A Boron Activating Effect Enables Cobalt-Catalyzed Asymmetric Hydrogenation of Sterically Hindered Alkenes

Article abstract of DOI:10.1021/jacs.9b12214

Unsymmetric 1,1-diboryl alkenes bearing one -[BPin] (BPin = pinacolatoboryl) and one -[BDan] (BDan = 1,8-diaminonaphthalatoboryl) substituent each were hydrogenated in high yield and enantioselectivity using C₁-symmetric pyridine(diimine) (PDI)

Full text of DOI:10.1021/jacs.9b12214

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Article
A Boron Activating Effect Enables Cobalt-Catalyzed
Asymmetric Hydrogenation of Sterically Hindered Alkenes
Peter Viereck, Simon Krautwald, Tyler P. Pabst, and Paul J. Chirik
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b12214 • Publication Date (Web): 02 Feb 2020
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Journal of the American Chemical Society
A Boron Activating Effect Enables Cobalt-Catalyzed Asymmetric
Hydrogenation of Sterically Hindered Alkenes
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Peter Viereck, Simon Krautwald, Tyler P. Pabst and Paul J. Chirik*
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Department of Chemistry, Princeton University, Princeton, New Jersey, 08544, U.S.A.
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ABSTRACT: Unsymmetric 1,1-diboryl alkenes bearing one –[BPin] (BPin = pinacolatoboryl) and one –[BDan] (BDan = 1,8-diaminonaphthalatoboryl)
substituent each were hydrogenated in high yield and enantioselectivity using C1-symmetric pyridine(diimine) (PDI) cobalt complexes. High activities and
stereoselectivities were observed with an array of 2-alkyl, 2-aryl, and 2-boryl-substituted 1,1-diboryl alkenes, giving rise to enantioenriched diborylalkane
building blocks. Systematic study of substrate substituent effects identified competing steric and electronic demands in the key activating role of the boron
substituents, whereby sterically unencumbered boronates such as –[BDan], –[BCat] (BCat = catecholatoboryl), and –[Beg] (Beg = ethyleneglycolatoboryl)
promote the hydrogenation of trisubstituted alkenes by enabling irreversible α-boron directed insertion pathways to achieve otherwise-challenging
hydrogenations of trisubstituted alkenes. Deuterium labeling studies with 1,1-diboryl alkenes support an insertion pathway generating a chiral intermediate with
two different boron substituents and cobalt bound to the same carbon.
INTRODUCTION
The asymmetric hydrogenation of prochiral vinyl boronates is an
The asymmetric hydrogenation of alkenes is a well-established and
attractive alternative for the preparation of enantioenriched building
powerful method for the preparation of enantioenriched compounds
blocks, and has been explored previously, principally with precious
with widespread application in the synthesis of pharmaceuticals,
metal catalysts.17,18 Such transformations can be powerful given the
fragrances, and fine chemicals.1 With state-of-the-art rhodium and
array of transformations for the preparation of vinyl boronates.19 Most
ruthenium catalysts, activated alkenes with coordinating functional
groups proximal to the C=C bond are often required to obtain high
enantioselectivities.2 Unfunctionalized olefins, however, are
recently, Lu has described
a class of sequential asymmetric
hydrometalation-hydrogenation reactions utilizing C1-symmetric,
enantioenriched cobalt dihalide complexes activated in situ by
borohydride reagents.20 Despite these advances, the effect of boronate
substitution on the rate and enantioselectivity of the hydrogenation
has not been elucidated, although it has been proposed that the π-
a
challenging class of substrate owing to a lack of directing assistance
from coordinating functional groups.3 Accordingly, the hydrogenation
of unactivated alkenes lacking directing groups with synthetically
useful enantioselectivities remains a frontier for catalyst development,
although significant advances have been made with iridium,4 titanium,5
zirconium6 and lanthanide7 complexes (Scheme 1A). Nevertheless,
opportunities remain to apply asymmetric hydrogenation to the
synthesis of new enantioenriched building blocks for organic synthesis.
Catalysts comprised of Earth-abundant, 3d transition metals such
as cobalt and nickel have exhibited outstanding performance in
asymmetric alkene hydrogenation and in many instances offer distinct
advantages over their precious metal counterparts.8 For example,
bis(phosphine) cobalt catalysts have been discovered that operate
optimally in methanol at lower loadings and with higher
enantioselectivities than reported rhodium catalysts for the
asymmetric hydrogenation of functionalized alkenes and precursors to
active pharmaceutical ingredients.9 Catalysts supported by redox-
active, C1-symmetric pyridine(diimine) ligands have proven both
active and in some cases highly enantioselective for the hydrogenation
of pure hydrocarbon substrates such as styrenes and indenes.10,11
Similarly, C1-symmetric oxazoline iminopyridine (OIP) ligands have
electron withdrawing nature of boron as well as its σ-donating
properties promote the catalytic reaction.18c
Scheme 1.
Transition-Metal Catalyzed Asymmetric
Hydrofunctionalization.
A. Retrosynthesis of Enantioenriched Alkylboronates
B
B
+ H-B
[M]*
+ H2
[M]*
Asymmetric Hydroboration
- Well Established
Asymmetric Hydrogenation
- Underexplored
B. C1-Symmetric (PDI)Co Complexes for Asymmetric Hydrogenation
[Co]
R
R
N
+ H2
Cy
N
Co
N
iPr
R
R
CH3
[Co]
+ H2
[Co] = CyCoMe
iPr
been subsequently applied to
a
host of cobalt-catalyzed
C. This Work: Asymmetric Hydrogenation of 1,1-Diboryl Alkenes
enantioselective hydrofunctionalization reactions.12,13
Of these hydrofunctionalization reactions, asymmetric alkene
hydroboration to prepare enantioenriched alkylboronates has been
explored extensively given the diverse array of transformations
available from the carbon–boron bond.14 Hence, the preparation of
enantioenriched polyorganoboron compounds is arguably among the
most powerful transformations in asymmetric synthesis – generating a
single chiral building block that could be used to prepare a host of
stereochemically defined products by known stereoretentive,
stereoinvertive or iterative transformations.15,16
N
BPin
BDan
BPin
BDan
Up to 98% ee
N
[Co]
+ H2
Co
R
R
N
iPr
R = alkyl aryl, or -BDan
[Co] = tBuCoCM
iPr
The discovery of a cobalt-catalyzed method for the selective 1,1-
diboration of terminal alkynes has provided a facile route for the
preparation of 1,1-diborylalkenes.21 Notably, use of the mixed diboron
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A. Cobalt-catalyzed Asymmetric Hydrogenation of 1,1-Diborylalkenes.
