Asymmetric Copper-Catalyzed C(sp)-H Bond Insertion of Carbenoids Derived from N-Tosylhydrazones

Article abstract of DOI:10.1055/s-0037-1611003

A chiral copper(I)-phosphoramidite complex efficiently catalyzed the asymmetric insertion of the carbenoids derived from N-tosyl hydrazones into alkyne C-H bonds to give the corresponding chiral alkynylated products in up to 77% yield and with up to 74% e

Full text of DOI:10.1055/s-0037-1611003

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2018, 29, A–F
letter
A
en
T. Osako et al.
Letter
Synlett
Asymmetric Copper-Catalyzed C(sp)–H Bond Insertion of Carben-
oids Derived from N-Tosylhydrazones
CuI (5 mol%)
L* (11 mol%)
Cs2CO3 (2.7 equiv)
Si
Takao Osako
Si
NNHTs
R
Makoto Nagaosa
Go Hamasaka
+
Ar
1,4-dioxane, 80 °C, 24 h, N2
*
Ar
R
H
Yasuhiro Uozumi*
15 examples
16–77% yield
2–74% ee
R = alkyl
Si = TBDPS
TIPS
Institute for Molecular Science (IMS) and JST-ACCEL, Okazaki,
Aichi 444-8787, Japan
uo@ims.ac.jp
O
P
N
O
L*
Received: 04.06.2018
Accepted after revision: 05.08.2018
Published online: 14.09.2018
asymmetric carbenoid insertions into X–H bonds (X = C, O,
N, etc.) with various chiral transition-metal catalysts have
been extensively investigated.5,6 However, there have been
few investigations of asymmetric alkynylations through
C(sp)–H insertions of carbenoids;7 in addition, details of the
enantioinduction step are still unclear. Herein, we report an
asymmetric copper-catalyzed insertion of carbenoids de-
rived from acetophenone N-tosylhydrazones8 into silyl-
substituted alkynes in the presence of a chiral copper–(S)-
Monophos catalyst to provide chiral (3-arylbut-1-yn-1-
yl)silane derivatives in up to 77% yield with up to 74% ee.
DFT calculations for possible intermediates suggest that the
energies of the copper carbene acetylide intermediates af-
fect the enantioselectivity of the asymmetric C(sp)–H in-
sertion.
By using the reaction conditions for the symmetric
C(sp)–H insertion that were reported by Wang and co-
workers,2f we initially studied the reaction of 4-methyl-N′-
[1-(1-naphthyl)ethylidene]benzenesulfonohydrazide (1a.
1.5 equiv), derived from 1-(1-naphthyl)ethanone, with tert-
butyl(ethynyl)diphenylsilane (2A) in the presence of CuI (5
mol%), (S)-Monophos (L1, 11 mol%), and t-BuOLi (2.7 equiv)
in 1,4-dioxane at 80 °C (Table 1, entry 1). The desired alky-
nylated product 3aA was obtained in 82% yield, but the en-
antioselectivity was poor (2% ee). As major byproducts,
1,1′-(but-2-ene-2,3-diyl)dinaphthalene and 1-ethylnaph-
thalene were detected; these were formed by decomposi-
tion of the diazo species generated in situ. Various bases
(K2CO3, Cs2CO3, K3PO4, CsOAc, CsOH, Et3N, and DBU) were
tested for the reaction (entries 2–8). When Cs2CO3 was
used, the enantiomeric excess of 3aA improved to 58% ee,
although the yield decreased to 77% (entry 3). The reaction
was also conducted in other solvents [DCE, toluene, MeCN,
DOI: 10.1055/s-0037-1611003; Art ID: st-2018-b0340-l
Abstract A chiral copper(I)–phosphoramidite complex efficiently cata-
lyzed the asymmetric insertion of the carbenoids derived from N-tosyl
hydrazones into alkyne C–H bonds to give the corresponding chiral
alkynylated products in up to 77% yield and with up to 74% ee.
