Efficient cross-coupling of dioxazaborocanes with α-phosphate enamides

Article abstract of DOI:10.1002/ejoc.201402927

A range of readily available α-phosphate enamides were subjected to (hetero) aromatic dioxazaborocanes (DABO boronates), providing the desired α-functionalized enamides in high yields via palladium-catalyzed cross-coupling reactions. Notably, the reaction proceeds in the presence of a slight excess of boron derivatives and tolerates cyclic, nonaromatic and/or electron-rich enamides.

Full text of DOI:10.1002/ejoc.201402927

Job/Unit: O42927
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Date: 28-10-14 11:25:30
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FULL PAPER
DOI: 10.1002/ejoc.201402927
Efficient Cross-Coupling of Dioxazaborocanes with α-Phosphate Enamides
Nicolas Gigant,*[a] Aurélien Honraedt,[b,c] Emmanuel Gras,*[b,c] and Isabelle Gillaizeau*[a]
Keywords: Homogeneous catalysis / Cross-coupling / Palladium / Boron heterocycles / Nitrogen heterocycles / Enols
A range of readily available α-phosphate enamides were
subjected to (hetero)aromatic dioxazaborocanes (DABO
boronates), providing the desired α-functionalized enamides
in high yields via palladium-catalyzed cross-coupling reac-
tions. Notably, the reaction proceeds in the presence of a
slight excess of boron derivatives and tolerates cyclic, non-
aromatic and/or electron-rich enamides.
Introduction
Among nitrogen-containing molecules, which are ubiqui-
tous in nature, enamides are very useful building blocks and
have found a wide range of applications over the last dec-
ade.[1] The amide conjugated C=C bond offers several op-
tions for reactivity. Indeed, the electronic bias can be modu-
lated by varying the nitrogen-protecting group as well as by
the degree of substitution of the C=C bond. Consequently,
explorations of novel enamide functionalization options
have attracted considerable attention.[2] In particular, α-
phosphate enamides (or α-phosphate ene-carbamates) can
be easily obtained from protected lactams and related com-
pounds through the agency of a lithium enolate that can be
trapped with diphenylchlorophosphate.[3] Recently, notable
progress has been made to exploit the reactivity of α-phos-
phate enamides using transition-metal catalysis,[4] and sev-
eral C–C bonds have been formed using boronic acids,[3,5]
stannanes,[3a–3c,6] simple alkynes,[6b,7] or carbon monoxide
as coupling partners in the presence of methanol (Fig-
ure 1).[8]
Figure 1. Pd-catalyzed functionalization strategies from α-phos-
phate enamides.
friendly approaches to these synthetic methods. In contrast
to previous reagents extensively involved in Suzuki–
Miyaura cross-coupling chemistries,[9] not much attention
has been paid to the reactivity of dioxazaborocanes (DABO
boronates). These species are easily isolated after simple
precipitation, offering excellent benchtop stability and a re-
markable capacity for slow in situ release of the corre-
sponding unstable boronic acids.[10,11] Enabled by consider-
able advances in the development of stable, crystalline bor-
ate salts and boronic acid derivatives,[12] we considered that
DABO boronates might be useful coupling partners for
cross-coupling reactions with readily available enol phos-
phates. To the best of our knowledge, this reactivity is sur-
prisingly unprecedented and would constitute a powerful
and selective strategy to generate differently substituted
aza-heterocycles. As an extension of our interest in enamide
functionalization using metal catalysis,[3d,5b,13] we report
herein an efficient cross-coupling of α-phosphate enamides
(i.e. ene-carbamates) and dioxazaborocanes (DABO
boronates) (Figure 1). As proof of their usefulness, the re-
sulting α-(hetero)arylenamides could be potential precur-
sors for the synthesis of α-(hetero)aryl cyclic amines which
Although these strategies provide access to α-substituted
enamides, the development of alternative practical method-
ologies starting from readily available, air-stable and highly
effective coupling partners, required in moderate or only
slight excess in the reaction, is still highly desirable. Indeed,
this creates the opportunity for user- and environmentally
[a] Institut de Chimie Organique et Analytique, UMR 7311 CNRS,
rue de Chartres, Université d’Orléans, 45067 Orléans Cedex 2,
France
E-mail: isabelle.gillaizeau@univ-orleans.fr,
gigant.n@laposte.net
http://www.icoa.fr/synthese/gillaizeau/
[b] CNRS, Laboratoire de Chimie de Coordination (LCC),
205, route de Narbonne, BP 44099, 31077 Toulouse cedex 4,
France
E-mail: emmanuel.gras@lcc-toulouse.fr
http://www.lcc-toulouse.fr
[c] Université de Toulouse, UPS, INPT,
31077 Toulouse cedex 4, France
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402927.
