Access to Enantioenriched Benzylic 1,1-Silylboronate Esters by Palladium-Catalyzed Enantiotopic-Group Selective Suzuki-Miyaura Coupling of (Diborylmethyl)silanes with Aryl Iodides

Article abstract of DOI:10.1021/acscatal.8b03979

This work describes the palladium-catalyzed enantiotopic-group selective Suzuki-Miyaura cross-coupling of (diborylmethyl)silanes with aryl iodides. The combination of a Pd(TFA)₂ and rev-Josiphos-type ligand bearing a 3,5-bis(trifluoromethyl)phe

Full text of DOI:10.1021/acscatal.8b03979

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Letter
Access to Enantioenriched Benzylic 1,1-Silylboronate Esters
by Palladium-Catalyzed Enantiotopic-Group Selective Suzuki–
Miyaura Coupling of (Diborylmethyl)silanes with Aryl Iodides
Junghoon Kim, and Seung Hwan Cho
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b03979 • Publication Date (Web): 06 Dec 2018
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Page 1 of 7
ACS Catalysis
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Access to Enantioenriched Benzylic 1,1-Silylboronate Esters by
Palladium-Catalyzed Enantiotopic-Group Selective Suzuki–Miyaura
Coupling of (Diborylmethyl)silanes with Aryl Iodides
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Junghoon Kim, and Seung Hwan Cho*
Department of Chemistry, Pohang University of Science and Technology (POSTECH), 37673, Pohang, Rep. of Korea
ABSTRACT: This work describes the palladium-catalyzed enantiotopic-group selective Suzuki–Miyaura cross-coupling of
(diborylmethyl)silanes with aryl iodides. The combination of a Pd(TFA)2 and rev-Josiphos-type ligand bearing a 3,5-
bis(trifluoromethyl)phenyl as benzylic phosphine substituent in the presence of NaI as an additive and NaOMe as a base promote the
reaction to high efficiency and enantioselectivity. This method provides a convenient approach for synthesizing chiral benzylic 1,1-
silylboronate esters from readily accessible reagents. Synthetic applications including stereospecific C–O, C–N, and C–C bond
forming reactions of boron group are also demonstrated.
KEYWORDS: palladium catalysis, cross-coupling, enantioselectivity, rev-Josiphos, silicon, boron
Chiral molecules that contain two different main group
elements at the same sp3 carbon center are highly versatile
intermediates in organic synthesis.1 Such reagents provide
significant advantages for increasing molecular diversity and
complexity through stereospecific and/or iterative carbon–
carbon and carbon–heteroatom bond forming reactions.2
Among them, chiral 1,1-silylboronate esters are particularly
appealing because of their stability, low toxicity, and ease of
handling. Nevertheless, despite their potential usefulness, only
a limited success for the preparation of chiral 1,1-silylboronate
esters have been reported.3-5 For example, Aggarwal3a,b and
Xu3c demonstrated the stereocontrolled homologation of chiral
lithiated carbamates with silylborane (Scheme 1a). Blakemore
et al. reported that chiral -silylmethyllithium carbamate,
prepared in the presence of a chiral bis(oxazoline)ligand,
reacted with alkylboronates to afford 1,1-silylboronate esters
with low to moderate enantioselectivity.3d Aggarwal et al.
elegantly improved the stereoselectivity by reacting a lithiated
Scheme 1. Approaches for Synthesizing Chiral 1,1-
Silylboronate Esters.
(a) Stoichiometric approaches for the preparation of enantioenriched 1,1-silylboronates
alkyl
X
X
R
R2 Bpin
Li
+
Si
Bpin
*
Me
R1
LG
(R2 = SiR3 or alkyl)
Me
(Aggarwal, Xu)
(Blakemore)
(Aggarwal)
Et Et
OMe
O
O
X
X
N
Li
N
N
Li
N
N
=
Li
Li
R1
LG
iPr
PhMe2Si
with alkyl Bpin
iPr
Si
Me Me
Cl
alkyl
OCb
OTIB
with R3Si Bpin
with alkyl Bpin
(b) Catalytic approaches for the preparation of enantioenriched 1,1-silylboronates
(Hoveyda)5a
(Morken)5b
cat. [Cu]/L*
MeOH
B2pin2
Bpin
*
cat. [Pt]/L*
R
R
R
PhMe2Si
This work
pinB
PhMe2Si
HSiMe2Ph
-chloromethylsilane,
tethered
with
group,
a
chiral
with
(c)
(methoxymethyl)pyrrolidinomethyl
Bpin
SiR3
cat. Pd/L*
NaOMe, NaI
Bpin
SiR3
alkylboronates.3e However, these methods required the use of
I
+
R1
R1
stoichiometric enantioenriched reagents.4 In this context,
pinB
Hoveyda and co-workers disclosed
a copper-catalyzed
broad substrate scope
high yields
excellent enantioselectivity
enantioselective proto-boryl addition to vinylsilanes in the
presence of B2pin2 and MeOH (Scheme 1c).5a Recently, Morken
et al. reported the Pt-catalyzed enantioselective hydrosilylation
of alkenylboronates with good to moderate enantioselectivity
