Three-component carboboration of alkenes under copper catalysis

Article abstract of DOI:10.1055/s-0033-1341267

Three-component carboboration of alkenes takes place efficiently by the reaction with a diboron compound and carbon electrophiles with the aid of a copper-NHC catalyst. The carboboration afforded diverse multisubstituted borylalkanes via the regioselective formation of carbon-boron and carbon-carbon bonds. Georg Thieme Verlag Stuttgart New Yorks.

Full text of DOI:10.1055/s-0033-1341267

1924▌
SPECIAL TOPIC
special topic
Three-Component Carboboration of Alkenes under Copper Catalysis
Three-Component Carboboration of Alkenes
Ikuo Kageyuki, Hiroto Yoshida,* Ken Takaki
Department of Applied Chemistry, Graduate School of Engineering, Hiroshima University, Higashi-Hiroshima 739-8527, Japan
Fax +81(82)4245494; E-mail: yhiroto@hiroshima-u.ac.jp
Received: 28.02.2014; Accepted after revision: 01.04.2014
NHC) complexes improved the efficiency of the carbobo-
Abstract: Three-component carboboration of alkenes takes place
ration (Table 1, entries 4–6), and chloro(1,3-dimesityl-
efficiently by the reaction with a diboron compound and carbon
imidazolidin-2-ylidene)copper (SIMesCuCl) (Figure 1)
electrophiles with the aid of a copper–NHC catalyst. The carbobo-
gave the best result (77%) among the catalysts surveyed
(Table 1, entry 6). A drop in basicity led to a decrease in
yield: the reaction using potassium acetate or potassium
carbonate afforded 4aa in only 13% or 51% yield (Table
1, entries 7 and 8).
ration afforded diverse multisubstituted borylalkanes via the regio-
selective formation of carbon–boron and carbon–carbon bonds.
Key words: alkenes, carboboration, copper, equol, multicompo-
nent reaction
Table 1 Optimization of Reaction Conditionsa
The development of new synthetic routes to organoboron
compounds,1 in which the carbon–boron bonds can be
transformed into various functional groups and carbon–
carbon bonds through Suzuki–Miyaura cross-coupling,2
the Petasis reaction,3 etc., has been of great importance in
modern organic synthesis. Recently, much attention has
focused on unique copper catalysis for carbon–boron
bond-forming reactions by the use of unsaturated hydro-
carbons and organic halides,4 and we have also reported
the copper-catalyzed diborylation5a and borylstannyl-
ation5b of alkynes, in which β-borylalkenylcopper species
arising from insertion of alkynes into borylcopper
species6 act as common intermediates. Furthermore, β-
borylalkenylcopper species are captured by carbon elec-
trophiles leading to the catalytic three-component carbob-
oration of alkynes,7–11 which provides a direct entry to
multisubstituted borylalkenes through simultaneous car-
bon–carbon and carbon–boron bond-forming processes.
In view of the high affinity of the borylcopper species for
unsaturated hydrocarbons other than alkynes,4k,12 we have
also applied the carboboration protocol to simple al-
kenes,13 which should lead to a direct approach to multi-
substituted borylalkanes.
Cu catalyst (2 mol%)
Bn
Ph
B(pin)
KOt-Bu (1.5 equiv)
+
(pin)B B(pin) + Bn Cl
Ph
DMF, r.t.
1a
2
3a
4aa
(1 equiv)
(1.3 equiv)
(3 equiv)
O
B(pin) =
B
O
Entry
Cu Catalystb
Time (h)
Yieldc (%)
1
Cu(OAc)2, Cy3Pd
CuI, Xantphos
CuCl, rac-BINAP
IPrCuCl
0.5
0.5
1
57
53
66
71
70
77
13
51
2
3
4
1
5
IMesCuCl
0.5
0.5
7
6
SIMesCuCl
7e
8f
SIMesCuCl
SIMesCuCl
4
a Reaction conditions: styrene (0.30 mmol), (pin)B–B(pin) (0.39
mmol), BnCl (0.90 mmol), KOt-Bu (0.45 mmol), Cu catalyst (6.0
μmol), DMF (0.55 mL).
Initially we carried out the reaction of styrene (1a) with
bis(pinacolato)diboron [2, (pin)B–B(pin)] and benzyl
chloride (3a) in N,N-dimethylformamide at room temper-
ature in the presence of copper(II) acetate–tricyclohex-
ylphosphine, which produces a copper(I) complex in
situ,14 and potassium tert-butoxide, and observed the re-
gioselective formation of a carbon–boron (at the terminal
carbon of 1a) and a carbon–carbon (at the internal carbon
of 1a) bond to provide 1-boryl-2,3-diphenylpropane 4aa
in 57% yield (Table 1, entry 1). Although the reaction
with such a bidentate phosphine ligand as Xantphos or
rac-BINAP proceeded in similar yield (Table 1, entries 2
and 3), the use of copper–N-heterocyclic carbene (Cu–
b See also Figure 1.
c Determined by 1H NMR.
d A copper(I) complex is produced in situ.14
e KOAc instead of KOt-Bu.
f K2CO3 instead of KOt-Bu.
i-Pr
i-Pr
N
N
N
N
N
N
Mes
Mes Mes
Mes
Cu
Cl
Cu
Cl
Cu
Cl
i-Pr
i-Pr
IMesCuCl
SIMesCuCl
IPrCuCl
Figure 1 NHC ligands utilized
SYNTHESIS 2014, 46, 1924–1932
Advanced online publication: 14.05.2014
DOI: 10.1055/s-0033-1341267; Art ID: ss-2014-c0143-st
© Georg Thieme Verlag Stuttgart · New York
The optimized reaction was then examined using a range
of monosubstituted alkenes (Table 2). The carboboration
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

SPECIAL TOPIC
Three-Component Carboboration of Alkenes
1925
of styrene derivatives bearing an electron-donating 1b or dihydronaphthalene (1o) regio- and stereoselectively af-
electron-withdrawing substituent 1c also proceeded with fording syn-adduct 4oa in 75% yield (Table 3, entry 6).
high regioselectivity to afford the respective products, al-
The versatility of the carboboration was further expanded
though the yields were lower (Table 2, entries 2 and 3).15
by employing various carbon electrophiles (Table 4). The
The reaction was applied to 2-vinylpyridine (1d), vinylbo-
reaction of para- or ortho-substituted benzyl chlorides
rane 1e, and vinylsilanes 1f and 1g and gave borylalkanes
3b–g with vinylsilane 1f and diboron 2 furnished high
4da–ga in good to high yields, in which the benzyl moiety
yields of the respective products (Table 4, entries 1–6), ir-
was attached to the internal carbon of the alkene (Table 2,
respective of the electronic character of the substituents,
entries 4–7). In marked contrast, aliphatic alkenes, such as
and sterically congested 2,4,6-triisopropylbenzyl chloride
oct-1-ene (1h) or vinylcyclohexane (1i), underwent the re-
(3h), 2,4,6-trimethylbenzyl chloride (3i), and 1-naphthyl-
action with the inverse regioselectivity to furnish 4h′ and
methyl chloride (3j) could also act as a carbon electro-
4i′ as the major products with the benzyl moiety at the ter-
phile (Table 4, entries 7–9). In addition to benzyl
chlorides, the present reaction was applied to butyl bro-
minal carbon of the alkene (Table 2, entries 8 and 9).
mide (3k) and methyl iodide (3l) to provide the alkylbora-
Table 2 Copper-Catalyzed Carboboration of Monosubstituted Al-
tion products in 70% and 50% yield, respectively (Table
4, entries 10 and 11). The sole formation of the cyclopro-
pylmethylated product 4fm in the reaction with 3m sug-
gested that a radical pathway is not operating in the
carboboration (Table 4, entry 12),17 and moreover che-
moselective reaction with 1,5-dibromopentane (3n) or
ethyl 4-bromobutanoate (3o) occurred, leaving the reac-
tive functional groups (C–Br and ester moieties) intact
(Table 4, entries 13 and 14).
kenesa
+
(pin)B B(pin)
+
Bn Cl
R
1
2
3a
(1 equiv)
(1.3 equiv)
(3 equiv)
SIMesCuCl (2 mol%)
Bn
B(pin) Bn
B(pin)
R
KOt-Bu (1.5 equiv)
DMF, r.t
R
4
4′
As was the case with the previous copper-catalyzed car-
boboration of alkynes,11 a β-borylalkylcopper species 6,
generated by the addition of a borylcopper species 5 to an
alkene,4h,12b,18 should also serve as a key intermediate in
the present reaction (Scheme 1). Subsequent reaction of 6
with potassium tert-butoxide produces cuprate 7, which is
then captured by a carbon electrophile to provide a car-
boboration product and copper(I) tert-butoxide.19 The ob-
served regioselectivity in the reaction of aryl-, boryl-, and
silylalkenes should be ascribed to the selective formation
of the carbon–copper bond at the α position of these sub-
stituents in the borylcupration 5 to 6, induced by the elec-
tronic-directing effect of the substituents.
