Utilization of a Trimethylsilyl Group as a Synthetic Equivalent of a Hydroxyl Group via Chemoselective C(sp3)-H Borylation at the Methyl Group on Silicon

Article abstract of DOI:10.1021/acs.joc.6b02917

A conversion of trimethylsilylalkanes into the corresponding alcohols is established based on an iridium-catalyzed, chemoselective C(sp³)-H borylation of the methyl group on silicon. The (borylmethyl)silyl group formed by C(sp³)-H borylation is treated with H₂O₂/NaOH, and the resulting (hydroxymethyl)silyl group is converted into a hydroxyl group by Brook rearrangement, followed by oxidation of the resulting methoxysilyl group under Tamao conditions. An alternative route proceeding through the formylsilyl group formed from a (hydroxymethyl)silyl group by Swern oxidation is also established. The method is applicable to substituted trimethylsilylcycloalkanes and 1,1-dimethyl-1-silacyclopentane for conversion into the corresponding stereodefined cycloalkyl alcohols and 1,4-butanediol.

Full text of DOI:10.1021/acs.joc.6b02917

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Article
Utilization of a Trimethylsilyl Group as a Synthetic Equivalent of a Hydroxyl
Group via Chemoselective C(sp3)–H Borylation at the Methyl Group on Silicon
Takeru Torigoe, Toshimichi Ohmura, and Michinori Suginome
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02917 • Publication Date (Web): 10 Feb 2017
Downloaded from http://pubs.acs.org on February 10, 2017
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Utilization of a Trimethylsilyl Group as a Synthetic Equivalent of a Hydroxyl Group via
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Chemoselective C(sp )–H Borylation at the Methyl Group on Silicon
Takeru Torigoe, Toshimichi Ohmura,* Michinori Suginome*
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Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto
University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
ohmura@sbchem.kyoto-u.ac.jp; suginome@sbchem.kyoto-u.ac.jp
TOC graphic
SiMe3 Tamao-Fleming Oxidation
OH
unfunctionalized
=
alkyl and cycloalkyl
Me2
Si
B
C–H Borylation
Method A or B
Abstract: A conversion of trimethylsilylalkanes into the corresponding alcohols is established based
3
on an iridium-catalyzed, chemoselective C(sp )–H borylation of the methyl group on silicon. The
3
(
borylmethyl)silyl group formed by C(sp )–H borylation is treated with H
2
O
2
/NaOH, and the resulting
(
hydroxymethyl)silyl group is converted into a hydroxyl group by Brook rearrangement, followed by
oxidation of the resulting methoxysilyl group under Tamao conditions. An alternative route proceeding
through the formylsilyl group formed from a (hydroxymethyl)silyl group by Swern oxidation is also
established. The method is applicable to substituted trimethylsilylcycloalkanes and 1,1-dimethyl-1-
silacyclopentane for conversion into the corresponding stereodefined cycloalkyl alcohols and 1,4-
butanediol.
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Introduction
Silyl groups have been utilized as convertible yet stable handles for functionalization in
synthetic organic chemistry through their conversion into halogen, oxygen, nitrogen, and carbon based
functional groups. The conversions can be classified mainly into two scenarios. Halogenation of
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alkenyl/arylsilanes as well as the Hosomi-Sakurai reaction can be grouped into the first scenario. In
these cases, attack of electrophiles on the unsaturated organic groups precedes elimination of the silyl
group through attack of nucleophiles on the silicon atom (Scheme 1A). This conversion is best
performed with the trimethylsilyl (TMS) group because of its electron-rich, sterically less demanding
nature, which promotes both the initial electrophilic and the subsequent nucleophilic steps. On the other
hand, there is another class of conversions for which the TMS group works poorly. This type of
conversion involves "preactivation", that is, initial formation of five-coordinated silicate species that
participate in the subsequent reaction, in which the silyl group is actually converted into various
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functional groups (Scheme 1B).
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Scheme 1. Electrophilic Substitution of C–SiMe Bond
A: A class of conversion that is best performed with TMS group
Nu
SiMe
3
E
SiMe
3
E
E
Nu–SiMe
3
B: A class of conversion for which TMS group works poorly
E
alkyl SiMe
Nu
3
alkyl SiMe
Nu
3
alkyl
E
Nu–SiMe
3
A typical example of the latter conversion can be seen in Tamao-Fleming oxidation using
3
peroxides as oxidants, which is widely utilized in organic synthesis (Scheme 2). In this particular
transformation, a base, typically fluoride, is added to activate the silyl groups before accepting a
3
c,3d,4
hydroperoxide as the sixth ligand on the silicon atom.
To facilitate the formation of the five-
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coordinated intermediates, silyl groups that carry at least one heteroatom functional group such as
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alkoxy or halogen groups are utilized (Class I). More robust, non-hydrolyzable triorganosilyl groups
bearing organic groups such as phenyl, allyl, and 2-pyridyl groups, which can be easily converted into
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heteroatom functional groups, have also been utilized as a hydroxyl equivalent (Class II). However,
TMS groups have never been regarded as a hydroxyl equivalent, principally because of the difficulty in
forming five-coordinated silicate species and of converting it into heteroatom functional groups (Class
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III). It should be noted that there are reports on the conversion of the methyl group of a TMS group
8,9,10
into heteroatom functional groups under harsh reaction conditions.
Indeed, Woerpel and coworkers
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1
reported oxidation of trimethylsilyldecane into decanol. However, low yields as well as forcing
reaction conditions involving the use of t-BuOOH with KH at 120 °C prevents this procedure from
being adopted as a general protocol for the utilization of the TMS group in Tamao-Fleming oxidation, in
spite of the fact that the TMS group shows extremely high tolerability to a range of reaction conditions
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and that it is easily available from inexpensive silicon sources such as ClSiMe , or by transfer
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2
3
hydrosilylation using HSiMe equivalent.
Scheme 2. Conversion of Silylalkanes into Alcohols
Tamao-Fleming Oxidation
SiY3
(oxidant: peroxides)
OH
convertible
inert
SiMe3
Class III
SiMe2X
SiMe2R
Class I
X = alkoxy, F, Cl
Class II
R = Ph, allyl, 2-pyridyl
This Work
via C–H Borylation
=
unfunctionalized alkyl and cycloalkyl
We envisioned that utilization of the TMS groups in Tamao-Fleming oxidation may become
1
3
possible through the use of C–H functionalization chemistry. We recently established an iridium-
3
catalyzed C(sp )–H borylation system that can be used to borylate the methyl group on silicon atoms
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selectively over the other C(sp )–H bonds. It was expected that this reaction would allow the
conversion of a highly-stable TMS group into more reactive silyl groups that form five-coordinated
silicates. Herein, we describe new protocols for conversion of the TMS groups in trimethylsilylalkanes
and -cycloalkanes into hydroxyl group to give the corresponding alcohols and cycloalkyl alcohols
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through initial iridium-catalyzed C(sp )–H borylation.
Results and Discussion
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Modification of Iridium-Catalyzed C(sp )–H Borylation. Upon conversion of
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trimethylsilylcyclohexane (1a) into cyclohexanol, we first made a modification of our original C(sp )–H
1
5
borylation protocol, in which a large excess of silicon reagents over the diboron reagent were used. We
recently reported an iridium catalyst system using t-BuOK as an additive that accelerated the iridium-
3
14c,16,17
catalyzed C(sp )–H borylation of aliphatic compounds and a trialkoxy(methyl)silane.
We applied
this system to convert 1a by using an excess of the boron source (Table 1). The reaction took place
efficiently in the presence of t-BuOK (1.25 mol %) to give monoboryl compound 3a and diboryl
1
8
compound 4a in 93% combined yield (3a:4a = 71:29, entry 2). In sharp contrast, the borylated product
was obtained only in 4% in the absence of t-BuOK (entry 1), indicating that significant rate acceleration
was accomplished by the catalytic amount of t-BuOK. The amount of t-BuOK is important for high
1
4c,16
catalyst efficiency, as observed in the previous study (entries 2-5).
with t-BuOK/Ir = 0.5-0.125 (entries 2-4), whereas no acceleration was observed with t-BuOK/Ir = 1
entry 5). Other additives such as MeONa, Cs CO , and CsF were equally effective in the C–H
Rate-acceleration was observed
(
2
3
borylation of 1a (entries 6-8). t-BuOMe was the optimal solvent for obtaining the borylated products
with high yields (entry 2). Other ether solvents including CyOMe, THF, and 1,4-dioxane suffered from
1
9
the formation of their C–H borylation products (entries 9-11). The C–H borylation was slow in
cyclooctane (entry 12), which could be improved by elevation of the reaction temperature (80%
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combined yield at 135 °C, entry 13). Finally, we established a protocol for 1 mmol scale synthesis using
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reduced amount of the iridium catalyst (5 mol % Ir) and 2 (1a:2 = 1:1.5), by which 3a (71%) and 4a
2
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(17%) were isolated after 36 h (entry 14).
