Copper(I)-catalyzed diastereoselective borylative exo-cyclization of alkenyl aryl ketones

Article abstract of DOI:10.1055/s-0035-1560721

Copper(I)-catalyzed diastereoselective borylative exo-cyclization of alkenyl ketones with bis(pinacolato)diboron is reported. The reaction of alkenyl aryl ketones under a CuCl/Xantphos catalyst system provides four- or five-membered-ring syn-2-(borylmethy

Full text of DOI:10.1055/s-0035-1560721

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© Georg Thieme Verlag Stuttgart · New York
2016, 27, 272–276
letter
272
E. Yamamoto et al.
Letter
Synlett
Copper(I)-Catalyzed Diastereoselective Borylative Exo-Cyclization
of Alkenyl Aryl Ketones
Eiji Yamamoto
Ryoto Kojima
Koji Kubota
CuCl/Xantphos (5 mol%)
O
OH
Ar
(pin)B–B(pin) (1.2 equiv)
(pin)B
H
Ar
n
K(O-t-Bu) (1.2 equiv)
n
n = 1 or 2
Hajime Ito*
DME, 30 °C
62–87%
cis product only
chemo-, regio-, and
diastereoselective
Division of Chemical Process Engineering and Frontier Chemistry
Center, Faculty of Engineering, Hokkaido University, Sapporo,
Hokkaido 060-8628, Japan
6 examples
hajito@eng.hokudai.ac.jp
Received: 26.06.2015
Accepted after revision: 10.09.2015
Published online: 09.11.2015
building blocks through various transformations with con-
comitant C–C bond activation driven by the relief of the
ring strain.12 However, the routes to access stereodefined
cyclobutanols containing multiple stereogenic centers are
still relatively limited compared with those for three-, five-
and six-membered carbocyclic compounds.12a,13 The bory-
lative cyclization of γ-alkenyl ketones is a novel and effi-
cient route for the synthesis of 2-(borylmethyl)cyclobuta-
nol derivatives. Clark and co-workers have already reported
that carbonyl borylation proceeds exclusively over alkene
borylation in the presence of a CuCl/N-heterocyclic carbene
(NHC) catalyst when the two groups are present in the
same molecule. To achieve the exo-borylative cyclization of
alkenyl ketones, the chemoselectivity preference of the bor-
ylation must be switched from the ketone group to the
alkene group using appropriate substrates, catalysts and re-
agents (Scheme 1, b).14
Herein, we report the diastereoselective exo-borylative
cyclization of alkenyl aryl ketones catalyzed by a cop-
per(I)/Xantphos catalyst system, which provides syn-1-
aryl-2-(borylmethyl)cyclobutanol derivatives in high yields
and with excellent diastereoselectivity. It is noteworthy
that syn-selective synthesis of 1,2-substituted tertiary cy-
clobutanols has been scarcely reported.15,16 Furthermore,
the reaction of δ-alkenyl aryl ketone also affords the corre-
sponding five-membered-ring product.
DOI: 10.1055/s-0035-1560721; Art ID: st-2015-u0477-l
Abstract Copper(I)-catalyzed diastereoselective borylative exo-cycliza-
tion of alkenyl ketones with bis(pinacolato)diboron is reported. The re-
action of alkenyl aryl ketones under a CuCl/Xantphos catalyst system
provides four- or five-membered-ring syn-2-(borylmethyl)cycloalkanol
derivatives in good yields with high syn selectivities. The utility of this
method is demonstrated by further transformations of the cyclic prod-
ucts.
Key words boron, cyclization, stereoselective synthesis, copper, catal-
ysis
Borylation of multiple bonds with concomitant C–C
bond formation can provide a rapid access to complex orga-
noboron compounds,1–6 which are regarded as useful build-
ing blocks in organic synthesis.7 Recently, copper-catalyzed
borylation has emerged as a useful method for synthesizing
organoboron compounds.8,9 Our research group is interest-
ed in the efficient synthesis of small-ring carbocyclic orga-
noboron compounds such as cyclopropyl- or cyclobutylbor-
onates, and have reported several copper(I)-catalyzed bory-
lative cyclization reactions of alkenes bearing a good
leaving group (Scheme 1, a).10 In this reaction, the in situ
generated borylcopper species preferably reacts with the
alkene moiety to afford the alkylcopper species. Then, sub-
sequent intramolecular substitution leads to exo-cycliza-
tion products (Scheme 1, a).
