Cobalt-Catalyzed 1,1-Diboration of Terminal Alkynes: Scope, Mechanism, and Synthetic Applications

Article abstract of DOI:10.1021/jacs.7b00445

A cobalt-catalyzed method for the 1,1-diboration of terminal alkynes with bis(pinacolato)diboron (B₂Pin₂) is described. The reaction proceeds efficiently at 23 °C with excellent 1,1-selectivity and broad functional group tolerance. With the unsymmetrical diboron reagent PinB-BDan (Dan = naphthalene-1,8-diaminato), stereoselective 1,1-diboration provided products with two boron substituents that exhibit differential reactivity. One example prepared by diboration of 1-octyne was crystallized, and its stereochemistry established by X-ray crystallography. The utility and versatility of the 1,1-diborylalkene products was demonstrated in a number of synthetic applications, including a concise synthesis of the epilepsy medication tiagabine. In addition, a synthesis of 1,1,1-triborylalkanes was accomplished through cobalt-catalyzed hydroboration of 1,1-diborylalkenes with HBPin. Deuterium-labeling and stoichiometric experiments support a mechanism involving selective insertion of an alkynylboronate to a Co-B bond of a cobalt boryl complex to form a vinylcobalt intermediate. The latter was isolated and characterized by NMR spectroscopy and X-ray crystallography. A competition experiment established that the reaction involves formation of free alkynylboronate and the two boryl substituents are not necessarily derived from the same diboron source.

Full text of DOI:10.1021/jacs.7b00445

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Article
Cobalt-catalyzed 1,1-Diboration of Terminal Alkynes:
Scope, Mechanism and Synthetic Applications
Simon Krautwald, Mate J. Bezdek, and Paul J. Chirik
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b00445 • Publication Date (Web): 15 Feb 2017
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Cobalt-Catalyzed 1,1-Diboration of Terminal Alkynes: Scope,
Mechanism and Synthetic Applications
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Simon Krautwald, Máté J. Bezdek, and Paul J. Chirik*
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States
ABSTRACT: A cobalt-catalyzed method for the 1,1-diboration of terminal alkynes with bis(pinacolato)diboron (B2Pin2) is described. The
reaction proceeds efficiently at 23 °C with excellent 1,1-selectivity and broad functional group tolerance. With the unsymmetrical diboron
reagent PinB–BDan (Dan = naphthalene-1,8-diaminato), stereoselective 1,1-diboration provided products with two boron substituents that
exhibit differential reactivity. One example prepared by diboration of 1-octyne was crystallized and its stereochemistry established by X-ray
crystallography. The utility and versatility of the 1,1-diborylalkene products was demonstrated in a number of synthetic applications, includ-
ing a concise synthesis of the epilepsy medication tiagabine. In addition, a synthesis of 1,1,1-triborylalkanes was accomplished through cobalt-
catalyzed hydroboration of 1,1-diborylalkenes with HBPin. Deuterium-labeling and stoichiometric experiments support a mechanism involv-
ing selective insertion of an alkynylboronate to a Co–B bond of a cobalt boryl complex to form a vinylcobalt intermediate. The latter was iso-
lated and characterized by NMR spectroscopy and X-ray crystallography. A competition experiment established that the reaction involves
formation of free alkynylboronate and the two boryl substituents are not necessarily derived from the same diboron source.
Introduction. Organoboron compounds are among the most
versatile in organic synthesis owing to their stability, ease of han-
dling and utility for the synthesis of carbon-carbon and carbon
heteroatom bonds.1 Among this important class of reagents,
alkenyldiboronates are particularly attractive because they offer two
distinct boron substituents for elaboration, ideally in a site and
stereoselective manner. As a consequence, alkenyldiboronates have
found applications in the stereocontrolled synthesis of multisubsti-
tuted olefins,2 an important challenge in synthesis.3 Specifically,
1,2-diborylalkenes have been used as key intermediates en route to
natural products4 and π-conjugated materials,5 while the utility of
1,1-diborylalkenes has been demonstrated in a concise synthesis of
the anti-cancer agent tamoxifen.6
Synthesis of alkenyldiboronates is typically accomplished by di-
boration of terminal or internal alkynes and is often promoted by
transition metal catalysts,7 base,8 Lewis acid,9 and in some cases
proceeds in the absence of catalysts.10 Regardless of the synthetic
route, these methods almost exclusively result in 1,2-
difunctionalization,11 a common reactivity mode for addition to C-
C multiple bonds (Scheme 1).