BPin
BPin
BDan
5 mol% [Co]*, 1 or 4 atm H2
Me
Me
N
N
Cy
0.07 M C H , 23 °C, 17 h
BDan
N
N
6
6
4
5
6
7
1a
-BDan =
(S)-2a
Co
Co
N
N
iPr
iPr
CH3
-BPin =
Entry
[Co]* P (H2)
ee
1
2
3
CyCoMe 1 atm 83% ee
CyCoMe 4 atm 90% ee
tBuCoCM 4 atm 96% ee
O
B
HN
B
CyCoMe
tBuCoCM
iPr
iPr
O
N
8
H
9
B. Scope of Hydrogenation
BPin
C. Solid State Structure of 2m
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BPin
BDan
BPin
BPin
Me
TBSO
AcO
BDan Me
BDan
BDan
2a 98%, 96% ee
BPin
2b 98%, 96% ee
BPin
2c 75%, 93% ee
2d 83%, 97% ee
BPin
BPin
BDan
O
O
Me
Ph
BDan
PhthN
2f 90%, 97% ee
BPin
BDan
2j 98%, 98% eeb
BDan
BDan
Me
2e 87%, 91% eea
2g 98%, 20:1 d.r.
BPin
BDan
2l 98%, 98% eec
2h 84%, 97% ee
BPin
BPin
BPin
Ph
DanB
Ph
BDan
BDan
2k 90%, 93% eec
BDan
2m 50%, 85% eec
2i 93%, 97% ee
Scheme 2. Method Development. A. Reactions conducted on 0.1 mmol scale in a thick walled glass vessel. B. Scope of the cobalt-catalyzed
asymmetric hydrogenation. Standard conditions: 0.1 mmol alkene, 5 mol % tBuCoCM, 4 atm of H2, 0.07 M benzene, 23 ºC, 17 h. a Isolated as a 1:1
mixture of diastereomers. b. 0.025 mmol alkene, 10 mol % tBuCoCM, 24 h. 10 mol % tBuCoCM, 24 h. Isolated yields. Enantioselectivities determined
c.
by chiral SFC chromatography. Absolute stereochemistry of 2a-l assigned based on the solid-state structure of 2k (See SI). C. Solid-state structure of
2m. Thermal ellipsoids at 30% probability. H-atoms at non-stereogenic sites omitted for clarity.
reagent, BPin–BDan (-BPin
= pinacolatoboryl, -BDan = 1,8-
RESULTS AND DISCUSSION
diaminonaphthalatoboryl)22 led to a stereoselective reaction resulting
in the formation of isomerically pure 1,1-diborylalkenes. These
compounds represent an unexplored yet promising class of prochiral
alkenes as asymmetric hydrogenation would provide enantiomerically
enriched 1,1-diborylalkanes containing two chemically inequivalent
boronates on one carbon. These reagents have been shown to be
versatile building blocks for the iterative preparation of
enantioenriched compounds.23
Because previous studies from our group established that C yCoMe
(
CyCoMe
=
2-(2,6-iPr2-C6H3N=CMe)-6-(C(Me)=N-((S)-
(CH(CH3)Cy)))-(C5H3N)CoCH3) is an effective precatalyst for the
enantioselective hydrogenation of minimally functionalized alkenes,10a
this compound was explored for the hydrogenation of 1,1-
diborylalkenes. With 1 atmosphere of H2, the hydrogenation of 1a in
the presence of 5 mol% of C yCoMe produced the corresponding 1,1-
diborylalkane in 83% enantiomeric excess (ee), favoring the (S)
enantiomer (Scheme 2A, entry 1). Increasing the H2 pressure to 4 atm
improved the ee to 90% (Scheme 2A, entry 2). Previous studies
established that the tert-butyl variant tBuCoCM (tBuCoCM = 2-(2,6-
iPr2-C6H3N=CMe)-6-(C(Me)=N-((S)-(CH(CH3)C(CH3)2CH2-))-
(C5H3N)Co) produced little activity for the hydrogenation of 1,1-
disubstituted styrene derivatives. However this precatalyst produced
high activity for the asymmetric hydrogenation of 1a with 4 atm of H2,
improving the enantioselectivity to 96% (Scheme 2A, entry 3).
In addition to their synthetic utility, the hydrogenation of 1,1-
diborylalkenes is of fundamental interest as electron-deficient alkenes
are activated toward hydrogenation as compared to their more
electron-rich counterparts24 and α-boryl substituents appear to
stabilize metal alkyls as evidenced by transition-metal-mediated alkene
isomerizations that favor α-boryl metal intermediates.25 These
properties may be exploited to enhance both the activity and selectivity
of asymmetric hydrogenation. Here we describe the cobalt-catalyzed
Having identified an active and enantioselective cobalt catalyst for
the hydrogenation of 1a, the scope of the transformation was
asymmetric hydrogenation of 1,1-diborylalkenes as
enantioenriched diborylalkanes. Systematic variation of the boronate
ester established the BDan substituent as activating for hydrogenation
a route to
evaluated.
A range of linear, alkyl-substituted 1,1-diborylalkenes
underwent hydrogenation using the standard, optimized reaction
conditions (Scheme 2B). Common functional groups such as a silyl
protected alcohol (2c), an ester (2d), an acetal (2e), and phthalimide
(2f) were all tolerated. Notably, the citronellol-derived diene, 2g was
selectively hydrogenated at the diboryl alkene, leaving the all-aliphatic
alkene untouched. This chemoselectivity demonstrates the activating
effect of the 1,1,-diboryl substituent as compared to 1,1-dimethyl
substituent. More sterically hindered 1,1-diborylalkenes incorporating
cyclopentyl (2k) and cyclohexyl (2l) substituents also underwent
catalysis, as well as for supporting α-boryl metal intermediates.
Mechanistic investigations revealed the insertion preferences for
boron-substituted alkenes. The resulting enantioenriched 1,1-diboron
species have been shown to be versatile synthons in enantioretentive
Suzuki couplings as well as homologation-type reactions,23 and our
synthetic approach to these building blocks is complementary to
existing methods for the enantioselective hydroboration of mono-
boryl alkenes.
hydrogenation in high yield and enantioselectivity.
substituted diboryl alkene was also hydrogenated with high
A phenyl-
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enantioselectivity (2j), suggesting that an aryl group does not perturb indenes was conducted (Scheme 5 & 6). Notably, the attempted
1
2
3
4
5
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the preferred insertion pathway. Additionally, unsymmetric,
trisubstituted 1,1,2-triborylalkene (1m) was sucessfully hydrogenated
with tBuCoCM to the corresponding hindered alkane (2m) and was
obtained in 85% ee favoring the (S) enantiomer. The absolute
configuration of the triborylalkane product was established by X-ray
crystallography (Scheme 2C).
