Copper-catalyzed diastereoselective synthesis of β-boryl-α-quaternary carbon carboxylic esters

Article abstract of DOI:10.1039/c8ob02469c

Cu(i)-Catalyzed diastereoselective carboboration of α-alkyl-substituted α,β-unsaturated carboxylic esters to produce β-boryl-α-quaternary carbon esters was developed. The carbon skeletons of dialkyl sulfates, primary allyl halides, and benzyl bromides were transferred to the α-position of the substrates to provide products in moderate to good yields with a diastereoselectivity of >95% in most cases. Substrates bearing a β-(hetero)aryl substituent gave higher diastereoselectivities than those bearing a linear β-alkyl substituent. The crystal structure of the potassium trifluoroborate derivative shows that the reactions probably go through a copper(i) enolate intermediate and the diastereoselectivity arises from the electrophilic attack of electrophiles to the less hindered side of the enolates.

Full text of DOI:10.1039/c8ob02469c

Organic &
Biomolecular Chemistry
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Copper-catalyzed diastereoselective synthesis of
β-boryl-α-quaternary carbon carboxylic esters†
Cite this: Org. Biomol. Chem., 2018,
16, 9237
Ya-Jie Zuo,a Zhuoran Zhong,b,c Yinkun Fan,b Xiangyu Li,b Xiaolu Chen,b
Yuwei Chang,c Ruihu Song,b Xinpeng Fu,b Anling Zhangb and
b
Chong-Min Zhong
*
Cu(I)-Catalyzed diastereoselective carboboration of α-alkyl-substituted α,β-unsaturated carboxylic esters
to produce β-boryl-α-quaternary carbon esters was developed. The carbon skeletons of dialkyl sulfates,
primary allyl halides, and benzyl bromides were transferred to the α-position of the substrates to provide
products in moderate to good yields with a diastereoselectivity of >95% in most cases. Substrates bearing
a β-(hetero)aryl substituent gave higher diastereoselectivities than those bearing a linear β-alkyl substitu-
ent. The crystal structure of the potassium trifluoroborate derivative shows that the reactions probably go
through a copper(I) enolate intermediate and the diastereoselectivity arises from the electrophilic attack
of electrophiles to the less hindered side of the enolates.
Received 4th October 2018,
Accepted 19th November 2018
DOI: 10.1039/c8ob02469c
rsc.li/obc
strates typically results in two tertiary carbon centers
(Scheme 1a).4 Although there are many reports on copper-
Introduction
Construction of quaternary carbon stereogenic centers catalyzed carboboration of alkenes and alkynes,5 the examples
remains one of the most significant challenges in modern syn- of copper-catalyzed carboboration of α-functionalized
thetic chemistry.1 Carbonyl compounds bearing a β-functional α,β-unsaturated carbonyl substrates leading to a α quaternary
and α-quaternary carbon center are versatile building blocks in carbon center are rare.6 Carboboration of unsaturated com-
organic synthesis (Chart 1), and numerous methods have been pounds is associated with several potential challenges because
developed to access the corresponding β-hydroxyl and amino of the use of a stoichiometric amount of base additive. One is
compounds.2 Boronyl is a versatile functional group that can
be transferred to hydroxyl, amino, aryl, vinyl, and many others.
Copper-catalyzed hydroboration of α,β-unsaturated carbonyl
compounds is the most widely used procedure to access
β-boron functionalized carbonyl compounds.3 However, hydro-
boration of α-functionalized α,β-unsaturated carbonyl sub-
Chart 1
aCollege of Natural Resources and Environment, Northwest A&F University, Yangling
712100, P. R. China
bCollege of Chemistry and Pharmacy, Northwest A&F University, Yangling 712100,
P. R. China. E-mail: zhongcm@nwsuaf.edu.cn
cXi’an Gaoxin No.1 High School, Xi’an 710075, P. R. China
†Electronic supplementary information (ESI) available: Experimental details and
spectra of new compounds (1H NMR, 13C NMR, and HRMS). CCDC 1869279. For
ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c8ob02469c
Scheme 1 Copper-catalyzed borylation of α,β-unsaturated compounds.