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a
Table 1. Modification of Iridium-Catalyzed C(sp )–H Borylation
(
pin)B–B(pin) (2, 2 equiv)
[Ir(OMe)(cod)] (5 mol %)
Me phen (10 mol %)
Me Me
Si
Me
Si
2
SiMe
3
B(pin)
B(pin)
B(pin)
4
+
additive (0-10 mol %)
solvent
1
a
3a
4a
110 °C, 20 h
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c
entry additive (mol %) additive/Ir solvent
% yield (3a:4a)
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1
1
1
1
1
-
0
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
CyOMe
4 (100:0)
t-BuOK (1.25)
t-BuOK (2.5)
t-BuOK (5.0)
t-BuOK (10)
MeONa (2.5)
0.125
0.25
0.50
1.0
93 (71:29)
90 (76:24)
87 (82:18)
5 (100:0)
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
87 (77:23)
76 (88:12)
93 (80:20)
46 (96:4)
2 3
Cs CO (2.5)
CsF (2.5)
t-BuOK (2.5)
t-BuOK (2.5)
t-BuOK (2.5)
t-BuOK (2.5)
t-BuOK (2.5)
t-BuOK (2.5)
0
1
2
3
4
THF
57 (95:5)
1,4-dioxane
cyclooctane
cyclooctane
t-BuOMe
27 (96:4)
7 (100:0)
d
e
80 (85:15)
f
88 (81:19)
a
1
a (0.50 mmol), 2 (1.0 mmol), [Ir(OMe)(cod)]
2
(0.025 mmol), Me
4
phen
(0.050 mmol), and additive (0–0.050 mmol) were stirred in solvent (0.5 mL)
b 1
c
at 110 °C for 20 h unless otherwise noted. H NMR yield based on 1a.
1
d
e
Determined by H NMR. Reaction at 135 °C. Optimized Conditions for 1
mmol scale reaction: 1a (1.0 mmol), 2 (1.5 mmol), [Ir(OMe)(cod)] (0.025
mmol), Me phen (0.050 mmol), and t-BuOK (0.0125 mmol) were stirred in
t-BuOMe (0.8 mL) at 110 °C for 36 h. Combined yield of isolated 3a
71%) and 4a (17%) based on 1a.
2
4
f
(
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Conversion of Borylmethyl Group into Hydroxyl Group. With the borylated products 3a/4a
in hand, we designed two oxidation methods, both of which include conversion of 3a/4a into the
corresponding (hydroxymethyl)silanes via oxidation with H /NaOH. One approach was to utilize
Brook rearrangement of (hydroxymethyl)dimethylsilylcyclohexane (5) giving
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methoxydimethylsilylcyclohexane (6), which can be oxidized to cyclohexanol (7a) under Tamao
conditions (Method A, Scheme 3). The second approach was to oxidize 5 to formylsilanes 8, which
may undergo oxidation to 7a upon further oxidation (Method B, Scheme 4). To demonstrate the
feasibility of Method A, 5 was treated with a catalytic amount of MeOK (10 mol %) at room
temperature in DMSO, giving 6 via Brook rearrangement (Scheme 3). Compound 7a was finally
3 2 2
obtained by application of a standard Tamao protocol with KF, KHCO , and H O at room temperature.
The total reaction yield for three steps from 3a was calculated to be 71%. On the other hand, we found
that Method B also worked efficiently. Indeed, 5 was subjected to Swern oxidation conditions to give
2
1
formylsilane 8 (Scheme 4). The unstable intermediate 8 was found to be oxidized directly to 7a under
standard Tamao reaction conditions. The total reaction yield for three steps from 3a was 71%. It should
be noted here that the double-borylated minor product 4a was also converted into 7a by Methods A and
B in 78% and 67% yields, respectively (For details, see Experimental Section). We thus established that
both Method A and Method B gave rise to 7a in good yields in three steps from 3a/4a (71% via Method
A and 70% via Method B, entry 1, Table 2).
Scheme 3. Conversion of (Borylmethyl)silyl Group into Hydroxyl Group via Brook Rearrangement
(Method A)
MeOK
Me Me
Si
H2O2
B(pin) NaOH
Me Me
Si
Me Me
Si
(10 mol %)
OH
OMe
THF/H2O
rt, 4 h
DMSO
rt, 8 h
3a
5
6
H2O2, KF, KHCO3
OH
THF/MeOH/H2O
rt, 15 h
7
a (71% from 3a)
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Scheme 4. Conversion of (Borylmethyl)silyl Group into Hydroxyl Group via Swern Oxidation
(Method B)
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H2O2
NaOH
DMSO, (ClCO)
Et N, CH Cl
2
Me Me
Si
O
H2O2, KF
KHCO3
3
2
2
3a
5
7a
THF/H2O
rt, 4 h
– 78 °C to rt
0.5 h
H O
THF/MeOH
rt, 15 h
(71% from 3a)
H
2
8
Synthesis of Alcohols from Trimethylsilylalkanes. A range of trimethylsilylalkanes
3
and -cycloalkanes were subjected to the modified C(sp )–H borylation and following conversion into
3
alcohols (Table 2). Primary alkyl-substituted compounds 1b–g underwent C(sp )–H borylation in
4
t-BuOMe at 110 °C using 2 (1.5 equiv) in the presence of Ir-Me phen catalyst (5 mol %) with t-BuOK
(1.25 mol %), giving the corresponding (borylmethyl)silanes 3b–g and bis(borylmethyl)silane 4b–g in
3
7
1-89% combined yields, respectively (entries 2-7). In the reaction of trimethylsilyloctane (1d), C(sp )–
H borylation at the octyl terminus also took place to give (borylmethyl)(8-boryloctyl)dimethylsilane 9 in
% yield, therby resulting in a slight decrease of the combined yield of 3d/4d (71%, entry 4). Alkyl
7
ether (entry 5), pivalate (entry 6), and pinacol-derived acetal (entry 7) were tolerant under the conditions
using Ir/t-BuOK, although 3-[(trimethylsilyl)methyl]cyclohexan-1-one did not give the corresponding 3
22
and 4. Following three-step conversion of the borylated compounds using Method A resulted in the
formation of the corresponding alcohols 7b–g with reasonable yields, except for pivalate 7f (entries 2-7).
For conversion of 3f/4f into 7f, Method B gave a significantly better yield than Method A (63% vs. 41%,
entry 6).
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a
Table 2. Alcohol Synthesis from Trimethylsilylalkanes
C–H Borylation
Method A or B
R
SiMe3
R
SiMe3-n[CH2B(pin)]n
R OH
1
3 (n = 1), 4 (n = 2)
7
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
b
c
entry
1
substrate
% yield (3:4)
alcohol
Method: % yield
SiMe3
OH
88 (81:19)
A: 71; B: 70
1
a
7a
SiMe
3
OH
2
3
4
89 (73:27)
77 (69:31)
A: 62
1
b
7b
SiMe
3
OH
A: 70; B: 71
A: 65
1c
7c
SiMe
3
OH
d
71 (72:28)
1d
7d
SiMe
3
OH
O
O
5
6
7
81 (68:32)
74 (76:24)
86 (76:24)
A: 69; B: 76
A: 41; B: 63
A: 73
1e
7e
SiMe3
OH
OPiv
OPiv
1
f
7f
O
O
O
O
SiMe3
OH
1
g
7g
SiMe3
OH
8
87 (80:20)
89 (80:20)
88 (83:17)
78 (92:8)
A: 61; B: 60
1
h
7h
SiMe
3
OH
e
f
9
A: 58
1
i
7i
g
g
1
1
0
1
SiMe3
OH
A: 56
1
j
7j
h
h
SiMe3
OH
A: 65 ; B: 29
1k
7k
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1
1
1
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1
1
1
1
1
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
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3
3
3
3
4
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4
4
4
4
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5
5
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5
5
5
5
5
6
a
2
C–H Borylation: 1 (1.0 mmol), 2 (1.5 mmol), [Ir(OMe)(cod)] (0.025 mmol),
Me
(0.8 mL) at 110 °C for 36 h. Method A: 1) H
MeOK (10 mol %), DMSO, rt, 8 h; 3) H , KF, KHCO
5 h. Method B: 1) H , NaOH, THF/H O, rt, 4 h; 2) DMSO, (ClCO)
CH Cl , –78 °C to rt,; 3) H , KF, KHCO , THF/MeOH/H
4
phen (0.050 mmol), and t-BuOK (0.0125 mmol) were stirred in t-BuOMe
, NaOH, THF/H O, rt, 4 h; 2)
, THF/MeOH/H O, rt,
, Et
2
O
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
O
2
3
2
1
2
O
2
2
2
3
N,
b
2
2
2
O
2
3
2
O, rt, 15 h.
c
Combined yield of isolated 3 and 4 based on 1. Isolated yield from 3/4 (3 steps).
d
e
(
pin)B(CH
2
)
8
SiMe
2
(CH
2
B(pin)) (9) was also formed in 7% yield. exo:endo =
f
g
h
9
4:6. exo:endo = 95:5. only endo. 40 h for the 3rd step (oxidation).