(Scheme 1d).5b Despite these notable advances, the
development of complementary method for synthesizing 1,1-
silylboronate esters is still desirable. Herein, we describe a
highly enantiotopic-group selective Pd-catalyzed Suzuki–
Miyaura cross-coupling of (diborylmethyl)silanes with aryl
iodides. This process represents the attractive features of
efficiently utilizing (diborylmethyl)silane as a new type of
1,1,1-triorganometalics in enantiotopic-group selective
reaction.6
group selective C–C bond forming reactions.7-10 Within this
field, Morken and Hall have independently demonstrated that a
palladium catalyst ligated to a chiral phosphoramidite ligand
could promote the enantiotopic-group selective cross-coupling
of 1,1-diborylalkanes with aryl10a,10b or vinyl10c halides in the
presence of excess aqueous NaOH. Based on these seminal
precedents, we envisioned palladium-catalyzed enantiotopic-
group selective cross-coupling of (diborylmethyl)silanes with
aryl halides might afford chiral benzylic 1,1-silyl boronate
esters. In fact, the group of Endo reported the racemic version
of cross-coupling of (diborylmethyl)silanes with aryl bromides
1,1-Diborylalkanes have been used in several enantiotopic-
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Scheme 2. Optimization Study for Pd-catalyzed
Enantiotopic-Group Selective Cross-Coupling of 2a with
Aryl Electrophiles
Page 2 of 7
segphos (L3) or Josiphos (L4) were employed, the reaction
occurred in excellent to low efficiency (91% and 32 %) with
poor enantioselectivity (6% and 7% ee). We found that the use
of Josiphos ligand PPF-tBu (L5), which displayed promising
enantioselectivity for the Pd-catalyzed enantiotopic-group
selective coupling of 1,1-diborylalkanes with vinyl bromides,9c
led to the racemic product of 3a in low yield. Gratifyingly, the
use of rev-Josiphos (L6) furnished product 3a in 74% yield and
84% ee, indicating the cyclohexylphosphine (Cy) at the
cyclopetadienyl ring had significant effect on yield and
enantioselectivity. Further optimization study revealed that the
use of 1.0 equivalent of NaI improved the yield of 3a to 99%
without compromising enantioselectivity (84% ee), while the
exact role of NaI remains unclear at this stage. The use of other
salts as additives resulted in negligible or negative effects on
yield and enantioselectivity.12,13
1
2
3
4
5
6
7
8
Pd(TFA)2 (5.0 mol %)
ligand (5.0-10 mol %)
NaOMe (3.0 equiv)
with or w/o NaI (1.0 equiv)
Bpin
SiMe2Ph
X
Bpin
SiMe2Ph
+
1,4-dioxane, RT, 3 h
pinB
MeO
MeO
1
2a
3a
9
a
1a
a) Effects of chiral phosphine ligands with 4-iodoanisole (
)
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11
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O
Ar
Ar
Ph
N
O
P
O
O
O
O
O
PAr2
PAr2
O
O
Me
Me
NMe2
P
Ar Ar
Ph
O
Ar = 3,5-tBu-4-MeOC6H2-
Ar = 4-Me-C6H4-
b
b
To improve enantioselectivity, we screened rev-Josiphos-
type ligands with different R1 substituents (Scheme 2b). When
the phenyl group (R1) of rev-Josiphos was replaced with a 4-
methoxyphenyl group (L7), the yield and enantioselectivity
decreased dramatically (54%, 42% ee). Introduction of a 4-
trifluoromethylphenylgroup (L8) in the R1 position afforded 3a
in a good yield (92%) and slightly higher enantioselectivity
(88% ee). Further ligand variation revealed that the installation
L1
L2
)
L3
(
)
(
(
)
91%, 6% ee
(w/o NaI)
99%, 20% ee
(w/o NaI)
31%, 0% ee
(w/o NaI)
Me
Me
Me
PPh2
P(tBu)2
PPh2
PCy2
PCy2
PPh2
Fe
Fe
Fe
L4
)
L5
)
L6
( )
(
(
32%, 7% ee
(w/o NaI)
28%, 0% ee
(w/o NaI)
74%, 84% ee (w/o NaI)
99%, 84% ee (with NaI)
of more electron withdrawing group, such as
a 3,5-
bis(trifluoromethyl)phenyl (L9), as the R1 substituent provided
3a in almost quantitative yield (99%) and with excellent
enantioselectivity (96% ee). In contrast, the ligand containing
3,5-bis(methyl)phenyl as a R1 substituent (L10) afforded 3a in
43% yield and 63% ee. These results strongly suggested that the
electronic properties of the benzylic phosphine substituent (R1)
had a profound effect on the enantioselectivity.14 The use of
NaOtBu instead of NaOMe as a base afforded 3a in an almost
1
a
1a
b) Substituent (R ) effects of rev-Josiphos type ligands with 4-iodoanisole (
)
Me
L7
L9
)
R = OMe (
)
R = CF3
99%, 96% ee
(with NaI)
(
R
R
54%, 42% ee
(with NaI)
P(R1)2
PCy2
R1
=
R
Fe
L8
)
L10
)
R = CF3
(
R = Me (
43%, 63% ee
(with NaI)
92%, 88% ee
(with NaI)
c) Reactions with other aryl (pseudo)halidesa
Br
quantitative yield with
a diminished enantioselectivity.