significant degree of synthetic flexibility. In 2015, Sawamura and
coworkers reported the direct preparation of 1,1-diborylalkenes
from terminal alkynes and B2Pin2 using LiOt-Bu as the catalyst
(Scheme 2A).13 While effective and an important advance, this
reaction is limited to alkynes bearing electron-withdrawing substit-
uents such as propiolates.
Scheme 2. Summary of current methods for the synthesis of 1,1-
diborylalkenes.
Scheme 1. 1,2 vs 1,1-selectivity in alkyne diboration.
numerous
examples
R
BX2
1,2-selectivity
BX2
H
X2B BX2
+
R
underexplored
reagents in
synthesis
BX2
BX2
rare
R
1,1-selectivity
Rhodium-catalyzed dehydrogenative borylation of alkenes has
been reported as a route to 1,1-diborylalkenes but the selectivity is
poor as mixtures of (di)borylated products were obtained and high
temperatures were required.14 A more selective palladium-catalyzed
method has since been described but is restricted to terminal al-
kenes bearing electronically activating groups such as aryl and
alkenyl substituents (Scheme 2A).15
Since Miyaura and Suzuki’s seminal discovery of platinum-
catalyzed alkyne 1,2-diboration,12 a number of catalysts for this
transformation have been reported. By contrast, examples of the
direct synthesis of the isomeric 1,1-diborylalkenes from terminal
alkynes and diboron reagents are rare. In addition, the full potential
of 1,1-diborylalkenes in synthesis has not been explored beyond the
singular tamoxifen example, even though these reagents offer a
Two-step procedures starting from terminal alkynes (Scheme
2B)16-18 and methods involving stoichiometric amounts of organo-
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lithium reagents (Scheme 2C) have also been reported.19,20 Howev-
diborations reported to date, the cobalt-catalyzed reaction docu-
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er, these approaches suffer from low volumetric throughput and
poor functional group compatibility, respectively.. Given the limita-
tions of the methods currently available for the synthesis of 1,1-
diborylalkenes, the direct 1,1-diboration of terminal alkynes with
simple alkyl and aryl substituents would be an attractive, atom eco-
nomical method for the synthesis of these valuable building blocks
and likely open new avenues for synthesis.
mented here proceeds with excellent 1,1-selectivity. The new
method exhibits broad scope and functional group tolerance, and
its utility and mildness was demonstrated in a concise synthesis of
tiagabine, a medication for the treatment of epilepsy. To highlight
the synthetic versatility of the 1,1-diborylalkene products, they
were used to access a diverse set of structural motifs, including 1,1-
dihaloalkenes, a carboxylic acid, a 1,1-diborylalkane, and 1,1,1-
triborylalkanes. In addition, the method could be extended to ste-
reoselective synthesis of trisubstituted olefins through 1,1-
diboration of terminal alkynes with the mixed diboron reagent
PinB–BDan. The chemically differentiated boron substituents
allowed selective cross coupling at [BPin]. Finally, mechanistic
studies established the intermediacy of a cobalt vinyl intermediate
that was crystallographically characterized.
Our laboratory recently reported that the cyclohexyl-substituted
pyridine(diimine) cobalt methyl complex 1 promotes the Z-
selective hydroboration of terminal alkynes (Scheme 3).21 Stoichi-
ometric experiments, isolation of intermediates, and deuterium
labeling studies established a unique mechanistic pathway involv-
ing initial formation of a cobalt acetylide (I) which, following en-
gagement with pinacolborane (HBPin), forms an alkynylboronate
complex (III). Regioselective syn-hydrocobaltation forms vinylco-
balt intermediate (IV, E=H), resulting in the unusual Z-selectivity.