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the hydroboration reaction of the substrate.7 Other two side encountered in our previous study,7 hydroboration is the main
reactions are transesterification between a methyl ester sub- side reaction in the copper-catalyzed carboboration of unsatu-
strate and base,8 and nucleophilic substitution between an rated compounds.11 Thus, a series of phosphine ligands were
electrophile and base. A skillful choice of a base and electro- screened to improve the selectivity of 4aa (Table 1, entries
phile is crucial to access the carboboration product efficiently.
2–11). As indicated in Table 1, 1,1′-bis(diphenylphosphino)
We previously reported intramolecular carboboration of ferrocene (dppf, entry 3), 1,4-bis(diphenylphosphino)ethane
α,β-unsaturated esters and ketones to produce cis-boryl-substi- (dppe, entry 5), and 2-dicyclohexylphosphino-2′,6′-dimethoxy-
tuted cycloalkyl esters and ketones, respectively (Scheme 1b).9 biphenyl (Sphos, entry 7) yield 4aa in higher yields (66–70%)
Herein, we report the first copper-catalyzed diastereoselective with improved selectivity. In contrast, 1,1-bis(diphenylpho-
carboboration of α-alkyl-substituted α,β-unsaturated esters to sphino)methane (dppm, entry 4) and tris(2,4-di-tert-butylphe-
synthesize β-boryl-α,α-disubstituted esters (Scheme 1c). The nyl)phosphite (entry 10) do not produce 4aa at all. NaOMe
presence of an ester and an allyl on the quaternary center as (entry 12) decreases the yield, while LiOMe (entry 13) is not
well as a boryl on the neighboring carbon offers many possibi- active for carboboration. The use of either KO-t-Bu or NaO-t-Bu
lities for further transformations.
should be avoided because it will result in transesterification
between the bases and 1a.12 The reactions in DMF and THF
were also conducted (entries 14 and 15). 4aa was not observed
by 1H NMR when DMF was used as a solvent.
Results and discussion
The scope of electrophiles was studied using 1a as the sub-
strate (Table 2). The reactions using 2-substituted allyl bro-
mides (entries 1–3) provide the corresponding borylallylation
products 4ab, 4ac, and 4ad in yields of 42–45%, with a dr of
>98 : 2, 91 : 9, and >99 : 1, respectively. In addition, 3-methyl-
and 3,3-dimethyl-substituted allyl bromides are also effective
electrophiles (entries 4 and 5). However, the reactions using
2-phenyl- and 2-bromoallyl bromides do not produce the
desired products, but rather ca. 10% yield of side product 5a
(entries 6 and 7). Allyl chloride (3i) also reacts with 1a to
produce 4aa in 63% yield (entry 8, 80 °C, 30 min). Considering
the similar reactivity of benzyl bromide (3j) to that of allyl
bromide in an SN2 substitution reaction, the electrophile was
subjected to the reaction with 1a to produce 4aj in 45% yield
(entry 9). Dialkyl sulfates are other types of electrophiles
widely used in alkylation reactions. Indeed, dialkyl sulfates 3k,
3l, and 3m are effective electrophiles because they produce
4ak, 4al, and 4am, respectively, in 80–84% yields (entries
10–12). Perhaps the balance between reactivity and resistance
to the side reaction of dialkyl sulfates is responsible for the
high yields.
The reaction of α-substituted α,β-unsaturated esters (1) with
3a was also studied, and the results are shown in Table 3.