OTf
Cl
Moreover, when lithium or potassium alkoxide was employed
as a base, no desired product 3a was given.12 These results
implied that the enantiotopic-group selective cross-coupling
was sensitive to the alkoxide base cation.
MeO
MeO
MeO
1a-Br
1a-Cl
1a-OTf
L6
L9
L6
with , <1% (with NaI)
with , 99%, 40% ee (with NaI)
with , 13%, 44% ee (with NaI)
L6
with , <1% (with NaI)
L9
with , <1% (with NaI)
L9
with , <1% (with NaI)
To examine whether the developed enantiotopic-group
selective reaction proceeded using other aryl halides or
pseudohalides, we examined the reaction with various aryl
electrophiles (Scheme 2c). When 2a and 4-bromoanisole (1a-
Br) were subjected under the standard reaction conditions,
using L9 as a ligand, the desired product 3a was obtained in
13% yield with 44% ee. A higher yield (99%) of 3a was
obtained when L6 was used in place of L9 as a ligand, but the
enantioselectivity remained low (40% ee). These results
indicated that the enantioselectivity is greatly affected by the
halide of the aryl electrophiles.15 No reaction occurred when 4-
chloroanisole or 4-methoxyphenyl triflate was employed as a
coupling reagent. The absolute configuration of the major
enantiomer was determined as S after oxidation of the Bpin of
3g, 3h, and 3l to known compounds (vide infra).16
aReaction conditions: 1 (0.20 mmol), 2a (1.5 equiv), Pd(TFA)2 (5.0
mol %), ligand (5.0 mol %), NaOMe (3.0 equiv), NaI (1.0 equiv, if
necessary), 1,4-dioxane (1.5 mL), room temperature, 3 h. b10 mol
% ligand was used. In all cases, 1H-NMR yields are given.
Enantiomeric excess was determined using HPLC after oxidation
of Bpin.
in the presence of Pd[P(tBu)3]2catalyst, aqueous KOH, and
stoichiometric Ag2O.11 However, to the best of our knowledge,
the enantioselective variants of these reactions are undeveloped.
To test the viability of our envisioned strategy, we examined
a range of chiral phosphine ligands with a substoichometric
amount of Pd(TFA)2 (5.0 mol %) and 3.0 equivalents of
NaOMe employing (diborylmethyl)dimethyl(phenyl)silane
(2a), which was easily prepared from diborylmethane and
chlorodimethyl(phenyl)silane in the presence of LDA, and 4-
iodoaniole (1a) as model substrates in 1,4-dioxane at room
temperature (Scheme 2a). The reaction with 10 mol % taddol-
derived monodentate phosphine ligand (L1), which gave high
enantioselectivity for the cross-coupling of 1,1-diborylalkanes
with aryl iodides,10a,10b afforded the desired the product (3a) in
excellent yield (99%) and low enantioselectivity (20% ee). The
reaction with 10 mol % (R)-binol-derived phosphoramidite
ligand (L2) was also ineffective. Our attention next switched to
chiral bidentate phosphine ligands. When 5.0 mol % DTBM-
With optimized conditions in hand, we investigated the scope
of
the
(diborylmethyl)silanes
(Table
1a).
(2c)
When
or
(diborylmethyl)diphenylmethylsilane
(diborylmethyl)dimethyl-tert-butylsilane (2d) were subjected
under the standard reaction conditions, the corresponding
products 3c and 3d were obtained in 97% and 77% yields with
94% ee and 92% ee, respectively. In addition, (diborylmethyl)
trimethylsilane (2e) proved to be a suitable coupling reagent,
affording 3e in 90% yield with 95% ee. Unfortunately, when 1-
methylsiletane containing diborylmethane was applied
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Table 1. Substrate Scope of (Diborylmethyl)silanes and
instability on silica gel. Reactions conducted with 4-chloro- and
4-fluoro-iodobenzene afforded products 3k and 3l in good
yields (78% and 84%) with high enantioselectivity (98% ee).
Unfortunately, the reaction with 4-iodomethylbenzoate failed to
provide coupled product 3m because of substrate
decomposition. Aryl iodides bearing a benzyl protected phenol,
and tert-butyldimethylsilyl protected alcohol, and a masked
aldehyde yielded products 3n-3p in good to excellent yields
(80%-95%) with excellent enantioselectivity (95%-97% ee),
although 3n required a prolonged reaction time (5 h) for a full
conversion. 3-Methyl-iodobenzene resulted in the formation of
3q in 74% yield with 98% ee, while 2-methyl-iodobenzene
afforded 3r in 97% yield with modest enantioselectivity (80%
ee). This loss of enantioselectivity was probably because of
steric hindrance between the substrate and catalyst. The
reactions with aryl iodides containing two substituents on the
arene ring gave the products 3s–3u in excellent yields (97-98%)
with high enantioselectivity (98-99% ee). This enantiotopic-
group selective Suzuki-Miyaura reaction was applicable to 2-
naphthyliodide, affording 3v in 81% with 99% ee. Heteroaryl
iodides reacted to form 3w and 3x in moderate to good yields
(68% and 89%) with excellent enantioselectivity (99% ee and
97% ee). When 1-silyl-substituted-1,1-diborylethane 4 and 4-
iodoanisole (1a) were subjected to the optimized reaction
conditions (Scheme 3), protodeboronation product 5 was
mainly observed (56%) along with vinylsilane 6 (10%), which
might be formed by the coupling of 4 and 1a followed by a
second transmetallation of the remaining Bpin to Pd catalyst
and -hydride elimination.