Looking to extend our borylative cyclization strategy,
we envisioned a copper(I)-catalyzed borylative cyclization
of γ-alkenyl ketones to provide 2-(borylmethyl)cyclobuta-
nol derivatives containing two adjacent congested stereo-
centers (Scheme 1, c). Cyclobutanols are an important
structural motif in organic chemistry because they are of-
ten found in natural products,11 and are used as versatile
First, we screened reaction conditions for the borylative
cyclization of γ-alkenyl ketone 1a with copper catalyst sys-
tems (Table 1). The boryl cyclization of 1a with CuCl/
Xantphos (5 mol%), bis(pinacolato)diboron (1.2 equiv), and
t-BuOK (1.2 equiv) in dimethoxyethane (DME) afforded the
corresponding syn-2-(borylmethyl)cyclobutanol syn-2a in
high yield (Table 1, entry 1, 87% yield),17 and the corre-
sponding diastereomer was not detected by 1H NMR and 13
NMR analyses of the crude reaction mixture. Using catalytic
C
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 272–276

273
E. Yamamoto et al.
Letter
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Table 1 Optimization of the Reaction Conditions for Copper(I)-Cata-
previous works
a. copper-catalyzed borylative exo-cyclization (Ito)
lyzed Boryl Cyclizationa
Cu
B
B
B
B
CuCl/ligand (5 mol%)
base (1.2 equiv)
OH
Ph
O
O
C
C
Br
C
C
C
C
B
n
Cu cat.
base
n
Ph
n
O
(pin)B–B(pin) (1.2 equiv)
solvent, 30 °C, 11 h
high chemo- and
regioselectivity
Br
1a
n = 1–3
syn-2a
b. copper-catalyzed diboration of ketones (Clark)
Entry
Ligand
Base
Solvent
Yield (%)b,c
CuCl/ICy (3 mol%)
Na(O-t-Bu) (5 mol%)
OB(pin)
B(pin)
O
1d
2e
3
Xantphos
Xantphos
none
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
DME
DME
DME
DME
DME
DME
DME
DME
DME
DME
DME
DME
DME
DME
THF
87 (56)
66
0
1,2-addition
(74% yield)
(pin)B–B(pin)
2
2
Me
Me
toluene, 50 °C, 6 h
this work
c. copper-catalyzed diastereoselective exo-cyclization
4
Ph3P
0
Cu
B
C
C
O
B
B
OH
Ar
C
H
5
dppe
25
34
12
10
0
B
C
C
Ar
O
n
C
Ar
Cu cat.
base
6
dppp
n
n-1
n = 2 or 3
7
dppb
high chemo-, regio-, and diastereoselectivity
8
dppf
Scheme 1 Copper(I)-catalyzed borylative cyclization
9
ICy·HCl
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
10f
11
12
13
14
15
16
17
0
none
0
amount of t-BuOK (10 mol%) retarded the yield (Table 1,
66%, entry 2). The reaction of 1a in the absence of the Xant-
phos ligand resulted in no reaction (Table 1, entry 3). Prod-
uct 2a is unstable during purification using silica gel chro-
matography. Thus, purification was conducted after esteri-
fication of the hydroxy group of the crude product 2a (56%
isolated yield, Table 1, entry 1).18 The relative configuration
of the major product was unambiguously determined to be
the syn configuration by X-ray crystallographic analysis of
the boryl cyclization product after esterification (Figure S1).