Entry Alkene
R
Time Product
(h)
Yieldb Ratioc
(%)
(4/4′)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
Ph
1
1
1
1
7
8
1
1
1
4aa
65
>99:1
88:12
>99:1
91:9
4-MeOC6H4
4-ClC6H4
2-pyridyl
B(pin)
4ba, 4ba′ 47
4ca 12
4da, 4da′ 52
4ea, 4ea′
4fa, 4fa′
68
85
98:2
SiMe2Ph
TMS
94:6
1g
1h
1i
4ga, 4ga′ 82
4ha, 4ha′ 45
93:7
(CH2)5Me
Cy
2:98
R1
R2
(pin)B Ot-Bu
4ia, 4ia′
38
17:83
(pin)B CuL
a Reaction conditions: alkene (0.30 mmol), (pin)B–B(pin) (0.39
mmol), BnCl (0.90 mmol), KOt-Bu (0.45 mmol), SIMesCuCl (6.0
μmol), DMF (0.55 mL).
5
(pin)B B(pin)
b Yield of isolated 4 and 4′.
KOt-Bu
(pin)B
R1
CuL
c Determined by 1H NMR.
LCuCl
(pin)B
LCuOt-Bu
R2
[L: SIMes]
6
KCl
As shown in Table 3, disubstituted alkenes could also par-
ticipate in the carboboration; perfect regioselectivity was
observed in the reaction of 1,1-disubstituted alkenes 1j–l
(Table 3, entries 1–3), but a mixture of stereoisomers16
was formed with 1,2-disubstituted alkenes cis-stilbene
(1m) or norbornene (1n) (Table 3, entries 4 and 5). How-
ever, boryl and benzyl moieties were introduced into 1,2-
KOt-Bu
C
(pin)B
R1
CuL(Ot-Bu)
KX +
R1
R2
K
C
X
R2
4
7
Scheme 1 A plausible catalytic cycle for carboboration
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1924–1932

1926
I. Kageyuki et al.
SPECIAL TOPIC
Table 3 Copper-Catalyzed Carboboration of Disubstituted Alkenesa
SIMesCuCl (2 mol%)
KOt-Bu (1.5 equiv)
1
+
(pin)B B(pin)
+
Bn Cl
3a
4 + 4′
DMF, r.t
2
(1 equiv)
Entry
1
(3 equiv)
(1.3 equiv)
Alkene
Time (h)
Product
Yieldb (%)
Ratioc (4/4′)
1j
1
4ja
34
>99:1
Bn
Bn
(pin)B
(pin)B
Ph
Ph
2
3
4
5
1k
1l
1
4ka
40
35
40
60
>99:1
>99:1
77:23d
62:38d
CO2Me
CO2Me
Ph
Bn
0.5
4
4la
Ph
Ph
(pin)B
Ph
Ph
(pin)B
Ph
Bn
1m
1n
4ma, 4ma′
4na, 4na′
Ph
Ph
0.5
B(pin)
Bn
Bn
6
1o
0.5
4oa
75
>99:1d
B(pin)
a Reaction conditions: alkene (0.30 mmol), (pin)B–B(pin) (0.39 mmol), BnCl (0.90 mmol), KOt-Bu (0.45 mmol), SIMesCuCl (6.0 μmol), DMF
(0.55 mL).
b Yield of isolated 4 and 4′.
c Determined by 1H NMR.
d Ratio of stereoisomers.
Table 4 Copper-Catalyzed Carboboration with Various Carbon Electrophilesa
SIMesCuCl (2 mol%)
C
B(pin)
C
B(pin)
KOt-Bu (1.5 equiv)
+
C–X
R
B(nip) B(pin)
+
PhMe2Si
1f
(1 equiv)
C
X
+
PhMe2Si
SiMe2Ph
DMF, r.t
2
3
4
4′
(1.3 equiv)
(3 equiv)
Entry
R
3
Time (h)
Product
Yieldb (%)
Ratioc (4/4′)c
1
2
3
4
i-Pr
Me
Cl
3b
3c
3d
3e
4
3
3
3
4fb, 4fb′
4fc, 4fc′
4fd, 4fd′
4fe, 4fe′
90
88
85
90
92:8
95:5
95:5
97:3
Cl
OMe
Cl
R
3f
5
6
Me
Cl
4
4
4ff, 4ff′
4fg, 4fg′
90
73
96:4
98:2
3g
R
3h
3i
7
8
i-Pr
Me
2
2
4fh, 4fh′
4fi, 4fi′
46
58
88:12
91:9
Cl
R
R
Synthesis 2014, 46, 1924–1932
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Three-Component Carboboration of Alkenes
1927
Table 4 Copper-Catalyzed Carboboration with Various Carbon Electrophilesa (continued)
SIMesCuCl (2 mol%)
C
B(pin)
C
B(pin)
KOt-Bu (1.5 equiv)
+
B(nip) B(pin)
+
PhMe2Si
1f
(1 equiv)
C
X
+
PhMe2Si
SiMe2Ph
DMF, r.t
2
3
4
4′
(1.3 equiv)
(3 equiv)
Entry
C–X
R
3
Time (h)
7
Product
Yieldb (%)
Ratioc (4/4′)c
Cl
9
3j
4fj, 4fj′
72
97:3
10
11
BuBr
MeI
3k
3l
10
3
4fk, 4fk′
70
50
97:3
4fl
>99:1
Br
12
3m
7
4fm
85
>99:1
Br
Br
13
14
3n
3o
7
7
4fn, 4fn′
4fo, 4fo′
70
37
98:2
96:4
EtO2C
Br
a Reaction conditions: dimethyl(phenyl)vinylsilane (0.30 mmol), (pin)B–B(pin) (0.39 mmol), carbon electrophile (0.90 mmol), KOt-Bu (0.45
mmol), SIMesCuCl (6.0 μmol), DMF (0.55 mL).
b Yield of isolated 4 and 4′.
c Determined by 1H NMR.
Finally, the synthetic utility of the carboboration product
Br
was demonstrated by the formal total synthesis (Scheme
2) of equol, which has potential anti-osteoporosis and
Br
(pin)B B(pin)
+
+
anti-breast cancer activity with its estrogen-like ef-
fects.20,21 Thus, the carboboration using 4-methoxystyrene
(1b), diboron 2, and 2-bromo-4-methoxybenzyl bromide
(3p) afforded the borylalkane 4bp, in which the C–B bond
was readily converted into a C–OH bond by oxidation
with hydrogen peroxide. The resulting alcohol 8 has pre-
viously been transformed into equol (9) by a palladium-
catalyzed intramolecular C–O bond-forming reaction and
demethylation of the methoxy moieties.21a
MeO
MeO
Br
1b
2
3p
Br
OMe
OMe
OMe
b)
a)
(pin)B
HO
84%
32%
OMe
8
4bp
In conclusion, we have demonstrated that the three-
component carboboration of alkenes with a diboron com-
pound and carbon electrophiles proceeds efficiently with
the aid of a catalytic amount of a Cu–NHC complex in a
straightforward approach to diverse multisubstituted bor-
ylalkanes. Moreover, the synthetic utility of the carbobo-
ration is shown by the formal total synthesis of
biologically significant equol. Further studies on catalytic
three-component borylation reactions using other electro-
philes are in progress.
O
OH
ref. 18a
HO
equol (9)
Scheme 2 Formal total synthesis of equol. Reagents and conditions:
(a) 4-methoxystyrene (1 equiv), 2 (1.3 equiv), 2-bromo-4-methoxy-
benzyl bromide (3 equiv), KOt-Bu (1.5 equiv), SIMesCuCl (2 mol%),
DMF, r.t., 13 h; (b) 32 wt% H2O2 (5 equiv), NaOH (5 equiv), THF,
0 °C, 0.5 h.
All manipulations of O2- and moisture-sensitive materials were
conducted with standard Schlenk techniques under a purified argon
atmosphere. NMR spectra were taken on a Varian 400-MR (1H, 400
MHz; 13C, 100 MHz) spectrometer or a Varian System 500 (1H, 500
MHz; 13C, 125 MHz) spectrometer using residual CHCl3 (1H,
δ = 7.26 ppm) or CDCl3 (13C, δ = 77.0 ppm) as an internal standard.
