C.
Ni(bpy)(cod): A Convenient Entryway into the Efficient Hydro-
boration of Ketones, Aldehydes, and Imines. Eur. J. Inorg. Chem. 2016,
2016, 1635−1640.
Hydroboration of Aldehydes and Ketones. J. Org. Chem. 2017, 82,
12857−12862. (c) Baishya, A.; Baruah, S.; Geetharani, K. Efficient
hydroboration of carbonyls by an iron(ii) amide catalyst. Dalton Trans
2018, 47, 9231. (d) Das, U. K.; Higman, C. S.; Gabidullin, B.; Hein, J.
E.; Baker, R. T. Efficient and Selective Iron-Complex-Catalyzed
Hydroboration of Aldehydes. ACS Catal. 2018, 8, 1076−1081.
(10) Zhang, G.; Zeng, H.; Wu, J.; Yin, Z.; Zheng, S.; Fettinger, J. C.
Highly Selective Hydroboration of Alkenes, Ketones and Aldehydes
Catalyzed by a Well-Defined Manganese Complex. Angew. Chem., Int.
Ed. 2016, 55, 14369−14372.
(11) (a) Mannig, D.; Noth, H. Catalytic Hydroboration with
Rhodium Complexes. Angew. Chem., Int. Ed. Engl. 1985, 24, 878−879.
(b) Burgess, K.; Ohlmeyer, M. J. Transition-metal promoted
hydroborations of alkenes, emerging methodology for organic
transformations. Chem. Rev. 1991, 91, 1179−1191. (c) Evans, D.
A.; Fu, G. C.; Hoveyda, A. H. Rhodium(I)- and iridium(I)-catalyzed
hydroboration reactions: scope and synthetic applications. J. Am.
Chem. Soc. 1992, 114, 6671−6679. (d) Beletskaya, I.; Pelter, A.
Hydroborations catalysed by transition metal complexes. Tetrahedron
1997, 53, 4957−5026. (e) Crudden, C. M.; Edwards, D. Catalytic
Asymmetric Hydroboration: Recent Advances and Applications in
Carbon−Carbon Bond-Forming Reactions. Eur. J. Org. Chem. 2003,
2003, 4695−4712. (f) Yamamoto, Y.; Fujikawa, R.; Umemoto, T.;
Miyaura, N. Iridium-catalyzed hydroboration of alkenes with
pinacolborane. Tetrahedron 2004, 60, 10695−10700.
(12) (a) Greenhalgh, M. D.; Thomas, S. P. Chemo-, regio-, and
stereoselective iron-catalysed hydroboration of alkenes and alkynes.
Chem. Commun. 2013, 49, 11230−11232. (b) Obligacion, J. V.;
Chirik, P. J. Highly Selective Bis(imino)pyridine Iron-Catalyzed
Alkene Hydroboration. Org. Lett. 2013, 15, 2680−2683. (c) Zhang,
L.; Peng, D.; Leng, X.; Huang, Z. Iron-Catalyzed, Atom-Economical,
Chemo- and Regioselective Alkene Hydroboration with Pinacolbor-
ane. Angew. Chem., Int. Ed. 2013, 52, 3676−3680. (d) Chen, J.; Xi, T.;
Lu, Z. Iminopyridine Oxazoline Iron Catalyst for Asymmetric
Hydroboration of 1,1-Disubtituted Aryl Alkenes. Org. Lett. 2014,
16, 6452−6455. (e) Greenhalgh, M. D.; Jones, A. S.; Thomas, S. P.
Iron-Catalysed Hydrofunctionalisation of Alkenes and Alkynes.
ChemCatChem 2015, 7, 190−222.
(13) (a) Obligacion, J. V.; Chirik, P. J. Bis(imino)pyridine Cobalt-
Catalyzed Alkene Isomerization−Hydroboration: A Strategy for
Remote Hydrofunctionalization with Terminal Selectivity. J. Am.
