Palladium-catalysed regio- And stereoselective arylative substitution of γ,δ-epoxy-α,β-unsaturated esters and amides by sodium tetraaryl borates

Article abstract of DOI:10.1039/d0ob01226b

Palladium-catalysed reactions of γ,δ-epoxy-α,β-unsaturated esters and amides with NaBAr4 reagents proceeded regio- and stereoselectively, producing allylic homoallyl alcohols with aryl-substituents in the allylic position for a wide range of substrates. A

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Organic & Biomolecular Chemistry
ARTICLE
Palladium-catalysed regio- and stereoselective arylative
substitution of ,-epoxy-α,-unsaturated esters and amides by
sodium tetraaryl borates†
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Yasemin Bilgi, Melih Kuş‡ and Levent Artok *
Palladium-catalysed reactions of ,-epoxy-α,-unsaturated esters and amides with NaBAr4 reagents proceeded regio- and
stereoselectively, producing allylic homoallyl alcohols with aryl-substituents in the allylic position for a wide range of
substrates. AsPh3 was found to be a competent ligand for the arylation reaction, whereas phosphine ligand/Lewis acidic
organoboron combinations favoured the substitution reaction by oxygen nucleophiles (e.g. H2O, ROH).
present in the form of boronic acid, water, or alcohol
additives.2 Nevertheless, herein,
Introduction
(a) Lewis-catalysed arylation with electron rich benzene derivatives (Akita)5d-g
Stereoselective ring opening reactions of epoxides constitute
one of the most important methods in organic chemistry.1
Specifically, epoxy-functionalized acrylic acid derivatives are
versatile reagents in epoxide ring-opening substitution
reactions with oxygen,2 nitrogen,3 hydride,4 and carbon-
centered5,6 nucleophiles, which mainly take place in the form
of 1,2-addition (SN2).
(OMe)n
OH
OH
CO2Me
CO2Me
(H)Me
CO2Me
(H)Me
(H)Me
+
O
BF3 Et2
O
(OMe)n
(OMe)n
(b) Arylation with arylcopper reagents (Akita)5h,i
OH
OH
Ar2CuLi
CO2Me
CO2Me
CO2Me
+
H
O
To date, arylative ring-opening reactions of γ,δ-epoxy-α,β-
unsaturated carboxylic acid derivatives have been possible
using methods involving π-electron-rich aromatics in the
presence of a Lewis acid catalyst (Scheme 1a),5dg arylcoppers
(Scheme 1b),5h,i or Grignard reagents in the presence of an iron
catalyst (Scheme 1c)5j. The first two methods usually suffer
from occasionally low regioselectivity or unsatisfactory yields.
Furthermore, any method using hard organometal
nucleophiles, such as organocopper or Grignard reagents,
requires an absolutely moisture-free environment and has low
functional group tolerance. Nevertheless, soft arylborons are
generally preferable reagents for C-C bond formation because
of their low toxicity, availability, high functional group
tolerance, longer shelf lives, and moisture insensitivity.7
Interestingly, to the best of our knowledge, there is no
reported method in the literature utilizing arylboron reagents
in the C-C bond formation of epoxy acrylic acid derivatives,
except for those methods involving simple vinyl epoxides8 and
styrenyl epoxides9, wherein the reactions took place by 1,4-
addition (SN2’) and α–aryl substitution, respectively. Perhaps,
the most important reason for this is that exposure of the
allypalladium, a putative intermediate in palladium-catalysed
reactions of allylic reagents, to the Lewis acidic boron-
promoted attack of oxygen nucleophiles, which may be
Ar
Ar
(c) Iron-catalysed reactions with Grignard reagents (Urabe)5j
OH
R2MgBr
COX
COX
R1
R1
O
FeCl2 (cat)
R2
X = OR, NR2
(d) Palladium-catalysed arylation with NaBAr4 reagents (this work)
OH
NaBAr4
COX
COX
R1
R
Pd(OAc)2/AsPh3 (cat)
O
Ar
X = OR, NR2
Scheme 1 Previous studies on the arylation of γ,δ-epoxy-α,β-unsaturated carboxylic
acid derivatives.
we demonstrate that stereoselective SN2-type arylation of γ,δ-
epoxy-α,β-unsaturated carboxylic acid derivatives can be
successfully performed by the use of NaBAr4 as the non-acidic
a. Department of Chemistry, Faculty of Science, Izmir Institute of Technology, Urla,
Izmir 35430, Turkey. E-mail: leventartok@iyte.edu.tr
†Electronic Supplementary Information (ESI) available: General procedures, tables
for optimisation studies and robustness screening data, spectroscopic data for new
compounds. See DOI: 10.1039/x0xx00000x
‡Present address: Integrated Research Centres, Izmir Institute of Technology, Urla,
Izmir 35430, Turkey
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Journal Name
organoboron reagent and AsPh3 ligand under palladium
catalysis (Scheme 1d).