For synthetic utility, the cobalt-catalyzed asymmetric
hydrogenation should be scalable. With 1 mol % of tBuCoCM and 4
atm of H2 gas, 1.0 gram of 1a was hydrogenated to the corresponding
1,1-diboryl alkane in 95 % isolated yield with 95 % enantiomeric excess
without the need of further purification (Scheme 3). Efficient and
rapid stirring was key to achieving high enantiomeric excess. The
scalability of the hydrogenation highlights a potential advantage of this
method compared to hydroboration for the preparation of
enantioenriched alkyl boronates.
hydrogenation of the 2,2-diborylheptene (3a), or 2,2-diborylstyrene
(3b) with 5 mol % of tBuCoCM under standard conditions produced
no detectable amounts of alkane after 24 hours (Scheme 5, entry 1 &
3). Replacement of the (E)–[BPin] substituent with a –[BDan] group
resulted in complete conversion to the alkane 1a or 1j under identical
conditions. A similar effect was observed with 1,2-diborylstyrenes. The
[BPin]-substituted variant (3c) was hydrogenated to 33% conversion
after 24 hours under standard conditions while the [BDan] variant
(3d) reached complete conversion to the desired alkane as observed
by 1H NMR spectroscopy.
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BPin
BPin
A.
Me
Me
BPin
BPin
3a
4a, 0% conv.
BPin
BDan
BPin
BDan
B.
Me
Me
BPin
1 mol % tBuCoCM
BPin
BDan
1a
2a, 99% conv.
BPin
C5H11
C5H11
BDan
H2 (4 atm.)
C6H6, 23 °C, 36 h
BPin
BPin
A.
B.
Ph
Ph
Ph
BPin
1a, 1 gram
2a, 95 % IY, 95 % ee
3b
4b, 0% conv.
BPin
BPin
Scheme 3. Gram Scale Enantioselective Hydrogenation of
the 1,1-Diboryl Alkene (1a).
Ph
BDan
BPin
BDan
BDan
1j
2j, 99% conv.
BPin
Sigman, Biscoe and co-workers recently reported conditions for
ligand-controlled, palladium-catalyzed stereoretentive and invertive
cross couplings of enantioenriched alkyl trifluoroborates.26 To
determine whether such enantiodiversity can be applied to
enantioenriched 1,1-diboryl alkanes, 1a was converted to its respective
trifluoroborate analogue, and directly subjected to Suzuki-Miyaura
cross coupling conditions using Pd-G327a as a precatalyst (Scheme 4).
Interestingly, both XPhos27b and PAd327c produced the arylated product
with stereoinversion, in 32% ee (49% yield), and 84% ee (93% yield)
respectively. This demonstrates the unique reactivitiy in
enantioenriched 1,1-diboryl alkanes from their purely alkyl substituted
counterparts.
BPin
A.
A.
BPin
Ph
Ph
4c, 33% conv.
BDan
3c
BDan
BDan
Ph
Ph
3d
4d, 99% conv.
Scheme 5.
Hydrogenation of Alkenyl Boronates. A.
Hydrogenation reaction was conducted in a J-Young NMR tube with
0.025 mmol alkene, in benzene-d6 with 10 mol % tBuCoCM, 4 atm H2,
1
23 °C and the conversions determined by H NMR spectroscopy after
24 h. See SI for experimental details. B. From scheme 2B.
PhI (1 equiv.)
K2CO3 (3 equiv.)
BF3K
A.
2a (95 % ee)
To further elucidate the effect of each boronate substituent, a
series of substituted indenes was prepared from 1H-inden-3-yl boronic
acid and subjected to standard hydrogenation conditions with
C5H11
Pd-G3 (10 mol %)
L (20 mol %)
PhMe:H2O (2:1)
80 °C, 17 h
BDan
1.5 equiv.
C5H11
BDan
(S)-Ph-2a,
(not isolated)
tBuCoCM as the precatalyst. Each conversion was determined by H
1
NH
Pd
L = XPhos - 49%, 32% ee
L = PAd3 - 93%, 84 % ee
NMR spectroscopy after 2 hours (Scheme 6). Consistent with our
previous study, both 1-methyl (5a) and 1-phenyl (5b) indenes were
poor substrates for hydrogenation and only trace quantities of the
corresponding alkane were detected. Introduction of common
MsO
2
Pd-G3
Scheme 4. Suzuki-Miyaura Cross-Coupling of an
enantioenriched 1,1-diboryl alkane. Isolated yields.
Enantioselectivities determined by chiral SFC chromatography. A. Sat.
aq. KHF2 (10 equiv.), MeCN (0.125 M), rt, h. Absolute
boronate esters such as [BNeop] (5c) (BNeop
=
neopentanolatoboryl), [BPin] (5d), [BDan] (5e), and [Beg] (5f)
(Beg = ethyleneglycolatoboryl) all likewise produced low conversions
during the two-hour reaction time frame. Notably, the hydrogenation
of [BCat] (BCat = catecholatoboryl) (5g) reached full conversion over
this time period, demonstrating a remarkable activating effect. Even
when the conversions were low, the observed enantioselectivities also
offered insight. Alkenes bearing a phenyl substituent (5b) as well as
[BNeop] (5c) and [BPin] (5d) produced low selectivities (6, 8 and
0% ee, respectively) while [BDan] (5e) and [Beg] (5f) groups
furnished the corresponding alkane in 60 and 64% ee, respectively.
The most activated substrate in the series, 5g ([BCat]) also gave the
highest ee at 76% (Scheme 6). The higher enantioselectivities
observed with the [BDan], [Beg] and [BCat] substituents suggest that
2
configuration of (S)-Ph-2a determined by deprotection and
oxidation of boronate ester.
The discovery of a highly enantioselective route for the synthesis of
polyboryl alkanes prompted studies to uncover the source of the high
activity. Recall that tBuCoCM was inactive for the hydrogenation of
1,1-disubstituted styrenes and only the boron-substituted alkene was
hydrogenated en route to 2g.10a This supports an activating effect of
the boron groups – and despite its steric encumbrance in comparison
to the alkyl substituted alkene – is hydrogenated in good yield. To
elucidate the origins of this phenomenon, a systematic study of the
hydrogenation of a selected group of boryl alkenes, styrenes and
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sterically unencumbered boronates may be required for high
enantioselectivity.