Chem. Soc. 2013, 135, 19107−19110. (b) Chen, J.; Xi, T.; Ren, X.;
Cheng, B.; Guo, J.; Lu, Z. Asymmetric cobalt catalysts for
hydroboration of 1,1-disubstituted alkenes. Org. Chem. Front. 2014,
1, 1306−1309. (c) Zhang, L.; Zuo, Z.; Leng, X.; Huang, Z. A Cobalt-
Catalyzed Alkene Hydroboration with Pinacolborane. Angew. Chem.,
Int. Ed. 2014, 53, 2696−2700. (d) Zhang, L.; Zuo, Z.; Wan, X.;
Huang, Z. Cobalt-Catalyzed Enantioselective Hydroboration of 1,1-
Disubstituted Aryl Alkenes. J. Am. Chem. Soc. 2014, 136, 15501−
15504. (e) Zhang, H.; Lu, Z. Dual-Stereocontrol Asymmetric Cobalt-
Catalyzed Hydroboration of Sterically Hindered Styrenes. ACS Catal.
2016, 6, 6596−6600.
̈
̈
(14) (a) Espinal-Viguri, M.; Woof, C. R.; Webster, R. L. Iron-
Catalyzed Hydroboration: Unlocking Reactivity through Ligand
Modulation. Chem. - Eur. J. 2016, 22, 11605−11608. (b) MacNair,
A. J.; Millet, C. R. P.; Nichol, G. S.; Ironmonger, A.; Thomas, S. P.
Markovnikov-Selective, Activator-Free Iron-Catalyzed Vinylarene
Hydroboration. ACS Catal. 2016, 6, 7217−7221. (c) Chen, X.;
Cheng, Z.; Lu, Z. Iron-Catalyzed, Markovnikov-Selective Hydro-
boration of Styrenes. Org. Lett. 2017, 19, 969−971.
(15) (a) Palmer, W. N.; Diao, T.; Pappas, I.; Chirik, P. J. High-
Activity Cobalt Catalysts for Alkene Hydroboration with Electroni-
cally Responsive Terpyridine and α-Diimine Ligands. ACS Catal.
2015, 5, 622−626. (b) Scheuermann, M. L.; Johnson, E. J.; Chirik, P.
J. Alkene Isomerization−Hydroboration Promoted by Phosphine-
Ligated Cobalt Catalysts. Org. Lett. 2015, 17, 2716−2719. (c) Reilly,
S. W.; Webster, C. E.; Hollis, T. K.; Valle, H. U. Transmetallation
from CCC-NHC pincer Zr complexes in the synthesis of air-stable
(7) (a) Guo, J.; Chen, J.; Lu, Z. Cobalt-catalyzed asymmetric
hydroboration of aryl ketones with pinacolborane. Chem. Commun.
2015, 51, 5725−5727. (b) Docherty, J. H.; Peng, J.; Dominey, A. P.;
Thomas, S. P. Activation and discovery of earth-abundant metal
catalysts using sodium tert-butoxide. Nat. Chem. 2017, 9, 595.
(c) Wu, J.; Zeng, H.; Cheng, J.; Zheng, S.; Golen, J. A.; Manke, D. R.;
Zhang, G. Cobalt(II) Coordination Polymer as a Precatalyst for
Selective Hydroboration of Aldehydes, Ketones, and Imines. J. Org.
Chem. 2018, 83, 9442.
(8) Bagherzadeh, S.; Mankad, N. P. Extremely efficient hydro-
boration of ketones and aldehydes by copper carbene catalysis. Chem.
Commun. 2016, 52, 3844−3846.
(9) (a) Bai, T.; Janes, T.; Song, D. Homoleptic iron(ii) and
cobalt(ii) bis(phosphoranimide) complexes for the selective hydro-
functionalization of unsaturated molecules. Dalton Trans 2017, 46,
12408−12412. (b) Tamang, S. R.; Findlater, M. Iron Catalyzed
E
DOI: 10.1021/acs.orglett.8b02775
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
CCC-NHC pincer Co(iii) complexes and initial hydroboration trials.
Dalton Trans 2016, 45, 2823−2828.
(16) (a) Noh, D.; Chea, H.; Ju, J.; Yun, J. Highly Regio- and
Enantioselective Copper-Catalyzed Hydroboration of Styrenes.
Angew. Chem., Int. Ed. 2009, 48, 6062−6064. (b) Iwamoto, H.;
Kubota, K.; Ito, H. Highly selective Markovnikov hydroboration of
alkyl-substituted terminal alkenes with a phosphine-copper(i) catalyst.