View Article Online
DOI: 10.1039/D0OB01226B
Results and discussion
As the first attempt, the reaction of ester-functionalized vinyl
epoxide 1a and PhBneop was carried out at room temperature
(rt), in the presence of (i-Pr)2NH base and the Pd2(dba)3-
CHCl3/PPh3 (P/Pd = 4.1:1) catalyst combination, in a THF/water
(4:1) mixture, in a Schlenk flask, and under Ar gas. In line with
the reactivity trend mentioned above, this reaction proceeded
with complete conversion, producing a vicinal diol, structure
4a, in exclusively the syn-configuration as the major product,
albeit formed in low yield (Table 1, entry 1).10 No detectable
amount
2 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/D0OAB0R1T22IC6BLE
Table 1. Reaction optimization with vinyl epoxide 1a.a
Organoboron (3 equiv)
5% mol Pd
As or P/Pd = 4.1:1
OH
OH
CO2Et
CO2Et
CO2Et
+
Pr
O
Pr
Pr
(i-Pr)2NH (2 equiv)
Solvent
Ph
3aa
OH
4a
1a
entry
organoboron
Pd/ligand
solvent (mL)
T (℃)
time
yield%b
1
2
3
4
5
6
7
8
9d
10
11
12
13
14
15
PhBneop
PhBneop
NaBPh4
PhBneop
PhBneop
PhBneop
PhBneop
NaBPh4
NaBPh4
NaBPh4
NaBPh4
NaBPh4
NaBPh4
Pd2(dba)3-CHCl3/PPh3
Pd2(dba)3-CHCl3/dppe
Pd2(dba)3-CHCl3/dppe
Pd2(dba)3-CHCl3/AsPh3
Pd2(dba)3-CHCl3
Pd2(dba)3-CHCl3/AsPh3
Pd2(dba)3-CHCl3/AsPh3
Pd2(dba)3-CHCl3/AsPh3
Pd2(dba)3-CHCl3/AsPh3
Pd(OAc)2/AsPh3
THF/H2O (4:1)
THF/H2O (4:1)
THF/H2O (4:1)
rt
rt
rt
rt
rt
50
50
50
50
50
70
70
110
110
110
45 min
O.N.
O.N.
48 h
48 h
O.N.
3 h
3.5 h
5 h
4 h
1 h
40 min
2 min
2.5 min
4 min
34 4a
77 (69)c 4a
N.D.
55 3aa
N.C.
55 3aa
55 3aa
76 3aa
48 3aa
78 3aa
82 3aa
85 3aa
90 (87) 3aa
90 3aa
50 3aa
THF/H2O (4:0.5)
THF/H2O (4:0.5)
THF/H2O (4:0.5)
THF/MeOH (4:0.5)
THF/MeOH (4:0.5)
THF/MeOH (4:0.5)
THF/MeOH (4:0.5)
THF/MeOH (4:0.5)
dioxane/MeOH (4:0.5)
dioxane/MeOH (4:0.5)
dioxane/MeOH (4:0.5)
dioxane/MeOH (4:0.5)
Pd(OAc)2/AsPh3
Pd(OAc)2/AsPh3
Pd(OAc)2/AsPh3
e
NaBPh4
Pd(OAc)2/AsPh3
e
f
NaBPh4
Pd(OAc)2/AsPh3
aEpoxide 1a: 0.2 mmol; Phneop: phenylboronic acid neopentylglycol ester; N.D.: not determined; N.C.: no conversion; dppe: 1,2-
b
1
c
d
e
bis(diphenylphosphino)ethane. Determined by H-NMR using benzaldehyde as the internal standard. Isolated yield. Without added base. 2.0 equiv.
f1.0% Pd.
observed using 1,4-dioxane, Pd(OAc)2, and elevated reaction
of any arylated product could be detected to form by
GC/MS and 1H-NMR techniques.
temperatures (entries 10-12).