First, the effect of different substituents on the R1 group was
studied (4ba–4ga). Substrates bearing p-MeO, p-Br, and p-Cl on
R1 afforded products in 53% (4ba), 63% (4ca), and 60% (4da)
yields, respectively, accompanied by the formation of side
product 5 in 10–16% yields. Improved yield and suppressed
side reaction are achieved when there is an o-Cl in 1e (4ea,
67%; 5e < 1%). When Cl is situated at the meta position, the
yield of side product 5f increases to 7%. For the substrate with
a p-nitro group, no products (4ga and 5g) are formed.4b For the
substrate with an α-butyl group (1h), 4ha is obtained in 66%
yield. We also studied the carboboration of the substrate with
a β-2-furyl group (1i). In this case, 4ia is produced in 35% yield
with a diastereomeric ratio (dr) of 98 : 2. The steric effect of the
β-substituent of the substrate on diastereoselectivity is illus-
trated when a substrate with a β-2-phenylethyl group (1j) is
used. Owing to the smaller size of the β group in 1j, 4ja is gen-
Carboboration of 1a by bis(pinacolato)diboron (2) and allyl
bromide (3a) (as the electrophile) was carried out in the pres-
ence of CuCl/Xantphos/KOMe (Xantphos = 4,5-bis(diphenyl-
phosphino)-9,9-dimethylxanthene) in toluene at 28 °C. In
addition to the carboboration product 4aa (58% yield), the
hydroboration product 5a is produced in 27% yield as a
mixture of diastereoisomers (Table 1, entry 1). 5a cannot be
transformed to 4aa under the reaction conditions.10 As we
Table 1 Screening of reaction conditionsa
Yieldb (%)
Entry
Ligand
Base
Solvent
4aa c
5a d
1
2
3
4
5
6
7
8
Xantphos
BINAP
dppf
dppm
dppe
KOMe
KOMe
KOMe
KOMe
KOMe
KOMe
KOMe
KOMe
KOMe
KOMe
KOMe
NaOMe
LiOMe
KOMe
KOMe
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
58
36
66
0
66
57
70
25
50
0
50
36
0
64
0
27
24
34
13
32
27
29
20
45
16
40
30
6
dppp
Sphos
Xphos
PCy3
9
10
11
12
13
14
15
L1e
L2f
Sphos
Sphos
Sphos
Sphos
28
7
DMF
a Reaction conditions: 1a (0.4 mmol), 2 (0.44 mmol), 3a (0.8 mmol),
CuCl (0.02 mmol), ligand (entries 1–6, 0.02 mmol; entries 7–13,
0.04 mmol), base (0.4 mmol), toluene (0.8 mL), 3 h. B2Pin2 = bis(pina-
colato)diboron. b Determined by 1H NMR analysis. c The relative con-
figuration of 4aa was determined by X-ray single crystal structure ana-
lysis of its derivatives (see Fig. 1). The diastereoselectivities of 4aa are
>99 : 1 in all cases. d 5a was produced as a mixture of diastereoisomers
with dr = 71 : 29–26 : 74. e L1 = tris(2,4-di-tert-butylphenyl)phosphite.
f L2 = 1,1′-bis(di-tert-butylphosphino)ferrocene.
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Table 2 Copper-catalyzed carboboration of methyl (2E)-2-methyl-3-
phenylacrylate (1a)a
Table 3 Copper-catalyzed allylboration of methyl(2E)-2-alkyl-3-aryla-
crylate (1) with B2Pin2 (2) and allyl bromide (3a)a
Entry
1
3
4 b
2
3
4c
5
6
7
8d
9
44aa, 63%, dr > 99 : 1 (16%)
10
11
12
a Reaction conditions: 1 (0.4 mmol), 2 (0.44 mmol), 3a (0.8 mmol),
CuCl (0.04 mmol), dppe (0.04 mmol), KOMe (0.4 mmol), toluene
(0.8 mL), 60 °C, 30 min. Isolated yields are shown for 4 and yields of 5
were determined by 1H NMR analysis of crude products. The dr ratio
of 4 is determined by 1H NMR analysis based on the percentage
decrease of the integral area of ester methyl or the β proton close to
boron, after purification. The dr ratio of 5 is determined by the 1H
NMR integral area ratio of ester methyls or β protons close to boron.
a Reaction conditions: 1a (0.4 mmol), 2 (0.44 mmol), 3 (0.8 mmol),
CuCl (0.02 mmol), Sphos (0.04 mmol), KOMe (0.4 mmol), toluene
(0.8 mL), 28 °C, 3 h. b Isolated yields. The dr ratio of 4 is determined
by 1H NMR analysis based on the percentage decrease of the integral
area of ester methyl or the β proton close to boron, after purification.