1
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5
Secondary alkyl-substituted compounds 1h–j were converted efficiently into 3h–j/4h–j under
3
the modified C(sp )–H borylation conditions (entries 8-10, Table 2). The reaction of sterically more
demanding 1k also gave 3k and 4k in good combined yield with higher selectivity for the formation of
monoborylated product 3k (entry 11). Treatment of 3h–k/4h–k under the conditions of Method A
afforded 7h-k in 56–65% yields (entries 8–11). Although Methods A and B were comparably effective,
the yield of 7k dropped significantly in the conversion of 3k/4k using Method B, in which oxidation of
the formylsilanes was rather slow (entry 11). The stereochemistry of 1i and 1j was retained during the
C–H borylation and following oxidation (entries 9 and 10).
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Application to the Synthesis of a Stereodefined Cyclopentanol Derivative. The present C–H
borylation-based conversion of trimethylsilylalkanes was applied to the synthesis of stereodefined
organic compounds starting from readily available TMS-based reagents, such as allyltrimethylsilane
(
10) and diallyldimethylsilane (13) (Schemes 5 and 6). Jung and coworkers reported an AlCl
3 3
/Me SiCl-
mediated reaction of 10 with 2,3-dimethyl-1,3-butadiene (11), which gives [3+2] cycloaddition product
2
3
12 diastereoselectively (Scheme 5). We focused on the potential usefulness of the stereodefined five-
3
membered ring. Compound 1l was obtained by hydrogenation of 12 and subjected to the C(sp )–H
borylation, which was followed by conversion into alcohol 7l. C–H borylation of 1l took place
chemoselectively at the methyl group on silicon to afford 3l and 4l in 83% yield (3l:4l = 77:23). Alcohol
7l was obtained in 66–64% yield by the following conversions using either Method A or B.
1
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8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Scheme 5. Synthesis of a Stereodefined Cyclopentanol Derivative Starting from Allyltrimethylsilane
(
10)
SiMe
3
SiMe
3
11
, Me
pentane
Pd/C, H
2
SiMe
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
AlCl
3
3
SiCl
EtOH
rt, 1 h
10
–30 to –20 °C
12
1l (42% from 10)
ref. 21
2
[
(1.5 equiv)
Ir(OMe)(cod)]
2.5 mol %)
phen (5 mol %)
2
(
SiMe3-n[CH B(pin)]
OH
2
n
Me
4
Method A or B
t-BuOK (1.25 mol %)
t-BuOMe
3l (n = 1), 4l (n = 2)
83% (3l:4l = 77:23)
7l
110 °C, 36 h
via Method A 64%
via Method B 66%
Application to the Synthesis of (±)-Sphaeric acid. The present method was extended to
conversion of 1,1-dimethyl-1-silacyclopentane into 1,4-diol via double oxidative cleavage of Si–C
bonds, leading to the synthesis of (±)-Sphaeric acid (Scheme 6). Takahashi and coworkers reported the
stereoselective synthesis of silacyclopentane 14 via formation of zirconacyclopentane from 13, followed
24
by treatment with MeOH and I
2
.
Copper-catalyzed alkylation of 14 with heptylmagnesium bromide
3
gave 15, which was then subjected to the modified iridium-catalyzed C(sp )–H borylation. The reaction
took place selectively at the methyl group on the silicon atom to give 16 and 17 in 73% combined yield
2
5
(
16:17 = 88:12). Conversion of 16/17 according to Method B resulted in the formation of diol 18 in
26
7
4
0% yield. Finally, oxidation of 18 with KMnO under basic conditions afforded (±)-Sphaeric acid. It
is interesting to note that the use of Method A in the conversion of 19 never led to the formation of 18
(Scheme 7). Instead, mono-ols 20 and 21 were obtained, albeit in low yields. 20 and 21 were probably
formed through ring opening of 19 to form acyclic alkylsilanes in the presence of MeOK. A possible
mechanism is that an alkoxide attacks to the silicon center of 19 to form silicate A, which undergoes
2
7
protonation by the hydroxyl group accompanied with opening of the five-membered ring to give B.
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8
9
Scheme 6. Synthesis of (±)-Sphaeric Acid Starting from Diallyldimethylsilane (13)
1
. Cp
n-BuLi
2
ZrCl
2
n-C
7
H
15MgBr
(5 mol %)
Li CuCl
2
4
SiMe
2
SiMe
2
SiMe
2
2. MeOH
. I
ref. 22
I
THF
0 °C to rt
8 17
n-C H
3
2
1
3
14 (56%)
15 (67%)
2
(1.5 equiv)
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
[Ir(OMe)(cod)]2 (2.5 mol %)
Me4phen (5 mol %)
Method B
OH
OH
SiMe2-n[CH2B(pin)]n
t-BuOK (1.25 mol %)
t-BuOMe
8 17
n-C H
n-C
8
H
17
1
6 (n = 1), 17 (n = 2)
18 (70%)
110 °C, 36 h
7
3% (16:17 = 88:12)
KMnO
NaOH
4
2
CO H
H
2
O/t-BuOH
CO
±)-Sphaeric acid (83%)
2
H
rt, 24 h
(
Scheme 7. Attempted Conversion of 19 through Method A
1
. MeOK (10 mol %)
DMSO, rt, 8 h
Me
Si
OH
2 2
2. H O , KF, KHCO
3
8 17
n-C H
THF/MeOH/H
2
O, rt, 15 h
1
9
(Method A)
OH
OH
+
+
OH
OH
n-C
8
H
17
n-C
8
H
17
n-C
8
H
17
Me
1
8 (0%)
20 (16%)
21 (13%)
Possible Pathway:
R1
R1
R2
OR
OR
Me
RO
Me
19
Si
R2
Si
20, 21
CH3
H
O
O
A
B
Conclusion
We have established a new method to utilize unreactive alkylsilanes in organic synthesis. The
trimethylsilyl group of trimethylsilylalkanes and -cycloalkanes could be converted into hydroxyl group
3
to give alcohols. The conversion is based on iridium-catalyzed chemoselective C(sp )–H borylation of
the methyl group on silicon for the conversion into (borylmethyl)silanes, which are further converted
2 2
into (hydroxymethyl)silanes via H O oxidation. Two complementary oxidation protocols have been
established: Method A involves formation of methoxysilanes via Brook rearrangement, and Method B
involves formation of formylsilanes via Swern oxidation. Both protocols are finalized by application of
1
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Tamao-Fleming oxidation to give the corresponding alcohols. These protocols have enabled the use of
stereodefined TMS-substituted cycloalkanes, which has not been commonly employed in synthetic
applications.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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9
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2
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0
Experimental Section
General: All iridium-catalyzed reactions were performed in Glove Box or using Schlenk
technique under an atmosphere of nitrogen with magnetic stirring. Other reactions were also carried out
under an atmosphere of nitrogen unless otherwise noted. Materials were weighted by an electric balance
(readability: 0.01 mg). Gas chromatography (GC) was performed on a FID detector with a column
(100% dimethylpolysiloxane, φ 0.32 mm x 15 m). Column chromatography was performed with silica
gel (pH 7.0, 40-63 µm, 60 Å). Gel Permeation Chromatography (GPC) was performed with series-
connected a column for exclusion limit of 1000 (φ 20 mm x 600 mm) and a column for exclusion limit
1
13
11
of 5000 (φ 20 mm x 600 mm). H NMR (399.89 MHz), C NMR (100.55 MHz), and B NMR (128.30
1
13
MHz) spectra were recorded at ambient temperature using CDCl
3
as a solvent. For H and C NMR,
chemical shifts (δ) in parts per million (ppm) were referenced to the solvent residual peak as an internal
1
13
11
standard: CHCl
3
for H NMR (δ 7.26) and CDCl
3
for C NMR (δ 77.0). For B NMR, chemical shifts
1
(δ) in ppm were referenced to BF
3
·OEt
2
as an external standard. H NMR data were reported as follows:
chemical shifts, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, and m = multiplet),
coupling constant (J), and integration. High resolution mass spectra were recorded on a magnetic sector
mass spectrometer (EI) and a Fourier-transform mass spectrometer (ESI, APCI, DART). Infrared
spectra were recorded on a FT-IR spectrometer attached a single-reflection horizontal attenuated total
reflection attachment.
Solvents and reagents: t-BuOMe, CyOMe, cyclooctane, and DMSO were distilled over calcium
hydride and degassed. THF and 1,4-dioxane were dried and degassed by benzophenone ketyl. Dry
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4
5
CH
2
Cl
2
was purchased and used as received. Bis(pinacolato)diboron (2) was purchased and purified by
recrystallization (pentane) before use. Other reagents were used as received from commercial sources.
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
8
Catalysts and a ligand: [Ir(OMe)(cod)]
,4,7,8-Tetramethyl-1,10-phenanthroline (Me phen) was used as received from commercial source.