To maintain volatile MeOH and (i-Pr)2NH in solution with
high proportion, all reactions at 70 °C were carried out in a
sealed Schlenk tube. The reaction was incredibly fast at 110
°C, completed within just 2 minutes, as judged by the
appearance of palladium black (entry 13). The amount of 2a
could be reduced to 2 equivalents without sacrificing the
yield (entry 14).13 On the other hand, reducing the amount
of palladium catalyst resulted in a lower yield of the product
(entry 15).
Having established effective conditions, an array of vinyl
epoxide substrates was then subjected to the reactions with
a number of NaBAr4 reagents and the related results are
listed in Table 2. When reacted with 2a, high yields of
homoallyl alcohols were able to be achieved with epoxy
alkenyl ester substrates having a primary alkyl-substituted
and trans-configured epoxy moiety, regardless of the
structure of the ester group (entries 13).
Numerous electron-rich and poor monodentate, as well
as bidentate ligands were screened in the reaction (see the
supporting file). Generally, phosphine ligands favoured the
formation of 4a, among which dppe provided the highest
yield of 4a (entry 2). In the presence of dppe, a non-acidic
borate reagent, NaBPh4, was also tried, but a complex
mixture formed as a result of the reaction (entry 3).
Nevertheless, it was intriguing to find that the use of a
more labile ligand, such as AsPh3, for the reaction of 1a and
PhBneop rendered the arylative ring-opening reaction from
the allylic position, thereby leading to γ-aryl-substituted
homoallyl alcohols 3aa in a moderate yield with almost
clean stereoselectivity,11 and no trace of 4a was detected
(entry 4). It is apparent that the presence of a ligand is
essential for the reaction because no conversion occurred
under a ligand-free conditions (entry 5).
Substitution of water with MeOH co-solvent resulted in
considerable acceleration of the reaction at 50 °C (entries 6
and 7). Contrary to the result obtained under the conditions
of entry 3, a good yield of 3aa was obtained by using NaBPh4
(2a) instead of PhBneop under the conditions of entry 8;12
however, the presence of a base is required for a reasonable
yield (entry 9). Gradual increments in the yield were
The relative stereoisomeric configuration of homoallyl
alcohol 3da was decidedly verified by NOE interaction
studies and the H-NMR coupling constant (10 Hz) of the
vicinal tertiary hydrogen signals of its -lactone derivative
(eq 1); these data clearly indicated that 3da possessed 4,5-
anti-configuration.5,c,f,j,14
1
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DOI: 10.1039/JDo0uOrBn0a1l22N6aBme
The reaction of the substrate 1e, containing a cyclohexyl
group on the epoxy terminus, and 2a led to a relatively
lower yield (3ea). This result may imply that the method is
sensitive to sterical effects at the epoxy site for ester
compounds (entry 8). Moreover, when the epoxy group is
tri-substituted, the reaction proceeded with a lower level of
stereoselectivity (dr = 89:11), and furnished the homoallyl
product 3fa in a moderate yield (entry 9). Aryl-substituted
substrates do not appear to be suitable for the method; the
reaction of the epoxy ester 1g led to an intricate mixture
(entry 10).
This protocol was also be successfully implemented on
NaBAr4 reagents having electron-rich or moderately
electron-poor phenyl groups (entries 46). The desired
arylated product 3de, was also be obtained in a good yield
(72%) from the reaction of 1d and the highly electron
deficient NaB(p- CF3C6H4)4 (2e) reagent. However, its
formation was accompanied by an amount of methoxylated
side product 6d (entry 7).15
It was surprising that the reaction of the substrate 1h,
having a cis-configured epoxy moiety, gave rise to an
unsaturated lactone product, 7ha, with trans-configuration
in a reasonable yield, along with the expected homoallyl
product 3ha, which is the diastereomer of 3ba. The
formation of 7ha requires a homoallyl structure, 3ha’, with
Z- and anti-4,5-configurations (eq 2), because the inherent
structures of all the E-configured 3 structures do not allow
the hydroxyl and ester groups to provide sufficient distance
to undergo cyclative condensation.
Table 2. Allylic arylation of γ,δ-epoxy-α,β-unsaturated esters with NaBAr4
reagents a
.