Aryliodidesa-c
1
2
3
4
5
6
7
8
Pd(TFA)2 (5.0 mol %)
L9
(5.0 mol %)
NaOMe (3.0 equiv)
NaI (1.0 equiv)
Bpin
SiR3
I
Bpin
SiR3
R
+
1,4-dioxane, RT, 3 h
pinB
R
1
2
3
(a) Scope of (diborylmethyl)silanes
Bpin
Bpin
Bpin
SiMePh2
9
SiMe2Ph
SiEt2Ph
10
11
12
13
14
15
16
17
18
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21
22
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24
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MeO
3a
MeO
3b
MeO
3c
, 97%, 94% ee
, 98%, 96% ee
Bpin
, 95%, 96% ee
Bpin
Bpin
Si
SitBuMe2
SiMe3
Me
MeO
MeO
3e
MeO
3d
, 77%, 92% ee
3f
, <1%
, 90%, 95% ee
(b) Scope of aryl iodides
Bpin
Bpin
Bpin
SiMe2Ph
SiMe2Ph
SiMe2Ph
Me
tBu
3g
3h
3i
, 80%, 97% ee
, 85%, 96% ee
, 81%, 90% ee
Bpin
Bpin
Bpin
SiMe2Ph
SiMe2Ph
SiMe2Ph
F3C
Cl
F
d
3j
3k
3l
, 46% , 90% ee
, 78%, 98% ee
, 84%, 98% ee
Bpin
Bpin
Bpin
Scheme 3. Coupling of 1a with 1-Silyl-substituted-1,1-
SiMe2Ph
SiMe2Ph
SiMe2Ph
diborylethane (4)
TBSO
Bpin
MeO2C
BnO
e
Me
SiMe2Ph
, 56%
3m
, <1%
3o
, 83%, 96% ee
3n
, 95%, 97% ee
standard
conditions
5
I
Bpin
Bpin
SiMe2Ph
Bpin
Me Bpin
SiMe2Ph
+
+
pinB
SiMe2Ph
Me
MeO
Me
SiMe2Ph
SiMe2Ph
O
1a
4
MeO
Me
Me
O
6
, 10%
3p
3q
, 74%, 98% ee
3r
, 80%, 95% ee
, 97%, 80% ee
Bpin
The chiral benzylic 1,1-silylboronate esters obtained from
our reaction are versatile intermediates for further synthetic
elaborations (Scheme 4). The selective oxidation of Bpin in the
presence of H2O2 and NaOH in THF/H2O provided optically
active -hydroxysilane 7-10. Because chiral -hydroxysilanes
were previously synthesized by asymmetric hydrogenation of
acylsilanes16a,b or the catalytic enantioselective addition of
silicon nucleophiles to aldehydes,16c-e our method provides a
complementary approach to the synthesis of chiral -
hydroxysilanes. The reaction of 3a with LiNHOMe in THF,
followed by Boc protection17 yielded the corresponding -
aminosilane 11, an important precursor in peptide mimics,18 in
modest yield (47%) with a slight erosion of enantiopurity (90%
ee, 94% es) probably because of the potential for deprotonation
of benzylic proton.19 The stereospecific vinylation of 3g could
be achieved to form the -trisubstituted chiral allylsilane 12
(71%, 97% ee) under slightly modified conditions developed by
Aggarwal and coworkers.20 Product 12 was then transformed to
the homoallylic alcohol 13 in 70% yield and 91% ee (94% es)
by TiCl4-mediated allylation with pivalaldehyde.21 After
converting 3a to -silylboronate ester 14 via one-carbon
homologation reaction with LiCH2Cl (74%, 96% ee),
subsequent Suzuki-Miyaura cross-coupling afforded chiral
benzylic silane 15 in 74% yield aminosilane 16. A single
Bpin
Bpin
SiMe2Ph
Me
SiMe2Ph
Cl
O
O
SiMe2Ph
Me
Me
3s
3t
3u
, 98%, 99% ee
, 98%, 99% ee
, 97%, 98% ee
Bpin
Bpin
Bpin
SiMe2Ph
SiMe2Ph
SiMe2Ph
N
S
Me
3v
, 81%, 98% ee
3w
, 68%, 99% ee
3x
, 89%, 97% ee
aReaction conditions: 1 (0.2 mmol), 2a (1.5 equiv), Pd(TFA)2 (5.0
mol %), L9 (5.0 mol %), NaOtBu (3.0 equiv), NaI (1.0 equiv), 1,4-
dioxane (1.5 mL), rt, 3 h. bIsolated yields are given. cEnantiomeric
excess was determined using HPLC after oxidation of Bpin.
dIsolated yield after oxidation of Bpin is given. eRuns for 5 h.
to the reaction conditions, the anticipated product (3f) was not
obtained and all of starting materials were decomposed.