HRMS were obtained with a Thermo Fisher Scientific LTQ Orbi-
trap XL. Preparative recycling gel permeation chromatography was
performed with Jai LC-908 or Jai LC-9201 equipped with Jai GEL-
1H and 2H columns (CHCl3). Column chromatography was carried
out using Merck Kieselgel 60. Unless otherwise noted, commercial-
ly available reagents were used without purification. DMF was dis-
tilled from CaH2. 2-Bromo-4-methoxybenzyl bromide (3p) was
prepared according to a literature procedure.21a IPrCuCl, IMesCuCl,
and SIMesCuCl were prepared according to literature procedures.22
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1924–1932

1928
I. Kageyuki et al.
SPECIAL TOPIC
Copper-Catalyzed Carboboration of Alkenes; General Proce-
dure
2,2′-(3-Phenylpropane-1,2-diyl)bis(4,4,5,5-tetramethyl-1,3,2-
dioxaborolane) (4ea)
A Schlenk tube equipped with a magnetic stirring bar was charged
with SIMesCuCl (6.0 μmol), alkene 0.30 mmol), bis(pinacolato)di-
boron (0.39 mmol), a carbon electrophile (0.90 mmol), 1 M KOt-Bu
in THF (0.45 mmol), and DMF (0.55 mL). The mixture was stirred
at r.t. for the period specified in Tables 2–4, and diluted with EtOAc
before filtration through a Celite plug. The organic solution was
washed with brine (2 ×) and dried (MgSO4). Evaporation of the sol-
vent followed by column chromatography (silica gel, hexane–
EtOAc or hexane–CH2Cl2) or gel-permeation chromatography
(CHCl3) gave the product.
Pale yellow oil; yield: 75.9 mg (0.204 mmol, 68%).
1H NMR (CDCl3): δ = 0.82 (d, J = 7.9, 2 H), 1.16 (s, 6 H), 1.19 (s,
6 H), 1.22 (s, 12 H), 1.46 (m, J = 7.9 Hz, 1 H), 2.60 (dd, J = 13.4,
8.5 Hz, 1 H), 2.79 (dd, J = 13.7, 7.4 Hz, 1 H), 7.13 (t, J = 7.0 Hz, 1
H), 7.18–7.24 (m, 4 H).
13C NMR (CDCl3): δ = 24.74, 24.77, 24.82, 24.89, 39.48, 82.86,
82.93, 125.45, 127.91, 129.09, 142.31.
HRMS: m/z [M + Na]+ calcd for C21H34O4B2Na: 395.25354; found:
395.25458.
In the 13C NMR spectra, boron-bound carbons were not detected be-
cause of quadrupolar relaxation.
Dimethyl(phenyl)[1-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxa-
borolan-2-yl)propan-2-yl]silane (4fa)
Pale yellow oil; yield: 97.0 mg (0.255 mmol, 85%).
2-(2,3-Diphenylpropyl)-4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lane (4aa)
Pale yellow oil; yield: 62.8 mg (0.195 mmol, 65%).
1H NMR (CDCl3): δ = 1.06 (s, 6 H), 1.08 (s, 6 H), 1.15–1.25 (m, 2
H), 2.84–2.93 (m, 2 H), 3.11–3.18 (m, 1 H), 7.05 (d, J = 7.0 Hz, 2
H), 7.12–7.24 (m, 8 H).
1H NMR (CDCl3): δ = 0.23 (s, 3 H), 0.23 (s, 3 H), 0.75 (dd, J = 16.3,
7.4 Hz, 1 H), 0.89 (dd, J = 16.2, 6.4 Hz, 1H), 1.14 (s, 6 H), 1.16 (s,
6 H), 1.52–1.57 (m, 1 H), 2.49 (dd, J = 13.8, 9.8 Hz, 1 H), 2.76 (dd,
J = 13.9, 5.7 Hz, 1 H), 7.12–7.16 (m, 3 H), 7.21–7.24 (m, 2 H),
7.33–7.35 (m, 3 H), 7.52–7.54 (m, 2 H).
13C NMR (CDCl3): δ = –4.27, –4.21, 22.10, 24.79, 24.96, 38.45,
82.79, 82.87, 125.53, 127.57, 127.98, 128.68, 129.10, 134.10,
138.60, 142.42.
HRMS: m/z [M + Na]+ calcd for C23H33O2BNaSi: 403.22351;
found: 403.22391.
13C NMR (CDCl3): δ = 24.53, 24.65, 43.57, 46.17, 82.89, 125.68,
125.84, 127.50, 127.90, 127.94, 129.31, 140.69, 146.41.
HRMS: m/z [M + Na]+ calcd for C21H27O2BNa: 345.19963; found:
345.19992.
2-[2-(4-Methoxyphenyl)-3-phenylpropyl]-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (4ba)
Trimethyl[1-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)propan-2-yl]silane (4ga)
Pale yellow oil; yield: 49.7 mg (0.141 mmol, 47%).
Pale yellow oil; yield: 78.3 mg (0.246 mmol, 82%).
1H NMR (CDCl3): δ = 106 (s, 6 H), 1.07 (s, 6 H), 1.24–1.37 (m, 2
H), 2.83 (d, J = 7.4 Hz, 2 H), 3.04–3.12 (m, 1 H), 3.76 (s, 3 H), 6.76
(d, J = 8.5 Hz, 2 H), 7.02 (d, J = 7.7 Hz, 2 H), 7.06 (d, J = 8.5 Hz, 2
H), 7.13 (t, J = 7.1 Hz, 1 H), 7.19 (t, J = 7.5 Hz, 2 H).
13C NMR (CDCl3): δ = 24.57, 24.71, 42.74, 46.38, 55.20, 82.89,
113.28, 125.63, 128.36, 129.34, 138.60, 140.80, 157.66.
1H NMR (CDCl3): δ = –0.07 (s, 9 H), 0.73 (dd, J = 16.5, 4.5 Hz, 1
H), 0.83 (dd, J = 16.5, 6.6 Hz, 1 H), 1.18 (s, 6 H), 1.19 (s, 6 H),
1.24–1.27 (m, 1 H), 2.51 (dd, J = 14.0, 9.6 Hz, 1 H), 2.74 (dd,
J = 13.8, 6.2 Hz, 1 H), 7.15 (tt, J = 6.9, 1.3 Hz, 1 H), 7.19–7.27 (m,
4 H).
13C NMR (CDCl3): δ = –2.71, 22.68, 24.73, 24.84, 25.02, 38.67,
39.65, 82.86, 125.51, 128.01, 129.11, 142.72.
HRMS: m/z [M + Na]+ calcd for C22H29O3BNa: 357.21020; found:
375.21027.
HRMS: m/z [M + Na]+ calcd for C18H31O2BNaSi: 341.20786;
2-[2-(4-Chlorophenyl)-3-phenylpropyl]-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (4ca)
found: 341.20831.
Pale yellow oil; yield: 12.8 mg (0.036 mmol, 12%).
4,4,5,5-Tetramethyl-2-(1-phenylnonan-3-yl)-1,3,2-dioxaboro-
lane (4ha′)
Pale yellow oil; yield: 44.6 mg (0.135 mmol, 45%).
1H NMR (CDCl3): δ = 0.87 (t, J = 6.9 Hz, 3 H), 1.00–1.08 (m, 1 H),
1.23–1.31 (m, 20 H), 1.34–1.48 (m, 3 H), 1.59–1.68 (m, 1 H), 1.69–
1.79 (m, 1 H), 2.59 (dt, J = 10.1, 6.4 Hz, 2 H), 7.16 (tt, J = 7.1, 2.3
Hz, 1 H), 7.18 (d, J = 7.1 Hz, 2 H), 7.26 (t, J = 7.3 Hz, 2 H).
13C NMR (CDCl3): δ = 14.11, 22.62, 24.80, 24.86, 29.15, 29.59,
31.26, 31.82, 33.55, 35.68, 82.89, 125.50, 128.19, 128.38, 143.12.
HRMS: m/z [M + H]+ calcd for C21H36O2B: 331.28029; found:
331.28006.
1H NMR (CDCl3): δ = 1.06 (s, 6 H), 1.09 (s, 6 H), 1.13 (dd, J = 16.0,
9.5 Hz, 1 H), 1.21 (dd, J = 15.7, 6.5 Hz, 1 H), 2.81 (dd, J = 13.1, 8.1
Hz, 1 H), 2.86 (dd, J = 13.8, 7.4 Hz, 1 H), 3.11 (tdd, J = 7.7, 7.7, 7.7
Hz, 1 H), 6.99 (d, J = 7.7 Hz, 2 H), 7.05 (d, J = 8.0 Hz, 2 H), 7.12–
7.21 (m, 5 H).
13C NMR (CDCl3): δ = 24.56, 24.70, 43.03, 46.01, 83.03, 125.83,
127.99, 128.02, 128.90, 129.26, 131.38, 140.24, 144.85.
HRMS: m/z [M + Na]+ calcd for C21H26O2BClNa: 356.17144;
found: 356.17219.