Entry
1
Yield%
89
Epoxide
Product
OH
CO2Et
CO2Et
3ba
Bu
Bu
O
1b
1c
Ph
Ph
OH
CO2t-Bu
CO2Et
CO2t-Bu
82
2
Me
Me
O
O
Bu
3ca
EtO2C
OH
O
OH
HO
(2)
CO2Et
Me
Ph
CO2Et
Bu
7ha
Me
Bu
O
1d
Ar
Ph
Ph
3ha'
Ar: Ph
3
4
5
6
7
3da
3db
3dc
3dd
3de
90
79
81
87
72b
p-Me-C6H4
m-MeOC6H4
m-FC6H4
The reaction mechanism should be similar to its iron-
catalysed counterpart using Grignard reagents as the
nucleophilic source (Scheme 1c).5j The reaction cycle should
begin with ring-opening by the attack of a palladium
complex to 1 in anti-mode, leading to the formation of π-
allylpalladium complex A (Scheme 2).16 Then, in the case
where the ligand is AsPh3, sequential transmetalation (B)
and reductive elimination steps should furnish the arylated
homoallyl alcohol structure 3. The formation of 6d from the
p-CF3C6H4
OH
CO2Et
CO2Et
CO2Et
67
8
Cy
Me
Ph
Cy
O
3ea
1e
Ph
OH
CO2Et
56c
9
Me
Ph
O
Me
3fa
1f
Ph
Me
OH
CO2Et
CO2Et
N.D.
10
O
1g
3ga
A
B
Ph
L = AsPh3
NaBAr4
OH
H
O
H
-Pd(0)
CO2R'
[Pd], L
CO2R'
Bu
O
OH
R
3
CO2R'
R
O
R
-BAr3
CO2Et
50d
PdLn-1
-Pd(0)
1
CO2Et
1h
PdLn
11
Ar
Bu
3ha
Ph
Bu
Bu
C
D
NaBAr4
-BAr3
[Pd], AsPh3
3ha
CO2Et
CO2Et
1h
O
HO
PdLn
PdLn-1
aThe reaction conditions of entry 14 in Table 1 were applied in the
reactions. The reactions were complete within 25 minutes. bThe
reaction also gave rise to an allylic methoxylated product (6d, 12%). cdr =
89:11. dThe reaction also gave rise to a phenyl-substituted unsaturated
lactone (7ha, 32%).
Ar

transition

transition
F
E
Ar
Bu
PdLn-1
Bu
PdLn
NaBAr4
-BAr3
-Pd(0)
7ha
3ha'
HO
O
CO2Et
CO2Et
Scheme 2 General reaction mechanisms
.
reaction of 1d and 2e, even in the presence of AsPh3 (Table
2, entry 7), could be ascribed to the lower transmetalation
activity of highly electron deficient 2e with A. At this stage,
4 | J. Name., 2012, 00, 1-3
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Scheme 4 Allylic arylation of γ,δ-epoxy-α,β-unsaturated amides (8) with
NaBAr4 (2) reagents.a
probably with a promotive effect of the by-product BPh3
after reaching a critical concentration, A was exposed, to
some extent, to nucleophilic attack by MeOH.2,3
It has been previously shown that AsPh3 is an activating
palladium ligand that is superior to the most phophines in
accelerating the rate determining transmetalation step in
the Stille coupling reaction.17 Consistent with this finding, it
seems that the transmetalation step was the preferred
pathway in the presence of the softer ligand, AsPh3,
whereas the presence of the more strongly coordinating
Entry
Yield%
Epoxide
Product
OH
CON(Et)2
CON(Et)2
Me
Me
O
Ar
Ar: Ph
8a
9aa
9ab
9ad
90
79
87
1
2
3
p-Me-C6H4
m-FC6H4
OH
dppe ligand probably led to
a deceleration of the
transmetalation step. In turn, A was more exposed to
nucleophilic oxygen attack in the presence of a Lewis acidic
boron compound.
The formation of 3ha’, which is presumed to be an
intermediate structure for the formation of cyclic
CON(Bn)2
CON(Bn)2
4
Me
Me
92
Me
O
O
8b
8c
9ba
Ph
OH
CON(i-Pr)2
CON(i-Pr)2
5
6
73
88
Me
unsaturated
lactone
7ha,
should
necessitate
9ca
Ph
πallylpalladium intermediates E or F, in which planar allyl
ligands bear ester groups oriented anti with respect to the
middle allylic C-H bond. Further, since the reaction of 1h,
under the standard conditions, primarily yields
πallylpalladium intermediates C and D, with ester groups
oriented syn, the formation of C or D should be followed by
a  interconversion. For the underlying reasons, it is
difficult for us to explain this configurational transition at
this time.