Scheme 7C; 99%, R, Scheme 7D respectively) to the opposite
enantiomer than that derived from indenyl-BPin.
1
2
3
4
5
6
7
8
R
R
As the most hydrolytically sensitive alkenyl boronates (e.g. –
[BCat] 6f, and –[Beg] 6g) are hydrogenated to the greatest
enantioselectivity, the effect of free boronic acid was tested in this
hydrogenation reaction. Upon H2 gas addition (4 atm) to a C6D6
solution of 0.025 mmol 5g, 10 mol % tBuCoCM, and 10 mol % of
(1H-inden-3-yl)boronic acid resulted in a color change from dark
purple to a light red, and showed no conversion of 5g. It is concluded
that the presence of free boronic acid is not involved in the
hydrogenation of indenyl boronates.
10 mol% tBuCoCM, 4 atm H2
C6D6, 23 °C, 2 h
5a-g
Me
6a-g
Ph
BNeop
BPin
9
5a
0% conv.
5b
5c
5d
< 5% conv.
6% ee
< 5% conv.
6% ee
12% conv.
< 5% ee
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Selective deuterium incorporation at the 1- and 2-position of the
indanol product is consistent with an α-boron-directed insertion
BDan
Beg
BCat
pathway, where turnover proceeds through an α-boron alkyl cobalt
intermediate (Scheme 7E). This pathway is favored with sterically
unencumbered boronates such as –[Beg] and –[BCat]. Although –
[BDan] is sterically unencumbered, the boron p-orbital is partially
occupied as evidenced by its resistance to oxidation,22 and the
hyperconjugative stabilization from the boron to the cobalt-carbon
bond may be less pronounced. Thus, a small amount of isomerization
is observed. Sterically encumbered boronates such as –[BPin] prevent
5e
5f
5g
7% conv.
60% ee
15% conv.
64% ee
> 99% conv.
76% ee
-BNeop =
-Beg =
-BCat =
O
B
O
B
O
B
O
O
O
the bulky cobalt complex from inserting α to boron, and thus a large
amount of isomerization originating from a β-boron-directed insertion
pathway is observed (Scheme 7E, left). A similar effect has been
observed by Yun, where a vinyl –[BDan] substrate shows greater α-
Scheme 6. Hydrogenation of Indenyl Boronates. Reactions
were conducted on 0.025 mmol scale in a J-Young NMR tube and the
1
conversions determined by H NMR spectroscopy. Enantioselectivies
of all boronates were determined by chiral SFC chromatography on
the corresponding alcohols following oxidation with a THF:H2O 10:1
solution of H2O2 and NaOH, with the exception of 6e, which was
determined directly. See SI for complete experimental details.
boron selectivity in hydroboration than a vinyl –[BPin].23b This α-
boron-directed insertion pathway enables high levels of
enantioselectivity by outcompeting isomerization pathways (Scheme
7E, right).
Previously reported isotopic labeling studies on the asymmetric
hydrogenation of aryl-substituted indenes promoted by C yCoMe with
D2 gas established deuterium incorporation occurred at every site of
the indanyl core.10b These observations are consistent with a slow 2,3-
insertion (for definition of the labeling scheme see Scheme 7),
resulting in the cobalt bound to the less-substituted carbon as the most
catalytically relevant insertion event. This step is followed by fast
isomerization to the benzylic position along the π-face of the indene
before release of alkane either by cyclometallation of
a ligand
substituent or reaction with dihydrogen. Because the enantioselectivity
of the hydrogenation of indenyl boronates was strongly influenced by
the substituent on the boronate, the identity of this substituent may
also be influencing the preferred alkene insertion and ultimately
turnover pathway.
To probe this hypothesis, a series of indenyl boronates were
deuterated with D2 gas in the presence of 5 mol % of tBuCoCM for
24 hours to maximize conversion of the alkene. The resulting
boronates were subsequently oxidized to the corresponding alcohol for
2
ease of analysis by H and 13C NMR spectroscopies (Scheme 7). The
indanol obtained from deuteration of 5a (BPin) (Scheme 7A)
exhibited isotopic incorporation at all of the saturated positions and
overall poor enantioselectivity (10% ee, S). By contrast, with the –
[BDan]-substituted indene (5e), deuterium incorporation was
observed predominantly at the 1- and 2-positions, although a small
amount (<5%) of deuterium was observed in the 3-position. In
addition, deuterium was incorporated at both positions at the 2
carbon. The enantioselectivity of this hydrogenation was modest (60%
ee, R, Scheme 7B), and favored the opposite enantiomer. However
hydrogenation of the –[Beg] (5f) and –[BCat] (5g) substituted
indenes under deuterium atmosphere generated only one detectable
isotopomer, where deuterium was exclusively incorporated at the 1-
and 2-position with remarkably high enantioselectivities (97% ee, R,
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A.
pathway, generating an intermediate where the metal center shares a
OH
D
BPin
10 mol% tBuCoCM, D2 (4 atm)
1
16%
1
2
3
4
5
6
7
8
3
carbon with two chemically inequivalent boronates. Similar behavior
has been observed previously in the cobalt-catalyzed hydroboration of
1,1-diboryl alkenes used to selectively generated 1,1,1-triboryl
alkanes.21 Under stoichiometric conditions, the β-boron-directed
insertion pathway was also competitive and is likely the origin of the
diminished enantioselectivity (81% ee), however the lower pressure of
D2 (1 atm) is another possible source of the lower selectivity.
C6H6, 23 °C, 24 h
10%
91%
D
D
2
2
Then NaOH, H2O2
3
D
1
D
77%
11%
5a
5e
7a-d, 10% ee
B.
C.
D.
BDan
D
BDan
10 mol% tBuCoCM, D2 (4 atm)
1
95%
3
C6H6, 23 °C, 24 h
99%
D
2
2
D
< 5%
3
1
D
< 5%
A. Catalytic
7e-d, 60% ee
9
H
PinB
D
95%
BPin
BDan
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
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59
60
5 mol % tBuCoCM
OH
D
Beg
10 mol% tBuCoCM, D2 (4 atm)
1
97%
Ph
BDan
D2 (4 atm.)