The yield of 5a is determined by 1H NMR analysis of crude products
and is shown in parentheses. c 3e is an isomeric mixture consisting of
(E)-1-bromobut-2-ene (73%), (Z)-1-bromobut-2-ene (14.6%), and 3-bro-
mobut-1-ene (12.4%). d The reaction was conducted at 60 °C.
THF/H2O at 28 °C (eqn (1)). The high yields are probably due
to the high stability of the alcohols lacking an α-proton. Using
KHF2 in MeCN/H2O at 28 °C, 4aa is transferred to potassium
alkyl trifluoroborate (7) in 93% yield (eqn (2)). The crystal
structure of 7 was studied by single-crystal X-ray structural ana-
lysis, and the results indicated that the relative configurations
of the two chiral carbons are (2SR, 3RS) (Fig. 1).
erated at a lower dr of 74 : 26. We are pleased to find that sub-
strate 1k, which contains an electron-withdrawing 4-CF3 sub-
stituent, produces 4ka in 87% yield (dr = 96 : 4).
In order to illustrate the derivatization of the products, 4aa
and 4ak are oxidized to the corresponding alcohols 6aa and
6ak in 96% and 100% yields, respectively, using NaBO3·H2O in
ð1Þ
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Scheme 3 The effect of Z-isomer in 1a on the diastereoselectivity.
bromide) to form product 4 and LCuOMe. When the R group
in 1 is an aryl group, the large steric hindrance makes an SN2
attack on the opposite side more favorable and only one dia-
stereoisomer is formed. However, when R is a linear alkyl
group, such as 2-phenylethyl in 1j, there is less steric differ-
ence between the two sides of C, which results in decreased
diastereoselectivity. Path b is the protonation of the C- or
O-terminal of the enolate, which produces side product 5.
According to the proposed catalytic cycle (Scheme 2), E-1a
and Z-1a should produce the same diastereoisomer 4aa.
An EZ mixture of 1a (EZ-1a, E/Z = 91 : 9) was synthesized and
applied to the reaction (Scheme 3). 4aa is produced in 62%
yield with a dr of >99 : 1. EZ-1a is recovered in 8% yield with
E/Z = 94 : 6. This result provides an additional support for the
mechanism.
Fig. 1 The asymmetric unit of 7, with 50% probability displacement
ellipsoids. Hydrogen atoms are omitted for clarity.
ð2Þ
Conclusions
In summary, we successfully developed Cu-catalyzed, diastereo-
selective carboboration of α-substituted α,β-unsaturated carboxylic
esters.13 The reaction affords β-boryl-α-quaternary carbon
esters in moderate to good yields using a widely available cata-
lyst system under mild reaction conditions. The reaction pro-
ceeds through an enolate intermediate, whose less sterically
hindered side is attacked by the electrophile to produce the
major diastereoisomer. Primary allyl bromides and chlorides,
dialkyl sulfates, and benzyl bromides are effective electrophiles
in this reaction. The diastereoselectivity of the reaction
remarkably depends on the steric effect of the β-substituent of
the substrate, that is, a larger substituent leads to higher
diastereoselectivity. The major side reaction is hydroboration
of the substrate, which is affected by both the substrate and
catalyst. A detailed mechanistic study will be helpful in the
development of an effective method to further reduce side
product formation.
On the basis of the experimental results and crystal struc-
ture of 7, a plausible reaction mechanism of carboboration is
proposed (Scheme 2). The syn addition of borylcopper (A,
formed in situ from LCuCl, KOMe, and 2) to the double bond
of substrate 1 produces adduct B, which then undergoes a fast
tautomerization process to form intermediate C. Enolation is
facilitated by the α-substituent of 1. An interaction between
boron and the enolate oxygen presumably keeps C in a rigid
conformation. There are two possible pathways for product for-
mation from C. Path a involves an SN2 attack of the less steri-
cally hindered side of C by the electrophile E-X (e.g., allyl
Experimental
General procedure for the copper-catalyzed reaction
In a glovebox, a 5 mL screw-capped reaction vial was charged
with CuCl (4.0 mg, 0.04 mmol), Sphos (33 mg, 0.08 mmol),
KOMe (30 mg, 0.4 mmol), B2(Pin)2 (122 mg, 0.044 mmol),
1 (0.04 mmol), toluene (0.8 mL), and a stirrer bar. The vial was
sealed and moved out of the glove box and heated at 80 °C
until the solution changed to a brownish red or black color.