OH
CON
CON
Me
Pr
Me
Pr
O
O
9da
8d
8e
Ph
OH
CON(Et)2
86
91
CON(Et)2
7
8
9ea
Ph
OH
CON(Et)2
CON(Et)2
Cy
Cy
O
8f
9fa
The versatility of this protocol has been further
demonstrated by the reaction of an optically active ester
Ph
reagent and
a scale-up experiment. The asymmetric
epoxidation of the corresponding diene ester by Shi’s
method and subsequent reaction of the produced epoxide
(2R,3R)1d and 2a under standard conditions afforded
(4R,5R)3da with a high level of ee%, which proves that,
combined with the Shi’s procedure,18 the present method
would be a convenient strategy for the synthesis of optically
active aryl-functionalized homoallyl compounds (Scheme
3a).19 The method was also successfully applied on a gram
scale (Scheme 3b); the reaction of 1.00 g of 1b with 2
equivalents of 2a was complete within 9 minutes, providing
the desired product, 3da, in a yield comparable to the
counterpart mg scale reaction.
aThe reaction conditions of entry 14 in Table 1 were applied, but with
1.5 equivalent of 2.
Finally, a robustness screen, which was formulized by
Glorius and co-workers,20 was performed with 9 different
functional group additives (1 equivalent), including
aldehyde, terminal alkyne, terminal alkene, primary alcohol,
primary alkyl chloride, phenyl chloride, nitrile, and aniline
(see Supporting Information), to the optimized conditions
though it should be qualified that these results only
(a) Synthesis of optically active 3da
2a
OH
precisely
diagnose
intermolecular
competitions.
standard
conditions
CO2Et
CO2Et
Shi epoxidation
Me
Me
CO2Et
Subsequently, we followed the yield of 3da and recovery of
the additive. While the protocol generally well-tolerated
these additives in terms of 3da formation, more or less
reduction in additive recovery was observed.
After revealing that γ,δ-epoxy-α,β-unsaturated esters
are perfectly amenable reagents toward allylic arylation, we
then extended our studies to their amide derivatives (8).
Gladly, the use of a relatively smaller amount of 2 (1.5
equiv) was sufficient for effective conversion of 8, generally
yielding the desired products in good to high yields (Scheme
4). The method operates well with both electron-rich and
O
Me
Ph
(2R,3R)-1d
94.6% ee
(4R,5R)-3da
89% yield
90% ee
(b) Scale-up experiment
OH
2a (2 equiv)
Pd(OAc)2 (5%), AsPh3 (22.5%)
CO2Et
CO2Et
Me
Me
O
(i-Pr)2NH (2 equiv)
1,4-dioxane/MeOH (120:15 mL)
110°C, 9 min
Ph
3da
1d
1000 mg
6.4 mmol
1286 mg, 5.5 mmol
86% yield
Scheme 3 Synthesis of an optically active product and scale-up experiment.
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DOI: 10.1039/JDo0uOrBn0a1l22N6aBme
poor reagents 2 (entries 13). Although the structure of the
amide group does not seem too critical for the process
(entries 46), 9ca could be isolated at a somewhat lower
corresponding yield from the reaction of 8c, containing
relatively bulkier diisopropyl amide group (entry 5). Having
larger groups on the oxirane terminus, such as propyl (8e) or
cyclohexyl (8f), had no influence on the behaviour of the
amide substrate (entries 7 and 8). It should be noted that an
inferior result was obtained with its ester counterpart 1f
(Table 2, entry 8).
Acknowledgements
Dedicated in memory of Prof. D. Nüket Öcal-Sunguroğlu.
The financial support of the Scientific and Technological
Research Council of Turkey (216Z094) and IZTECH
(2017İYTE85) is gratefully acknowledged. We thank Mr. S.
Sakrak of Redoks Analytical Laboratory Equipments Ltd. Co.,
Dr. O. N. Aslan of Atatürk University, and Ms. T. Tunceli of
Trakya University for HRMS analyses.
Notes and references
Conclusions
1
(a) A. Gansäuer, In Aziridines and Epoxides in Organic
Synthesis; A. Yudin, Ed.; Wiley-VCH: Weinheim, 2006; p.