Key words copper catalysis, asymmetric catalysis, carbenoids, hydra-
zones, alkynes
The transition-metal-catalyzed C–H insertion reaction
of carbenoid species has been recognized as a direct and ef-
ficient method for C–H functionalization, and has been
widely used for formation of C–C bonds in organic synthe-
sis.1 In particular, carbenoid insertion into C(sp)–H bonds of
terminal alkynes has recently emerged as a powerful tool
for the introduction of alkynyl or allenyl units into organic
molecules.2 In 2004, Suárez and Fu reported the first exam-
ple of a copper-catalyzed insertion of carbenoids derived
from diazo esters or diazo amides into terminal alkynes to
give functionalized 3-alkynoates.2c Following this pioneer-
ing work, Fox and co-workers developed an efficient syn-
thesis of 4-disubstituted allenoates through copper-cata-
lyzed C(sp)–H insertion with -substituted -diazo esters.2d
Recently, Wang and co-workers found that N-tosylhydra-
zones, readily prepared from aldehydes or ketones, are ef-
fective carbenoid precursors3 for a copper-catalyzed car-
benoid insertion into silyl-, alkyl-, or aryl-substituted
alkynes to provide ethynylated2f or allenylated2e,g,i products
in excellent yields with a wide substrate tolerance. Howev-
er, the asymmetric insertion of carbenoids into C(sp)–H
bonds still remains an immature methodology,4 whereas
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

B
T. Osako et al.
Letter
Synlett
EtOAc, DME, and cyclopentyl methyl ether (CPME)] (entries
9–14), but the desired product 3aA was not obtained effi-
ciently. The use of other copper(I) and copper(II) sources
[CuBr, CuCl, CuCl2, Cu(OAc)2, and Cu(acac)2] in the presence
of L1 gave similar enantioselectivities (50–57% ee) to that
obtained by using CuI, but the yield of 3aA decreased to 32–
49% (entries 15–19).
tBu
Ph
Ph
CuI (5 mol%)
Ph chiral ligand (5.5 or 11 mol%)
Cs2CO3 (2.7 equiv)
tBu
Si
Ph
NNHTs
Si
+
1,4-dioxane, 80 °C, 24 h, N2
*
H
1a
(1.5 equiv)
2A
3aA
Table 1 Optimization of the Conditions for the Insertion of the Car-
benoid Derived from 1a into 2A in the Presence of Copper/(S)-Mono-
phos (L1) Catalyst a
H2N
NH2
O
O
PPh2
PPh2
L3 23%, 1% ee
P
N
O
O
tBu
Ph
Ph
copper source (5 mol%)
L1 (11 mol%)
tBu
Si
N
N
Ph
Ph
NNHTs
Si
base (2.7 equiv)
L1 77%, 58% ee
L2 16%, 1% ee
Ph
Ph
+
L4 45%, 1% ee
solvent, 80 °C, 24 h, N2
*
Ph
Ph
H
O
O
O
O
O
N
P
N
1a
2A
O
P
3aA
N
N
N
N
O
N
(1.5 equiv)
O
–
Ph
Ph
Ph
PF6
Ph
L1
L5 26%, 3% ee
L6 36%, 11% ee
L7 18%, 2% ee
Entry
[Cu]
Base
Solvent
Yieldb of
3aA (%)
eec of
3aA (%)
O
O
O
O
O
P
O
P
P
N
N
N
O
O
1
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuBr
CuCl
CuCl2
t-BuOLi
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
DCE
82
5
2
2
K2CO3
Cs2CO3
K3PO4
16
58
22
–
L8 9%, 2% ee
L9 33%, 31% ee
L10 44%, 58% ee
3
77
45
0
Ph
4
Ph
Ph
Ph
Ph
5
CsOAc
CsOH
O
O
P
O
P
6
0
–
P
N
N
N
O
O
O
7
Et3N
0
–
8
DBU
0
–
Ph
Ph
Ph
9
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
trace
0
–
L11 42%, 59% ee
L12 27%, 14% ee
L13 18%, 49% ee
10
11
12
13
14
15
16
17
18
19
toluene
–
Ph
N
Ph
MeCN
17
trace
13
0
1
O
O
EtOAc
–
P
P
N
O
O
DME
14
–
Ph
Ph
CPME
L14 24%, 60% ee
L15 41%, 59% ee
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
49
32
44
44
37
57
55
54
55
50
Scheme 1 Screening of chiral ligands for the copper-catalyzed insertion
of the carbenoid derived from 1a into 2A. Reaction conditions: 1a (0.30
mmol), 2A (0.20 mmol), CuI (0.010 mmol), chiral ligand [0.020 mmol
(for L1, L6–L15) or 0.011 mmol (for L2–L5)], Cs2CO3 (0.54 mmol), 1,4-
dioxane (2 mL), 80 °C, 24 h, under N2. Isolated yields are shown. The ee
values were determined by HPLC on a chiral stationary column (DAICEL
CHIRALPAK AD-H).