Scheme 2 A plausible reaction mechanism.
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After the temperature was cooled to 28 °C (Tables 1 and 2) or
60 °C (Table 3), the electrophile (3, 0.8 mmol) was added
Conflicts of interest
through a micro syringe. The reaction mixture was stirred for a There are no conflicts of interest to declare.
specified time (changed to pale yellow). Then the reaction
mixture was diluted with DCM and then passed through a
short silica gel column (eluent DCM). After evaporation under
reduced pressure, the residue was purified by silica gel column
Acknowledgements
chromatography to obtain the desired product.
This work was supported by the Natural Science Foundation of
Shaanxi Province (Grant No. 2016JM2005), and the National
Natural Science Foundation of China (Grant No. 21673183).
Derivatization of 4aa and 4ak to 6aa, 6ak
The reaction was conducted according to a reported pro-
cedure.14 A 5 mL vial was charged with 4 (0.5 mmol),
NaBO3·4H2O (5 mmol, 770 mg), THF (0.6 mL), H2O (0.4 mL),
and a stirrer bar. The mixture was stirred at 28 °C for 12 h. The
mixture was extracted with ethyl acetate (4 × 1 mL). The
organic phase was dried over Na2SO4 and concentrated under
reduced pressure. The residue was purified by silica gel
column chromatography.
Notes and references
1 (a) T. Ling and F. Rivas, Tetrahedron, 2016, 72, 6729–6777;
(b) Y. Minko and I. Marek, Chem. Commun., 2014, 50,
12597–12611; (c) J. P. Das and I. Marek, Chem. Commun.,
2011, 47, 4593–4623; (d) E. A. Peterson and L. E. Overman,
Proc. Natl. Acad. Sci. U. S. A., 2004, 101, 11943–11948;
(e) C. J. Douglas and L. E. Overman, Proc. Natl. Acad.
Sci. U. S. A., 2004, 101, 5363–5367; (f) J. Christoffers and
A. Mann, Angew. Chem., Int. Ed., 2001, 40, 4591–4597;
(g) K. W. Quasdorf and L. E. Overman, Nature, 2014, 516,
181; (h) J. Feng, M. Holmes and M. J. Krische, Chem. Rev.,
2017, 117, 12564–12580.