2-[1-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)propan-2-yl]pyridine (4da)
2-(2-Cyclohexyl-3-phenylpropyl)-4,4,5,5-tetramethyl-1,3,2-di-
oxaborolane (4ia) and 2-(1-Cyclohexyl-3-phenylpropyl)-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane (4ia′)
Pale yellow oil; yield: 50.4 mg (0.156 mmol, 52%).
1H NMR (CDCl3): δ = 0.86–0.92(m, 1 H), 1.05–1.09 (m, 1 H), 1.16
(s, 6 H), 1.93 (s, 6 H), 2.83 (dd, J = 13.3, 8.2 Hz, 1 H), 3.14 (dd,
J = 13.5, 6.8 Hz, 1 H), 3.45 (m, J = 7.5 Hz, 1 H), 7.15–7.20 (m, 4
H), 7.22–7.26 (m, 3 H), 7.68 (ddd, J = 7.7, 7.7, 1.7 Hz, 1 H), 8.59
(ddd, J = 5.1, 1.4, 1.1 Hz, 1 H).
13C NMR (CDCl3): δ = 25.33, 25.59, 43.18, 44.47, 80.85, 121.99,
122.52, 125.91, 128.15, 129.20, 138.42, 140.36, 144.78, 165.51.
Pale yellow oil; yield: 37.4 mg (0.114 mmol, 38%).
1H NMR (CDCl3): δ = 0.69 (dd, J = 15.5, 7.7 Hz, 0.2 H), 0.78 (dd,
J = 15.6, 6.5 Hz, 0.2 H), 0.91–1.24 (m, 10.4 H), 1.28 (s, 12 H), 1.37–
1.45 (m, 1.3 H), 1.62–1.64 (m, 8.3 H), 1.67–1.71 (m, 4.1 H), 1.72–
1.78 (m, 2.6 H), 1.81–1.86 (m, 0.3 H), 2.42 (dd, J = 13.2, 8.3 Hz,
0.2 H), 2.49 (ddd, J = 13.4, 10.7, 6.1 Hz, 1 H), 2.63 (ddd, J = 13.7,
11.1, 5.2 Hz, 1 H), 2.68 (dd, J = 13.4, 6.6 Hz, 0.2 H), 7.16 (tt, J =
7.5, 1.3 Hz, 1.1 H), 7.18 (d, J = 7.1 Hz, 2.5 H), 7.26 (t, J = 7.6 Hz,
2.1 H).
HRMS: m/z [M + H]+ calcd for C20H27O2NB: 324.21294; found:
324.21558.
13C NMR (CDCl3): δ = 24.79, 24.83, 24.86, 25.10, 26.74, 26.77,
26.78, 26.85, 28.92, 30.33, 31.05, 32.42, 32.80, 36.06, 39.66, 39.92,
Synthesis 2014, 46, 1924–1932
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Three-Component Carboboration of Alkenes
1929
41.46, 41.89, 82.79, 82.91, 125.40, 125.49, 128.02, 128.18, 128.34,
129.33, 142.24, 143.19.
HRMS: m/z [M + H]+ calcd for C21H34O2B: 329.26464; found:
1H NMR (CDCl3): δ = 1.02–1.09 (m, 2 H), 1.10 (s, 4.2 H), 1.10 (s,
4.2 H), 1.14–1.20 (m, 1.9 H), 1.23 (s, 6 H), 1.24 (s, 6 H), 1.33–1.57
(m, 5 H), 1.68 (d, J = 9.5 Hz, 1.7 H), 1.92 (d, J = 3.9 Hz, 1 H), 2.01
(ddd, J = 12.6, 9.1, 3.4 Hz, 1 H), 2.08 (t, J = 2.08 Hz, 0.7 H), 2.16–
2.21 (m, 1.3 H), 2.27 (d, J = 2.9 Hz, 1 H), 2.33 (dd, J = 13.7, 11.6
Hz, 1 H), 2.58 (dd, J = 13.2, 7.9 Hz, 0.7 H), 2.65 (dd, J = 13.4, 7.3
Hz, 0.7 H), 2.77 (dd, J = 13.5, 4.5 Hz, 1 H), 7.13 (t, J = 7.1 Hz, 1
H), 7.17 (d, J = 7.2 Hz, 3.6 H), 7.23 (t, J = 7.5 Hz, 1.4 H), 7.27 (t,
J = 7.3 Hz, 2 H).
13C NMR (CDCl3): δ = 22.14, 24.54, 24.58, 24.84, 25.01, 29.91,
31.55, 32.93, 34.89, 38.84, 39.11, 39.38, 39.70, 40.31, 40.66, 45.32,
46.75, 82.63, 82.87, 125.36, 125.49, 128.07, 128.09, 128.86,
129.01, 142.40, 142.55.
329.26447.
4,4,5,5-Tetramethyl-2-(2-methyl-2,3-diphenylpropyl)-1,3,2-di-
oxaborolane (4ja)
Pale yellow oil; yield: 34.3 mg (0.102 mmol, 34%).
1H NMR (CDCl3): δ = 1.12 (s, 6 H), 1.06 (s, 6 H), 1.11 (d, J = 15.4
Hz, 1 H), 1.42 (s, 3 H), 1.45 (d, J = 15.0 Hz, 1 H), 2.94 (q, J = 12.4
Hz, 2 H), 6.80 (dd, J = 6.3, 3.2 Hz, 2 H), 7.10–7.11 (m, 3 H), 7.14
(tt, J = 7.0, 1.5 Hz, 1 H), 7.23–7.29 (m, 4 H).
13C NMR (CDCl3): δ = 24.46, 24.70, 26.37, 40.38, 52.21, 82.67,
125.40, 125.72, 126.54, 127.30, 127.61, 130.60, 138.95, 148.84.
HRMS: m/z [M + H]+ calcd for C20H30O2B: 313.23334; found:
313.23334.
HRMS: m/z [M + Na]+ calcd for C22H29O2BNa: 359.21528; found:
359.21536.
2-(1-Benzyl-1,2,3,4-tetrahydronaphthalen-2-yl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (4oa)
Pale yellow solid; yield: 78.4 mg (0.225 mmol, 75%); mp 71.4–
73.5 °C.
Methyl 2-Benzyl-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxa-
borolan-2-yl)propanoate (4ka)
Pale yellow oil; yield: 38.2 mg (0.12 mmol, 40%).
1H NMR (CDCl3): δ = 1.31 (s, 12 H), 1.53 (m, J = 4.0 Hz, 1 H),
1.70–2.02 (m, 2 H), 2.68 (dd, J = 12.8, 10.1 Hz, 1 H), 2.83 (m,
J = 8.7 Hz, 1 H), 2.90 (t, J = 4.6 Hz, 1 H), 2.96 (dd, J = 12.9, 3.5 Hz,
1 H), 3.21 (dt, J = 10.2, 3.7 Hz, 1 H), 6.24 (d, J = 7.6 Hz, 1 H), 6.79
(td, J = 7.3, 1.1 Hz, 1 H), 7.03–7.08 (m, 4 H), 7.19 (t, J = 7.2, 1.8
Hz, 1 H), 7.24 (t, J = 7.3 Hz, 2 H).
13C NMR (CDCl3): δ = 19.71, 24.80, 25.16, 29.02, 42.24, 42.33,
83.22, 124.07, 125.70, 127.93, 129.14, 129.17, 129.77, 135.94,
140.62, 141.46.
1H NMR (CDCl3): δ = 0.87 (d, J = 15.4 Hz, 1 H), 1.19 (d, J = 15.5
Hz, 1 H), 1.22 (s, 6 H), 1.23 (s, 6 H), 1.24 (s, 3 H), 2.91 (s, 2 H),
3.63 (s, 3 H), 7.11 (d, J = 7.6 Hz, 2 H), 7.19 (tt, J = 7.1, 2.0 Hz, 1
H), 7.22–7.25 (m, 2 H).
13C NMR (CDCl3): δ = 24.41, 24.72, 24.84, 45.26, 46.89, 51.51,
82.96, 126.30, 127.84, 130.34, 138.87, 178.04.
HRMS: m/z [M + Na]+ calcd for C18H27O4BNa: 341.18946; found:
341.19022.
HRMS: m/z [M + H]+ calcd for C23H30O2B: 349.23334; found:
349.23343.
4,4,5,5-Tetramethyl-2-(2,2,3-triphenylpropyl)-1,3,2-dioxaboro-
lane (4la)
Pale yellow solid; yield: 41.8 mg (0.105 mmol, 35%); mp 139.7–
141.0 °C.