Cu(OAc)2
Cu(acac)2
a Reaction conditions: 1a (0.30 mmol), 2A (0.20 mmol), copper source
(0.010 mmol), (S)-Monophos (L1) (0.022 mmol), base (0.54 mmol), sol-
vent (2 mL), 80 °C, 24 h, under N2.
b Isolated yield.
Next, we screened a series of chiral ligands (Scheme 1).
The reaction of hydrazone 1a with tert-butyl(ethynyl)di-
phenylsilane (2A) in the presence of CuI (5 mol%), (S)-BINAP
(L2, 5.5 mol%), and Cs2CO3 (2.7 equiv) in 1,4-dioxane at
80 °C afforded the product 3aA in 16% yield with 1% ee. The
c Determined by HPLC on a chiral stationary column (DAICEL CHIRALPAK
AD-H).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

C
T. Osako et al.
Letter
Synlett
use of chiral diamine, oxazoline, or carbene ligands L3–L6
was not effective in terms of asymmetric induction (up to
11% ee). Phosphoramidite ligands bearing TADDOL (L7), bi-
phenyl (L8), or spirobiindane (L9) moieties did not enhance
the reactivity or the enantioselectivity. The reaction with a
phosphoramidite ligand bearing an octahydrobinaphthyl
backbone (L10) gave 3aA in moderate yield (44%) with a
similar enantioselectivity (58% ee) to L1. The presence of
phenyl substituents at the 5,5′-positions of the binaphthyl
backbone of (S)-Monophos (L11) slightly improved the ee
value to 59% ee, but the yield was not improved. Phenyl
substitution at the 3,3′- and 4,4′-positions (L12 and L13, re-
spectively) resulted in low reactivity and enantioselectivity.
Replacing the N-methyl substituents of L1 with chiral 2-
phenylethyl groups (L14 and L15) slightly improved the en-
antioselectivity, but the product 3aA was obtained in mod-
erate yield. On the basis of these results, we selected (S)-
Monophos (L1) as the optimal chiral ligand for the asym-
metric insertion of the carbenoid into alkynes.