2 (a) S. Qin, S. Liu, Y. Cao, J. Li, C. Chong, T. Liu, Y. Luo,
J. Hu, S. Jiang, H. Zhou, G. Yang and C. Yang, Org. Lett.,
2018, 20, 1350–1354; (b) G. Fráter, U. Müller and
W. Günther, Tetrahedron, 1984, 40, 1269–1277; (c) G. Fráter,
Helv. Chim. Acta, 1979, 62, 2825–2828; (d) H. Ishitani,
Y. Yamashita, H. Shimizu and S. Kobayashi, J. Am. Chem.
Soc., 2000, 122, 5403–5404; (e) Y. C. DePorre, J. R. Annand,
S. Bar and C. S. Schindler, Org. Lett., 2018, 20, 2580–2584;
(f) M. Duplessis, M.-E. Waltz, M. Bencheqroun,
B. Cardinal-David and Y. Guindon, Org. Lett., 2009, 11,
3148–3151; (g) Z. Chen, H. Morimoto, S. Matsunaga and
M. Shibasaki, J. Am. Chem. Soc., 2008, 130, 2170–2171;
(h) M. Hatano, T. Horibe and K. Ishihara, J. Am. Chem. Soc.,
2010, 132, 56–57; (i) P. Gu, Y. Su, X.-P. Wu, J. Sun, W. Liu,
P. Xue and R. Li, Org. Lett., 2012, 14, 2246–2249.
3 (a) G. Stavber and Z. Časar, Appl. Organomet. Chem., 2013,
27, 159–165; (b) J.-L. Zhang, L.-A. Chen, R.-B. Xu,
C.-F. Wang, Y.-P. Ruan, A.-E. Wang and P.-Q. Huang,
Tetrahedron: Asymmetry, 2013, 24, 492–498; (c) H. Wu,
S. Radomkit, J. M. O’Brien and A. H. Hoveyda, J. Am. Chem.
Soc., 2012, 134, 8277–8285; (d) K. Toribatake, L. Zhou,
A. Tsuruta and H. Nishiyama, Tetrahedron, 2013, 69, 3551–
3560; (e) C. Sole, A. Bonet, A. H. M. de Vries, J. G. de Vries,
L. Lefort, H. Gulyás and E. Fernández, Organometallics,
2012, 31, 7855–7861; (f) J.-E. Lee and J. Yun, Angew. Chem.,
Int. Ed., 2008, 47, 145–147; (g) J. C. H. Lee, R. McDonald
and D. G. Hall, Nat. Chem., 2011, 3, 894–899;
(h) W. J. Fleming, H. Muller-Bunz, V. Lillo, E. Fernandez
and P. J. Guiry, Org. Biomol. Chem., 2009, 7, 2520–2524;
(i) X. Feng and J. Yun, Chem. – Eur. J., 2010, 16, 13609–
13612; ( j) J. M. O’Brien, K.-s. Lee and A. H. Hoveyda, J. Am.
Methyl (SR)-2-((SR)-hydroxy(phenyl)methyl)-2-methylpent-4-
enoate (6aa)15
6aa was obtained as a colorless viscous liquid (111 mg, 96%).
1H NMR (500 MHz, CDCl3) δ 7.37–7.21 (m, 5H), 5.75–5.60 (m,
1H), 5.05 (m, 2H), 4.87 (s, 1H), 3.69 (s, 3H), 3.15 (d, J = 2.8 Hz,
1H), 2.50 (dd, J = 13.5, 7.1 Hz, 1H), 2.00 (dd, J = 13.5, 7.5 Hz,
1H), 1.07 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 176.78, 140.22,
133.35, 127.96, 127.95, 127.70, 118.63, 78.43, 52.10, 51.98,
41.47, 16.24. HRMS (ESI) m/z calcd for C14H17O2 (M − OH)+
217.1229, found 217.1235.
Methyl 3-hydroxy-2,2-dimethyl-3-phenylpropanoate (6ak)16
6ak was obtained as a white solid (106 mg, 100%), m.p. =
60–62 °C. 1H NMR (500 MHz, CDCl3) δ 7.41–7.21 (m, 5H), 4.89
(d, J = 3.7 Hz, 1H), 3.72 (s, 3H), 3.07 (d, J = 3.9 Hz, 1H), 1.14
(s, 3H), 1.11 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 178.29,
140.12, 127.90, 127.78, 78.85, 52.21, 47.88, 23.16, 19.23.
Methyl
(RS)-2-methyl-2-((RS)-phenyl(trifluoro-boranyl)
methyl)pent-4-enoate, potassium salt (7). A 5 mL vial was
charged with 4aa (103 mg, 0.3 mmol), KHF2 (94 mg,
1.2 mmol), MeCN (2 mL), H2O (270 μL), and a stirrer bar. The
mixture was stirred at 28 °C for 12 h. Then the mixture was
concentrated at reduced pressure. The residue was washed
with hexane (3 × 1 mL) (discarded). Then the solid residue was
washed with MeCN (4 × 1 mL). The MeCN solution was evapor-
ated under reduced pressure and 7 was obtained as a white
solid (90 mg, 93%). M.p. = 204–208 °C. Crystals suitable for
X-ray structure analysis are prepared by recrystallization from
1
MeCN/Et2O solution. H NMR (500 MHz, DMSO) δ 7.17 (d, J =
7.3 Hz, 1H), 7.08 (t, J = 7.4 Hz, 1H), 6.98 (t, J = 7.2 Hz, 1H), 5.48
(td, J = 17.0, 8.2 Hz, 1H), 4.82 (d, J = 9.2, 1H), 4.77 (d, J = 17.2,
1H), 3.43 (s, 3H), 2.26 (dd, J = 13.3, 6.3 Hz, 1H), 2.05 (d, J = 4.5
Hz, 1H), 1.62 (dd, J = 13.3, 8.3 Hz, 1H), 1.09 (s, 3H). 13C NMR
(126 MHz, DMSO) δ 177.61, 145.80, 131.43, 126.43, 123.50,
116.22, 78.91 (d, J = 33.4 Hz), 50.39, 47.77, 44.19, 19.00.