3
Ph
C6H6, 23 °C, 24 h
99%
D
D
C6H6, 23 °C, 17 h
2
2
H
Then NaOH, H2O2
99%
3
1i
B. Stoichiometric
2ia-d, 95% ee
1
H
5f
7f-d, 99% ee
H
PinB
OH
D
D
44%
BCat
10 mol% tBuCoCM, D2 (4 atm)
1
93%
3
+
1i
tBuCoCM-d +
Ph
C6H6, 23 °C, 24 h
tBuCoCM
BDan
99%
D
H
2
D2 (1 atm.)
C6D6, 23 °C, 17 h
2
Then NaOH, H2O2
D
84%
3
1
H
2ib-d, 81% ee
5g
7g-d, 97% ee
Scheme 8. Catalytic (A) and stoichiometric (B)
deuteration studies of 1i.
E. Proposed Pathways
BX2
b-Boron Insertion
a-Boron Insertion
Pathway
Pathway
BDan,
BPin
An α-boron directed insertion pathway would place the metal
center on the prochiral carbon of the alkane. This in turn may allow for
the enantioselective hydrogenation of E/Z mixtures to the same
enantiomer of the diboryl alkane.3 The pyridine(diimine) iron
BCat and
Beg
+
Co-D
BX2
D
BX2
Co
D
Co
dinitrogen complex,
( ( = 2,6-(2,6-Me2-
MePDI)Fe(N2)1.5 MePDI
C6H3N=CMe)2C5H3N)28 was competent for the isomerization of 1i
under low H2 pressure (0.1 atm), resulting in an 84:16 Z:E mixture
(Scheme 9A).
1) b-H Elim
2) D2
D2
BX2
D
BX2
D
After subjecting the E/Z mixture to the standard reaction
conditions under an atmosphere of D2 gas (4 atm D2), deuterium
incorporation was observed at both positions at the homobenzylic
position (82% syn, 18% anti) and the alkane observed in 68% ee
(84:16 e.r., Scheme 9B). This is consistent with each isomer of the
alkene being hydrogenated to a different major enantiomer. Though it
may suggest a β−boron-directed insertion pathway, the results of the
stoichiometric deuterium labeling study (Scheme 8) supports an α-
boron directed insertion pathway, thus a model where each isomer of
the alkene is hydrogenated to a different enantiomer, while still
proceeding through an α-boron-directed insertion pathway cannot be
excluded.
D
D
D
Scheme 7. Deuteration of Indenyl Boronates. Reactions
conducted on a 0.1 mmol scale in a thick-walled glass vessel.
Enantioselectivities determined by chiral SFC. Relative configuration
of (b) determined by conversion of BDan to BPin and oxidation with
NaOH, H2O2.
The discovery that different boronates promote distinct insertion
pathways prompted similar studies with 1,1-diboryl alkenes.
Deuteration of 1i in the presence of tBuCoCM under 4 atmospheres of
D2 gas at room temperature for 17 hours generated a single isotopomer
in high enantioselectivity (95% ee; Scheme 8A), implying that no
isomerization events are competitive with catalytic turnover.
The insertion preferences of the diboryl alkene into the cobalt–
hydride bond were also investigated. Ideally, the alkene could be added
to an isolated cobalt deuteride, and the resulting intermediate of
insertion could be quenched with a proton source. Because the cobalt–
deuteride derived from tBuCoCM has eluded isolation,10a a single
turnover experiment with 1i was conducted under a D2 atmosphere to
promote selective labeling of the product alkane that would in turn
inform on the site of attachment of the putative cobalt–alkyl. Low (1
atm) pressures of deuterium were used to maximize turnover from a
cyclometallation pathway, thus lowering deuterium incorperation at
the position the cobalt inserted. Deuterium was predominantly and
A. E/Z Isomerization of 1i
BPin
5 mol % (MePDI)Fe(N2)1.5
BPin
BDan
Ph
BDan
H2 (0.1 atm.)
Ph
C6D6, 23 °C, 1 h
1i
B. Hydrogenation of E/Z Mixture
84:16 Z:E
H
PinB
D
93%
5 mol % tBuCoCM
BPin
BDan
Ph
BDan
D2 (4 atm.)
Ph
D
D
82% 18%
C6H6, 23 °C, 17 h
84:16 Z:E
68% ee (84:16 e.r.)
Scheme 9. Preparation and hydrogenation of an E/Z
mixture.
stereoselectively incorporated in a syn disposition at the β position
(84%), and to a lesser extent α to boron (44%) (Scheme 8B). This
result is consistent with a dominant α-boron directed insertion
CONCLUDING REMARKS
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A cobalt-catalyzed method for the asymmetric hydrogenation of
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1,1-diboryl alkenes was discovered as a route to versatile, enantiopure
polyboryl alkanes. Both the steric and electronic properties of the
boronate substituents influence the yield and enantioselectivity of the
hydrogenation reaction and in some cases activate the alkene for
hydrogenation. Deuterium labeling experiments support an insertion
pathway where the metal center is selectively bound to the sterically
congested carbon of the substrate and demonstrate the powerful
effects of alkenyl boronates to overcome otherwise repulsive steric
effects. The results of the indene deuteration studies are in agreement
with the deuteration studies with the 1,1-diboryl alkenes – where
sterically unencumbered boronates containing available p-orbitals
enabled high conversion and enantioselectivity. Leveraging this boron
activating effect may be broadly applicable in asymmetric catalysis
involving boron-containing substrates.
AUTHOR INFORMATION
Corresponding Author
*E-mail for P.J.C.: pchirik@princeton.edu
ORCID
Peter Viereck: 0000-0003-4691-8434
Tyler P. Pabst: 0000-0003-4595-2833
Paul J. Chirik: 0000-0001-8473-2898
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGEMENTS
ASSOCIATED CONTENT
We would like to thank Christina Kraml, Laura Wilson, and Neal Byrne of
Lotus Separations for enantiomeric excess determinations. Financial
support was provided by the U.S. National Science Foundation Grant
Opportunities for Academic Liaison with Industry (GOALI) grant (CHE-
1855719). Simon Krautwald is grateful to the Swiss National Science
Foundation for a postdoctoral fellowship.
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website.
Crystallographic information for 2k and 2m (CIF)
Hoyt, J. M.; Campeau, L.-C.; Chirik, P. J. Nickel-Catalyzed Asymmetric Alkene
Hydrogenation of α,β-Unsaturated Esters: High-Throughput Experimentation-
Enabled Reaction Discovery, Optimization, and Mechanistic Elucidation. J.
Am. Chem. Soc. 2016, 138 (10), 3562–3569.
REFERENCES
1Shultz, C. S.; Krska, S. W. Unlocking the Potential of Asymmetric
Hydrogenation at Merck. Acc. Chem. Res. 2007, 40 (12), 1320–1326.