Next, the scope of aryl iodides was explored (Table 1b). Aryl
iodides having electron-neutral (3g), electron-donating (3h and
3i), and electron withdrawing (3j) substituents at para-position
underwent coupling in good to moderate yields (46–85%) with
good to excellent enantioselectivity (90–97% ee). Note that the
coupled product 3j was isolated after oxidation of Bpin due to
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Page 4 of 7
Scheme 4. Further Transformation of Chiral Benzylic 1,1-
ACKNOWLEDGMENT
1
2
3
4
5
6
7
8
Silylboronate esters
This research was supported by the Technology Development
Program to Solve Climate Changes through the National Research
Foundation (NRF) funded by the Ministry of Science, ICT &
Future Planning (NRF-2017M1A2A2049102). S. H. Cho thanks
Cheongam Science Fellowship for their generous support.
NHBoc
SiMe2Ph
OH
Me
Me
MeO
Me
13, 70%, 91% ee
11, 47%, 90% ee
b
d
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OH
Bpin
SiMe2Ph
SiMe2Ph
a
c
SiMe2Ph
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(2) (a) Xu, L.; Zhang, S.; Li, P. Boron-Selective Reactions as
Powerful Tools for Modular Synthesis of Diverse Complex Molecules.
Chem. Soc. Rev. 2015, 44, 8848-8858. (b) Cherney, A. H.; Kadunce,
N. T.; Reisman, S. E. Enantioselective and Enantiospecific Transition-
Metal-Catalyzed Cross-Coupling Reactions of Organometallic
Reagents to Construct C–C bonds. Chem. Rev. 2015, 115, 9587-9652.
(c) Rygus, J. P. G.; Crudden, C. M. Enantiospecific and Iterative
Suzuki-Miyaura Cross-Couplings. J. Am. Chem. Soc. 2017, 139,
18124-18137.
R
R
9
12, 71%, 97% ee
7, R = OMe, 91%, 96% ee
8, R = H, 90%, 97% ee
9, R = Me, 90%, 96% ee
10, R = F, 93%, 98% ee
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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33
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40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
e
Ph
Bpin
NHBn
f
g
SiMe2Ph
SiMe2Ph
SiMe2Ph
MeO
MeO
MeO
15, 74%, 96% ee
14, 74%, 96% ee
16, 71%, 99% ee
(isolated by recrystallization)
a
b
Reaction conditions: H2O2, NaOH, THF/H2O, RT NH2OMe, n-
BuLi, THF, -78 oC to 60 oC, then Boc2O. cTetravinyltin, n-BuLi -
78 oC then I2, MeOH. dTiCl4, pivalaldehyde, CH2Cl2, -78 oC, then
e
o
f
H2O. ICH2Cl, n-BuLi, THF, -78 C to RT. cat. Pd(OAc)2, cat.
(rac)-BINAP, NaOH, bromobenzene, THF/H2O, 100 C. BCl3,
o
g
BnN3, CH2Cl2, RT.
recrystallization of 16 from n- hexane and 96% ee. The reaction
of 14 with BCl3, followed by the addition of benzyl azide gave
-furnished essentially enantiopure product (71%, 99% ee).
These successful manipulations display the synthetic usefulness
of the chiral benzylic 1,1-silylboronate esters for the
preparation of various chiral silane compounds.
In conclusion, we have developed an efficient Pd-catalyzed
system for the enantiotopic-group selective cross-coupling of
(diborylmethyl)silanes with aryl iodides. The use of L9, a rev-
Josiphos ligand comprising cyclohexylphosphine at the
cyclopetadienyl ring and 3,5-bis(trifluoromethyl)phenyl groups
on the benzylic phosphine, significantly enhanced the
enantioselectivity. A broad range of aryl iodides could be
coupled with (diborylmethyl)silanes, affording chiral benzylic
(3) (a) Aggarwal, V. K.; Binanzer, M.; de Ceglie, M. C.; Gallanti,
M.; Glasspoole, B. W.; Kendrick, S. J. F.; Sonawane, R. P.; Vázquez-
Romero, A.; Webster, M. P. Asymmetric Synthesis of Tertiary and
Quaternary Allyl- and Crotylsilanes via the Borylation of Lithiated
Carbamates. Org. Lett. 2011, 13, 1490-1493. (b) Millán, A.; Grigol
Martinez, P. D.; Aggarwal, V. K. Stereocontrolled Synthesis of
Polypropionate Fragments Based on a Building Block Assembly
Strategy using Lithiation-Borylation Methodologies. Chem. Eur. J.
2018, 24, 730-735. (c) Zhao, H.; Tong, M.; Wang, H.; Xu, S.
Transition-Metal-Free Synthesis of 1,1-Diboronate Esters with a Fully
Substituted Benzylic Center via Diborylation of Lithiated Carbamates.