The reaction with monodentate PPh3 provided no boryla-
tive cyclization product (Table 1, entry 4), and bidentate
phosphines afforded lower yields than Xantphos (entries 5–
8). Clark et al. reported that selective diboration of the ke-
tone moiety in γ-alkenyl methyl ketone using a borylcop-
per(I)/ICy complex and t-BuONa gives the corresponding
tertiary α-hydroxy boronate ester.14 In our case, the reac-
tion with an NHC ligand precursor (ICy∙HCl = 1,3-dicyclo-
hexylimidazolium chloride) led to a complex mixture
(Table 1, entry 9). When the reaction was performed with
t-BuOCu (1 equiv), instead of the catalytic CuCl and stoi-
chiometric t-BuOK conditions, no desired product was ob-
tained (Table 1, entry 10). Next, the effect of the base was
investigated. Without the base, the desired product was not
formed (Table 1, entry 11). The use of t-BuONa, KOMe or
KOEt in DME, or the use of THF, Et2O or toluene solvent with
t-BuOK afforded inferior results compared with those using
the standard conditions (Table 1, entries 12–17).
t-BuONa
KOMe
KOEt
70
19
39
85
87
84
t-BuOK
t-BuOK
t-BuOK
Et2O
toluene
a Reaction conditions: 1a (0.5 mmol), (pin)B–B(pin) (0.6 mmol), CuCl (0.025
mmol), ligand (0.025 mmol), and base (0.6 mmol) in a solvent (1 mL) at 30
°C.
b Determined by 1H NMR analysis.
c Isolated yield after esterification of the hydroxyl group in the product 2a is
shown in parentheses. For details, see supporting information.
d The dr of the crude reaction mixture was determined to be syn/anti = 97:3
based on the 1H NMR analysis. The dr of the crude reaction mixtures with
ligands except for Xantphos could not be determined because of overlap-
ping signals.
e Amount of base used was 10 mol%.
f t-BuOCu (1 equiv) was used instead of CuCl/t-BuOK.
in moderate to good yields (79%, 75%, 62%, 75%, respective-
ly, Table 2, entries 1−4). Furthermore, the corresponding
minor anti isomers were not detected by H NMR analysis.
1
However, the isolated yields of derivatized products were
generally low due to instability of 2 under the silica gel pu-
rification conditions (32%, 23%, 21%, 20%, respectively). Un-
fortunately, only aromatic ketone substrates gave the de-
sired products in this reaction. γ-Alkenyl ketones contain-
ing an alkyl, alkenyl or alkynyl moiety instead of an
aromatic group resulted in complex mixtures. These results
can be attributed to possible competitive side reactions in-
cluding 1,2-diboration reaction of ketone, protoboration of
carbon–carbon multiple bonds, and aldol reactions.
With the optimized conditions in hand, the substrate
scope for this boryl cyclization was investigated (Table 2).
Alkenyl aryl ketones with 3,5-xylyl, 2-naphthyl, 4-bromo-
or 4-methoxyphenyl groups provided the desired products
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 272–276

274
E. Yamamoto et al.
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Table 2 Substrate Scope for the Copper(I)-Catalyzed Borylative Cy-
O
boryl
cyclization
OH
Ph
clization of Alkenyl Aryl Ketonesa
(pin)B
(pin)B
Ph
i)
2a
1a
CuCl/Xantphos (5 mol%)
(pin)B–B(pin) (1.2 equiv)
O
OH
R
(pin)B
ii)
iii)
R
Ar
K(O-t-Bu) (1.2 equiv)
DME, 30 °C
OTMS
Ph
OH
O
2b–e
1b–e
HO
(pin)B
Ph
O
Ph
Entry
Substrate (R)
Product
Yield (%)
6a, 33%, 2 steps
8a, 12%, 2 steps
4a, Ar = 4-CF3C6H4
iv)
ii)
1
1b (3,5-xylyl)
2b
2c
2d
2e
79 (32)
75 (23)
62 (21)
75 (20)
Ar
(pin)B
OTMS
Ph
O
2
1c (2-naphthyl)
1d (4-BrC6H4)
1e (4-MeOC6H4)
HO
3
O
Ph
4b
7a, 68%
5a, 51%, 3 steps
a Reaction conditions: alkenyl ketone 1 (0.5 mmol), (pin)B–B(pin) (0.6
mmol), CuCl (0.025 mmol), Xantphos (0.025 mmol), and t-BuOK (0.6
mmol) in DME (1 mL) at 30 °C. Yields were determined by 1H NMR analysis
of the crude product 2, and isolated yields of the corresponding esterified
products 4 are shown in parentheses.