The cyclohexyl-substituents were found to be important for the
observed reactivity and formation of the key cobalt-acetylide in-
termediate. Analogous experiments with aryl-substituted
bis(imino)pyridine cobalt compounds resulted in E–selective al-
kyne hydroboration due to preferential formation of the cobalt
hydride over the cobalt acetylide. In the Z-selective method, the
[H] and [BPin] of the borane are both transferred to the terminal
carbon of the alkyne, suggesting that complex 1 may serve as a cata-
lyst for other cobalt-catalyzed 1,1-difunctionalization methods.22
Specifically, replacement of HBPin with B2Pin2 would generate a
cobalt boryl intermediate (III), which after syn-borylcobaltation
and product release would result in a method for the direct synthe-
sis of 1,1-diborylalkenes (I-IV, E=BPin).
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Results and Discussion. Initial catalyst evaluation was conducted
with equimolar quantities of 1-heptyne and B2Pin2 in the presence
of 5 mol% of 1 at 23 °C for 13 hours in a 1.0 M toluene solution.
1
Analysis of the unpurified reaction mixture by H NMR spectros-
copy established clean and complete conversion to 1,1-
diborylalkene 4a, which was isolated in 75% yield (Scheme 4). A
control experiment demonstrated that no 1,1-diborylalkene prod-
uct formed in the absence of cobalt complex 1. As shown in
Scheme 4, a range of alkynes participated in cobalt-catalyzed 1,1-
diboration to yield 1,1-diborylalkene products 4b-4m. Common
organic functional groups such as tert-butyldimethylsilyl ether
(4c), acetal (4d), ester (4e, 4f), phthalimide (4g), nitrile (4i), and
secondary amides (4j) were all compatible with the reaction condi-
tions. Remarkably, a substrate bearing a terminal olefin underwent
chemoselective 1,1-diboration of the alkyne without isomerization
of the double bond (4h).
Scheme 3. Proposed mechanism for Z-selective hydroboration as
inspiration for the 1,1-diboration of terminal alkynes.
Scheme 4. Scope of the 1,1-diboration of terminal alkynes with
B2Pin2 and (CyAPDI)CoCH3 (1).a
Here we describe a cobalt-catalyzed method for the synthesis of
1,1-diborylalkenes from readily available terminal alkynes and di-
boron reagents. In contrast to all other transition metal-catalyzed
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Suginome reported the use of PinB–BDan (Dan = naphthalene-
1,8-diaminato) in Pt- and Ir-catalyzed 1,2-diboration of alkynes.2d
The reaction was regioselective, leading to exclusive transfer of the
[BDan] substituent to the terminal carbon. As shown in Scheme 5,
cobalt-catalyzed 1,1 diboration of 1-heptyne with PinB–BDan pro-
ceeded efficiently and stereoselectively to afford 6a in 77% yield. A
related 1,1-diborylalkene derived from 1-octyne and PinB–BDan
was also prepared and crystallized. Its structure and stereochemis-
try were confirmed by X-ray crystallography (Scheme 5, bottom).
The generality and functional group compatibility of this stereose-
lective process was demonstrated with selected, representative
alkyne substrates bearing common functional groups to afford
products 6d, 6e and 6g (Scheme 5).
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Scheme 5. Stereoselective cobalt-catalyzed 1,1-diboration of ter-
minal
alkynes
with
PinB–BDan.a
aReaction conditions: alkyne 2 (0.50 mmol), B2Pin2 (0.50 mmol, 1.0
equiv), 1 (0.025 mmol, 5 mol%), toluene (0.5 mL), 23 °C. Numbers in
parentheses are yields of isolated products obtained after purification
b
by flash chromatography on silica gel. 0.25 mmol 2, 0.25 mmol 3, 10
c
d
e
f
mol% 1. 2.0 equiv 3. 4.0 equiv 3. 1.5 equiv 3. Thermal ellipsoids at
50% probability.
Aryl- and heteroaryl acetylenes also were suitable substrates (4l,
4m), although increased amounts of diboron reagent were required
to suppress competitive homodimerization of the alkynes to the
corresponding enynes. It is noteworthy that this side reaction was
not observed when alkyl-substituted alkynes were used (4a-4k).