492; for reviews on the metal-catalysed reactions of
epoxides, see: (b) J. Muzart, Eur. J. Org. Chem., 2011,
4717; (c) C. Wang, L. Luo, H. Yamamoto, Acc. Chem. Res.
2016, 49, 193; for reviews on the reactions of vinyl
epoxides, see: (d) A. Kar, N. P. Argade, Synthesis, 2005,
2995; (e) M. Pineschi, F. Bertolini, V. D. Bussolo, P. Crotti,
Curr. Org. Chem., 2009, 13, 290; (f) J. He, J. Ling, P. Chiu,
Chem. Rev., 2014, 114, 8037.
(a) A. Hirai, X.-Q. Yu, T. Tonooka, M. Miyashita, Chem.
Commun., 2003, 2482; (b) X.-Q. Yu, A. Hirai, M. Miyashita,
Chem. Lett., 2004, 33, 764; (c) X.-Q. Yu, Y. Fumihiko, K.
Tanino, M. Miyashita, Tetrahedron Lett., 2008, 49, 7442;
(d) X.-Q. Yu, F. Yoshimura, F. Ito, M. Sasaki, A. Hirai, K.
Tanino, M. Miyashita, Angew. Chem., Int. Ed., 2008, 47,
750.
In conclusion, the palladium-catalysed reaction of γ,δ-
epoxy-α,β-unsaturated esters or amides with NaBAr4
reagents proceeded regio- and stereoselectively, specifically
in anti-mode to produce allylic aryl-substituted homoallyl
alcohols. While phosphine ligands showed very poor
performance in terms of producing the desired product,
AsPh3 was found to be more suitable for the method, most
likely because it increased the activity of the palladium at
transmetalation step.
2
3
Experimental
General procedure for catalytic reactions.
(a) T. Tsuda, Y. Horii, Y. Nakagawa, T. Ishida, T. Saegusa, J.
Org. Chem., 1989, 54, 977; (b) M. Miyashita, T. Mizutani,
G. Tadano, Y. Iwata, M. Miyazawa, K. Tanino, Angew.
Chem. Int. Ed., 2005, 44, 5094.
M. Oshima, H. Yamazaki, I. Shimizu, M. Nisar, J. Tsuji, J.
Am. Chem. Soc., 1989, 11, 6280.
The reactions at <70 ℃ were carried out in a two-necked
Schlenk attached to a condenser and inert gas-line, while
those at 70 ℃ were performed in a sealed Schlenk tube
under an inert gas.
4
5
The Pd-catalyst, ligand, and dry solvent (half of the
volume required for reaction) were added, successively, into
the Schlenk (dried in an oven and cooled under Ar gas)
connected to an inert gas-line. The mixture was stirred for 5
min at rt, and then, organoboron, epoxide compound in a
dry solvent (another quarter volume required for the
reaction), additive, and base (in remaining last quarter
volume of the dry solvent) were added successively. The
mixture was stirred magnetically in a preheated oil bath.
The reaction period was monitored by TLC when carried out
in a two-necked Schlenk, while completion of the reaction
was judged by the formation of palladium black when a
sealed Schlenk tube was used. After completion of the
reaction, the mixture was filtered through a short column of
silica gel (height: 10 cm and width: 2 cm), washed with Et2O,
and concentrated under reduced pressure. The crude
product was analysed by 1H NMR using benzaldehyde as the
internal standard. The residue was purified using silica gel
column chromatography to afford the target product, the
homoallylic alcohol 3 or 9 usually as a colourless oil.
(a) N. Ishibashi, M. Miyazawa, M. Miyashita, Tetrahedron
Lett. 1998, 39, 3775; (b) M. Miyashita, M. Hoshino, A.
Yoshikoshi, J. Org. Chem., 1991, 56, 6483; (c) T. Ibuka, M.
Tanaka, H. Nemoto, Y. Yamamoto, Tetrahedron, 1989, 45,
435; (d) H. Akita, I. Umezawa, M. Takano, C. Ohyama, H.
Matsukura, T. Oishi, Chem. Pharm. Bull., 1993, 41, 55; (e)
M. Ono, R. Todoriki, Y. Yamamoto, H. Akita, Chem. Pharm.
Bull., 1994, 42, 1590; (f) M. Ono, T. Ehara, H. Yokomoya,
N. Ohtani, Y. Hoshino, H. Akita, Chem. Pharm. Bull., 2005,
53, 1259; (g) T. Ehara, S. Takinawa, M. Ono, H. Akita,
Chem. Pharm. Bull., 2007, 55, 1361; (h) S. Nagumo, S. lrie,
H. Akita, J. Chem. Soc., Chem. Commun., 1995, 2001; (i) S.
Nagumo, S. Irie, H. Akita, Chem. Pharm. Bull. 1996, 44,
675; (j) T. Hata, R. Bannai, M. Otsuki, H. Urabe, Org. Lett.,
2010, 12, 1012.