Having determined the optimal conditions, we exam-
ined the asymmetric insertion of the carbenoid derived
from various N-tosylhydrazones into the C(sp)–H bonds of
alkynes (Scheme 2). The asymmetric insertion of 1a with
ethynyl(triisopropyl)silane (2B) gave the alkynylated prod-
uct 3aB in 62% yield and with 58% ee. The reactions of the
other alkynes such as phenylacetylene (2C), oct-1-yne (2D),
and 3,3-dimethylbut-1-yne (2E) resulted in poor yields and
enantioselectivities of the products (3aC; 25% yield, 0% ee,
CuI (5 mol%)
L1 (11 mol%)
R
R
NNHTs
Cs2CO3 (2.7 equiv)
+
Ar
1,4-dioxane, 80 °C, 24 h, N2
H
Ar
1
2
3a
(1.5 equiv)
tBu
tBu
tBu
iPr
iPr
iPr
Ph
Ph
Ph
Ph
Ph
Ph
Si
Si
Si
Si
3aA 77%, 58% ee
3aB 62%, 58% ee
tBu
3cA 36%, 55% ee
tBu
3bA 28%, 23% ee
tBu
iPr
iPr
iPr
Ph
Ph
Ph
Ph
Ph
Ph
Si
Si
Si
Si
MeO
F
3cB 77%, 74% eeb
tBu
3dA 44%, 66% ee
3eA 19%, 49% ee
tBu
3fA 24%, 43% ee
tBu
tBu
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Si
Si
Si
Si
Cl
Br
I
F3C
3jA 30%, 2% eec
tBu
3hA 23%, 35% eec,d
3iA 20%, 25% eec,d
3gA 23%, 20% ee
tBu
tBu
tBu
tBu
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Si
Si
Si
Si
Si
O
O
3mA 16%, 47% ee
3nA 25%, 54% ee
3oA 30%, 43% ee
3kA 26%, 53% ee
3lA 36%, 52% ee
Scheme 2 Substrate scope for the copper-catalyzed insertion of carbenoids derived from hydrazones 1 into 2. Reaction conditions: 1 (0.30 mmol), 2
(0.20 mmol), CuI (0.010 mmol), L1 (0.022 mmol), Cs2CO3 (0.54 mmol), 1,4-dioxane (2 mL), 80 °C, 24 h, under N2. a The isolated yields are reported.
The ee values were determined by HPLC on chiral stationary columns. The absolute configuration of 3cB was determined to be S (see Scheme 3), and
those of the other products were tentatively assigned on the basis of the mechanistic similarity of the asymmetric induction. b The ee value was deter-
mined after conversion into 4 in Scheme 3. c The reaction was performed at 60 °C. d The reaction was performed for 48 h.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

D
T. Osako et al.
Letter
Synlett
3aD; 29% yield, 2% ee, and 3aE; 12% yield, 0% ee). The pres-
ence of -substituents on the naphthyl group significantly
affected the reactivity and enantioselectivity. The asym-
metric insertion of N-tosylhydrazone 1b, derived from 1-
(2-naphthyl)ethanone, with ethynylsilane 2A afforded the
insertion product 3bA in 28% yield with 23% ee. The reac-
tion of N-tosylhydrazone 1c, derived from acetophenone,
with tert-butyl(ethynyl)diphenylsilane (2A) gave 3cA in
36% yield and 55% ee. Replacement of tert-butyl(ethynyl)di-
phenylsilane (2A) with ethynyl(triisopropyl)silane (2B) im-
proved the yield and the enantioselectivity of the reaction
and the insertion product 3cB was obtained in 77% yield
with 74% ee.9 The reaction of ethynylsilane 2A with N-tosyl-
hydrazones 1d–m, derived from various substituted ace-
tophenones, also gave the desired products in low to mod-
erate yields (16–44%) and with moderate enantioselectivi-
ties (2–66% ee). Halogen substituents (F, Cl, Br, or I)
remained intact under the reaction conditions. When the
reactions of N-tosylhydrazone bearing electron-deficient
substituents were conducted, low yields and enantioselec-
tivities were observed. The reactions of N-tosylhydrazones
1n and 1o, derived from propiophenone and -tetralone,
respectively, with 2A gave the corresponding products 3nA
and 3oA with comparable enantioselectivities. Unfortu-
nately, this catalytic system was not effective for the asym-
metric insertion using N-tosylhydrazones derived from ali-
phatic or diaryl ketones.
was R on the basis of the reported value of the specific rota-
tion of 5 {[]D –11.6 (c 15.7, CHCl3) for 77% ee (R)}.10 The ab-
solute configuration of 3cB was therefore assigned as S.