To highlight the practicality of the method, products 4a and 4g
were prepared on gram scale in 68 and 81% yield, respectively, with
a reduced catalyst loading of 2 mol% (see SI for details). Diboron
reagents other than B2Pin2 also participated in the catalytic reaction
(eq. 1), andcobalt-catalyzed reaction of 1-heptyne with bis[(+)-
pinanediolato]diboron afforded 1,1-diborylalkene 5 in 73% yield.
aReagents and conditions: alkyne 2 (0.50 mmol), PinB–BDan
(0.50 mmol), 1 (5 mol%), THF, 50 °C, 36 h. Numbers in parentheses
are yields of isolated products obtained after purification by flash
chromatography on silica gel. Thermal ellipsoids in ORTEP diagram at
50% probability, hydrogen atoms except vinyl C–H omitted for clarity.
Olefin geometry of products 6a, 6d, 6e, 6g assigned by analogy to the
solid state structure.
The differential reactivity of the two boron substituents in 6a al-
lowed selective Suzuki-Miyaura cross coupling at BPin to proceed
efficiently, furnishing 7 in 78% yield (eq. 2). The olefin geometry in
7 was confirmed by NOESY (see SI). From a synthetic perspective,
the two-step sequence of 1,1-diboration and cross coupling to give
7 represents a formal 1,1-carboboration of 1-heptyne.23
Stereoselective 1,1-diboration. The stereocontrolled synthesis
of alkenes is fundamentally important in organic synthesis.3 In this
context, a stereoselective cobalt-catalyzed 1,1-diboration with an
unsymmetrical diboron reagent would result in the formation of a
trisubstituted olefin of well-defined configuration, providing access
to an underexplored class of diborylalkenes. In 2010, Iwadate and
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Scheme 7. Synthetic applications of 1,1-diborylalkenes.
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Synthetic applications of 1,1-diborylalkenes. The synthetic
utility of the 1,1-diboration method was demonstrated as an ena-
bling step in the highly concise synthesis of of tiagabine (13), an
epilepsy medication (Scheme 6). Alkylation of commercially avail-
able (R)-ethyl piperidine-3-carboxylate (8) with 4-bromo-1-
butyne gave terminal alkyne 9 in 64% yield. A one-pot sequence
consisting of cobalt-catalyzed 1,1-diboration followed by Suzuki-
Miyaura cross-coupling yielded tiagabine ethyl ester 12 in 60%
yield over 2 steps. Importantly, the reaction conditions were com-
patible with the ester and amine functionality, and the integrity of
the stereogenic center was preserved throughout the sequence of
reactions (see SI for SFC traces). Ethyl ester 12 was then converted
to tiagabine hydrochloride via a known series of steps involving
saponification of the ester and formation of the hydrochloride
salt.24
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Synthesis of 1,1,1-triborylalkanes. The use of 1,1-
diborylalkenes in the synthesis of an unusual class of organoboron
compounds was also explored. Selective hydroboration of 1,1-
diborylalkenes would provide
a unique route to 1,1,1-
triborylalkanes, an underexplored class of reagents with considera-
ble potential in organic synthesis. Huang recently reported high
yields in deborylative alkylation reactions between 1,1,1-
triborylalkanes and simple alkyl bromides,29a while our own labora-
tory demonstrated the utility of benzyltriboronates in diastereose-
lective conjugate additions.29b While the synthesis and reactivity of
1,1-diborylalkanes have received considerable attention due to
their aforementioned utility in cross-coupling and alkylation reac-
tions,25 the chemistry of the corresponding 1,1,1-triboronates is by
comparison much less developed. This is likely due to the paucity
of reliable and general synthetic methods for their synthesis. More
than four decades ago, Matteson reported a synthesis of triborylme-
thane by reaction of chloroform with ClB(OR)2 in the presence of
lithium metal.19,30 All methods developed since have been limited to
narrow sets of substrates, such as derivatives of 2-ethylpyridine,31
styrene,29,32 or toluene.33 Accordingly, a two-step, one-pot sequence
consisting of Co-catalyzed 1,1-diboration of terminal alkynes fol-
lowed by selective hydroboration would provide a general synthesis
of 1,1,1-triboronates with a set of structurally diverse alkyl groups
attached to the triborylated carbon.