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Chem. Soc., 2010, 132, 10630–10633; (k) T. Iwai, Y. Akiyama
Chem., Int. Ed., 2018, 57, 9945–9949; (s) J. Royes, S. Ni,
A. Farre, E. La Cascia, J. J. Carbo, A. B. Cuenca, F. Maseras
and E. Fernandez, ACS Catal., 2018, 8, 2833–2838;
(t) H.-M. Wang, H. Zhou, Q.-S. Xu, T.-S. Liu, C.-L. Zhuang,
M.-H. Shen and H.-D. Xu, Org. Lett., 2018, 20, 1777–1780;
(u) A. Whyte, K. I. Burton, J. Zhang and M. Lautens, Angew.
Chem., Int. Ed., 2018, 57, 13927–13930; (v) M. Xiong,
H. Hu, X. Hu and Y. Liu, Org. Lett., 2018, 20, 3661–
3665; (w) G. Zhang, A. Cang, Y. Wang, Y. Li, G. Xu,
Q. Zhang, T. Xiong and Q. Zhang, Org. Lett., 2018, 20,
1798–1801.
6 (a) K. Hayama, K. Kubota, H. Iwamoto and H. Ito, Chem.
Lett., 2017, 46, 1800–1802; (b) I. Kageyuki, H. Yoshida and
K. Takaki, Synthesis, 2014, 1924–1932.
7 H.-Y. Bin, X. Wei, J. Zi, Y.-J. Zuo, T.-C. Wang and
C.-M. Zhong, ACS Catal., 2015, 6670–6679.
and M. Sawamura, Tetrahedron: Asymmetry, 2013, 24, 729–
735; (l) R. Cano, D. J. Ramón and M. Yus, J. Org. Chem.,
2010, 75, 3458–3460; (m) A. Bonet, H. Gulyás and
E. Fernández, Angew. Chem., Int. Ed., 2010, 49, 5130–5134;
(n) K. Knott, J. Fishovitz, S. B. Thorpe, I. Lee and
W. L. Santos, Org. Biomol. Chem., 2010, 8, 3451–3456;
(o) E. Yamamoto, Y. Takenouchi, T. Ozaki, T. Miya and
H. Ito, J. Am. Chem. Soc., 2014, 136, 16515–16521;
(p) A. Bonet, C. Sole, H. Gulyás and E. Fernández, Chem. –
Asian J., 2011, 6, 1011–1014; (q) X. Feng and J. Yun, Chem.
Commun., 2009, 6577–6579.
4 (a) Z.-T. He, Y.-S. Zhao, P. Tian, C.-C. Wang, H.-Q. Dong
and G.-Q. Lin, Org. Lett., 2014, 16, 1426–1429; (b) J.-B. Xie,
S. Lin, J. Luo, J. Wu, T. R. Winn and G. Li, Org. Chem.
Front., 2015, 2, 42–46; (c) J.-B. Xie, S. Lin, S. Qiao and G. Li,
Org. Lett., 2016, 18, 3926–3929.
8 See the ESI for details. The copper-catalyzed carboboration
of the produced tert-butyl ester provide 11% desired
product and 80% hydroboration side product. A further
study using this reactant was not continued.†
9 Y.-J. Zuo, X.-T. Chang, Z.-M. Hao and C.-M. Zhong, Org.
Biomol. Chem., 2017, 15, 6323–6327.