Org. Biomol. Chem. 2017, 15, 3418-3422. (d) Barsamian, A. L.; Wu,
Z.; Blakemore, P. R. Enantioselective Synthesis of []-Phenyl- and
[]-(Dimethylphenylsilyl)alkylboronic Esters by Ligand Mediated
1,1-silylboronate
esters
in
excellent
yields
and
enantioselectivities. The obtained chiral benzylic 1,1-
silylboronate esters can be transformed to other synthetically
useful compounds through C–O, C–N, and C–C bond forming
reactions, highlighting the usefulness of the obtained boronate
esters. Further studies are ongoing in our laboratory to develop
Stereoinductive
Reagent-Controlled
Homologation
Using
Configurationally Labile Carbenoids. Org. Biomol. Chem. 2015, 13,
3781-3786. (e) Bootwicha, T.; Feilner, J. M.; Myers, E. L.; Aggarwal,
V. K. Iterative Assembly Line Synthesis of Polypropionates with Full
Stereocontrol. Nat. Chem. 2017, 9, 896-902.
(4) Liu and coworkers disclosed the stereospecific conversion of
chiral -hydroxyboronate ester into chiral 1,1-silylboronate ester in the
presence of silylborane and NaOtBu, where they studied only one
substrate and the product was obtained in moderate yield, see: Wang,
L.; Zhang, T.; Sun, W.; He, Z.; Xia, C.; Lan, Y.; Liu, C. C–O
metal-catalyzed
asymmetric
transformations
of
(diborylmethyl)silanes using other electrophiles.
ASSOCIATED CONTENT
Supporting Information.
Experimental procedures, characterization data, NMR and HPLC
spectra for new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
Functionalization of α-Oxyboronates:
Diborylation and gem-Silylborylation of Aldehydes and Ketones. J.
Am. Chem. Soc. 2017, 139, 5257-5264.
A Deoxygenative gem-
AUTHOR INFORMATION
(5) (a) Meng, F.; Jang, H.; Hoveyda, A. H. Exceptionally E- and β-
Selective NHC–Cu-Catalyzed Proto-Silyl Additions to Terminal
Alkynes and Site- and Enantioselective Proto-Boryl Additions to the
Resulting Vinylsilanes: Synthesis of Enantiomerically Enriched
Vicinal and Geminal Borosilanes. Chem. Eur. J. 2013, 19, 3204-3214.
(b) Szymaniak, A. A.; Zhang, C.; Coombs, J. R.; Morken, J. P.
Enantioselective Synthesis of Nonracemic Geminal Silylboronates by
Pt-Catalyzed Hydrosilylation. ACS Catal. 2018, 8, 2897-2901.
Corresponding Author
*seunghwan@postech.ac.kr
Notes
The authors declare no competing financial interest.
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(6) An alternative synthetic utilization of (diborylmethyl)silane, see:
E. LaꢀCascia, A. B. Cuenca, E. Fernández, Opportune
gem‐Silylborylation of Carbonyl Compounds: Modular and
Stereocontrolled Entry to Tetrasubstituted Olefins. Chem. Eur. J. 2016,
22, 18737-18741.
(11) Kohei, E.; Fumiya, K.; Yutaka, U. Silver(I) Oxide-Promoted
Chemoselective Cross-Coupling Reaction of (Diborylmethyl)
trimethylsilane. Chem. Lett. 2013, 42, 1363-1365.
1
2
3
4
5
6
7
8
A
(12) See the Supporting Information for details.
(13) (a) Burckhardt, U.; Baumann, M.; Togni, A. A Remarkable
Anion Effect on the Enantioselectivity of the Pd-catalyzed Allylic
Amination Using Ferrocenyl Ligands. Tetrahedron Asym. 1997, 8,
155-159. (b) Fagnou, K.; Lautens, M. Halide Effects in Transition
Metal Catalysis. Angew. Chem., Int. Ed. 2002, 41, 26-47. (c) Xu; Wei;
Zhang Influences of Electronic Effects and Anions on the
Enantioselectivity in the Oxazaborolidine-Catalyzed Asymmetric
Borane Reduction of Ketones. J. Org. Chem. 2004, 69, 6860-6866. (d)
Liao, X.; Weng, Z.; Hartwig, J. F. Enantioselective α-Arylation of
Ketones with Aryl Triflates Catalyzed by Difluorphos Complexes of
Palladium and Nickel. J. Am. Chem. Soc. 2008, 130, 195-200.
(14) Morken and coworkers observed that the use of rev-Josiphos
type ligand containing 4-trifluoromethylphenyl as benzylic phosphine
substituent showed good enantioselectivity for Pd-catalyzed
enantiotopic-group selective coupling of 1,1-diborylalkanes and vinyl
bromides. For details, see ref 10c.
(7) For recent reviews, see: (a) Nallagonda, R.; Padala, K.; Masarwa,
A. gem-Diborylalkanes: Recent Advances in Their Preparation,
Transformation and Application. Org. Biomol. Chem. 2018, 16, 1050-
1064. (b) Fernández, E.; Miralles, N.; Maza, R. J. Synthesis and
Reactivity of 1,1-Diborylalkanes Towards C-C Bond Formation and
Related Mechanisms. Adv. Synth. Catal. 2018, 360, 1306-1327. (c) Wu,
C.; Wang, J. Geminal Bis(boron) compounds: Their Preparation and
Synthetic Applications. Tetrahedron Lett. 2018, 59, 2128-2140.