Scheme 3 Transformations of product 2a. Reagents and conditions: (i)
4-(trifluoromethyl)benzoyl chloride (1.05 equiv), i-Pr2NEt (1.05 equiv),
DMAP (10 mol%), DME, 0 °C, 3 h; (ii) NaBO3·4H2O (10 equiv), THF–H2O,
r.t., 2 h; (iii) TMSOTf (5.0 equiv), 2,6-lutidine (10 equiv), CH2Cl2, 0 °C, 3
h; (iv) ClCH2Br (2.0 equiv), n-BuLi (1.5 equiv), THF, −78 °C to r.t., 19 h.
b Isolated yield of derivatized product from 2e is shown in parentheses.
Reaction of δ-alkenyl phenyl ketone 1f provided product
3f bearing a bicyclic structure containing a 1,2-oxaborolane
in high yield and with good diastereoselectivity (81%,
Scheme 2).
carbonyl carbon would then occur, followed by reductive
elimination of the resultant dialkylcopper(III) species E to
lead to the formation of the boryl cyclization product. The
high chemoselectivity with the Xantphos ligand may likely
be attributed to the formation of a sterically congested bor-
ylcopper species.10d This catalyst tuning would enable the
preferential addition of intermediate B to the less sterically
hindered alkene moiety over the more bulky aromatic ke-
tone group. The high HOMO level of B with the Xantphos
ligand is also important for alkene selectivity.10d Regarding
the origin of the syn selectivity, the favored transition state
would go through less sterically hindered pathway, which
leads to the observed high diastereoselectivity.
CuCl/Xantphos (5 mol%)
(pin)B–B(pin) (1.2 equiv)
Ph
O
O
K(O-t-Bu) (1.2 equiv)
B
OH
Ph
THF, 30 °C
1f
H
3f, 81%
Scheme 2 Reaction of δ-alkenyl phenyl ketone 1f
Further derivatization of the products from the crude
mixtures was then investigated (Scheme 3). The crude
product 4a was subjected to NaBO3 oxidation to afford the
corresponding mono alcohol 5a in good yield as a single
isomer (51%, three steps). We also carried out TMS protec-
tion of the crude product 2a to provide a 33% yield of the
desired silylated product 6a over two steps, followed by ho-
mologation to give 7a in good yield (68%). Crude product 2a
also afforded the corresponding diol 8a after NaBO3 oxida-
tion.
A proposed mechanism of the borylative cyclization is
shown in Scheme 4. The reaction starts with the generation
of Cu(O-t-Bu) complex A followed by σ-bond metathesis
with a diboron species to form borylcopper(I) active species
B. This then adds to the C–C double bond in 1 to form alkyl-
copper(I) species C. Subsequently, the tert-butoxide base
coordinates with the alkylcopper(I) species C to form a
more nucleophilic tert-butoxy(alkyl)cuprate D.19 This step
would be facilitated by using a strong base, which is com-
patible with the results shown in Table 1 (entries 10–14). In
addition, Lewis acidity of the counter cations might also be
involved in this step forming a cuprate-π complex.19 Intra-
molecular nucleophilic attack of the copper(I) center on the
CuCl/Xantphos/K(O-t-Bu)
HO
B(pin)
(pin)B–B(pin)
Ar
LCu(O-t-Bu)
A
(pin)B–(O-t-Bu)
L = Xantphos
K+
O
L
O-t-Bu
III
LCu B(pin)
Cu
B
Ar
B(pin)
1
E
K+
B(pin)
I
L
t-Bu-O
B(pin)
t-Bu
B
O
I
LCu
O
Cu
Cu
L'
O
O
Ar
+
K(O-t-Bu)
Ar
favored TS
Ar
C
D
Scheme 4 Proposed mechanism of the borylative cyclization
In conclusion, we have developed a novel method for
preparing
syn-1-aryl-2-(borylmethyl)cycloalkanols
through a highly chemo-, regio-, and diastereoselective bor-
ylative cyclization of alkenyl ketones catalyzed by a cop-
per(I)/Xantphos complex. This method provides a rapid ac-
cess to four- or five-membered-ring 2-(borylmethyl)cy-
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E. Yamamoto et al.
Letter
Synlett
cloalkanols with high syn selectivity from simple starting
materials. Although the isolation of the cyclized products is
difficult, synthetic application should be possible using in
situ transformations of the crude products. Development of
effective transformations and further work toward an en-
antioselective synthesis are now ongoing in our group.
of Syntheses; Vol. 6; Kaufmann, D., Ed.; Georg Thieme Verlag:
Stuttgart, 2005.