In an initial experiment, an additional 5 mol%of cobalt complex
1 (5 mol%) and HBPin (4 equiv) were added to a 1,1-diboration
reaction of 1-heptyne that had reached completion as judged by
GC analysis. Although a new product was observed by GC analysis
after a few hours, the reaction was sluggish. Heating the reaction
mixture to 80 °C resulted in increased conversion and the major
product, 1,1,1-triboronate 19a, was isolated in 18% yield after 24
hours (eq. 3).
Scheme 6. Synthesis of tiagabine hydrochloride via one-pot 1,1-
diboration/cross-coupling.
To highlight the versatility of the 1,1-diborylalkene products,
they were also elaborated to other useful building blocks (Scheme
7). Hydrogenation of 4a catalyzed by terpyridine-ligated cobalt
complex 14 afforded the corresponding 1,1-diborylalkane 15 in
98% yield. 1,1-diborylalkanes have recently received increasing
attention due to their utility in cross-coupling and alkylation reac-
tions.25 In addition, 1,1-dichloro- and 1,1-dibromoolefins 16 and
17 were prepared by treating 4g with the appropriate cupric salt.
The 1,1-dihaloolefin motif is found in a number of commercial
insecticides26 as well as in natural products.27 Oxidation of 1,1-
diborylalkene 4b with sodium perborate furnished carboxylic acid
18. The sequence of 1,1-diboration/oxidation is thus formally
equivalent to oxidative hydration of a terminal alkyne.28 Important-
ly, the transformations yielding products 16-18 have not been pre-
viously reported.
Having established that selective cobalt-catalyzed hydroboration
of 1,1-diborylalkenes was possible, a more active alkene hydrobora-
tion catalyst was sought. Our laboratory recently reported a terpyr-
idine cobalt complex that is active for the hydroboration of unacti-
vated, trisubstituted alkenes,34 a relatively challenging class of sub-
strates. Use of this complex in the hydroboration of styrene led to
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branched selectivity,34 likely involving a benzylcobalt intermediate.
within 4 hours. Recrystallization of vinylcobalt complex 21b from
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3
4
5
6
7
8
Accordingly, its use with 1,1-diborylalkenes could proceed via in-
termediacy of a stabilized α-borylcobalt intermediate.35 As shown in
Scheme 8, sequential 1,1-diboration-hydroboration of terminal
pentane at –35 °C yielded single crystals suitable for X-ray diffrac-
tion analysis. A representation of the solid-state structure is pre-
sented in Scheme 9 (bottom). The cobalt is five-coordinate with
coordination sphere defined by the tridentate pyridine(diimine),
the carbon of the alkenyl group and an oxygen (d(Co-O) =
2.2071(12) Å) of the syn [BPin] substituent. The bond distances
of the bis(imino)pyridine are consistent with one-electron reduc-
tion36 as evidenced by the slightly elongated Cimine–Nimine bonds of
alkynes
involving
(
CyAPDI)CoCH3
(1)
and
(Ter-
py)Co(CH2SiMe3) (14)34 furnished
a
collection of 1,1,1-
triboronates 19 in 50-76% yield over two steps. Importantly, car-
bonyl-based functional groups were compatible with this hydrobo-
ration protocol, as evidenced by the synthesis of triboronates 19e,
19i, and 19g.
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1.326(2) Å and 1.334(2) Å as well as the slightly contracted Cimine
Cipso bonds of 1.438(2) Å and 1.431(2) Å.
–
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Scheme 8. One-pot, sequential 1,1-diboration-hydroboration of
terminal alkynes.a
To assess its catalytic competence, complex 21a was treated with
1
one equivalent of phenylacetylene, and analysis by H NMR spec-
troscopy established the presence of only cobalt acetylide 20a and
1,1-diborylalkene 4l, with vinylcobalt 21a having been completely
consumed within 10 minutes. The analogous experiment with
complex 21b and one equivalent of 1-octyne resulted in slow con-
version to the cobalt acetylide 20b and 1,1-diborylalkene 4o over
the course of approximately 36 hours. These results indicate that
the relative rates of the individual steps (formation of vinylcobalt
and protonation) are dependent on the identity of the alkyne. With
aliphatic alkynes such as 1-octyne, the protonation is likely rate-
determining, as was observed in the previously reported Z-selective
hydroboration.21 In contrast, with more acidic alkynes such as phe-
nylacetylene, the protonation step is comparatively fast, such that
formation of the vinylcobalt complex is likely rate-determining.