Eur. J. Org. Chem. 0000, 0–0
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N. Gigant, A. Honraedt, E. Gras, I. Gillaizeau
FULL PAPER
are important structures found in numerous natural and (Table 1, Entries 2 and 3). Na2CO3, which is less toxic than
bioactive molecules as illustrated in Figure 2.[14]
Ba(OH)2·8H2O, was selected to pursue the present study.
Encouraged by these results, subsequent studies indi-
cated that the application of fewer equivalents of 2a did not
significantly alter coupling efficiencies (Table 1, Entries 3–
5). No erosion in yield was observed when using between
1.5 or 1.25 equiv. of 2a and the later conditions continued
to provide excellent yields relative to reactions using only
1 equiv. of 2a. The use of 1.25 equiv. 2a to achieve a yield
of desired product 3aa significantly contrasts with the strict
requirement of a higher excess of boron reagents to ef-
ficiently perform Suzuki–Miyaura cross-couplings (1.5 or
3 equiv.). With the optimized conditions (Table 1, Entry 4)
in hand, the scope of dioxazaborocanes 2 as coupling part-
ners was explored as depicted in Table 2. Dioxazaborocanes
were obtained according to previously reported conditions
or, when the solubility of the intermediate boronic was
found to be insufficiently low in ether, by reaction of this
intermediate in methanol, evaporation and precipitation
from CH3CN/Et2O (1:10 vol). A range of 2-(hetero)aryl
azepanes 3aa–3ae were isolated in high yields. This scope
appears rather large as the reaction readily tolerates an
acetal moiety, a free alcohol, a pyridyl or a benzofuranyl
Figure 2. Representative examples of α-(hetero)aryl cyclic amines.
Results and Discussion
Guided by recent advances in this area, our representa-
tive efforts are summarized in Table 1. Initially, we explored
the reaction of lactam-derived enol phosphate 1a and diox-
azaborocane 2a with Pd/C 5% in the presence of MeOH/
H2O (99:1) without base as described previously by
Gras[11a] from aryl diazonium salts (Table 1, Entry 1). Un-
fortunately, no conversion occurred under these conditions.
The use of PdCl2(PPh3)2 with aq. Ba(OH)2·8H2O (2 m) or
aq. Na2CO3 (2 m) in the presence of THF/H2O/EtOH (v:v
= 4:1:few drops) was essential for the reaction to proceed
Table 2. Scope of dioxazaborocane 2.[a]
Table 1. Optimization of arylation using enol phosphate 1a.[a]
Entry Cat. [Pd]
Base
none
2a [equiv.] Yield 3aa [%][b]
1
2
3
4
5
Pd/C 5%
1.5
1.5
1.5
0[c]
84[d]
95
PdCl2(PPh3)2 Ba(OH)2·8H2O
PdCl2(PPh3)2 Na2CO3
PdCl2(PPh3)2 Na2CO3
PdCl2(PPh3)2 Na2CO3
1.25
1.0
93
84
[a] Reaction conditions unless otherwise specified: enol phosphate
1a (0.11 mmol, 1 equiv.), base (c = 2 m, 3 equiv.), cat. (10 mol-%)
in THF/H2O/EtOH (4/1/2 drops, c = 0.8 molL–1) for 90 min under
reflux. [b] Isolated yields after purification by column chromatog-
raphy. [c] The reaction was conducted with Pd/C 5% (5 mol-%) in
MeOH/H2O (99:1) at 50 °C for 5 h. [d] The reaction was conducted
with 1.5 equiv. of base for 4 h.