1H NMR (CDCl3): δ = 1.02 (s, 12 H), 1.54 (s, 2 H), 3.63 (s, 2 H),
6.61 (dd, J = 7.9, 1.5 Hz, 2 H), 7.04 (tt, J = 7.2, 1.3 Hz, 2 H), 7.09
(tt, J = 7.2, 1.7 Hz, 1 H), 7.13–7.16 (m, 6 H), 7.21 (t, J = 7.4 Hz, 4
H).
13C NMR (CDCl3): δ = 24.64, 45.13, 48.37, 82.76, 125.49, 125.67,
127.04, 127.51, 128.08, 131.03, 138.65, 149.89.
HRMS: m/z [M + Na]+ calcd for C27H31O2BNa: 421.23093; found:
421.23099.
[1-(4-Isopropylphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)propan-2-yl]dimethyl(phenyl)silane (4fb)
Pale yellow oil; yield: 114.1 mg (0.27 mmol, 90%).
1H NMR (CDCl3): δ = 0.22 (s, 3 H), 0.22 (s, 3 H), 0.73 (dd, J = 16.2,
7.7 Hz, 1 H), 0.89 (dd, J = 16.3, 5.7 Hz, 1 H), 1.12 (s, 6 H), 1.13 (s,
6 H), 1.22 (d, J = 6.8 Hz, 6 H), 1.50–1.56 (m, 1 H), 2.44 (dd,
J = 13.8, 9.9 Hz, 1 H), 2.73 (dd, J = 14.2, 5.8, 1 H), 2.84 (m, J = 6.9
Hz, 1 H), 7.07 (s, 4 H), 7.31–7.33 (m, 3 H), 7.44–7.52 (m, 2 H).
13C NMR (CDCl3): δ = –4.38, –4.26, 21.97, 24.07, 24.79, 24.94,
33.65, 36.45, 38.02, 82.82, 125.99, 127.51, 128.61, 128.96, 134.08,
138.68, 139.61, 145.97.
4,4,5,5-Tetramethyl-2-(1,2,3-triphenylpropyl)-1,3,2-dioxaboro-
lane (4ma, 4ma′)
Pale yellow solid; yield: 47.8 mg (0.12 mmol, 40%); mp 74.4–
76.5 °C.
HRMS: m/z [M + Na]+ calcd for C26H39O2BNaSi: 445.27046;
found: 445.27017.
Dimethyl(phenyl)[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)-3-(4-tolyl)propan-2-yl]silane (4fc)
Pale yellow oil; yield: 104.1 mg (0.264 mmol, 88%).
1H NMR (CDCl3): δ = 0.83 (s, 6 H), 0.84 (s, 6 H), 1.25 (s, 1.3 H),
1.28 (s, 1.3 H), 2.50 (dd, J = 13.4, 11.2 Hz, 1 H), 2.78 (d, J = 12.1
Hz, 1 H), 2.82 (d, J = 12.7 Hz, 0.3 H), 2.87 (dd, J = 13.4, 11.3 Hz,
0.3 H), 2.89 (dd, J = 13.3, 3.2 Hz, 1 H), 3.16 (dd, J = 13.1, 3.1 Hz,
0.3 H), 3.32 (td, J = 11.4, 3.0 Hz, 1 H), 3.44 (td, J = 11.3, 3.4 Hz,
0.4 H), 6.68 (dd, J = 7.4, 1.6 Hz, 2 H), 6.82 (dd, J = 7.9, 1.4 Hz, 0.6
H), 6.91–7.11 (m, 10.3 H), 7.17 (t, J = 8.0 Hz, 2.1 H), 7.22 (tt, J =
7.2, 1.0 Hz, 1.3 H), 7.36 (tt, J = 7.7, 1.1 Hz, 2.2 H), 7.45 (dd, J = 8.2,
0.9 Hz, 2.2 H).
13C NMR (CDCl3): δ = 23.99, 24.31, 24.60, 24.75, 41.82, 43.85,
50.64, 50.71, 83.06, 83.57, 124.99, 125.32, 125.49, 125.60, 125.64,
126.05, 127.45, 127.57, 127.76, 127.80, 128.34, 128.49, 128.65,
129.06, 129.11, 129.19, 129.27, 140.50, 140.57, 141.22, 144.04.
1H NMR (CDCl3): δ = 0.22 (s, 3 H), 0.22 (s, 3 H), 0.73 (dd, J = 16.0,
7.3 Hz, 1 H), 0.86 (dd, J = 16.0, 6.4 Hz, 1 H), 1.13 (s, 6 H), 1.15 (s,
6 H), 1.48–1.54 (m, 1 H), 2.29 (s, 3 H), 2.44 (dd, J = 13.8, 9.8 Hz,
1 H), 2.71 (dd, J = 14.1, 6.1 Hz, 1 H), 7.23 (s, 4 H), 7.32–7.34 (m,
3 H), 7.51–7.52 (m, 2 H).
13C NMR (CDCl3): δ = –4.24, –4.18, 20.98, 22.09, 24.79, 24.96,
37.97, 82.85, 127.54, 128.63, 128.67, 128.96, 134.12, 134.86,
138.69, 139.22.
HRMS: m/z [M + Na]+ calcd for C24H35O2BNaSi: 417.23916;
found: 417.23886.
HRMS: m/z [M + H]+ calcd for C27H32O2B: 399.24899; found:
399.24899.
[1-(4-Chlorophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)propan-2-yl]dimethyl(phenyl)silane (4fd)
Pale yellow oil; yield: 105.8 mg (0.255 mmol, 85%).
2-(3-Benzylbicyclo[2.2.1]heptan-2-yl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (4na, 4na′)
Pale yellow solid; yield: 56.2 mg (0.18 mmol, 60%); mp 78.7–
79.7 °C.
1H NMR (CDCl3): δ = 0.23 (s, 3 H), 0.24 (s, 3 H), 0.70 (dd, J = 16.4,
7.2 Hz, 1 H), 0.87 (dd, J = 16.4, 6.0 Hz, 1 H), 1.14 (s, 6 H), 1.15 (s,
6 H), 1.44–1.50 (m, 1 H), 2.42 (dd, J = 13.8, 10.1 Hz, 1 H), 2.70 (dd,
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1924–1932

1930
I. Kageyuki et al.
SPECIAL TOPIC
J = 14.0, 5.6 Hz, 1 H), 7.05 (d, J = 8.4 Hz, 2 H), 7.16 (d, J = 8.3 Hz,
2 H), 7.33–7.34 (m, 3 H), 7.49–7.51 (m, 2 H).
13C NMR (CDCl3): δ = –4.49, –4.08, 22.16, 24.80, 24.94, 37.80,
82.95, 127.62, 128.03, 128.76, 130.42, 131.19, 134.04, 138.32,
140.89.
HRMS: m/z [M + Na]+ calcd for C23H32O2BClNaSi: 437.18454;
found: 437.18442.
13C NMR (CDCl3): δ = –5.08, –4.27, –4.15, –4.01, 21.70, 22.31,
23.76, 24.04, 24.07, 24.41, 24.55, 24.62, 24.83, 24.96, 25.12, 28.39,
28.70, 29.06, 33.90, 37.55, 82.69, 82.77, 113.39, 120.64, 120.71,
127.55, 128.64, 128.73, 129.94, 132.92, 133.66, 134.07, 138.86,
145.67, 146.42, 147.32.
HRMS: m/z [M + Na]+ calcd for C32H51O2BNaSi: 529.36436;
found: 529.36395.
[1-Mesityl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pro-
pan-2-yl]dimethyl(phenyl)silane (4fi) and [3-Mesityl-1-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]dimethyl(phe-
nyl)silane (4fi′)
[1-(4-Methoxyphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)propan-2-yl]dimethyl(phenyl)silane (4fe)
Pale yellow oil; yield: 110.8 mg (0.27 mmol, 90%).
1H NMR (CDCl3): δ = 0.21 (s, 3 H), 0.21 (s, 3 H), 0.73 (dd, J = 16.2,
7.4 Hz, 1 H), 0.86 (dd, J = 16.4, 6.2 Hz, 1 H), 1.14 (s, 6 H), 1.15 (s,
6 H), 1.45–1.51 (m, 1 H), 2.42 (dd, J = 13.8, 9.7 Hz, 1 H), 2.69 (dd,
J = 13.8, 5.7 Hz, 1 H), 3.77 (s, 3 H), 6.76 (d, 8.6 Hz, 2 H), 7.05 (d,
J = 8.6 Hz, 2 H), 7.32–7.34 (m, 3 H), 7.50–7.52 (m, 2 H).
13C NMR (CDCl3): δ = –4.28, –4.15, 22.31, 24.80, 24.98, 37.55,
55.20, 82.86, 113.44, 127.54, 128.63, 129.93, 134.10, 134.43,
138.68, 157.60.
Pale yellow oil; yield: 73.5 mg (0.174 mmol, 58%).