Scheme 9. Synthesis of vinylcobalt complexes, solid-state struc-
ture of 21b and single-turnover experiments.a
aReaction conditions: alkyne 2 (0.50 mmol), B2Pin2 (0.50 mmol, 1.0
equiv), 1 (0.025 mmol, 5 mol%), toluene (0.5 mL), 23 °C; then 14
(0.025 mmol, 5 mol%), HBPin (0.50 mmol, 1.0 equiv). Numbers in
parentheses are yields of isolated products after purification by flash
chromatography on silica gel. b2 equiv of B2Pin2 and HBPin were used.
Mechanistic Studies. Having established the scope and utility
of the 1,1-diboration method, attention was devoted toward under-
standing the mechanistic features of the transformation. Cobalt-
catalyzed 1,1-diboration of 1-d1-octyne (90% isotopic purity) with
B2Pin2 furnished 1,1-diborylalkene 4n with the deuterium label at
the internal alkene carbon, as judged by 1H and quantitative 13C
NMR spectroscopy (eq. 4). This result is consistent with the mech-
anism depicted in Scheme 3.
A set of stoichiometric experiments aimed at observing and iso-
lating the proposed vinylcobalt intermediates were also conducted.
Cobalt acetylide complexes 20a and 20b, derived from phenyla-
cetylene and 1-octyne, respectively, were prepared by a previously
described procedure.21 As shown in Scheme 9, treatment of cobalt
acetylide complex 20a with 1 equivalent of B2Pin2 in benzene-d6
cleanly generate a single new species within 60 hours as judged by
1H and 13C NMR spectroscopy. In contrast, the reaction of 20b
with B2Pin2 to give vinylcobalt 21b proceeded to 95% conversion
aThermal ellipsoids at 50% probability. Hydrogen atoms omitted for
clarity.
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The intermediacy of a cobalt-alkynylboronate complex (III) was
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probed with a competition experiment. If dissociation of the al-
kynylboronate is competitive with insertion, the two BPin substitu-
ents in the product may not necessarily be derived from the same
molecule of B2Pin2. Indeed, cobalt-catalyzed reaction of 1-heptyne
with one equivalent of B2Pin2 in the presence of one equivalent of
1-octynyl-BPin resulted in formation of a 1:1 ratio of the two 1,1-
diborylalkene products 4a and 4o (Scheme 10). In addition, both
alkynylboronates were observed by GC analysis upon complete
consumption of B2Pin2. This result is consistent with alkynyl-
boronates being intermediates en route to the 1,1-diborylalkenes,
and confirms that the alkynylboronate is labile in the presence of
excess alkynylboronate.
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Scheme 10. Competition experiment probing formation of free
alkynylboronate.a
In the latter scenario, the structure of or relative rates of reductive
elimination from complex IIa could affect what type of alkynyl-
boronate complex (e.g. IIIa) forms. A stoichiometric experiment
was performed to probe this question. Treatment of cobalt acety-
lide 20b with 1 equivalent of PinB–BDan in benzene-d6 at room
temperature resulted in formation of a single new species as judged
1
by H and 13C NMR spectroscopy (Scheme 12). Addition of one
equivalent of 1-octyne to 22 in benzene-d6 at room temperature
resulted in only 5% conversion to diborylalkene product and com-
plex 20b over the course of 18 hours. However, after heating the
solution in the NMR tube to 50 °C for 29 hours, a 33/66 mixture of
20b/22 along with a single diborylalkene product was detected by
1H NMR spectroscopy This result is consistent with the require-
ment for heating 1,1-diborations with PinB–BDan and indicates
that the protonation step is considerably slower when the vinylco-
balt bears a BDan substituent instead of BPin. The observation of a
single new species upon addition of PinB–BDan to 20b suggests
that stereoselective formation of vinylcobalt 22 may be the origin
of the overall high stereoselectivity of the process.
aReagents and conditions: (a) 1-heptyne (0.50 mmol), 1-octynyl-
BPin (0.50 mmol), B2Pin2 (0.50 mmol), 1 (5 mol%), toluene (0.5 mL),
23 °C, 15 h.