(8) For selected examples, see: (a) Takahashi, K.; Ishiyama, T.;
Miyaura, N. Chem. Lett. 2000, 29, 982. (b) Laitar, D. S.; Müller, P.;
Sadighi, J. P. J. Am. Chem. Soc. 2005, 127, 17196. (c) Mun, S.; Lee,
J.-E.; Yun, J. Org. Lett. 2006, 8, 4887. (d) Lillo, V.; Fructos, M. R.;
Ramírez, J.; Braga, A. A. C.; Maseras, F.; Díaz-Requejo, M. M.;
Pérez, P. J.; Fernández, E. Chem. Eur. J. 2007, 13, 2614.
(e) Kleeberg, C.; Dang, L.; Lin, Z.; Marder, T. B. Angew. Chem. Int.
Ed. 2009, 48, 5350. (f) Park, J. K.; Lackey, H. H.; Ondrusek, B. A.;
McQuade, D. T. J. Am. Chem. Soc. 2011, 133, 2410. (g) Matsuda,
N.; Hirano, K.; Satoh, T.; Miura, M. J. Am. Chem. Soc. 2013, 135,
4934.
(9) (a) Ito, H.; Yamanaka, H.; Tateiwa, J.-I.; Hosomi, A. Tetrahedron
Lett. 2000, 41, 6821. (b) Ito, H.; Kawakami, C.; Sawamura, M.
J. Am. Chem. Soc. 2005, 127, 16034. (c) Ito, H.; Ito, S.; Sasaki, Y.;
Matsuura, K.; Sawamura, M. J. Am. Chem. Soc. 2007, 129, 14856.
(d) Ito, H.; Okura, T.; Matsuura, K.; Sawamura, M. Angew. Chem.
Int. Ed. 2010, 49, 560. (e) Ito, H.; Kunii, S.; Sawamura, M. Nat.
Chem. 2010, 2, 972. (f) Ito, H.; Kubota, K. Org. Lett. 2012, 14, 890.
(g) Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2015, 137,
420.
Acknowledgment
This work was financially supported by the NEXT (Japan) program
(Strategic Molecular and Materials Chemistry through Innovative
Coupling Reactions) of Hokkaido University. This work was also sup-
ported by JSPS KAKENHI Grant Numbers 15H03804 and 15K13633.
This work was supported by JSPS KAKENHI Grant number 26·2447.
E.Y. was supported by Grant-in-Aid for JSPS Fellows.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1560721.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
(10) For copper(I)-catalyzed borylative cyclizations, see: (a) Ito, H.;
Kosaka, Y.; Nonoyama, K.; Sasaki, Y.; Sawamura, M. Angew.
Chem. Int. Ed. 2008, 47, 7424. (b) Ito, H.; Toyoda, T.; Sawamura,
M. J. Am. Chem. Soc. 2010, 132, 5990. (c) Zhong, C.; Kunii, S.;
Kosaka, Y.; Sawamura, M.; Ito, H. J. Am. Chem. Soc. 2010, 132,
11440. (d) Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc.
2013, 135, 2635. (e) Kubota, K.; Iwamoto, H.; Yamamoto, E.; Ito,
H. Org. Lett. 2015, 17, 620.
(11) For selected examples, see: (a) Paquette, L. A.; Parker, G. D.; Tei,
T.; Dong, S. J. Org. Chem. 2007, 72, 7125. (b) Tanaka, N.; Okasaka,
M.; Ishimaru, Y.; Takaishi, Y.; Sato, M.; Okamoto, M.; Oshikawa,
T.; Ahmed, S. U.; Consentino, L. M.; Lee, K.-H. Org. Lett. 2005, 7,
2997. (c) Yoshikawa, K.; Kaneko, A.; Matsumoto, Y.; Hama, H.;
Arihara, S. J. Nat. Prod. 2006, 69, 1267.
(12) (a) Seiser, T.; Saget, T.; Tran, D. N.; Cramer, N. Angew. Chem. Int.
Ed. 2011, 50, 7740. (b) Leemans, E.; D’hooghe, M.; De Kimpe, N.