1H NMR (CDCl3): δ = 0.30 (s, 0.2 H), 0.31 (s, 0.2 H), 0.33 (s, 3 H),
0.34 (s, 3 H), 0.68 (dd, J = 16.6, 6.9 Hz, 1 H), 0.81 (dd, J = 16.2, 7.5
Hz, 1 H), 1.05 (s, 6 H), 1.06 (s, 6 H), 1.54–1.60 (m, 1 H), 2.16 (s, 6
H), 2.18 (s, 0.5 H), 2.20 (s, 3 H), 2.22 (s, 0.2 H), 2.51 (dd, J = 14.0,
12.4 Hz, 1 H), 2.63 (dd, J = 14.2, 4.6 Hz, 1 H), 6.74 (s, 2 H), 6.78
(s, 0.2 H), 7.30–7.32 (m, 0.3 H), 7.32–7.35 (m, 3 H), 7.50–7.52 (m,
0.2 H), 7.56–7.58 (m, 2 H).
HRMS: m/z [M + Na]+ calcd for C24H35O3BNaSi: 433.23407;
found: 433.23407.
13C NMR (CDCl3): δ = –4.69, –4.08, 19.53, 19.57, 20.44, 20.71,
24.78, 24.87, 24.91, 30.84, 82.71, 127.54, 128.63, 128.70, 128.84,
133.72, 134.12, 134.47, 135.52, 136.95, 138.71.
HRMS: m/z [M + Na]+ calcd for C26H39O2BNaSi: 445.27046;
found: 445.27042.
Dimethyl(phenyl)[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)-3-(2-tolyl)propan-2-yl]silane (4ff)
Pale yellow oil; yield: 106.5 mg (0.27 mmol, 90%).
1H NMR (CDCl3): δ = 0.26 (s, 3 H), 0.28 (s, 3 H), 0.75 (dd, J = 16.4,
6.8, Hz, 1 H), 0.88 (dd, J = 16.6, 6.4 Hz, 1 H), 1.10 (s, 6 H), 1.12 (s,
6 H), 1.51–1.56 (m, 1 H), 2.20 (s, 3 H), 2.43 (dd, J = 13.9, 10.7 Hz,
1 H), 2.76 (dd, J = 13.9, 5.0 Hz, 1 H), 7.05–7.06 (m, 3 H), 7.08–7.10
(m, 1 H), 7.33–7.34 (m, 3 H), 7.54–7.55 (m, 2 H).
13C NMR (CDCl3): δ = –4.44, –4.25, 19.42, 20.10, 24.75, 24.83,
24.93, 35.78, 82.82, 125.37, 125.64, 127.56, 128.71, 129.87,
130.10, 134.10, 136.56, 138.63, 140.22.
Dimethyl[1-(naphthalen-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-di-
oxaborolan-2-yl)propan-2-yl](phenyl)silane (4fj)
Pale yellow solid; yield: 93.0 mg (0.216 mmol, 72%); mp 87.9–
89.2 °C.
1H NMR (CDCl3): δ = 0.25 (s, 3 H), 0.26 (s, 3 H), 0.82 (dd, J = 16.7,
7.4 Hz, 1 H), 0.94 (dd, J = 16.5, 6.1 Hz, 1 H), 1.06 (s, 6 H), 1.12 (s,
6 H), 1.68–1.74 (m, 1 H), 2.90 (dd, J = 26.5, 16.1 Hz, 1 H), 3.20 (dd,
J = 14.0, 5.7 Hz, 1 H), 7.24 (d, J = 7.3 Hz, 1 H), 7.30 (t, J = 7.7 Hz,
1 H), 7.33–7.36 (m, 3 H), 7.37–7.43 (m, 2 H), 7.55 (dd, J = 7.1, 2.6
Hz, 2 H), 7.64 (d, J = 8.6 Hz, 1 H), 7.78 (d, J = 8.3 Hz, 1 H), 7.91
(d, J = 8.3 Hz, 1 H).
HRMS: m/z [M + Na]+ calcd for C24H35O2BNaSi: 417.23916;
found: 417.23914.
13C NMR (CDCl3): δ = –4.47, –4.17, 21.49, 24.82, 24.89, 35.97,
82.85, 124.41, 125.12, 125.14, 125.32, 126.48, 127.00, 127.59,
128.50, 128.76, 132.32, 133.95, 134.14, 138.22, 138.65.
[1-(2-Chlorophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)propan-2-yl]dimethyl(phenyl)silane (4fg)
Pale yellow oil; yield: 90.9 mg (0.219 mmol, 73%).
1H NMR (CDCl3): δ = 0.28 (s, 3 H), 0.30 (s, 3 H), 0.73 (dd, J = 16.4,
6.8 Hz, 1 H), 0.88 (dd, J = 16.6, 6.5 Hz, 1 H), 1.11 (s, 6 H), 1.13 (s,
6 H), 1.66 (tdd, J = 6.4, 4.7, 11.0 Hz, 1 H), 2.53 (dd, J = 13.8, 10.7
Hz, 1 H), 2.93 (dd, J = 13.9, 5.0 Hz, 1 H), 7.07 (td, J = 7.4, 1.9 Hz,
1 H), 7.10 (td, J = 7.3, 1.6 Hz, 1 H), 7.18 (dd, J = 7.4, 1.9 Hz, 1 H),
7.26 (dd, 7.6, 1.6 Hz, 1 H), 7.32–7.34 (m, 3 H), 7.54–7.56 (m, 2 H).
HRMS: m/z [M + Na]+ calcd for C27H35O2BNaSi: 453.23916;
found: 453.23880.
Dimethyl(phenyl)[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)hexan-2-yl]silane (4fk)
Pale yellow oil; yield: 72.7 mg (0.21 mmol, 70%).
13C NMR (CDCl3): δ = –4.37, –4.27, 20.02, 24.82, 24.93, 35.95,
82.85, 126.19, 126.97, 127.54, 128.72, 129.39, 131.26, 134.13,
134.38, 138.43, 139.56.
HRMS: m/z [M + Na]+ calcd for C23H32O2BClNaSi: 437.18454;
found: 437.18430.
1H NMR (CDCl3): δ = 0.26 (s, 6 H), 0.69 (dd, J = 16.1, 8.7 Hz, 1 H),
0.82 (t, J = 7.0 Hz, 3 H), 0.89 (dd, J = 15.9, 5.4 Hz, 1 H), 1.07–1.13
(m, 1 H), 1.16–1.31 (m, 17 H), 1.43–1.48 (m, 1 H), 7.31–7.36 (m, 3
H), 7.51 (dd, J = 6.3, 2.9 Hz, 2 H).
13C NMR (CDCl3): δ = –4.42, –4.04, 14.02, 20.00, 22.98, 24.76,
24.97, 31.36, 32.15, 82.88, 127.49, 128.54, 134.05, 139.17.
HRMS: m/z [M + Na]+ calcd for C20H35O2BNaSi: 369.23916;
found: 369.23938.
Dimethyl(phenyl)[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)-3-(2,4,6-triisopropylphenyl)propan-2-yl]silane (4fh) and Di-
methyl(phenyl)[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)-3-(2,4,6-triisopropylphenyl)propyl]silane (4fh′)
Dimethyl(phenyl)[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)propan-2-yl]silane (4fl)
Pale yellow oil; yield: 45.6 mg (0.15 mmol, 50%).
1H NMR (CDCl3): δ = 0.24 (s, 6 H), 0.57 (dd, J = 15.8, 11.4 Hz, 1
H), 0.94 (dd, J = 15.8, 3.9 Hz, 1 H), 0.95 (d, J = 7.4 Hz, 3 H), 1.07–
1.16 (m, 1 H), 1.22 (s, 6 H), 1.23 (s, 6 H), 7.31–7.32 (m, 1 H), 7.33
(d, J = 2.6 Hz, 2 H), 7.50 (dd, J = 6.8, 2.8 Hz, 2 H).
13C NMR (CDCl3): δ = –5.45, –5.11, 14.60, 16.90, 24.68, 25.04,
82.94, 127.52, 128.66, 134.07, 138.48.
HRMS: m/z [M + Na]+ calcd for C17H29O2BNaSi: 327.19221;
Pale yellow oil; yield: 69.9 mg (0.138 mmol, 46%).