In the cobalt-catalyzed Z-selective hydroboration of alkynes with
HBPin, a mixture of (Z) and (E)-vinylcobalt species were formed
upon addition of HBPin to acetylide complex 20a, and found to
interconvert (Scheme 11A).21 The high stereoselectivity observed
in the 1,1-diboration with PinB–BDan could be a result of selective
reaction of one vinylcobalt intermediate over another (IVa vs.
IVb), but is also consistent with the more Lewis acidic boron sub-
stituent (BPin)37 being transferred to the alkyne first and the result-
ing alkynyl–BPin cobalt complex (IIIa) undergoing syn-
borylcobaltation to give IVa selectively (Scheme 11B).
Scheme 12. Stereoselective synthesis of vinylcobalt species 22 and
single-turnover experiment.
Scheme 11. Mechanistic possibilities for the origin of stereoselec-
tivity.
Concluding Remarks. In summary, a general method for the 1,1-
diboration of terminal alkynes catalyzed by a cyclohexyl-substituted
pyridine diimine cobalt complex has been developed. The reaction
proceeds under mild conditions, displays broad scope and func-
tional group tolerance, and furnishes 1,1-diborylalkene products
with excellent selectivity. Chiral as well as unsymmetrical diboron
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Journal of the American Chemical Society
ACS Catal. 2012, 2, 1993; for a review on diboron(4) compounds and
reagents participate in the reaction, and the latter furnished alkene
1
2
3
4
5
6
7
8
their synthetic applications, including alkyne diboration, see: (d) Neeve, E.
C.; Geier, S. J.; Mkhalid, I. A. I.; Westcott, S. A.; Marder, T. B. Chem. Rev.
2016, 116, 9091; for representative examples involving particular metals,
see: Co: (e) Adams, C. J.; Baber, R. A.; Batsanov, A. S.; Bramham, G.;
Charmant, J. P. H.; Haddow, M. F.; Howard, J. A. K.; Lam, W. H.; Lin, Z.;
Marder, T. B.; Norman, N. C.; Orpen, A. G. Dalton Trans. 2006, 1370; Au:
(f) Au: Chen, Q.; Zhao, J.; Ishikawa, Y.; Asao, N.; Yamamoto, Y.; Jin, T.
Org. Lett. 2013, 15, 5766; Fe: (g) Nakagawa, N.; Hatakeyama, T.;
Nakamura, M. Chem. Eur. J. 2015, 21, 4257; Cu: (h) Yoshida, H.; Ka-
washima, S.; Takemoto, Y.; Okada, K.; Ohshita, J.; Takaki, K. Angew.
Chem., Int. Ed. 2012, 51, 235.
products with two different boron substituents in stereoselective
fashion. When used in tandem with Pd-catalyzed cross coupling,
this resulted in a formal 1,1-carboboration of the terminal alkyne. A
one-pot 1,1-diboration/cross-coupling sequence enabled a highly
concise synthesis of tiagabine, an approved treatment for epilepsy.
The synthetic versatility of the 1,1-diborylalkene products was
further demonstrated in C–halogen, C–O, C–H, and C–B bond
formation. The latter gave access to a set of 1,1,1-triborylalkanes
that are inaccessible by existing methods. Mechanistic studies re-
vealed that the 1,1-diboration proceeds via the intermediacy of a
vinylcobalt species, in analogy to the previously reported Z-
selective hydroboration and suggest this approach may be general
for 1,1-difunctionalization strategies.
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(8) (a) Nagao, K.; Ohmiya, H.; Sawamura, M. Org. Lett. 2015, 17,
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Soc. 2014, 136, 8532; for an example of organosulfide-catalyzed 1,2-
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13930.