, CsF, and KOMe were purchased and dried in vacuo (150 ºC, 12 h) before
2
was synthesized by the method reported previously.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
4
2 3
t-BuOK, MeONa, Cs CO
use.
Preparation of Substrates: Trimethylsilylalkanes 1a-k were synthesized as follows.
1
4b
Trimethylsilylcyclohexane (1a) : In a 200 mL three neck flask, a solution of
methylmagnesium iodide was prepared from iodomethane (3.1 g, 22 mmol) with magnesium turnings
2
(0.54 g, 22 mmol) in Et O (25 mL). The solution was cooled to 0 °C by ice-water bath.
Cyclohexyldimethylsilyl chloride (3.5 g, 20 mmol) was then added to the solution slowly. The cooling
bath was removed, and the reaction mixture was allowed to warm to room temperature. After stirring for
8
4
h, excess amount of sat. NH Cl aq. was added. The organic layer was separated, and the aqueous layer
was extracted with hexane (20 mL x 3). The combined organic portions were washed with water (10 mL
x 3), washed with brine (10 mL x 1), and dried over anhydrous magnesium sulfate. After removal of the
volatiles by a rotary evaporator, the crude product was distilled under reduced pressure (48.5-49.0 °C/9
1
mmHg) to afford 1a (2.5 g, 16 mmol, 81%) as a colorless oil. 1a: H NMR (400 MHz, CDCl
3
) δ 1.62-
13
1
.76 (m, 5H), 0.98-1.28 (m, 5H), 0.53 (tt, J = 12.8, 3.2 Hz, 1H), –0.07 (s, 9H). C NMR (101 MHz,
CDCl
3
) δ 28.1, 27.4, 27.0, 26.2, –3.6.
Trimethylsilylmethyl)cyclohexane (1b) : In a 300 mL three neck flask, a solution of
cyclohexylmethyl)magnesium bromide was prepared from bromomethylcyclohexane (18 g, 100 mmol)
1
2
(
(
with magnesium turnings (2.7 g, 110 mmol) in THF (100 mL). Trimethylsilyl chloride (13 g, 120
mmol) was then added to the solution slowly, and the reaction mixture was refluxed for 12 h. The
4
reaction was quenched by sat. NH Cl aq., and hexane (300 mL) was added. The organic layer was
1
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7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
washed with water (100 mL x 3), washed with brine (100 mL x 1), and dried over anhydrous
magnesium sulfate. After removal of the volatiles by a rotary evaporator, the crude product was distilled
under reduced pressure (81.0-82.0 °C/22 mmHg) to afford 1b (12 g, 73 mmol, 73%) as a colorless oil.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
H NMR (400 MHz, CDCl ) δ 1.56-1.72 (m, 5H), 1.31-1.42 (m, 1H), 1.05-1.29 (m, 3H), 0.85-0.98 (m,
1
3
2
–
3
H), 0.48 (d, J = 6.8 Hz, 2H), –0.01 (s, 9H). C NMR (101 MHz, CDCl ) δ 36.9, 34.4, 26.6, 26.3, 25.8,
0.5.
1
-(Trimethylsilyl)-3,7-dimethyloctane (1c): In a 100 mL two neck flask, a solution of (3,7-
dimethyloctyl)magnesium bromide was prepared from 1-bromo-3,7-dimethyloctane (4.4 g, 20 mmol)
with magnesium turnings (0.53 g, 22 mmol) in THF (20 mL). Trimethylsilyl chloride (2.6 g, 24 mmol)
was then added to the solution slowly, and the reaction mixture was refluxed for 12 h. The reaction was
4
quenched by sat. NH Cl aq., and hexane (50 mL) was added. The organic layer was washed with water
(20 mL x 3), washed with brine (20 mL x 1), and dried over anhydrous magnesium sulfate. After
removal of the volatiles by a rotary evaporator, the crude product was distilled under reduced pressure
1
(
89.0-90.0 °C/4 mmHg) to afford 1c (3.0 g, 14 mmol, 68%) as a colorless oil. H NMR (400 MHz,
CDCl
3
) δ 1.53 (septet, J = 6.4 Hz, 1H), 0.98-1.36 (m, 9H), 0.869 (d, J = 6.4 Hz, 3H), 0.867 (d, J = 6.4
13
3
Hz, 3H), 0.84 (d, J = 6.4 Hz, 3H), 0.36-0.54 (m, 2H), –0.03 (s, 9H). C NMR (101 MHz, CDCl ) δ 39.4,
+
+
3
6.7, 35.6, 30.9, 28.0, 24.8, 22.7, 22.6, 19.3, 13.4, –1.7. HRMS (EI) m/z calcd for C13
H30Si [M] :
214.2111, found: 214.2115.
14b
Trimethylsilyloctane (1d) : In a 200 mL three neck flask, a solution of octylmagnesium
bromide was prepared from 1-bromooctane (3.9 g, 20 mmol) with magnesium turnings (0.49 g, 20
mmol) in THF (20 mL). The solution was cooled to 0 °C by ice-water bath. Trimethylsilyl chloride (2.4
g, 22 mmol) was then added to the solution slowly. The cooling bath was removed, and the reaction
mixture was refluxed for 6 h. The reaction was quenched by sat. NH
4
Cl aq., and hexane (50 mL) was
added. The organic layer was washed with water (20 mL x 3), washed with brine (10 mL x 1), and dried
1
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2
3
over anhydrous magnesium sulfate. After removal of the volatiles by a rotary evaporator, the crude
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
product was distilled under reduced pressure (70.0-71.0 °C/13 mmHg) to afford 1d (2.9 g, 15 mmol,
1
77%) as a colorless oil. 1d: H NMR (400 MHz, CDCl
3
) δ 1.23-1.34 (m, 12H), 0.88 (t, J = 6.8 Hz, 3H),
) δ 33.7, 32.0, 29.4, 29.3, 23.9, 22.7, 16.7,
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9
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1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
0
.45-0.51 (m, 2H), –0.03 (s, 9H). C NMR (101 MHz, CDCl
3
14.1, –1.6.
,7-Dimethyloctyl 3-trimethylsilylpropyl ether (1e): In a 100 mL two neck flask was charged
with NaH (in oil, 50~72%, 0.99 g, 21~30 mmol), THF (25 mL) and 1-bromo-3,7-dimethyloctane (5.3 g,
4 mmol). The flask was cooled to 0 ºC by ice-water bath, and 3-trimethylsilylpropanol (2.7 g, 20
3
2
mmol) was added dropwise. After stirring at 0 ºC for 1 h, the cooling bath was removed and the reaction
mixture was stirred at room temperature for 24 h. The reaction was quenched by water, and diethyl ether
(50 mL) was added. The organic layer was washed with water (20 mL x 2), washed with brine (20 mL x
1), and dried over anhydrous magnesium sulfate. After removal of the volatiles by a rotary evaporator,
the resulting crude product was purified by column chromatography on silica gel (hexane:Et
2
O = 20:1).
1
1
e (3.6 g, 13 mmol, 66%) was obtained as a colorless oil. 1e: H NMR (400 MHz, CDCl
3
) δ 3.39-3.48
(m, 2H), 3.36 (t, J = 6.8 Hz, 2H), 1.46-1.66 (m, 5H), 1.19-1.43 (m, 4H), 1.04-1.19 (m, 3H), 0.88 (d, J
13
=
3
7.2 Hz, 3H), 0.86 (d, J =6.8 Hz, 6H), 0.45-0.50 (m, 2H), –0.01 (s, 9H). C NMR (101 MHz, CDCl ) δ
7
3.9, 69.2, 39.3, 37.4, 36.8, 29.9, 28.0, 24.7, 24.2, 22.7, 22.6, 19.7, 12.6, –1.7. HRMS (EI) m/z calcd for
+
+
C
16
H
35OSi [M - H] : 271.2452, found: 271.2452.
-(Trimethylsilyl)propyl pivalate (1f): In a 100 mL two neck flask was charged with 3-
trimethylsilylpropanol (2.6 g, 20 mmol), 4-(dimethylamino)pyridine (0.24 g, 2 mmol), triethylamine
(4.0 g, 40 mmol) and CH Cl (20 mL). Pivalic anhydride (5.6 g, 30 mmol) was added and the reaction
3
2
2
mixture was stirred at room temperature. After 24 h, water (10 mL) was added, and the aqueous layer
was extracted with dichloromethane (10 mL x 2). The organic layer was collected, and the combined
organic portions were washed with brine (10 mL x 1), and dried over anhydrous sodium sulfate. After
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
removal of the volatiles by a rotary evaporator, the resulting crude product was purified by column
chromatography on silica gel (hexane:Et
2
O = 20:1). 1f (2.2 g, 10 mmol, 51%) was obtained as a
) δ 4.01 (t, J = 6.8 Hz, 2H), 1.56-1.65 (m, 2H), 1.20 (s, 9H),
) δ 178.6, 66.9, 38.7, 27.2, 23.3, 12.4, –1.8.
Si [M + H] : 217.1618, found: 217.1618.