Chem. Rev. 2011, 111, 3268. (c) Namyslo, J. C.; Kaufmann, D. E.
Chem. Rev. 2003, 103, 1485.
(13) Parella, R.; Gopalakrishnan, B.; Babu, S. A. J. Org. Chem. 2013, 78,
11911.
References and Notes
(1) For examples of palladium-catalyzed carboborations, see:
(a) Marco-Martínez, J.; López-Carrillo, V.; Buñuel, E.; Simancas,
R.; Cárdenas, D. J. J. Am. Chem. Soc. 2007, 129, 1874. (b) Daini,
M.; Yamamoto, A.; Suginome, M. J. Am. Chem. Soc. 2008, 130,
2918. (c) Marco-Martínez, J.; Buñuel, E.; López-Durán, R.;
Cárdenas, D. J. Chem. Eur. J. 2011, 17, 2734.
(2) For examples of copper(I)-catalyzed borylative aldol reactions,
see: (a) Chen, I.-H.; Yin, L.; Itano, W.; Kanai, M.; Shibasaki, M.
J. Am. Chem. Soc. 2009, 131, 11664. (b) Burns, A. R.; Solana
González, J.; Lam, H. W. Angew. Chem. Int. Ed. 2012, 51, 10827.
(3) For examples of copper(I)-mediated carboboration of alkynes,
see: (a) Okuno, Y.; Yamashita, M.; Nozaki, K. Angew. Chem. Int.
Ed. 2011, 50, 920. (b) Zhang, L.; Cheng, J.; Carry, B.; Hou, Z. J. Am.
Chem. Soc. 2012, 134, 14314. (c) Alfaro, R.; Parra, A.; Alemán, J.;
García Ruano, J. L.; Tortosa, M. J. Am. Chem. Soc. 2012, 134,
15165. (d) Liu, P.; Fukui, Y.; Tian, P.; He, Z.-T.; Sun, C.-Y.; Wu, N.-
Y.; Lin, G.-Q. J. Am. Chem. Soc. 2013, 135, 11700.
(4) For examples of copper(I)-catalyzed intermolecular carbobora-
tion of C–C double bonds, see: (a) Yoshida, H.; Kageyuki, I.;
Takaki, K. Org. Lett. 2013, 15, 952. (b) Meng, F.; Haeffner, F.;
Hoveyda, A. H. J. Am. Chem. Soc. 2014, 136, 11304. (c) Semba, K.;
Bessho, N.; Fujihara, T.; Terao, J.; Tsuji, Y. Angew. Chem. Int. Ed.
2014, 53, 9007. (d) Meng, F.; McGrath, K. P.; Hoveyda, A. H.
Nature 2014, 513, 367.
(5) For transition-metal-free carboborations, see: (a) Nagao, K.;
Ohmiya, H.; Sawamura, M. J. Am. Chem. Soc. 2014, 136, 10605.
(b) Roscales, S.; Aurelio, G.; Csákÿ, A. G. Org. Lett. 2015, 17, 1605.
(c) Nagao, K.; Ohmiya, H.; Sawamura, M. Org. Lett. 2015, 17,
1304.
(14) McIntosh, M. L.; Moore, C. M.; Clark, T. B. Org. Lett. 2010, 12,
1996.
(15) For selected examples of stereoselective cyclobutanol synthesis
from simple starting materials, see: (a) Ihara, M.; Taniguchi, T.;
Makita, K.; Takano, M.; Ohnishi, M.; Taniguchi, N.; Fukumoto,
K.; Kabuto, C. J. Am. Chem. Soc. 1993, 115, 8107. (b) Takeda, K.;
Tanaka, T. Synlett 1999, 705. (c) Takasu, K.; Misawa, K.; Yamada,
M.; Furuta, Y.; Taniguchi, T.; Ihara, M. Chem. Commun. 2000,
1739. (d) Takasu, K.; Ueno, M.; Ihara, M. J. Org. Chem. 2001, 66,
4667. (e) Saphier, S.; Sinha, S. C.; Keinan, E. Angew. Chem. Int. Ed.
2003, 42, 1378. (f) Inanaga, K.; Takasu, K.; Ihara, M. J. Am. Chem.