1H NMR (CDCl3): δ = 0.30 (s, 0.4 H), 0.32 (s, 0.4 H), 0.34 (s, 3 H),
0.35 (s, 3 H), 0.72 (dd, J = 16.7, 6.6 Hz, 1 H), 0.82 (dd, J = 16.7, 7.1
Hz, 1 H), 1.02 (s, 6 H), 1.07 (s, 6 H), 1.11 (d, J = 6.8 Hz, 12 H), 1.15
(d, J = 5.2 Hz, 2.2 H), 1.21 (d, J = 6.9 Hz, 6 H), 1.23–1.27 (m, 2.2
H), 1.42–1.49 (m, 1 H), 2.43 (dd, J = 13.8, 9.7 Hz, 0.4 H), 2.56 (dd,
J = 14.4, 12.1 Hz, 1 H), 2.65 (dd, J = 14.4, 4.4 Hz, 1 H), 2.81 (sept,
J = 6.9 Hz, 1.2 H), 2.98 (sept, J = 6.8 Hz, 2 H), 3.10 (sept, J = 6.9
Hz, 0.4 H), 6.88 (s, 2 H), 6.92 (s, 0.3 H), 7.31–7.34 (m, 0.7 H), 7.36–
7.38 (m, 3 H), 7.50–7.53 (m, 0.4 H), 7.58–7.60 (m, 2 H).
found: 327.19223.
Synthesis 2014, 46, 1924–1932
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Three-Component Carboboration of Alkenes
1931
[1-Cyclopropyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)propan-2-yl]dimethyl(phenyl)silane (4fm)
Pale yellow oil; yield: 87.8 mg (0.255 mmol, 85%).
13C NMR (CDCl3): δ = 38.12, 47.66, 55.21, 55.44, 66.21, 113.29,
114.03, 117.82, 124.70, 129.02, 131.15, 11.56, 133.50, 158.36,
158.44.
1H NMR (CDCl3): δ = –0.10 (m, J = 4.6 Hz, 1 H), –0.01 (m, 4.6 Hz,
1 H), 0.26 (s, 3 H), 0.27 (s, 3 H), 0.30–0.38 (m, 2 H), 0.59–0.67 (m,
1 H), 0.83 (dd, J = 16.2, 8.8 Hz, 1 H), 0.94 (dd, J = 16.1, 5.3 Hz, 1
H), 1.10–1.12 (m, 1 H), 1.21 (s, 6 H), 1.21 (s, 6 H), 1.26–1.31 (m, 1
H), 1.36 (td, J = 6.3, 13.2 Hz, 1 H), 7.31–7.33 (m, 3 H), 7.52 (dd,
J = 6.5, 2.9 Hz, 2 H).
HRMS: m/z [M + Na]+ calcd for C17H19O3BrNa: 373.04098; found:
373.04126.
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
13C NMR (CDCl3): δ = –4.41, –3.92, 4.83, 5.52, 10.69, 20.92, 24.78,
10.1055/s-00000084.SunogIpimrfiantoSuIpg
n
fonirtat
ori
25.01, 37.72, 82.86, 127.48, 128.54, 134.04, 139.15.
HRMS: m/z [M + Na]+ calcd for C20H33O2BNaSi: 367.22351;
found: 367.22372.
References
(1) Boronic Acids; Hall, D. G., Ed.; Wiley-VCH: Weinheim,
2011.
(2) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Miyaura, N. Top. Curr. Chem. 2002, 219, 11.
[7-Bromo-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hep-
tan-2-yl]dimethyl(phenyl)silane (4fn)
Pale yellow oil; yield: 92.3 mg (0.21 mmol, 70%).
1H NMR (CDCl3): δ = 0.26 (s, 6 H), 0.69 (dd, J = 16.2, 8.7 Hz, 1 H),
0.90 (dd, J = 16.1, 5.5 Hz, 1 H), 1.07–1.12 (m, 1 H), 1.16–1.26 (m,
14 H), 1.28–1.37 (m, 3 H), 1.41–1.47 (m, 1 H), 1.76 (m, J = 7.1 Hz,
2 H), 3.33 (t, J = 6.9 Hz, 2 H), 7.31–7.34 (m, 3 H), 7.51 (dd, J = 6.6,
2.7 Hz, 2 H).
(3) (a) Petasis, N. A.; Goodman, A.; Zavialov, I. A. Tetrahedron
1997, 53, 16463. (b) Koolmeister, T.; Södergren, M.;
Scobie, M. Tetrahedron Lett. 2002, 43, 5965.
(4) For examples, see: (a) Ito, H.; Yamanaka, H.; Tateiwa, J.;
Hosomi, A. Tetrahedron Lett. 2000, 41, 6821.
13C NMR (CDCl3): δ = –4.60, –3.96, 19.97, 24.77, 24.99, 28.13,
28.40, 32.25, 32.68, 33.99, 82.93, 127.54, 128.63, 134.00, 138.99.
HRMS: m/z [M + Na]+ calcd for C21H36O2BBrNaSi: 461.16532;
found: 461.16519.
(b) Takahashi, K.; Ishiyama, T.; Miyaura, N. J. Organomet.
Chem. 2001, 625, 47. (c) Ito, H.; Ito, S.; Sasaki, Y.;
Matsuura, K.; Sawamura, M. J. Am. Chem. Soc. 2007, 129,
14856. (d) Ito, H.; Sasaki, Y.; Sawamura, M. J. Am. Chem.
Soc. 2008, 130, 15774. (e) Lee, J.-E.; Yun, J. Angew. Chem.
Int. Ed. 2008, 47, 145. (f) Ito, H.; Kosaka, Y.; Nonoyama,
K.; Sasaki, Y.; Sawamura, M. Angew. Chem. Int. Ed. 2008,
47, 7424. (g) Lee, J.-E.; Kwon, J.; Yun, J. Chem. Commun.
2008, 733. (h) Lee, Y.; Hoveyda, A. H. J. Am. Chem. Soc.
2009, 131, 3160. (i) Lee, Y.; Jang, H.; Hoveyda, A. H. J. Am.
Chem. Soc. 2009, 131, 18234. (j) Lillo, V.; Prieto, A.; Bonet,
A.; Díaz-Requejo, M. M.; Ramírez, J.; Pérez, P. J.;
Fernández, E. Organometallics 2009, 28, 659. (k) Sasaki,
Y.; Zhong, C.; Sawamura, M.; Ito, H. J. Am. Chem. Soc.
2010, 132, 1226. (l) Ito, H.; Toyoda, T.; Sawamura, M.
J. Am. Chem. Soc. 2010, 132, 5990. (m) Zhong, C.; Kunii,
S.; Kosaka, Y.; Sawamura, M.; Ito, H. J. Am. Chem. Soc.
2010, 132, 11440. (n) Sasaki, Y.; Horita, Y.; Zhong, C.;
Sawamura, M.; Ito, H. Angew. Chem. Int. Ed. 2011, 50,
2778. (o) Jang, H.; Zhugralin, A. R.; Lee, Y.; Hoveyda, A.
H. J. Am. Chem. Soc. 2011, 133, 7859. (p) Kobayashi, S.;
Xu, P.; Endo, T.; Ueno, M.; Kitanosono, T. Angew. Chem.
Int. Ed. 2012, 51, 12763. (q) Semba, K.; Fujihara, T.; Terao,
J.; Tsuji, Y. Angew. Chem. Int. Ed. 2013, 52, 12400.
(r) Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc.
2013, 135, 2635. (s) Yun, J. Asian J. Org. Chem. 2013, 2,
1016.
Ethyl 5-(Dimethylphenylsilyl)-6-(4,4,5,5-tetramethyl-1,3,2-di-
oxaborolan-2-yl)hexanoate (4fo)
Pale yellow oil; yield: 44.9 mg (0.111 mmol, 37%).
1H NMR (CDCl3): δ = 0.26 (s, 6 H), 0.69 (dd, J = 16.2, 8.5 Hz, 1 H),
0.90 (dd, J = 16.3, 5.3 Hz, 1 H), 1.07–1.13 (m, 1 H), 1.18–1.25 (m,
16 H), 1.42–1.55 (m, 2 H), 1.62–1.72 (m, 1 H), 2.17 (ddd, J = 15.2,
8.7, 6.5 Hz, 1 H), 2.23 (ddd, J = 15.2, 8.7, 6.5 Hz, 1 H), 4.07 (q,
J = 6.8 Hz, 2 H), 7.31–7.34 (m, 3 H), 7.5 (dd, J = 6.4, 3.1 Hz, 2 H).
13C NMR (CDCl3): δ = –4.63, 4.10, 14.23, 19.69, 24.47, 24.78,
24.95, 32.02, 34.61, 60.06, 82.97, 127.57, 128.67, 134.03, 138.76,
173.73.
HRMS: m/z [M + Na]+ calcd for C22H37O4BNaSi: 427.24464;
found: 427.24432.
2-[3-(2-Bromo-4-methoxyphenyl)-2-(4-methoxyphenyl)pro-
pyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4bp)
Pale yellow oil; yield: 147.6 mg (0.32 mmol, 32%).