1
colorless oil. 1f : H NMR (400 MHz, CDCl
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
0
.46-0.53 (m, 2H), 0.00 (s, 9H). C NMR (101 MHz, CDCl
3
+
+
HRMS (APCI) m/z calcd for C11
H
25
O
2
2
,2,3,3-Tetramethyl-7-trimethylsilylmethyl-1,4-dioxaspiro[4.5]decane (1g): The 1,4-addition
29
of Grignard reagent was performed in accordance with a reported procedure. In a 500 mL three neck
flask,
a
solution of (trimethylsilylmethyl)magnesium chloride was prepared from
(chloromethyl)trimethylsilane (8.6 g, 70 mmol) with magnesium turnings (1.9 g, 77 mmol) in diethyl
ether (70 mL). CuBr (0.39 g, 2.7 mmol) was added, and the reaction mixture was cooled to 0 ºC by ice-
water bath. 2-Cyclohexen-1-one (5.8 g, 60 mmol) in diethyl ether (45 mL, rinsed 5 mL x 2) was added
dropwise to the reaction mixture over 15 min. The cooling bath was removed, and the resulting mixture
was stirred at room temperature for 30 min. The reaction was quenched by water (90 mL) at 0 ºC and
the organic layer was washed with water (150 mL x 3), washed with brine (150 mL x 1), and dried over
anhydrous sodium sulfate. After removal of the volatiles by a rotary evaporator, the crude product was
purified by Kugelrohr distillation (80 °C/0.4 mmHg) to afford 3-[(trimethylsilyl)methyl]cyclohexan-1-
one (9.4 g, 51 mmol, 85%) as a colorless oil.
In a 200 mL flask, pinacol (12 g, 100 mmol), p-TsOH·H
(trimethylsilyl)methyl]cyclohexan-1-one (3.7 g, 20 mmol) were dissolved in toluene (80 mL). The
resulting mixture was refluxed with removing water using Dean-Stark apparatus for 24 h. After cooling
to room temperature, sat. NaHCO aq. was added to the reaction mixture and the organic layer was
2
O (0.39 g, 2 mmol) and 3-
[
3
washed with water (20 mL x 2). The aqueous layer was extracted with diethyl ether (20 mL x 2). The
organic layer was collected, and the combined organic portions were washed with brine (20 mL x 1),
and dried over anhydrous sodium sulfate. After removal of the volatiles by a rotary evaporator, the
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resulting crude product was purified by column chromatography on silica gel (hexane:Et
2
O = 20:1). 1g
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
(
2.6 g, 9.2 mmol, 46%) was obtained as a colorless oil. 1g: H NMR (400 MHz, CDCl
3
) δ 1.67-1.88 (m,
3
1
7
2
2
H), 1.47-1.67 (m, 3H), 1.38 (td, J = 12.8, 4.4 Hz, 1H), 1.23 (s, 6H), 1.22 (s, 6H), 1.17 (t, J = 12.4 Hz,
H), 0.77-0.89 (m, 1H), 0.52 [dd (AB pattern), J = 14.8, 6.4 Hz, 1H], 0.45 [dd (AB pattern), J = 14.8,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
3
.6 Hz, 1H], 0.00 (s, 9H). C NMR (101 MHz, CDCl ) δ 107.0, 82.4, 81.6, 48.9, 38.4, 35.6, 32.0, 25.4,
+
+
32 2
4.90 (2C), 24.88, 24.7, 23.5, –0.5. HRMS (EI) m/z calcd for C16H O Si [M] : 284.2166, found:
84.2165.
1
2
Trimethylsilylcycloheptane (1h) : In a 200 mL three neck flask, a solution of
(cycloheptyl)magnesium bromide was prepared from bromocycloheptane (8.9 g, 50 mmol) with
magnesium turnings (1.3 g, 55 mmol) in THF (50 mL). Dimethylsilyl chloride (5.7 g, 60 mmol) was
then added to the solution slowly, and the reaction mixture was stirred at room temperature for 2 h.
After removal of the volatiles under reduced pressure, hexane was added and filtered through a pad of
Celite and the resulting solution was concentrated to afford crude cycloheptyldimethylsilane. The crude
cycloheptyldimethylsilane was collected to a 200 mL three neck flask. THF (50 mL) was added to the
flask. The flask was cooled to –78 °C by dry ice-acetone bath and MeLi (3.0 M in diethoxymethane, 17
mL, 51 mmol) was added to the reaction mixture. After stirring for 1 h, the cooling-bath was removed,
and slowly warmed to room temperature. The resulting mixture was pored into hexane (200 mL) and
quenched by water. The organic layer was washed with water (10 mL x 3), washed with brine (10 mL x
1
), and dried over anhydrous magnesium sulfate. After removal of the volatiles by a rotary evaporator,
the crude product was distilled under reduced pressure (79.0-80.5 °C/14 mmHg) to afford 1h (2.0 g, 12
1
mmol, 24%) as a colorless oil. 1h: H NMR (400 MHz, CDCl
3
) δ 1.65-1.80 (m, 4H), 1.52-1.65 (m, 2H),
1
3
1.34-1.52 (m, 4H), 1.14-1.28 (m, 2H), 0.60 (tt, J = 11.2, 3.2 Hz, 1H), –0.06 (s, 9H). C NMR (101
MHz, CDCl ) δ 30.1, 28.8, 28.4, 26.7, –3.3.
3
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2
2
2
2
2
2
2
3
3
3
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6
12
(
1S*,2S*,4R*)-2-Trimethylsilylbicyclo[2.2.1]heptane (1i) : The hydrosilylation was
3
0
performed in accordance with a reported procedure. To a 200 mL three neck flask, norbornene (5.7 g,
60 mmol), PtCl (cod) (0.23 g, 0.60 mmol), toluene (60 mL) and dimethylchlorosilane (8.5 g, 90 mmol)
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
were added. The reaction mixture was stirred for 4 h at 80 ºC. After removal of the volatiles, the crude
product was distilled under reduced pressure (101.0-102.0 °C/22 mmHg) to afford exo-
bicyclo[2.2.1]heptan-2-ylchlorodimethylsilane (8.8 g, 47 mmol, 78%) as a colorless oil.
To a 100 mL three neck flask, exo-bicyclo[2.2.1]heptan-2-ylchlorodimethylsilane (3.8 g, 20
mmol) and THF (20 mL) were added. The flask was cooled to –78 °C by dry ice-acetone bath and MeLi
(
3.0 M in diethoxymethane, 7 mL, 21 mmol) was added to the reaction mixture over 10 min. The
reaction mixture was stirred for 1 h. The cooling-bath was removed, and after stirring at room
temperature for 1 h, the reaction was quenched by water, and hexane (50 mL) was added. The organic
layer was washed with water (10 mL x 3), washed with brine (10 mL x 1), and dried over anhydrous
magnesium sulfate. After removal of the volatiles by a rotary evaporator, the crude product was distilled
under reduced pressure (87.0-88.0 °C/25 mmHg) to afford 1i (2.8 g, 17 mmol, 84%) as a colorless oil.
1
1
i: H NMR (400 MHz, CDCl
3
) δ 2.23 (broad, 1H), 2.15 (broad, 1H), 1.47-1.57 (m, 2H), 1.33-1.39 (m,
1
3
2H), 1.06-1.25 (m, 4H), 0.50 (dt, J = 8.8, 1.6 Hz, 1H), –0.06 (s, 9H). C NMR (101 MHz, CDCl
7.79, 37.75, 36.9, 34.3, 32.5, 29.4, 28.9, –2.7.
1S*,2R*,4R*)-2-Trimethylsilylbicyclo[2.2.1]heptane (1j) : The deprotonation of norbornene
3
) δ
3
3
1
(
3
2
was performed in accordance with a reported procedure. To a 100 mL two neck flask, potassium tert-
butoxide (1.8 g, 16 mmol) and THF (9 mL) were added. The flask was cooled to –78 °C by dry ice-
acetone bath and THF solution of norbornene (5.6 g, 59 mmol, in THF 8 mL, rinsed twice with 0.5 mL)
was added. n-BuLi (1.6 M in hexane, 10 mL, 16 mmol) was added to the reaction mixture over 45 min.
The reaction mixture was slowly warmed to –40 ºC and stirred for 90 min, then re-cooled to –78 ºC.
Trimethylsilyl chloride (3.7 g, 34 mmol) was then added to the solution slowly, and the reaction mixture
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was stirred for 1 h. The cooling-bath was removed, and after stirring at room temperature for 1 h, the
reaction was quenched by sat. NH Cl aq., and hexane (50 mL) was added. The organic layer was
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
4
washed with water (10 mL x 3), washed with brine (10 mL x 1), and dried over anhydrous magnesium
sulfate. After removal of the volatiles by a rotary evaporator, the crude product was distilled under
reduced pressure (81.0-82.0 °C/30 mmHg) to afford 2-trimethylsilylbicyclo[2.2.1]hept-2-ene (1.3 g, 8
mmol, 49%) as a colorless oil.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
In a two neck Schlenk tube was charged with Rh/C (5 wt%, 0.83 g, 0.40 mmol). The tube was
evacuated and backfilled with H
2
. Ethanol (8 mL) was added to the tube and the mixture was stirred for
1
0 min. 2-Trimethylsilylbicyclo[2.2.1]hept-2-ene (0.67 g, 4.0 mmol) was added, and the resulting
mixture was stirred at room temperature. After 12 h, the reaction mixture was filtered through celite.