Soc. 2005, 127, 3668. (g) Avenoza, A.; Busto, J. H.; Canal, N.;
Peregrina, J. M.; Pérez-Fernández, M. Org. Lett. 2005, 7, 3597.
(h) Baktharaman, S.; Selvakumar, S.; Singh, V. K. Org. Lett. 2006,
8, 4335.
(16) For examples containing syn-selective cyclobutanol synthesis
from simple starting materials, see: (a) Canales, E.; Corey, E. J.
J. Am. Chem. Soc. 2007, 129, 12686. (b) Darses, B.; Greene, A. E.;
Poisson, J.-F. Org. Lett. 2010, 12, 3994. (c) Nagamoto, Y.;
Yamaoka, Y.; Fujimura, S.; Takemoto, Y.; Takasu, K. Org. Lett.
2014, 16, 1008.
(6) For carboboration with coorperative Cu/Pd catalysis, see:
(a) Semba, K.; Nakao, Y. J. Am. Chem. Soc. 2014, 136, 7567.
(b) Smith, K. B.; Logan, K. M.; You, W.; Brown, M. K. Chem. Eur. J.
2014, 20, 12032.
(7) (a) Boronic Acids: Preparation and Applications in Organic Syn-
thesis, Medicine and Materials; Hall, D. G., Ed.; Wiley-VCH:
Weinheim, 2011, 2nd revised ed. (b) Boron Compounds, Science
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Letter
Synlett
(17) Typical Procedure for the Borylative Cyclization/Esterifica-
tion of Aryl Alkenyl Ketones: CuCl (0.025 mmol) and (pin)B–
B(pin) (0.60 mmol), Xantphos (0.025 mmol), t-BuOK (0.60
mmol) were placed in an oven-dried vial in a glove box. After
the vial was removed from the glove box, DME (1.0 mL) was
added to the vial and stirred for 30 min. Then, 1a (0.50 mmol)
was added to the mixture at 30 °C. After the reaction was com-
plete, the reaction mixture was cooled to 0 °C. After that, DMAP
[0.05 mmol in THF (1 mL)] and i-Pr2NEt (0.52 mmol) were
added to the mixture, and 4-(trifluoromethyl)benzoyl chloride
(0.53 mmol) was added dropwise. After the reaction was com-
plete, the reaction mixture was passed through a short florisil
column eluting with Et2O. The crude material was purified by
silica gel column chromatography to give syn-4a (129.7 mg,
0.282 mmol, 56% yield) as a white solid.
(dd, J = 10.0, 15.9 Hz, 1 H), 1.46 (dd, J = 6.3, 15.7 Hz, 1 H), 1.68–
1.79 (m, 1 H), 2.06–2.16 (m, 1 H), 2.62–2.72 (m, 1 H), 2.80–2.91
(m, 1 H), 2.97–3.07 (m, 1 H), 7.21–7.28 (m, 1 H), 7.30–7.36 (m, 2
H), 7.47–7.51 (m, 2 H), 7.68 (d, J = 7.8 Hz, 2 H), 8.20 (d, J = 7.8 Hz,
2 H). 13C NMR (99 MHz, CDCl3): δ = 12.5 (br, BCH2), 23.0 (CH2),
24.80 (Me), 24.86 (Me), 30.2 (CH2), 44.0 (CH), 83.2 (C), 85.4 (C),
125.0 (q, JC–F = 273.8 Hz, C), 125.1 (CH), 125.2–152.4 (m, CH),
127.2 (CH), 128.3 (CH), 130.0 (CH), 134.22 (q, JC–F = 32.7 Hz, C),
134.28 (C), 143.1 (C), 163.8 (C). HRMS (ESI): m/z [M + Na]+ calcd
for C25H28O4BF3Na: 482.19613; found: 482.19653.
(18) Several derivatization methods were examined to improve the
isolated yield, but these were not successful.
(19) The cuprate-carbonyl π complex may be formed in this step;
see: Bertz, S. H.; Hardin, R. A.; Heavey, T. J.; Ogle, C. A. Angew.
Chem. Int. Ed. 2013, 52, 10250.
1H NMR (392 MHz, CDCl3): δ = 1.25 (s, 6 H), 1.26 (s, 6 H), 1.36
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 272–276