9
Friedfeld, M. R.; Zhong, H.; Ruck, R. T.; Shevlin, M.; Chirik, P. J. Cobalt-
Catalyzed Asymmetric Hydrogenation of Enamides Enabled by Single-
Electron Reduction. Science 2018, 360 (6391), 888–893.
2
Ohkuma, T.; Kitamura, M.; Noyori, R. Asymmetric Hydrogenation. In
Catalytic Asymmetric Synthesis; John Wiley & Sons, Ltd, New York, 2005; pp
1–110.
10 (a) Bianchini, C.; Mantovani, G.; Meli, A.; Migliacci, F.; Zanobini, F.; Laschi,
F.; Sommazzi, A. Oligomerisation of Ethylene to Linear α-Olefins by New Cs-
and C1-Symmetric [2,6-Bis(Imino)Pyridyl]Iron and -Cobalt Dichloride
Complexes. European Journal of Inorganic Chemistry 2003, 2003 (8), 1620–
1631. (b) Monfette, S.; Turner, Z. R.; Semproni, S. P.; Chirik, P. J. Enantiopure
C1-Symmetric Bis(Imino)Pyridine Cobalt Complexes for Asymmetric Alkene
Hydrogenation. J. Am. Chem. Soc. 2012, 134 (10), 4561–4564. (C) Friedfeld,
M. R.; Shevlin, M.; Margulieux, G. W.; Campeau, L.-C.; Chirik, P. J. Cobalt-
Catalyzed Enantioselective Hydrogenation of Minimally Functionalized
Alkenes: Isotopic Labeling Provides Insight into the Origin of Stereoselectivity
and Alkene Insertion Preferences. J. Am. Chem. Soc. 2016, 138 (10), 3314–
3324.
3
Margarita, C.; Andersson, P. G. Evolution and Prospects of the Asymmetric
Hydrogenation of Unfunctionalized Olefins. J. Am. Chem. Soc. 2017, 139 (4),
1346–1356.
4
(a) Lightfoot, A.; Schnider, P.; Pfaltz, A. Enantioselective Hydrogenation of
Olefins with Iridium–Phosphanodihydrooxazole Catalysts. Angew. Chem. Int.
Ed. 1998, 37 (20), 2897–2899. (b) Bell, S.; Wüstenberg, B.; Kaiser, S.;
Menges, F.; Netscher, T.; Pfaltz, A. Asymmetric Hydrogenation of
Unfunctionalized, Purely Alkyl-Substituted Olefins. Science 2006, 311
(5761), 642–644. https://doi.org/10.1126/science.1121977. (c) Roseblade,
S. J.; Pfaltz, A. Iridium-Catalyzed Asymmetric Hydrogenation of Olefins. Acc.
Chem. Res. 2007, 40 (12), 1402–1411. https://doi.org/10.1021/ar700113g.
11
For examples of high activity of iron, cobalt and nickel catalysts for racemic
hydrogenations: (a) Sandl, S.; Maier, T. M.; van Leest, N. P.; Kröncke, S.;
Chakraborty, U.; Demeshko, S.; Koszinowski, K.; de Bruin, B.; Meyer, F.;
Bodensteiner, M.; Herrman, C.; Wolf, R.; Jacobi von Wangelin, A. Cobalt-
catalyzed hydrogenation via olefin cobaltate and hydride intermediates. ACS
Catal. 2019, 9, 7596-7606. (b) Yu, R.; Darmon, J.; Milsmann, C.; Margulieux,
G. W.; Stieber, S. C. E.; DeBeer, S.; Chirik, P. J. Catalytic hydrogenation
activity and electronic structure determination of bis(arylimidazol-2-
ylidene)pyridine cobalt alkyl and hydride complexes. J. Am. Chem. Soc. 2013,
5
Broene, R. D.; Buchwald, S. L. Asymmetric Hydrogenation of
Unfunctionalized Trisubstituted Olefins with a Chiral Titanocene Catalyst. J.
Am. Chem. Soc. 1993, 115 (26), 12569–12570.
6
Troutman, M. V.; Apella, D. H.; Buchwald, S. L. Asymmetric hydrogenation
of unfunctionalized tetrasubstituted olefins with
catalyst. J. Am. Chem. Soc. 1999, 121, 4916-4917.
a cationic zirconocene
135, 13168-13184.(c) Leonard, N. G.; Chirik, P. J. Air-stable α-diimine nickel
precatalysts for the hydrogenation of hindered, unactivated alkenes. ACS Catal.
2018, 8, 342-348. (d) Yu, R. P.; Darmon, J. M.; Hoyt, J. M.; Margulieux, G.
W.; Turner, Z. R.; Chirik, P. J. High-activity iron catalysts for the
hydrogenation of hindered, unfunctionalized alkenes. ACS Catal. 2012, 2,
1760-1764.
7 Conticello, V. P.; Brard, L.; Giardello, M. A.; Tsuji, Y.; Sabat, M.; Stern, C. L.;
Marks, T. J. Chiral Organolanthanide Complexes for Enantioselective Olefin
Hydrogenation. J. Am. Chem. Soc. 1992, 114 (7), 2761–2762.
8
(a) Chirik, P. J. Iron- and Cobalt-Catalyzed Alkene Hydrogenation: Catalysis
with Both Redox-Active and Strong Field Ligands. Acc. Chem. Res. 2015, 48
(6), 1687–1695. (b) Shevlin, M.; Friedfeld, M. R.; Sheng, H.; Pierson, N. A.;
6
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Page 7 of 8
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12
18
1
2
3
4
5
6
7
8
For a review see: Obligacion, J. V.; Chirik, P. J. Earth-Abundant Transition
Selected Examples of Asymmetric Alkenylmetalloid hydrogenation: (a)
Ueda, M.; Saitoh, A.; Miyaura, N. Asymmetric Hydrogenation of 1-
Phenylethenylboronic Acid and Esters for the Synthesis of Chiral
Organoboron Compounds. J. Organomet. Chem. 2002, 642 (1), 145–147.
(b) Morgan, J. B.; Morken, J. P. Catalytic Enantioselective Hydrogenation of
Vinyl Bis(Boronates). J. Am. Chem. Soc. 2004, 126 (47), 15338–15339. (c)
Moran, W. J.; Morken, J. P. Rh-Catalyzed Enantioselective Hydrogenation of
Vinyl Boronates for the Construction of Secondary Boronic Esters. Org. Lett.