The solution was concentrated by using a rotary evaporator, and the resulting crude product was purified
1
by Kugelrohr distillation (60 ºC, 0.3 mmHg). 1j (0.59 g, 87%) was obtained as a colorless oil. 1j: H
NMR (400 MHz, CDCl
.32-1.40 (m, 2H), 1.20-1.32 (m, 2H), 1.03-1.12 (m, 2H), 0.85-0.95 (m, 1H), 0.00 (s, 9H). C NMR
101 MHz, CDCl ) δ 41.8, 39.4, 37.2, 31.5, 29.9, 28.9, 27.3, –1.5.
1-Trimethylsilyladamantane (1k) : Synthesis of 1k was performed in accordance with a
3
) δ 2.26 (broad, 1H), 2.25 (broad, 1H), 1.62-1.73 (m, 1H), 1.40-1.54 (m, 1H),
1
3
1
(
3
3
3
3
3
reported procedure. To a 100 mL two neck flask, HMPA (10 mL) and hexamethyldisilane (2.5 mL,
1
2.5 mmol) were added. The solution was cooled to 0 °C by ice-water bath and MeLi (1.0 M in diethyl
ether, 10 mL, 10 mmol) was added and the reaction mixture was stirred for 15 min. The reaction
mixture was frozen at –78 ºC. 1-Bromoadamantane (1.6 g, 7.4 mmol) in diethyl ether 10 mL was added
over 1 min. The cooling-bath was removed, and slowly warmed to 10 ºC (internal temp.). The reaction
mixture was poured into hexane (300 mL), and washed with water (100 mL x 3) and dried over
anhydrous magnesium sulfate. After removal of the volatiles by a rotary evaporator, the remained
starting material was removed by silica gel column chromatography (hexane). Pure 1k (0.45 g, 2.1
2
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
mmol, 29%) was obtained by purification using GPC (eluent: CHCl
δ 1.85 (broad, 3H), 1.68-1.81 (m, 6H), 1.63 (broad, 6H), –0.12 (s, 9H). C NMR (101 MHz, CDCl
7.7, 37.1, 27.7, 21.0, –5.6.
Modification of Iridium-Catalyzed C(sp )–H Borylation (Table 1): Reaction conditions for
3 3
). 1k: H NMR (400 MHz, CDCl )
1
3
3
) δ
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
3
C(sp )–H borylation of 1a were screened using excess amount of 2. In a glove box, a glass tube having
PTFE stopcock, equipped with a magnetic stirring bar, was charged with [Ir(OMe)(cod)] (17 mg, 0.025
mmol), Me phen (12 mg, 0.05 mmol), bis(pinacolato)diboron (2) (254 mg, 1.0 mmol), t-BuOK (0-0.10
2
4
mmol), a solvent (0.5 mL), and trimethylsilylcyclohexane (1a) (78 mg, 0.5 mmol). The tube was sealed
by the stopcock and was taken out from the glove box. The mixture was heated at 110 or 135 °C with
stirring for 20 h. After cooling to room temperature, undecane (39 mg, 0.25 mmol) was added, and the
resulting mixture was analyzed by GC to determine the yields of 3a and 4a.
3
Modified Procedure for C(sp )–H Borylation of 1a (entry 14, Table 1): In a glove box, a
glass tube having PTFE stopcock, equipped with a magnetic stirring bar, was charged with
[
2 4
Ir(OMe)(cod)] (17 mg, 0.025 mmol), Me phen (12 mg, 0.05 mmol), bis(pinacolato)diboron (2) (381
mg, 1.5 mmol), t-BuOK (1.4 mg, 0.013 mmol), t-BuOMe (0.8 mL), and trimethylcyclohexane (1a) (156
mg, 1.0 mmol). The tube was sealed by the stopcock and was taken out from the glove box. The mixture
was heated at 110 °C with stirring for 36 h. After cooling the solution to room temperature, the volatiles
were removed from the reaction mixture under reduced pressure. The residue was purified by column
chromatography on silica gel to afford 3a (200 mg, 0.71 mmol, 71%; eluent: hexane:Et
2
O = 20:1) and
4a (70 mg, 0.17 mmol, 17%; eluent: hexane:Et
2
O = 10:1). Cyclohexyldimethyl[(4,4,5,5-tetramethyl-
1
1
,3,2-dioxaborolan-2-yl)methyl]silane (3a): H NMR (400 MHz, CDCl
3
) δ 1.61-1.78 (m, 5H), 1.23 (s,
1
2H), 1.12-1.26 (m, 3H), 0.90-1.12 (m, 2H), 0.55 (tt, J = 12.8, 3.2 Hz, 1H), 0.04 (s, 2H), 0.02 (s, 6H).
1
3
C NMR (101 MHz, CDCl
3
) δ 82.7, 28.1, 27.2, 27.0, 26.6, 24.9, –3.4. The boron-bound carbon was not
1
1
detected due to quadrupolar relaxation. B NMR (128 MHz, CDCl
3
) δ 33.7. HRMS (APCI) m/z calcd
2
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2
3
+
+
for C15
H
32BO
2
Si [M + H] : 283.2259, found: 283.2254. Cyclohexylmethylbis[(4,4,5,5-tetramethyl-
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
1
,3,2-dioxaborolan-2-yl)methyl]silane (4a): H NMR (400 MHz, CDCl
3
) δ 1.62-1.77 (m, 5H), 1.20-
1
.28 (m, 5H), 1.22 (s, 24H), 0.61 (tt, J = 12.0, 2.4 Hz, 1H), 0.11 [d (AB pattern), J = 12.4 Hz, 2H], 0.07
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
[
d (AB pattern), J = 12.4 Hz, 2H], 0.05 (s, 3H). C NMR (101 MHz, CDCl
3
) δ 82.6, 28.1, 27.2, 27.0,
1
1
26.9, 25.0, –2.3 (C–B, broad), –3.2. B NMR (128 MHz, CDCl
3
) δ 33.4. HRMS (APCI) m/z calcd for
+
+
C
21
H
43
B
2
O
4
Si [M + H] : 409.3111, found: 409.3103.
Conversion of (Borylmethyl)silyl Group into Hydroxyl Group via Brook Rearrangement
(Method A) (Scheme 3): To a 50 mL flask, 3a (0.28 g, 1.0 mmol), THF (2 mL), NaOH (5 N aqueous
solution, 0.80 mL) and H (30% aqueous solution, 0.40 mL) were added in this order. The resulting
mixture was stirred for 4 h at room temperature under air. After cooling the solution to 0 °C by ice-
water bath, a saturated aqueous solution of Na (ca. 5 mL) was added slowly. The organic materials
were extracted with CH Cl (10 mL x 3), and the combined organic layer was washed with brine, and
2
O
2
2 2 3
S O
2
2
dried over anhydrous sodium sulfate. After removal of the volatiles under reduced pressure, pinacol was
removed by Kugelrohr distillation (50 °C/1 mmHg) to give 5 (0.16 g, 0.94 mmol, 94%) as a colorless
1
oil. Cyclohexyl(hydroxymethyl)dimethylsilane (5): H NMR (400 MHz, CDCl
3
) δ 3.43 (s, 2H), 1.64-
1
.78 (m, 5H), 1.07-1.29 (m, 5H), 0.87 (broad s, OH, 1H), 0.73 (tt, J = 12.0, 3.2 Hz, 1H), 0.00 (s, 6H).
1
3
C NMR (101 MHz, CDCl
3
) δ 54.5, 28.0, 27.4, 26.9, 24.0, –7.0. HRMS (APCI) m/z calcd for
+
+
–1
C
9
H
21OSi [M + H] : 173.1356, found: 173.1355. IR (neat) 3296 cm (νOH).
To a 5 mL Schlenk tube, 5 (35 mg, 0.20 mmol), KOMe (1.4 mg, 0.020 mmol) and DMSO (0.8
mL) were added. The resulting mixture was stirred at room temperature under nitrogen atmosphere.
After 8 h, KF (29 mg, 0.50 mmol), KHCO (60 mg, 0.60 mmol), THF/MeOH (v/v = 1/1, 1 mL) and
(30% aqueous solution, 120 µL) were added, and the resulting mixture was stirred for 15 h at
room temperature under air. After cooling the solution to 0 ºC by ice-water bath, a saturated solution of
Na (ca. 5 mL) was added slowly. The organic materials were extracted with CH Cl (ca. 10 mL x
3
2 2
H O
2
S
2
O
3
2
2
2
3
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
), and the combined organic layer was washed with brine, and dried over anhydrous sodium sulfate.