Our proposed catalytic cycle for the asymmetric copper-
catalyzed insertion of carbenoids derived from N-tosylhydra-
zones into silyl-substituted alkynes is shown in Scheme 4.2e,11
The chiral copper(I) complex reacts with ethynylsilane 2 to
afford the copper acetylide I. Copper acetylide I is convert-
ed into the copper carbene acetylide II by reaction with the
diazo compound 1′ generated from N-tosylhydrazone 1. En-
antioselective migratory insertion of the acetylide into the
carbenoid in intermediate II gives intermediate III bearing a
chiral carbon center, which provides the desired inserted
product 3 with regeneration of the chiral copper complex.
Si
3
H
Si
Ar
*
2
L*CuX
HX
HX
Si
L*Cu
Si
L*Cu
I
*
Ar
III
N2
NNHTs
base
Si
Ar
Δ
Ar
Product 3cB was derivatized to permit the determina-
tion of its absolute configuration (Scheme 3). Thus, desilyla-
tion of 3cB followed by Sonogashira coupling with iodoben-
zene gave chiral 1,1′-(but-1-yne-1,3-diyl)dibenzene (4) in
51% yield with 74% ee. Catalytic hydrogenation of 4 with
Pd/C gave (1-methyl-3-phenylpropyl)benzene (5) in 52%
yield. The specific rotation []D25 of 5 was –7.8 (c 0.32, CH-
Cl3, 25 °C), which suggested that its absolute configuration
1'
1
L*Cu
N2
Ar
II
Scheme 4 Proposed catalytic cycle
To gain insight into the asymmetric induction step from
intermediates II to III, we evaluated the energies of the four
possible isomers of intermediate II by DFT calculations. In
the reaction of 1-tosyl-2-[1-(1-naphthalenyl)-ethylidene]-
hydrazide (1a) with ethynyl(triisopropyl)silane (2B) in the
presence of the chiral copper–L1 complex, four possible
structural isomers IIa to IId of the carbine acetylide inter-
mediate might be formed (Scheme 5). Conversion of inter-
mediate IIa into the major isomer (S)-3cB showed the low-
est energy among the potential isomers. This calculated re-
sult is consistent with the experimental results [(S)-3cB,
74% ee]. Conversion of intermediate II-d into the minor iso-
mer (R)-3cB showed the second lowest energy. The energy
difference between intermediates II-a and II-d was 0.47
kcal/mol. We attribute this difference to the barrier to
asymmetric induction. The other isomers II-b and II-c
showed higher energies due to steric repulsion between the
chiral ligand and the naphthyl group of the carbenoid spe-
cies. Consequently, the involvement of intermediates II-b
and II-c in the asymmetric insertion is unlikely. A further
detailed DFT study is in progress.
iPr
iPr
iPr
Ph
Si
PhI (2 equiv)
Pd(PPh3)4 (10 mol%)
CuI (20 mol%)
Et3N (2 equiv)
TBAF
THF, rt, 4 h
THF, 60 °C, 14 h
4
3cB
51% yield, 74% ee
Ph
Pd/C (1 mol%)
2 (1 atm)
H
EtOAc, rt, 36 h
(R)-5
52% yield
[α]2D5 = –7.8 (c 0.32, CHCl3)
Scheme 3 Derivatization of 3cB
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

E
T. Osako et al.
Letter
Synlett
Scheme 5 Energy Evaluation for Isomers of Intermediate II by DFT Calculations aThe DFT calculations were performed by using the Gaussian 09 pro-
gram12 with B3LYP [6-31G(d)+LanL2DZ for Cu].
In conclusion, we have developed an asymmetric cop-
per-catalyzed insertion of carbenoids derived from N-tosyl-
hydrazones into C(sp)–H bonds of silyl-substituted alkynes
in the presence of a chiral copper–(S)-Monophos catalyst to
provide the chiral 3-(arylbut-1-yn-1-yl)silane derivatives in
up to 77% yield and with up to 74% ee. This study provides
the preliminary information necessary to permit the devel-
opment of a new catalytic method for efficient preparation
of enantiomerically enriched gem-aryl(alkynyl)alkanes.