For examples of C-C coupling reactions proceeded with
1,4-addition selectivity to form allyl alcohols: (a) J. Tsuji, H.
Kataoka, Y. Kobayashi, Tetrahedron Lett., 1981, 22, 2575;
(b) H. Nemoto, T. Ibaragi, M. Bando, M. Kido, M. Shibuya,
Tetrahedron Lett., 1999, 40, 1319; (c) A. Hirai, A. Matsui,
K. Komatsu, K. Tanino, M. Miyashita, Chem. Commun.,
2002, 1970.
6
7
8
Hall, D. Boronic Acids: Preparation and Applications in
Organic Synthesis and Medicine; Wiley-VCH: Weinheim,
Germany, 2005.
(a) N. Miyaura, Y. Tanabe, H. Suginome, J. Organomet.
Chem., 1982, 233, C13; (b) J. Kjellgren, J. Aydin, O. A.
Conflicts of interest
There are no conflicts to declare.
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Wallner, I. V. Saltanova, K. J. Szabó, Chem. Eur. J., 2005,
11, 5260.
14 S. Nagumo, M. Ono, Y.-i. Kakimoto, T. Furukawa, T.
Hisano, M. Mizukami, N. Kawahara, H. Akita, J. Org.
Chem., 2002, 67, 6618.
9
D. K. Nielsen, A. G. Doyle, Angew. Chem. Int. Ed., 2011, 50,
6056.
10 Diastereomeric form of diol compound 4a was determined
by NOE measurement of its acetonide derivative as
described elsewhere (see the reference 2a,b).
11 NMR analyses of crude and isolated products in CDCl3 or
C6D6 revealed the presence of only single diastereomer of
3, unless otherwise stated.
12 For selected examples of metal-mediated reactions using
NaBAr4 reagents as the transmetalation partner, see: (a)
P. G. Ciattini, E. Morera, G. Ortar, Tetrahedron Lett., 1992,
33, 4815; (b) K. Ueura, S. Miyamura, T. Satoh, M. Miura, J.
Organomet. Chem., 2006, 691, 2821; (c) H. Zeng, R. Hua, J.
Org. Chem., 2008, 73, 558; (d) R. Shintani, Y. Tsutsumi, M.
Nagaosa, T. Nishimura, T. Hayashi, J. Am. Chem. Soc.,
2009, 131, 13588; (e) R. Shintani, S. Isobe, M. Takeda, T.
Hayashi, Angew. Chem. Int. Ed. 2010, 49, 3795.
15 The diastereomeric form of 6d was tentatively estimated,
assuming that its occurrence was similar to that of
formation of 4a.
16 (a) Hayashi, T., Hagihara, T., Konishi, M., Kumada, M., J.
Am. Chem. Soc., 1983, 105, 7767; (b) M. Oshima, H.
Yamazaki, I. Shimizu, M. Nisar, J. Tsuji, J. Am. Chem. Soc.,
1989, 111, 6280.
17 V. Farina, B. Krishnan, J. Am. Chem. Soc., 1991, 113, 9585.
18 (a) Z.-X. Wang, Y. Tu, M. Frohn, J.-R. Zhang, Y. Shi, J. Am.
Chem. Soc., 1997, 119, 11224; (b) K. Uchida, K. Ishigami, H.
Watanabea, T. Kitahara, Tetrahedron, 2007, 63, 1281.
19 Although we do not have a precise description for the
slight erosion at the ee level, it can be caused by a minor
equilibrium pathway that cleaves the non-allylic C-O bond.
20 K. D. Collins, F. Glorius, Nat. Chem., 2013, 5, 597.
13 No trans-esterification or amide by-products were found
which may occur by the reaction of 1 or 3 with MeOH and
(i-Pr)2NH
additives,
respectively.
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ARTICLE
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The palladium-catalysed reaction of γ,δ-epoxy-α,β-unsaturated esters or amides with
NaBAr4 reagents proceeded regio- and stereo-selectively to produce aryl-substituted
homoallyl alcohols