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(11) Uncatalyzed diborations of trimethylsilyl-, trialkylstannyl-, and tri-
methylgermylacetylenes with 1,2-dichlorodiboron(4) reagents have in
select cases been shown to lead to formation of 1,1-diborylalkenes, possibly
via rearrangement of an initially formed 1,2-adduct: (a) Klusik, H.; Pues,
C.; Berndt, A. Z. Naturforsch. B 1984, 39B, 1042; (b) Siebert, W.; Hilden-
brand, M.; Hornbach, P.; Karger, G.; Pritzkow, H. Z. Naturforsch. B 1989,
44B, 1179; (c) Schulz, H.; Pritzkow, H.; Siebert, W. Z. Naturforsch. B
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(12) Ishiyama, T.; Matsuda, N.; Miyaura, N.; Suzuki, A. J. Am. Chem.
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(13) (a) Morinaga, A.; Nagao, K.; Ohmiya, H.; Sawamura, M. Angew.
Chem., Int. Ed. 2015, 54, 15859.
(14) (a) Coapes, R. B.; Souza, F. E. S.; Thomas, R. L.; Hall, J. J.; Marder,
T. B. Chem. Commun. 2003, 614; (b) Mkhalid, I. A. I.; Coapes, R. B.;
Edes, S. N.; Coventry, D. N.; Souza, F. E. S.; Thomas, R. L.; Hall, J. J.; Bi,
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(15) (a) Takaya, J.; Kirai, N.; Iwasawa, N. J. Am. Chem. Soc. 2011, 133,
12980; (b) Kirai, N.; Iguchi, S.; Ito, T.; Takaya, J.; Iwasawa, N. Bull. Chem.
Soc. Jpn. 2013, 86, 784; 1,1-diborylalkenes have also been detected as
intermediates in a cobalt catalyzed synthesis of 1,1,1-triborylalkanes from
styrenes, see ref. 29.
(16) (a) Ho, H. E.; Asao, N.; Yamamoto, Y.; Jin, T. Org. Lett. 2014, 16,
4670; (b) Li, H.; Carroll, P. J.; Walsh, P. J. J. Am. Chem. Soc. 2008, 130,
3521; (c) Weber, L.; Eickhoff, D.; Halama, J.; Werner, S.; Kahlert, J.;
Stammler, H.-G.; Neumann, B. Eur. J. Inorg. Chem. 2013, 2608.
(17) (a) Lee, C.-I; Shih, W.-C.; Zhou, J.; Reibenspies, J. H.; Ozerov, O.
V. Angew. Chem., Int. Ed. 2015, 54, 14003; (b) Abu Ali, H.; Al Quntar, A.
E. A.; Goldberg, I.; Srebnik, M. Organometallics 2002, 21, 4533; (c) Hyo-
do, K.; Suetsugu, M.; Nishihara, Y. Org. Lett. 2014, 16, 440; (d) Maderna,
A.; Pritzkow, H.; Siebert, W. Angew. Chem., Int. Ed. 1996, 35, 1501.
(18) (a) Jiao, J.; Nakajima, K.; Nishihara, Y. Org. Lett. 2013, 15, 3294;
(b) Jiao, J.; Hyodo, K.; Hu, H.; Nakajima, K.; Nishihara, Y. J. Org. Chem.
2014, 79, 285.
(19) Matteson, D. S. Synthesis 1975, 147, and references therein.
(20) (a) Hata, T.; Kitagawa, H.; Masai, H.; Kurahashi, T.; Shimizu, M.;
Hiyama, T. Angew. Chem., Int. Ed. 2001, 40, 790; (b) Kurahashi, T.; Hata,
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ASSOCIATED CONTENT
Supporting Information. Experimental details, characterization data,
NMR spectra, and crystallographic information. This material is availa-
ble free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
pchirik@princeton.edu
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENTS
S.K. gratefully acknowledges the Swiss National Science Foundation
for a postdoctoral fellowship. M.J.B. thanks the Natural Sciences and
Engineering Research Council of Canada for a predoctoral fellowship
(PGS-D). We are grateful to W. Neil Palmer and Jennifer V. Ob-
ligacion for insightful discussions. We also thank Dr. István Pelczer for
assistance with NMR spectroscopy as well as Dr. Charles Campana
(Bruker) for assistance with solving the X-ray structure shown in
Scheme 5. The staff at Lotus Separations are gratefully acknowledged
for measuring the ee of 12.
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