Acknowledgment
The computations were performed using Research Center for Compu-
tational Science, Okazaki, Japan.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611003.
S
u
p
p
o
nrtIo
g
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
References and Notes
Funding Information
(1) (a) Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev. 2003, 103, 2861.
(b) Davies, H. M. L.; Manning, J. R. Nature 2008, 451, 417.
(c) Slattery, C. N.; Ford, A.; Maguire, A. R. Tetrahedron 2010, 66,
6681. (d) Davies, H. M.; Morton, D. Chem. Soc. Rev. 2011, 40,
1857. (e) Archambeau, A.; Miege, F.; Meyer, C.; Cossy, J. Acc.
Chem. Res. 2015, 48, 1021. (f) Ford, A.; Miel, H.; Ring, A.;
This work was supported by the JST-ACCEL program (JPMJAC401). We
are also grateful for funding from the JSPS KAKENHI [Grant-in-Aid for
Challenging Exploratory Research (No. 26620090), for Young Scien-
tists (B) (No. 26810099), and for Scientific Research (C) (No.
16K05876)].
)(
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

F
T. Osako et al.
Letter
Synlett
Slattery, C. N.; Maguire, A. R.; McKervey, M. A. Chem. Rev. 2015,
115, 9981. (g) Xia, Y.; Qiu, D.; Wang, J. Chem. Rev. 2017, 117,
13810.
(8) (a) Fulton, J. R.; Aggarwal, V. K.; de Vicente, J. Eur. J. Org. Chem.
2005, 1479. (b) Shao, Z.; Zhang, H. Chem. Soc. Rev. 2012, 41, 560.
(c) Xiao, Q.; Zhang, Y.; Wang, J. Acc. Chem. Res. 2013, 46, 236.
(9) The ee value of 3cB could not be determined directly, conse-
quently, the ee value was determined after derivatization to
1,1′-(but-1-yne-1,3-diyl)dibenzene (4) as shown in Scheme 3.
(10) Galdi, N.; Della Monica, C.; Spinella, A.; Oliva, L. J. Mol. Catal. A:
Chem. 2006, 243, 106.
(11) Wang, T.; Wang, M.; Fang, S.; Liu, J.-y. Organometallics 2014, 33,
3941.
(12) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B. et al. Gaussian 09
(Revision D.01), Gaussian, Inc.: Wallingford, 2016;.
(13) Asymmetric Insertion Reactions; General Procedure
A mixture of CuI (1.9 mg, 10 mol), (S)-Monophos (7.9 mg, 22
mol), and Cs2CO3 (176 mg, 0.54 mmol) in 1,4-dioxane (2 mL)
under N2 was stirred at r.t. for 30 min. Hydrazone 1 (0.3 mmol)
and alkyne 2 (0.2 mmol) were added, and the mixture was
heated to 80 °C for 24 h. The resulting suspension was passed
through short plug of silica gel (eluent: EtOAc), concentrated,
and purified by preparative TLC and gel-permeation chroma-
tography to give the corresponding insertion products.
tert-Butyl[(3S)-3-(1-naphthyl)but-1-yn-1-yl]diphenylsilane
(3aA)
(2) (a) Che, J.; Xing, D.; Hu, W. Curr. Org. Chem. 2016, 20, 41.
(b) Torres, Ó.; Pla-Quitana, A. Tetrahedron Lett. 2016, 57, 3881.
(c) Suárez, A.; Fu, G. C. Angew. Chem. Int. Ed. 2004, 43, 3580.
(d) Hassink, M.; Liu, X.; Fox, J. M. Org. Lett. 2011, 13, 2388.