1H NMR (CDCl3): δ = 1.02 (s, 6 H), 1.05 (s, 6 H), 1.17 (d, J = 8.1
Hz, 2 H), 2.87 (dd, J = 13.5, 7.4 Hz, 1 H), 2.90 (dd, J = 13.4, 7.4 Hz,
2 H), 3.15 (quint, J = 7.7 Hz, 1 H), 3.74 (s, 3 H), 3.76 (s, 3 H), 6.66
(dd, J = 8.6, 2.7 Hz, 1 H), 6.76 (d, J = 8.6 Hz, 2 H), 6.84 (d, J = 8.5
Hz, 1 H), 7.05 (d, J = 2.6 Hz, 1 H), 7.09 (d, J = 8.6 Hz, 1 H).
13C NMR (CDCl3): δ = 24.49, 24.76, 40.94, 45.40, 55.22, 55.42,
82.89, 113.07, 113.33, 117.60, 124.90, 128.38, 131.85, 132.14,
138.51, 157.75, 158.15.
(5) (a) Yoshida, H.; Kawashima, S.; Takemoto, Y.; Okada, K.;
Ohshita, J.; Takaki, K. Angew. Chem. Int. Ed. 2012, 51, 235.
(b) Takemoto, Y.; Yoshida, H.; Takaki, K. Chem. Eur. J.
2012, 18, 14841.
(6) (a) Laitar, D. S.; Müller, P.; Sadighi, J. P. J. Am. Chem. Soc.
2005, 127, 17196. (b) Segawa, Y.; Yamashita, M.; Nozaki,
K. Angew. Chem. Int. Ed. 2007, 46, 6710.
HRMS: m/z [M + Na]+ calcd for C23H30O4BBrNa: 483.13127;
found: 483.13126.
(7) For catalytic carboboration via direct activation of a B–C
bond, see: (a) Suginome, M.; Yamamoto, A.; Murakami, M.
J. Am. Chem. Soc. 2003, 125, 6358. (b) Suginome, M.;
Yamamoto, A.; Murakami, M. Angew. Chem. Int. Ed. 2005,
44, 2380. (c) Suginome, M.; Yamamoto, A.; Murakami, M.
J. Organomet. Chem. 2005, 690, 5300. (d) Suginome, M.;
Shirakura, M.; Yamamoto, A. J. Am. Chem. Soc. 2006, 128,
14438. (e) Suginome, M.; Yamamoto, A.; Sasaki, T.;
Murakami, M. Organometallics 2006, 25, 2911.
3-(2-Bromo-4-methoxyphenyl)-2-(4-methoxyphenyl)propan-1-
ol (8)
Pale yellow oil; yield: 62.0 mg (0.176 mmol, 84%).
1H NMR (CDCl3): δ = 1.30 (t, J = 6.3 Hz, 1 H), 2.82–2.90 (m, 1 H),
3.10 (dd, J = 14.4, 7.3 Hz, 1 H), 3.13 (dd, J = 14.0, 7.1 Hz, 1 H),
3.75 (s, 3 H), 3.76–3.81 (m, 1 H), 3.79 (s, 3 H), 6.67 (dd, J = 8.5,
2.7 Hz, 1 H), 6.85 (d, J = 8.7 Hz, 2 H), 6.87 (d, J = 8.5 Hz, 1 H),
7.07 (d, J = 2.7 Hz, 1 H), 7.14 (d, J = 8.7 Hz, 2 H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1924–1932

1932
I. Kageyuki et al.
SPECIAL TOPIC
(8) For three-component carboboration with a boron
electrophile and a carbon nucleophile, see: (a) Yamamoto,
A.; Suginome, M. J. Am. Chem. Soc. 2005, 127, 15706.
(b) Daini, M.; Yamamoto, A.; Suginome, M. J. Am. Chem.
Soc. 2008, 130, 2918. (c) Daini, M.; Suginome, M. Chem.
Commun. 2008, 5224. (d) Daini, M.; Yamamoto, A.;
Suginome, M. Asian J. Org. Chem. 2013, 2, 968.
(9) For carboboration of other modes, see: (a) Mikhaikov, B.
M.; Bubnov, Y. N. Tetrahedron Lett. 1971, 12, 2127.
(b) Bubnov, Y. N.; Nesmeyanova, O. A.; Rudashevskaya, T.
Y.; Mikhaikov, B. M.; Kazansky, B. A. Tetrahedron Lett.
1971, 12, 2153. (c) Wrackmeyer, B.; Nöth, H. J. Organomet.
Chem. 1976, 108, C21. (d) Okuno, Y.; Yamashita, M.;
Nozaki, K. Angew. Chem. Int. Ed. 2011, 50, 920.
(10) For copper-catalyzed carboboration of alkynes, see:
(a) Alfaro, R.; Parra, A.; Alemeán, J. G.; Ruano, J. L.;
Tortosa, M. J. Am. Chem. Soc. 2012, 134, 15165. (b) Zhang,
L.; Cheng, J.; Carry, B.; Hou, Z. J. Am. Chem. Soc. 2012,
134, 14314. (c) Zhou, Y.; You, W.; Smith, K. B.; Brown, M.
K. Angew. Chem. Int. Ed. 2014, 53, 3475.
(15) A major byproduct was benzylboronic acid pinacol ester.
(16) The stereochemistry of the major products could not be
elucidated.
(17) For a review on radical clock reactions, see: Griller, D.;
Ingold, K. U. Acc. Chem. Res. 1980, 13, 317.
(18) For hydroboration of alkenes via a β-borylalkyl copper
species, see: (a) Lee, J.-E.; Yun, J. Angew. Chem. Int. Ed.
2007, 47, 145. (b) Corberán, R.; Mszar, N. W.; Hoveyda, A.
H. Angew. Chem. Int. Ed. 2011, 50, 7079.
(19) Another catalytic pathway, which involves direct reaction of
6 with a carbon electrophile, may also be possible, see ref.
10a.
(20) (a) Chang, Y. C.; Nair, M. G.; Nitiss, J. L. J. Nat. Prod.
1995, 58, 1901. (b) Setchell, K. D. R.; Brown, N. M.;
Lydeking-Olse, E. J. Nutr. 2002, 132, 3577. (c) Ingram, D.;
Sanders, K.; Kolybaba, M.; Lopez, D. Lancet 1997, 350,
990. (d) Lamartiniere, C. A. Am. J. Clin. Nutr. 2000, 71,
1705. (e) Adlercreutz, H.; Honjo, H.; Higashi, A. Am. J.
Clin. Nutr. 1991, 54, 1093. (f) Muthyala, R. S.; Ju, Y. H.;
Sheng, S.; Williams, L. D.; Doerge, D. R.;
(11) For our previous work on copper-catalyzed carboboration of
alkynes, see: Yoshida, H.; Kageyuki, I.; Ken, T. Org. Lett.
2013, 15, 952.
(12) (a) Laitar, D. S.; Tsui, E. Y.; Sadighi, J. P. Organometallics
2006, 25, 2405. (b) Mun, S.; Lee, J.-E.; Yun, J. Org. Lett.
2006, 8, 4887. (c) Sakaki, Y.; Horita, Y.; Zhong, C.;
Sawamura, M.; Ito, H. Angew. Chem. Int. Ed. 2011, 50,
2778. (d) Semba, K.; Shinomiya, M.; Fujihara, T.; Terao, J.;
Tsuji, Y. Chem. Eur. J. 2013, 19, 7125.
(13) For Pd-catalyzed carboboration of alkenes, see: Daini, M.;
Suginome, M. J. Am. Chem. Soc. 2011, 133, 4758.
(14) Copper(II) acetate would be reduced to a copper(I) complex
in situ, see: Hammond, B.; Jardine, F. H.; Vohra, A. G.
J. Inorg. Nucl. Chem. 1971, 33, 1017.
Katzenellenbogen, B. S.; Helferich, W. G.;
Katzenellenbogen, J. A. Bioorg. Med. Chem. 2004, 12, 1559.
(21) For the previous reports on total synthesis of equol, see:
(a) Heemstra, J. M.; Kerrigan, S. A.; Doerge, D. R.;
Helferich, W. G.; Boulanger, W. A. Org. Lett. 2006, 8, 5441.
(b) Gharpure, S. J.; Sathiyanarayanan, A. M.; Jonnalagadda,
P. Tetrahedron Lett. 2008, 49, 2974.
(22) (a) Díes-González, S.; Kaur, H.; Zinn, F. K.; Stevens, E. D.;
Nolan, S. P. J. Org. Chem. 2005, 70, 4784. (b) Chun, J.; Lee,
H. S.; Jung, I. G.; Lee, S. W.; Kim, H. J.; Son, S. U.
Organometallics 2010, 29, 1518.
Synthesis 2014, 46, 1924–1932
© Georg Thieme Verlag Stuttgart · New York