2006, 8 (11), 2413–2415. (d) Paptchikhine, A.; Cheruku, P.; Engman, M.;
Andersson, P. G. Iridium-Catalyzed Enantioselective Hydrogenation of Vinyl
Boronates. Chem. Commun. 2009, 0 (40), 5996–5998. (e) Ganić, A.; Pfaltz,
A. Iridium-Catalyzed Enantioselective Hydrogenation of Alkenylboronic
Esters. Chem. Eur. J. 2012, 18 (22), 6724–6728. (f) Han, Z.; Liu, G.; Zhang,
X.; Li, A.; Dong, X.-Q.; Zhang, X. Synthesis of Chiral β-Borylated Carboxylic
Esters via Nickel-Catalyzed Asymmetric Hydrogenation. Org. Lett. 2019, 21
(11), 3923–3926. (g) Park, Y.; Yun, J. Copper-Catalyzed Asymmetric
Reduction of β,β-Disubstituted Alkenylboramides. Org. Lett. 2019, 21 (21),
8779–8782. (h) Zuo, Z.; Xu, S.; Zhang, L.; Gan, L.; Fang, H.; Liu, G.; Huang,
Metal Catalysts for Alkene Hydrosilylation and Hydroboration. Nat. Rev.
Chem. 2018, 2 (5), 15.
13 (a) Chen, X.; Cheng, Z.; Guo, J.; Lu, Z. Asymmetric Remote C-H Borylation
of Internal Alkenes via Alkene Isomerization. Nat. Commun. 2018, 9 (1), 1–8.
(b) Chen, J. H.; Cheng, B.; Cao, M. Y.; Lu, Z. Iron-catalyzed asymmetric
hydrosilylation of 1,1-disubstituted alkenes. Angew. Chem. Int. Ed. 2015, 54,
4661-4464. (c) Cheng, B.; Lu, P.; Zhang, H. Y.; Cheng, X. P.; Lu, Z. Highly
enantioselective cobalt-catalyzed hydrosilylation of alkenes. J. Am. Chem. Soc.
2017, 139, 9439-9442. (d) Cheng, B.; Liu, W. B.; Lu, Z. Iron-catalyzed highly
enantioselective hydrosilylation of unactivated terminal alkenes. J. Am. Chem.
Soc. 2018, 140, 5014-5017.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
14
(a) Hall, D., Boronic Acids; John Wiley & Sons, Ltd, Weinheim, 2011. (b)
Rygus, J. P. G.; Crudden, C. M. Enantiospecific and Iterative Suzuki–Miyaura
Cross-Couplings. J. Am. Chem. Soc. 2017, 139 (50), 18124–18137. (c)
Sandford, C.; Aggarwal, V. K. Stereospecific Functionalizations and
Transformations of Secondary and Tertiary Boronic Esters. Chem. Commun.
2017, 53 (40), 5481–5494.
Z. Cobalt-Catalyzed Asymmetric Hydrogenation of Vinylsilanes with
Phosphine–Pyridine–Oxazoline Ligand: Synthesis of Optically Active
Organosilanes and Silacycles. Organometallics 2019, 38 (20), 3906–3911.
a
15
For recent examples for the preparation of polyboron compounds: (a)
19
Coombs, J. R.; Zhang, L.; Morken, J. P. Enantiomerically Enriched
Tris(Boronates): Readily Accessible Conjunctive Reagents for Asymmetric
Synthesis. J. Am. Chem. Soc. 2014, 136 (46), 16140–16143. (b) Palmer, W.
N.; Obligacion, J. V.; Pappas, I.; Chirik, P. J. Cobalt-Catalyzed Benzylic
Borylation: Enabling Polyborylation and Functionalization of Remote,
Unactivated C(Sp3)–H Bonds. J. Am. Chem. Soc. 2016, 138 (3), 766–769.
(c) Zuo, Z.; Huang, Z. Synthesis of 1,1-Diboronate Esters by Cobalt-Catalyzed
Sequential Hydroboration of Terminal Alkynes. Org. Chem. Front. 2016, 3
(4), 434–438. (d) Palmer, W. N.; Zarate, C.; Chirik, P. J. Benzyltriboronates:
Building Blocks for Diastereoselective Carbon–Carbon Bond Formation. J.
Am. Chem. Soc. 2017, 139 (7), 2589–2592. (e) Li, L.; Gong, T.; Lu, X.; Xiao,
B.; Fu, Y. Nickel-Catalyzed Synthesis of 1,1-Diborylalkanes from Terminal
Alkenes. Nat. Commun. 2017, 8 (1), 345. (f) Teo, W. J.; Ge, S. Cobalt-
Catalyzed Enantioselective Synthesis of Chiral Gem-Bis(Boryl)Alkanes.
Angew. Chem. Int. Ed. 2018, 57 (39), 12935–12939. (g) Hu, J.; Zhao, Y.; Shi,
Z. Highly Tunable Multi-Borylation of Gem-Difluoroalkenes via Copper
Catalysis. Nat. Catal. 2018, 1 (11), 860–869 (h). Yukimori, D.; Nagashima,
Y.; Wang, C.; Muranaka, A.; Uchiyama, M. Quadruple Borylation of Terminal
Alkynes. J. Am. Chem. Soc. 2019, 141 (25), 9819–9822. For reviews see: (i)
Wu, C.; Wang, J. Geminal Bis(Boron) Compounds: Their Preparation and
Synthetic Applications. Tetrahedron Lett. 2018, 59 (22), 2128–2140. (j)
Nallagonda, R.; Padala, K.; Masarwa, A. Gem-Diborylalkanes: Recent
Advances in Their Preparation, Transformation and Application. Org. Biomol.
Chem. 2018, 16 (7), 1050–1064.
(a) Ishiyama, T.; Matsuda, N.; Miyaura, N.; Suzuki, A. Platinum(0)-
Catalyzed Diboration of Alkynes. J. Am. Chem. Soc. 1993, 115 (23),
11018–11019. (b) Neeve, E. C.; Geier, S. J.; Mkhalid, I. A. I.; Westcott,
S. A.; Marder, T. B. Diboron(4) Compounds: From Structural Curiosity
to Synthetic Workhorse. Chem. Rev. 2016, 116 (16), 9091–9161. (c)
Yoshida, H. Borylation of Alkynes under Base/Coinage Metal Catalysis:
Some Recent Developments. ACS Catal. 2016, 6 (3), 1799–1811. (d)
Reid, W. B.; Watson, D. A. Synthesis of Trisubstituted Alkenyl Boronic
Esters from Alkenes Using the Boryl-Heck Reaction. Org. Lett. 2018, 20
(21), 6832–6835. (e) Procter, R. J.; Uzelac, M.; Cid, J.; Rushworth, P. J.;
Ingleson, M. J. Low-Coordinate NHC–Zinc Hydride Complexes Catalyze
Alkyne C–H Borylation and Hydroboration Using Pinacolborane. ACS
Catal. 2019, 9 (6), 5760–5771.