Undecane (31 mg, 0.20 mmol, internal standard) was added, and the resulting mixture was analyzed by
GC. 7a was formed in 76% yield from 5 (71% yield from 3a). 7a was assigned by comparison with GC
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
and H NMR data of authentic sample.
Conversion of Bis(borylmethyl)silyl Group of 4a into Hydroxyl Group via Method A: To a
5
2 2
0 mL flask, 4a (0.20 g, 0.5 mmol), THF (2 mL), NaOH (5 N aqueous solution, 0.80 mL) and H O
(30% aqueous solution, 0.40 mL) were added in this order. The resulting mixture was stirred for 4 h at
room temperature under air. After cooling the solution to 0 °C by ice-water bath, a saturated aqueous
2 2 3 2 2
solution of Na S O (5 mL) was added slowly. The organic materials were extracted with CH Cl (10
mL x 3), and the combined organic layer was washed with brine, and dried over anhydrous sodium
sulfate. After removal of the volatiles under reduced pressure, pinacol was removed by Kugelrohr
distillation (50 °C/1 mmHg) to give cyclohexylbis(hydroxymethyl)methylsilane (22) (86 mg, 0.46 mmol,
1
9
1%) as a white solid. Cyclohexylbis(hydroxymethyl)methylsilane (22): H NMR (400 MHz, CDCl
3
)
δ 3.68 [d (AB pattern), J = 14.0 Hz, 2H], 3.57 [d (AB pattern), J = 14.0 Hz, 2H], 2.03-2.20 (broad, OH,
13
2
H), 1.62-1.78 (m, 5H), 1.10-1.30 (m, 5H), 0.88 (tt, J = 12.0, 2.8 Hz, 1H), 0.04 (s, 3H). C NMR (101
+
+
MHz, CDCl
3
9 21 2
) δ 53.8, 27.8, 27.4, 26.8, 22.3, –9.8. HRMS (ESI) m/z calcd for C H O Si [M + H] :
–1
1
89.1305, found: 189.1304. IR (neat) 3221 cm (νOH).
To a 5 mL Schlenk tube, 22 (38 mg, 0.20 mmol), KOMe (1.4 mg, 0.020 mmol) and DMSO (0.8
mL) were added. The resulting mixture was stirred at room temperature under nitrogen atmosphere.
After 8 h, KF (29 mg, 0.50 mmol), KHCO (60 mg, 0.60 mmol), THF/MeOH (v/v = 1/1, 1.0 mL) and
(30% aqueous solution, 120 µL) were added, and the resulting mixture was stirred for 15 h at
room temperature under air. After cooling the solution to 0 ºC by ice-water bath, a saturated solution of
Na (5 mL) was added slowly. The organic materials were extracted with CH Cl (10 mL x 3), and
the combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. Undecane
3
2 2
H O
2
S
2
O
3
2
2
2
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3
(31 mg, 0.20 mmol, internal standard) was added, and the resulting mixture was analyzed by GC. 7a
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
was formed in 79% yield from 22 (72% yield from 4a).
Conversion of (Borylmethyl)silyl Group into Hydroxyl Group via Swern Oxidation
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
Method B) (Scheme 4): A procedure for conversion of 3a to 5 (94% yield) is same as described above.
To a 5 mL Schlenk tube, oxalyl chloride (78 mg, 0.61 mmol) and CH Cl (0.75 mL) were added. The
tube was cooled to –78 ºC by dry ice-acetone bath, and a CH Cl (0.75 mL) solution of DMSO (43 mg,
0.55 mmol) was added. After 5 min, and a CH Cl (0.75 mL) solution of 5 (86 mg, 0.5 mmol) was
added, and the resulting mixture was stirred at –78 ºC for 15 min. Et N (0.25 g, 2.5 mmol) was added
and the cooling bath was removed. KF (77 mg, 1.3 mmol), KHCO (150 mg, 1.5 mmol), THF/MeOH
(v/v = 1/1, 2.5 mL) and H (30% aqueous solution, 300 µL) were added, and the resulting mixture
was stirred for 15 h at room temperature under air. After cooling the solution to 0 ºC by ice-water bath,
a saturated solution of Na (5 mL) was added slowly. The organic materials were extracted with
CH Cl (10 mL x 3), and the combined organic layer was washed with brine, and dried over anhydrous
2
2
2
2
2
2
3
3
2
O
2
2 2 3
S O
2
2
sodium sulfate. Undecane (78 mg, 0.50 mmol, internal standard) was added, and the resulting mixture
was analyzed by GC. 7a was formed in 75% yield from 5 (71% yield from 3a).
Conversion of Bis(borylmethyl)silyl Group of 4a into Hydroxyl Group via Method B: A
procedure for conversion of 4a to 22 (91% yield) is same as described above. To a 5 mL Schlenk tube,
oxalyl chloride (78 mg, 0.61 mmol) and CH
by dry ice-acetone bath, and a CH Cl (0.75 mL) solution of DMSO (43 mg, 0.55 mmol) was added.
After 5 min, a CH Cl (0.75 mL) solution of 22 (47 mg, 0.25 mmol) was added, and the resulting
mixture was stirred at –78 ºC for 15 min. Et N (0.25 g, 2.5 mmol) was added and the cooling bath was
removed. KF (36 mg, 0.63 mmol), KHCO (75 mg, 0.75 mmol), THF/MeOH (v/v = 1/1, 1.3 mL) and
(30% aqueous solution, 150 µL) were added, and the resulting mixture was stirred for 15 h at
room temperature under air. After cooling the solution using ice-water bath, a saturated solution of
2 2
Cl (0.75 mL) were added. The tube was cooled to –78 ºC
2
2
2
2
3
3
2 2
H O
2
5
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2
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6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Na
2
S
2
O
3
2 2
(5 mL) was added slowly. The organic materials were extracted with CH Cl (10 mL x 3), and
the combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. Undecane
(39 mg, 0.25 mmol, internal standard) was added, and the resulting mixture was analyzed by GC. 7a
was formed in 74% yield from 22 (67% yield from 4a).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Alcohol Synthesis from Trimethylsilylalkanes (Table 2): General Procedure for the
Conversion of Alkyl–SiMe
given as follows. C–H Borylation: In a glove box, a glass tube having PTFE stopcock, equipped with a
magnetic stirring bar, was charged with [Ir(OMe)(cod)] (17 mg, 0.025 mmol), Me phen (12 mg, 0.050
mmol), bis(pinacolato)diboron (2) (381 mg, 1.5 mmol), t-BuOK (1.4 mg, 0.013 mmol), t-BuOMe (0.8
mL), and Alkyl–SiMe (1) (1.0 mmol). The tube was sealed by the stopcock and was taken out from the
3
(1) to Alkyl–OH (7): A procedure that is suitable for sequential operation is
2
4
3
glove box. The mixture was heated at 110 °C with stirring for 36 h. After cooling the solution to room
temperature, the volatiles were removed from the reaction mixture under reduced pressure. The residue
was purified by column chromatography on silica gel to afford 3 and 4. Although 3 and 4 were
generally separable, these were subjected to the next step together.
Brook Rearrangement-Based Conversion of 3 and 4 (Method A): A 50 mL flask was charged
2 2
with 3 and 4. To the flask, THF (2 mL), NaOH (5 N aqueous solution, 0.80 mL) and H O (30%
aqueous solution, 0.40 mL) were added in this order. The resulting mixture was stirred for 4 h at room
temperature under air. After cooling the solution to 0 °C by ice-water bath, a saturated aqueous solution
of Na
), and the combined organic layer was washed with brine, and dried over anhydrous sodium sulfate.
After removal of the volatiles under reduced pressure, pinacol was removed by Kugelrohr distillation
50 °C/1 mmHg). The obtained (hydroxylmethyl)silanes were subjected to Brook rearrangement
without further purification.
2 2 3 2 2
S O (ca. 5 mL) was added slowly. The organic materials were extracted with CH Cl (10 mL x
3
(
2
6
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2
3
4
5
The obtained (hydroxylmethyl)silanes were combined to a 20 mL Schlenk tube. To the Schlenk
tube, KOMe (7.0 mg, 0.10 mmol) and DMSO (4.0 mL) were added. The resulting mixture was stirred at
room temperature under nitrogen atmosphere. After 8 h, KF (145 mg, 2.5 mmol), KHCO (300 mg, 3.0
mmol), THF/MeOH (v/v = 1/1, 5.0 mL) and H (30% aqueous solution, 0.60 mL) were added, and
the resulting mixture was stirred for 15 h at room temperature under air. After cooling the solution to 0
ºC by ice-water bath, a saturated solution of Na (10 mL) was added slowly. The organic materials
were extracted with CH Cl (15 mL x 3), and the combined organic layer was washed with brine, and
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
O
2
2 2 3
S O
2
2
dried over anhydrous sodium sulfate. Pure 7 was obtained after purification with column
chromatography on silica gel.