(e) Xiao, Q.; Xia, Y.; Li, H.; Zhang, Y.; Wang, J. Angew. Chem. Int.
Ed. 2011, 50, 1114. (f) Ye, F.; Ma, X.; Xiao, Q.; Li, H.; Zhang, Y.;
Wang, J. J. Am. Chem. Soc. 2012, 134, 5742. (g) Hossain, M. L.; Ye,
F.; Zhang, Y.; Wang, J. J. Org. Chem. 2013, 78, 1236. (h) Li, J.;
Ding, D.; Liu, L.; Sun, J. RSC Adv. 2013, 3, 21260. (i) Xiao, T.;
Zhang, P.; Xie, Y.; Wang, J.; Zhou, L. Org. Biomol. Chem. 2014, 12,
6215. (j) Zhang, Z.; Zhou, Q.; Yu, W.; Li, T.; Wu, G.; Zhang, Y.;
Wang, J. Org. Lett. 2015, 17, 2474. (k) Ye, F.; Wang, C.; Ma, X.;
Hossain, M. L.; Xia, Y.; Zhang, Y.; Wang, J. J. Org. Chem. 2015, 80,
647. (l) Wang, C.; Ye, F.; Wu, C.; Zhang, Y.; Wang, J. J. Org. Chem.
2015, 80, 8748.
(3) (a) Allwood, D. M.; Blakemore, D. C.; Brown, A. D.; Ley, S. V.
J. Org. Chem. 2014, 79, 328. (b) Wang, H.; Deng, Y.-H.; Shao, Z.
Synthesis 2018, 50, 2281.
(4) Tang, Y.; Chen, Q.; Liu, X.; Wang, G.; Lin, L.; Feng, X. Angew.
Chem. Int. Ed. 2015, 54, 9512.
(5) (a) Zhao, X.; Zhang, Y.; Wang, J. Chem. Commun. 2012, 48,
10162. (b) Zhu, S.-F.; Zhou, Q.-L. Acc. Chem. Res. 2012, 45, 1365.
(c) Ren, Y.-Y.; Zhu, S.-F.; Zhou, Q.-L. Org. Biomol. Chem. 2018, 16,
3087, See also refs. 1 (a), 1 (c), and 1 (f).
(6) For our achievements in asymmetric carbenoid insertions into
phenolic O–H bonds, see: Osako, T.; Panichakul, D.; Uozumi, Y.
Org. Lett. 2012, 14, 194.
(7) A related investigated was recently reported by Wang and co-
workers, see: Chu, W.-D.; Guo, F.; Yu, L.; Hong, J.; Liu, Q.; Mo, F.;
Zhang, Y.; Wang, J. Chin. J. Chem. 2018, 36, 217.
Colorless oil; yield: 64.5 mg (77%, 58% ee); []D25 = +6.9 (c 0.37,
CHCl3). 1H NMR (396 MHz, CDCl3):  = 8.15 (d, J = 8.7 Hz, 1 H),
7.80–7.89 (m, 6 H), 7.75 (d, J = 8.7 Hz, 1 H), 7.43–7.54 (m, 3 H),
7.30–7.40 (m, 6 H), 4.70 (q, J = 7.1 Hz, 1 H), 1.75 (d, J = 7.1 Hz, 3
H), 1.10 (s, 9 H). 13C{1H} NMR (100 MHz, CDCl3):  = 138.6,
135.8, 134.2, 133.9, 130.6, 129.6, 129.2, 127.8, 127.7, 126.2,
125.8, 125.7, 124.6, 123.4, 114.2, 82.1, 30.0, 27.3, 23.7, 18.7.
HRMS (APCI): m/z [M + H]+ calcd for C30H31Si: 419.2195; found:
419.2203. HPLC: ChiralPak AD-H column (hexane, flow rate 0.5
mL/min,  = 280 nm); tR = 13.7 min (minor isomer; integration:
322916 V·s); tR = 17.4 min (major isomer; integration:
1223585 V·s).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F