20
(a) Guo, J.; Shen, X.; Lu, Z. Regio- and Enantioselective Cobalt-Catalyzed
Sequential Hydrosilylation/Hydrogenation of Terminal Alkynes. Angew.
Chem. Int. Ed. 2017, 56 (2), 615–618. (b) Guo, J.; Cheng, B.; Shen, X.; Lu, Z.
Cobalt-Catalyzed Asymmetric Sequential Hydroboration/Hydrogenation of
Internal Alkynes. J. Am. Chem. Soc. 2017, 139 (43), 15316–15319.
21 Krautwald, S.; Bezdek, M. J.; Chirik, P. J. Cobalt-Catalyzed 1,1-Diboration of
Terminal Alkynes: Scope, Mechanism, and Synthetic Applications. J. Am.
Chem. Soc. 2017, 139 (10), 3868–3875.
22
Iwadate, N.; Suginome, M. Differentially Protected Diboron for
Regioselective Diboration of Alkynes: Internal-Selective Cross-Coupling of 1-
Alkene-1,2-Diboronic Acid Derivatives. J. Am. Chem. Soc. 2010, 132 (8),
2548–2549.
16
Suginome, M.; Ohmura, T. Transition Metal-Catalyzed Element-Boryl
Additions to Unsaturated Organic Compounds. In Boronic Acids; John Wiley
& Sons, Ltd, Weinheim, 2011; pp 171–212.
23
(a) Lee, J. C. H.; McDonald, R.; Hall, D. G. Enantioselective Preparation
17
Selected Examples of Diastereoselective Alkenylmetalloid hydrogenation:
and Chemoselective Cross-Coupling of 1,1-Diboron Compounds. Nat. Chem.
2011,
(a) Lautens, M.; Zhang, C.; Crudden, C. M. The Hydroxyl-Directed
Hydrogenation of Vinylstannanes and Silanes: A Highly Diastereoselective
Route to β-Stannyl and β-Silyl Alcohols. Angew. Chem. Int. Ed. Eng. 1992, 31
(2), 232–234. (b) Murakami, M.; Oike, H.; Sugawara, M.; Suginome, M.; Ito,
Y. Stereoselective Synthesis of 1,2,4-Triols via Intramolecular Bis-Silylation of
Carbon-Carbon Triple Bonds Followed by Hydrogenation. Tetrahedron
1993, 49 (19), 3933–3946. (c) Hupe, E.; Marek, I.; Knochel, P.
Diastereoselective Reduction of Alkenylboronic Esters as a New Method for
Controlling the Stereochemistry of up to Three Adjacent Centers in Cyclic and
Acyclic Molecules. Org. Lett. 2002, 4 (17), 2861–2863. (d) Hupe, E.; Marek,
I.; Knochel, P. Diastereoselective Reduction of Alkenylboronic Esters as a New
Method for Controlling the Stereochemistry of up to Three Adjacent Centers
in Cyclic and Acyclic Molecules. Org. Lett. 2002, 4 (17), 2861–2863.
3 (11), 894–899. (b) Feng, X.; Jeon, H.; Yun, J. Regio- and
Enantioselective Copper(I)-Catalyzed Hydroboration of Borylalkenes:
Asymmetric Synthesis of 1,1-Diborylalkanes. Angew. Chem. Int. Ed. 2013, 52
(14), 3989–3992. (c) Cuenca, A. B.; Cid, J.; García-López, D.; Carbó, J. J.;
Fernández, E. Unsymmetrical 1,1-Diborated Multisubstituted Sp3-Carbons
Formed via a Metal-Free Concerted-Asynchronous Mechanism. Org. Biomol.
Chem. 2015, 13 (37), 9659–9664.
24
Candlin, J. P.; Oldham, A. R. Selective Hydrogenation of Unsaturated
Carbon-Carbon Bonds with Rhodium Complexes. Discuss. Faraday Soc.
1968, 46 (0), 60–71.
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3
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(a) Laitar, D. S.; Tsui, E. Y.; Sadighi, J. P. Copper(I) β-Boroalkyls from
Alkene Insertion: Isolation and Rearrangement. Organometallics 2006, 25
(10), 2405–2408. (b) Zheng, B.; Srebnik, M. Synthesis of a New Class of
Bidentate Lewis Acids Based on Boronic Esters and Zirconocene. Journal of
Organometallic Chemistry 1994, 474 (1), 49–53.
5
6
7
8
9
26
Zhao, S.; Gensch, T.; Murray, B.; Niemeyer, Z. L.; Sigman, M. S.;
Biscoe, M. R. Enantiodivergent Pd-Catalyzed C–C Bond Formation
Enabled through Ligand Parameterization. Science 2018, 362 (6415),
670–674.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
27
(a) Bruno, N. C.; Tudge, M. T.; Buchwald, S. L. Design and
Preparation of New Palladium Precatalysts for C–C and C–N Cross-
Coupling Reactions. (b) Barder, T. E.; Walker, S. D.; Martinelli, J. R.;
Buchwald, S. L. Catalysts for Suzuki−Miyaura Coupling
Processes: Scope and Studies of the Effect of Ligand Structure. J. Am.
Chem. Soc. 2005, 127 (13), 4685–4696. (c) Chen, L.; Ren, P.; Carrow, B.
P. Tri(1-Adamantyl)Phosphine: Expanding the Boundary of Electron-
Releasing Character Available to Organophosphorus Compounds. J. Am.
Chem. Soc. 2016, 138 (20), 6392–6395.
28
Russell, S. K.; Lobkovsky, E.; Chirik, P. J. Iron-Catalyzed Intermolecular [2π
+ 2π] Cycloaddition. J. Am. Chem. Soc. 2011, 133 (23), 8858–8861.
For Table of Contents Use
Boronates Increase Activity and Selectivity of Asymmetric Hydrogenation
O2
BPin
N4
O1
DanB
B3
N1
BDan
N
B1
B2
N2
N
N3
Co
N
iPr
- or -
85% ee
+ 4 atm. H2
BPin
BDan
R = Alkyl, Aryl
BPin
(S)
iPr
R
R
BDan
+ 12 examples, up to 98% ee
Deuterium Labeling Studies Establish Insertion Preferences
8
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