Swern Oxidation-Based Conversion of 3 and 4 (Method B): A 50 mL flask was charged with 3
2 2
and 4. To the flask, THF (2 mL), NaOH (5 N aqueous solution, 0.80 mL) and H O (30% aqueous
solution, 0.40 mL) were added in this order. The resulting mixture was stirred for 4 h at room
temperature under air. After cooling the solution to 0 °C by ice-water bath, a saturated aqueous solution
of Na
), and the combined organic layer was washed with brine, and dried over anhydrous sodium sulfate.
After removal of the volatiles under reduced pressure, pinacol was removed by Kugelrohr distillation
50 °C/1 mmHg). The obtained (hydroxylmethyl)silanes were subjected to Swern oxidation without
further purification.
To a 20 mL Schlenk tube, oxalyl chloride (152 mg, 1.2 mmol) and CH
The tube was cooled to –78 ºC by dry ice-acetone bath, and a CH Cl (1.5 mL) solution of DMSO (86
mg, 1.1 mmol) was added. After 5 min, a CH Cl (0.75 mL) solution of (hydroxymethyl)silanes was
added, and the resulting mixture was stirred at –78 ºC for 15 min. Et N (0.25 g, 2.5 mmol) was added
and the cooling bath was removed. KF (145 mg, 2.5 mmol), KHCO (300 mg, 3.0 mmol), THF/MeOH
v/v = 1/1, 5.0 mL) and H (30% aqueous solution, 0.60 mL) were added, and the resulting mixture
2 2 3 2 2
S O (ca. 5 mL) was added slowly. The organic materials were extracted with CH Cl (10 mL x
3
(
2
2
Cl (1.5 mL) were added.
2
2
2
2
3
3
(
2 2
O
2
7
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
was stirred for 15 h at room temperature under air. After cooling the solution using ice-water bath, a
saturated solution of Na (10 mL) was added slowly. The organic materials were extracted with
CH Cl (15 mL x 3), and the combined organic layer was washed with brine, and dried over anhydrous
2 2 3
S O
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
sodium sulfate. Pure 7 was obtained after purification with column chromatography on silica gel.
Synthesis of 7a from 1a (entry 1): See above.
Synthesis of 7b from 1b (entry 2): According to the General Procedure, C–H borylation of 1b
(170 mg, 1.0 mmol) was carried out. 3b (193 mg, 0.65 mmol, 65%) and 4b (101 mg, 0.24 mmol, 24%)
were obtained after purification by column chromatography on silica gel (hexane:Et
hexane:Et O = 10:1 for 4b). (Cyclohexylmethyl)dimethyl[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)methyl]silane (3b): H NMR (400 MHz, CDCl
2
O = 20:1 for 3b;
2
1
3
) δ 1.55-1.72 (m, 5H), 1.34-1.45 (m, 1H), 1.04-1.28
13
(
m, 3H), 1.23 (s, 12H), 0.85-0.97 (m, 2H), 0.52 (d, J = 7.2 Hz, 2H), 0.09 (s, 2H), 0.05 (s, 6H). C NMR
1
1
(101 MHz, CDCl
3
) δ 82.6, 36.8, 34.2, 26.6, 26.3, 26.1, 24.9, 0.3 (C–B, broad), –0.3. B NMR (128
+
+
MHz, CDCl
3
) δ 33.3. HRMS (APCI) m/z calcd for C16
H34BO
2
Si [M + H] : 297.2416, found: 297.2413.
1
(
Cyclohexylmethyl)(methyl)bis[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]silane (4b): H
NMR (400 MHz, CDCl
.84-0.98 (m, 2H), 0.57 (d, J = 6.8 Hz, 2H), 0.14 (s, 4H), 0.12 (s, 3H). C NMR (101 MHz, CDCl
82.6, 36.9, 34.0, 26.6, 26.3, 26.1, 25.0 [CH of B(pin), 4C], 24.9 [CH of B(pin), 4C], 0.7 (C–B, broad),
3
) δ 1.54-1.74 (m, 5H), 1.39-1.50 (m, 1H), 1.04-1.29 (m, 3H), 1.23 (s, 24H),
1
3
0
3
) δ
3
3
11
+
+
–
3 45 2 4
0.2. B NMR (128 MHz, CDCl ) δ 33.0. HRMS (ESI) m/z calcd for C22H B O Si [M + H] :
423.3268, found: 423.3260. The borylalkanes 3b and 4b (0.89 mmol total) were subjected to Method A.
An alcohol 7b (63 mg, 0.55 mmol, 62%) was obtained after purification by column chromatography on
3
4 1
silica gel (hexane:Et
2 3
O = 1:1). Cyclohexylmethanol (7b) : H NMR (400 MHz, CDCl ) δ 3.44 (d, J =
6.4 Hz, 2H), 1.64-1.79 (m, 5H), 1.42-1.54 (m, 1H), 1.38 (s, 1H, OH), 1.10-1.32 (m, 3H), 0.88-1.00 (m,
13
–1
2
3
H). C NMR (101 MHz, CDCl ) δ 68.8, 40.5, 29.5, 26.6, 25.8. IR (neat) 3287 cm (νOH).
2
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3
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5
Synthesis of 7c from 1c (entry 3): According to the General Procedure, C–H borylation of 1c
(
215 mg, 1.0 mmol) was carried out. 3c (180 mg, 0.53 mmol, 53%) and 4c (112 mg, 0.24 mmol, 24%)
were obtained after purification by column chromatography on silica gel (hexane:Et O = 20:1 for 3c;
hexane:Et O = 10:1 for 4c). (3,7-Dimethyloctyl)dimethyl[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)methyl]silane (3c): H NMR (400 MHz, CDCl
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
1
3
) δ 1.52 (septet, J = 6.4 Hz, 1H), 1.18-1.35 (m, 4H),
0.98-1.18 (m, 5H), 1.23 (s, 12H), 0.86 (d, J = 6.4 Hz, 6H), 0.83 (d, J = 6.0 Hz, 3H), 0.40-0.57 (m, 2H),
13
0
2
3
.08 (s, 2H), 0.03 (s, 6H). C NMR (101 MHz, CDCl ) δ 82.7, 39.4, 36.6, 35.6, 30.7, 28.0, 24.9, 24.8,
1
1
2.7 [CH of –CH(CH ) , 1C], 22.6 [CH of –CH(CH ) , 1C], 19.2, 13.8, –0.6 (C–B, broad), –1.5. B
3
3 2
3
3 2
+
+
NMR (128 MHz, CDCl
found: 341.3037.
yl)methyl]silane (4c): H NMR (400 MHz, CDCl
.23 (s, 24H), 0.86 (d, J = 6.8 Hz, 6H), 0.84 (d, J = 6.4 Hz, 3H), 0.46-0.62 (m, 2H), 0.13 (s, 4H), 0.09 (s,
3
) δ 33.9. HRMS (APCI) m/z calcd for C19
(3,7-Dimethyloctyl)(methyl)bis[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
) δ 1.52 (septet, J = 6.8 Hz, 1H), 1.00-1.39 (m, 9H),
2
H42BO Si [M + H] : 341.3042,
1
3
1
1
3
3
3
3H). C NMR (101 MHz, CDCl ) δ 82.6, 39.4, 36.6, 35.7, 30.6, 28.0, 25.0 [CH of B(pin), 4C], 24.94
[
CH of B(pin), 4C], 24.86, 22.7 [CH of –CH(CH ) , 1C], 22.6 [CH of –CH(CH ) , 1C], 19.2, 14.0, –
3 3 3 2 3 3 2
1
1
+
0
3 53 2 4
.2 (C–B, broad), –1.4. B NMR (128 MHz, CDCl ) δ 33.2. HRMS (ESI) m/z calcd for C25H B O Si
+
[
M + H] : 467.3894, found: 467.3888. The borylalkanes 3c and 4c (0.77 mmol total) were subjected to
either Method A or Method B. An alcohol 7c (85 mg, 0.54 mmol, 70% by Method A; 87 mg, 0.55 mmol,
1% by Method B) was obtained after purification by column chromatography on silica gel
7
3
5 1
(
hexane:Et
2
O = 1:1). 3,7-Dimethyl-1-octanol (7c) : H NMR (400 MHz, CDCl
3
) δ 3.63-3.73 (m, 2H),
1
.47-1.65 (m, 2H), 1.52 (septet, J = 6.8 Hz, 1H), 1.20-1.43 (m, 4H), 1.26 (s, 1H, OH), 1.08-1.20 (m, 3H),
1
3
0.89 (d, J = 6.8 Hz, 3H), 0.86 (d, J = 6.8 Hz, 6H). C NMR (101 MHz, CDCl
3
) δ 61.3, 40.0, 39.3, 37.4,
–1
2
9.5, 28.0, 24.7, 22.7 [CH of –CH(CH ) , 1C], 22.6 [CH of –CH(CH ) , 1C], 19.6. IR (neat) 3300 cm
3 3 2 3 3 2
(νOH).
2
9
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