5 (a) R. Alfaro, A. Parra, J. Alemán, J. L. García Ruano and
M. Tortosa, J. Am. Chem. Soc., 2012, 134, 15165–15168;
(b) K. Kubota, E. Yamamoto and H. Ito, J. Am. Chem. Soc.,
2013, 135, 2635–2640; (c) P. Liu, Y. Fukui, P. Tian, Z.-T. He,
C.-Y. Sun, N.-Y. Wu and G.-Q. Lin, J. Am. Chem. Soc., 2013,
135, 11700–11703; (d) H. Yoshida, I. Kageyuki and 10 A reaction of 5a with allyl bromide in the presence of
K. Takaki, Org. Lett., 2013, 15, 952–955; (e) Y. D. Bidal,
F. Lazreg and C. S. J. Cazin, ACS Catal., 2014, 4, 1564–1569;
(f) K. Semba, N. Bessho, T. Fujihara, J. Terao and Y. Tsuji,
MeOK (1 equiv.) and CuCl (0.05 equiv.) in toluene at 28 °C
for 3 h was conducted and no 4aa was detected by 1H
NMR.
Angew. Chem., Int. Ed., 2014, 53, 9007–9011; (g) Y. Zhou, 11 A control reaction was conducted in the absence of allyl
W. You, K. B. Smith and M. K. Brown, Angew. Chem., Int.
Ed., 2014, 53, 3475–3479; (h) K. Semba, T. Fujihara, J. Terao
bromide under the otherwise same conditions given in
Table 2, and 5a was produced in 83% yield.
and Y. Tsuji, Tetrahedron, 2015, 71, 2183–2197; (i) B. Chen, 12 See ref. 8.
P. Cao, Y. Liao, M. Wang and J. Liao, Org. Lett., 2018, 20, 13 Unsaturated ketones and nitriles were also subjected to the
1346–1349; ( j) T. Fujihara and Y. Tsuji, Synthesis, 2018, 50,
1737–1749; (k) J. T. Han and J. Yun, Org. Lett., 2018, 20,
2104–2107; (l) D. Hemming, R. Fritzemeier, S. A. Westcott,
W. L. Santos and P. G. Steel, Chem. Soc. Rev., 2018, 47,
7477–7494; (m) H. Ito, Pure Appl. Chem., 2018, 90, 703–710;
reaction. (E)-3-Methyl-4-phenylbut-3-en-2-one and 2-benzy-
lidenebutanenitrile (E/Z = 50 : 50) produce no desired pro-
ducts under the conditions shown in Table 3. The ketone
produced a complicated mixture with 35% conversion, and
the nitrile was recovered quantitatively.
(n) T. Itoh, Y. Kanzaki, Y. Shimizu and M. Kanai, Angew. 14 C. Zhong, S. Kunii, Y. Kosaka, M. Sawamura and H. Ito,
Chem., Int. Ed., 2018, 57, 8265–8269; (o) W. J. Jang and J. Am. Chem. Soc., 2010, 132, 11440–11442.
J. Yun, Angew. Chem., Int. Ed., 2018, 57, 12116–12120; 15 I. Fleming, R. Henning, D. C. Parker, H. E. Plaut and
(p) D. Li, J. Kim, J. W. Yang and J. Yun, Chem. – Asian J.,
2018, 13, 2365–2368; (q) C. Rasson, A. Stouse, A. Boreux,
P. E. J. Sanderson, J. Chem. Soc., Perkin Trans. 1, 1995, 317–
337.
V. Cirriez and O. Riant, Chem. – Eur. J., 2018, 24, 9234– 16 J. J. Song, Z. Tan, J. T. Reeves, N. K. Yee and
9237; (r) E. Rivera-Chao and M. Fananas-Mastral, Angew. C. H. Senanayake, Org. Lett., 2007, 9, 1013–1016.
9242 | Org. Biomol. Chem., 2018, 16, 9237–9242
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