(8) For a seminal report on the chemoselective Pd-catalyzed cross-
coupling of 1,1-diborylalkanes with aryl halides, see: Endo, K.;
Ohkubo, T.; Hirokami, M.; Shibata, T. Chemoselective and
Regiospecific Suzuki Coupling on a Multisubstituted sp3-Carbon in
1,1-Diborylalkanes at Room Temperature. J. Am. Chem. Soc. 2010,
132, 11033-11035.
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
(9) Examples for the transition-metal-catalyzed enantiotopic-group
selective transformation of 1,1-diborylalkanes, see: (a) 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, 16140-16143. (b) Joannou, M. V.;
Moyer, B. S.; Meek, S. J. Enantio- and Diastereoselective Synthesis of
1,2-Hydroxyboronates Through Cu-Catalyzed Additions of
Alkylboronates to Aldehydes. J. Am. Chem. Soc. 2015, 137, 6176-
6179. (c) Murray, S. A.; Green, J. C.; Tailor, S. B.; Meek, S. J. Enantio‐
and Diastereoselective 1,2-Additions to α‐Ketoesters with
Diborylmethane and Substituted 1,1-Diborylalkanes. Angew. Chem.,
Int. Ed. 2016, 55, 9065-9069. (d) Park, J.; Lee, Y.; Kim, J.; Cho, S. H.
Copper-Catalyzed Diastereoselective Addition of Diborylmethane to
N-tert-Butanesulfinyl Aldimines: Synthesis of β-Aminoboronates.
Org. Lett. 2016, 18, 1210-1213. (e) Shi, Y.; Hoveyda, A. H. Catalytic
SN2′- and Enantioselective Allylic Substitution with a Diborylmethane
Reagent and Application in Synthesis. Angew. Chem., Int. Ed. 2016,
55, 3455-3458. (f) Zhan, M.; Li, R.-Z.; Mou, Z.-D.; Cao, C.-G.; Liu, J.;
Chen, Y.-W.; Niu, D. Silver-Assisted, Iridium-Catalyzed Allylation of
Bis[(pinacolato)boryl]methane Allows the Synthesis of Chiral
Homoallylic Organoboronic esters. ACS Catal. 2016, 6, 3381-3386. (g)
Kim, J.; Ko, K.; Cho, S. H. Diastereo- and Enantioselective Synthesis
of β-Aminoboronate Esters by Copper(I)-Catalyzed 1,2-Addition of
1,1-Bis[(pinacolato)boryl]alkanes to Imines. Angew. Chem., Int. Ed.
2017, 56, 11584-11588. (h) Miura, T.; Nakahashi, J.; Murakami, M.
Enantioselective Synthesis of (E)-δ-Boryl-Substituted anti-
Homoallylic Alcohols using Palladium and a Chiral Phosphoric Acid.
Angew. Chem., Int. Ed. 2017, 56, 6989-6993. (i) Miura, T.; Nakahashi,
J.; Zhou, W.; Shiratori, Y.; Stewart, S. G.; Murakami, M.
Enantioselective Synthesis of anti-1,2-Oxaborinan-3-enes from
Aldehydes and 1,1-Di(boryl)alk-3-enes Using Ruthenium and Chiral
Phosphoric Acid Catalysts. J. Am. Chem. Soc. 2017, 139, 10903-10908.
(j) Park, J.; Choi, S.; Lee, Y.; Cho, S. H. Chemo- and Stereoselective
Crotylation of Aldehydes and Cyclic Aldimines with Allylic gem-
Diboronate ester. Org. Lett. 2017, 19, 4054-4057. (k) Li, X.; Hall, D.
G. Diastereocontrolled Monoprotodeboronation of -Sulfinimido gem-
Bis(boronates): A General and Stereoselective Route to , -
Disubstituted -Aminoalkylboronates. Angew. Chem., Int. Ed. 2018,
57, 10304-10308.
(15) Futher mechanistic studies are ongoing in our laboratory to
understand subtle differences on the enantioselectivity depending on
halides of aryl electrophiles.
(16) (a) Arai, N.; Suzuki, K.; Sugizaki, S.; Sorimachi, H.; Ohkuma,
T. Asymmetric Hydrogenation of Aromatic, Aliphatic, and
α,β‐Unsaturated Acyl Silanes Catalyzed by Tol-binap/Pica
ruthenium(II) Complexes: Practical Synthesis of Optically Active α-
Hydroxysilanes. Angew. Chem., Int. Ed. 2008, 47, 1770-1773. (b)
Matsuo, J.-i.; Hattori, Y.; Ishibashi, H. Brønsted Acid Catalyzed
Asymmetric Reduction of Ketones and Acyl silanes Using Chiral anti-
Pentane-2,4-diol. Org. Lett. 2010, 12, 2294-2297. (c) Cirriez, V.;
Rasson, C.; Hermant, T.; Petrignet, J.; DíazꢀÁlvarez, J.; Robeyns, K.;
Riant, O. Copper-Catalyzed Addition of Nucleophilic Silicon to
Aldehydes. Angew. Chem., Int. Ed. 2013, 52, 1785-1788. (d) Rong, J.;
Oost, R.; Desmarchelier, A.; Minnaard, A. J.; Harutyunyan, S. R.