Chem. Commun. 2016, 52, 5916−5919.
(17) Touney, E. E.; Van Hoveln, R.; Buttke, C. T.; Freidberg, M. D.;
Guzei, I. A.; Schomaker, J. M. Heteroleptic Nickel Complexes for the
Markovnikov-Selective Hydroboration of Styrenes. Organometallics
2016, 35, 3436−3439.
(18) Zhang, G.; Zeng, H.; Wu, J.; Yin, Z.; Zheng, S.; Fettinger, J. C.
Highly Selective Hydroboration of Alkenes, Ketones and Aldehydes
Catalyzed by a Well-Defined Manganese Complex. Angew. Chem., Int.
Ed. 2016, 55, 14369−14372.
(19) Zhang, L.; Zuo, Z.; Leng, X.; Huang, Z. A Cobalt-Catalyzed
Alkene Hydroboration with Pinacolborane. Angew. Chem., Int. Ed.
2014, 53, 2696−2700.
(20) (a) Ruddy, A. J.; Sydora, O. L.; Small, B. L.; Stradiotto, M.;
Turculet, L. (N-Phosphinoamidinate)cobalt-Catalyzed Hydrobora-
tion: Alkene Isomerization Affords Terminal Selectivity. Chem. - Eur.
J. 2014, 20, 13918−13922. (b) Ogawa, T.; Ruddy, A. J.; Sydora, O.
L.; Stradiotto, M.; Turculet, L. Cobalt- and Iron-Catalyzed Isomer-
ization−Hydroboration of Branched Alkenes: Terminal Hydro-
boration with Pinacolborane and 1,3,2-Diazaborolanes. Organo-
metallics 2017, 36, 417−423.
(21) Peng, J.; Docherty, J. H.; Dominey, A. P.; Thomas, S. P. Cobalt-
catalysed Markovnikov selective hydroboration of vinylarenes. Chem.
Commun. 2017, 53, 4726−4729.
(22) (a) Wekesa, F. S.; Arias-Ugarte, R.; Kong, L.; Sumner, Z.;
McGovern, G. P.; Findlater, M. Iron-Catalyzed Hydrosilylation of
Aldehydes and Ketones under Solvent-Free Conditions. Organo-
metallics 2015, 34, 5051−5056. (b) Brown, L. A.; Wekesa, F. S.;
Unruh, D. K.; Findlater, M.; Long, B. K. BIAN-Fe(η6-C6H6):
Synthesis, characterization, and l-lactide polymerization. J. Polym.
Sci., Part A: Polym. Chem. 2017, 55, 2824−2830.
(23) (a) Arias-Ugarte, R.; Wekesa, F. S.; Findlater, M. Selective aldol
condensation or cyclotrimerization reactions catalyzed by FeCl3.
Tetrahedron Lett. 2015, 56, 2406−2411. (b) Arias-Ugarte, R.; Wekesa,
F. S.; Schunemann, S.; Findlater, M. Iron(III)-Catalyzed Dimerization
of Cycloolefins: Synthesis of High-Density Fuel Candidates. Energy
Fuels 2015, 29, 8162−8167. (c) Tamang, S. R.; Findlater, M. Cobalt
catalysed reduction of CO2via hydroboration. Dalton Trans 2018, 47,
8199−8203. (d) Tamang, S. R.; Singh, A.; Unruh, D. K.; Findlater, M.
Nickel-Catalyzed Regioselective 1,4-Hydroboration of N-Heteroar-
enes. ACS Catal. 2018, 8, 6186−6191.
(24) 1H NMR showed peaks for α,β-unsaturated 3-phenyl-2-propen-
1-ol only. However, GC−MS revealed very few traces of 3-phenyl-1-
propanol in the reaction mixture as well.
(25) Labre, F.; Gimbert, Y.; Bannwarth, P.; Olivero, S.; Dunach, E.;
̃
Chavant, P. Y. Application of Cooperative Iron/Copper Catalysis to a
Palladium-Free Borylation of Aryl Bromides with Pinacolborane. Org.
Lett. 2014, 16, 2366−2369.
F
DOI: 10.1021/acs.orglett.8b02775
Org. Lett. XXXX, XXX, XXX−XXX