Catalytic Asymmetric Alkylation of Acylsilanes. Angew. Chem., Int.
Ed. 2015, 54, 3038-3042. (e) An, P.; Huo, Y.; Chen, Z.; Song, C.; Ma,
Y. Metal-Free Enantioselective Addition of Nucleophilic Silicon to
Aromatic Aldehydes Catalyzed by a [2.2]Paracyclophane-Based N-
Heterocyclic Carbene Catalyst. Org. Biomol. Chem. 2017, 15, 3202-
3206.
(17) Mlynarski, S. N.; Karns, A. S.; Morken, J. P. Direct
Stereospecific Amination of Alkyl and Aryl Pinacol Boronates. J. Am.
Chem. Soc. 2012, 134, 16449-16451.
(18) (a) Barberis, C.; Voyer, N. Preparation of Chiral α-Silyl-
Benzylcarbamates. Tetrahedron Lett. 1998, 39, 6807-6810. (b) Liu, G.;
Sieburth, S. M. Enantioselective -Silyl Amino Acid Synthesis by
Reverse-Aza-Brook Rearrangement. Org. Lett. 2003, 5, 4677-4679. (c)
Sieburth, S. M.; O'Hare, H. K.; Xu, J.; Chen, Y.; Liu, G. Asymmetric
Synthesis of α-Amino Allyl, Benzyl, and Propargyl Silanes by
Metalation and Rearrangement. Org. Lett. 2003, 5, 1859-1861. (d)
Nielsen, L.; Lindsay, K. B.; Faber, J.; Nielsen, N. C.; Skrydstrup, T.
Stereocontrolled Synthesis of Methyl Silanediol Peptide Mimics. J.
Org. Chem. 2007, 72, 10035-10044. (e) Bo, Y.; Singh, S.; Duong, H.
Q.; Cao, C.; Sieburth, S. M. Efficient, Enantioselective Assembly of
Silanediol Protease Inhibitors. Org. Lett. 2011, 13, 1787-1789. (f)
Hensel, A.; Nagura, K.; Delvos, L. B.; Oestreich, M. Enantioselective
Addition of Silicon Nucleophiles to Aldimines Using a Preformed
NHC–Copper(I) Complex as the Catalyst. Angew. Chem., Int. Ed.
2014, 53, 4964-4967. (g) Niljianskul, N.; Zhu, S.; Buchwald, S. L.
Enantioselective Synthesis of α‐Aminosilanes by Copper‐Catalyzed
Hydroamination of Vinylsilanes. Angew. Chem., Int. Ed. 2015, 54,
1638-1641.
(19) Wang, Y.; Noble, A.; Myers, E. L.; Aggarwal, V. K.
Enantiospecific Alkynylation of Alkylboronic Esters. Angew. Chem.,
Int. Ed. 2016, 55, 4270.
(20) Aggarwal, V. K.; Binanzer, M.; Ceglie, M. C. d.; Gallanti, M.;
Glasspoole, B. W.; Kendrick, S. J. F.; Sonawane R. P.; Vázquez-
Romero, A.; Webster, M. P. Asymmetric Synthesis of Tertiary and
Quaternary Allyl- and Crotylsilanes via the Borylation of Lithiated
Carbamates. Org. Lett. 2011, 13, 1490-1493.
(10) (a) Sun, C.; Potter, B.; Morken, J. P. A Catalytic Enantiotopic-
Group-Selective Suzuki Reaction for the Construction of Chiral
Organoboronates. J. Am. Chem. Soc. 2014, 136, 6534-6537. (b) Sun,
H.-Y.; Kubota, K.; Hall, D. G. Reaction Optimization, Scalability, and
Mechanistic
Insight
on
the
Catalytic
Enantioselective
Desymmetrization of 1,1-Diborylalkanes via Suzuki–Miyaura Cross-
Coupling. Chem. Eur. J. 2015, 21, 19186-19194. (c) Potter, B.;
Szymaniak, A. A.; Edelstein, E. K.; Morken, J. P. Nonracemic Allylic
Boronates Through Enantiotopic-Group-Selective Cross-Coupling of
Geminal Bis(boronates) and Vinyl h. J. Am. Chem. Soc. 2014, 136,
17918-17921.
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(21) Takeda, M.; Shintani, R.; Hayashi, T. Enantioselective
Synthesis of -Tri- and -Tetrasubstituted Allylsilanes by Copper-
Catalyzed Asymmetric Allylic Substitution of Allyl Phosphates with
Silylboronates. J. Org. Chem. 2013, 78, 5007-5017.
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Bpin
SiR3
cat. Pd/L*
NaOMe, NaI
I
Bpin
SiR3
R1
1
2
3
4
+
R1
pinB
1,4-dioxane, RT
Me
CF3
CF3
up to 98% yield
up to 99% ee
P
PCy2
L* =
Fe
5
2
6
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