[a] Reaction conditions: enol phosphate 1a (1 equiv.), dioxaza-
borocane 2 (1.25 equiv.), Na2CO3 2 m (3 equiv.), PdCl2(PPh3)2
(10 mol-%) in THF/H2O/EtOH (4/1/2 drops, c = 0.8 molL–1) for
90 min under reflux. [b] Isolated yields after purification by column
chromatography.
2
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Cross-Coupling of Dioxazaborocanes with α-Phosphate Enamides
group to name just a few functionalities (Table 2, Entries
Finally, to further expand the synthetic utility of the re-
1–5). We highlight that functionalized azepanes constitute action, we next turned our attention to analogous com-
the key backbone of several bioactive compounds and/or pounds (Table 3). First, lactone-derived enol phosphate 4a
natural products.[15] Unfortunately, no coupled enamide 3af was successfully engaged in this transformation, giving de-
was detected in the presence of aliphatic dioxazaborocane sired tetrahydrooxepine 6aa in a satisfying yield (Table 3,
2f (Table 2, Entry 6). This sp3-hybridized organoboron de- Entry 1). However, aromatic enamide α-phosphate indole
rivative is well-known to be a reluctant coupling partner.[16] 4b and simple aryl phosphate 4c both failed to undergo
The reaction of lactam- or imide-derived enol phos- coupling under the previous experimental conditions and
phates 1a–1i with dioxazaborocane 2a is presented in procedures (Table 3, Entries 2 and 4). Nevertheless, replace-
Scheme 1. In this series, modifications concerning both the ment of 4b and 4c phosphate moieties with triflate moieties
size of the ring and the electronic properties of the hetero- led to significant improvements, resulting in formation of
cycle were envisaged, and a wide range of substrates was indole 6bc and biaryl 6ca in very good yields (Table 3, En-
found to be reactive. First, six-, seven- or even thirteen- tries 3 and 5).[17] The importance of such indoles (Table 3)
membered ring enol phosphates readily underwent reaction is supported by their broad potential in medicinal chemis-
under the optimized reaction conditions, giving cyclic scaf- try.[18]
folds 3aa, 3ba and 3ca. Electron-rich lactam-derived enol
phosphates bearing heteroatoms (O or S) at the beta posi-
Table 3. Arylation of analogous compounds 6.[a]
tion such as benzo[b][1,4]oxazine 1d, pyrido[3,2-b][1,4]oxaz-
ine 1e or benzo[b][1,4]thiazine 1f were also suitable sub-
strates, demonstrating the broad applicability of the process.
The versatility of the coupling was also evaluated using
α,αЈ-bis-enol phosphates. Corresponding diarylated struc-
tures 3ga–3ia were delivered in good to excellent yields fol-
lowing double one-pot cross-couplings. Some of these com-
pounds are potentially valuable building blocks for more
complex derivatives.[3b,3c]
[a] Reaction conditions: enol phosphate 4 or enol triflate 5
(1 equiv.), dioxazaborocane 2 (1.25 equiv.), Na2CO3 2 m (3 equiv.),
PdCl2(PPh3)2 (10 mol-%) in THF/H2O/EtOH (4/1/2 drops, c =
0.8 molL–1) for 90 min under reflux. [b] Isolated yields after purifi-
cation by column chromatography.
Conclusions
In summary, we have developed a method by which to
access α-functionalized enamides starting from α-phosphate
Scheme 1. Scope of enol phosphate 1. Reaction conditions: enol
enamides and dioxazaborocanes. Remarkably, the substrate
phosphate 1a (1 equiv.), dioxazaborocane 2 (1.25 equiv.), Na2CO3
scope of the present transformation is broad, and various
2 m (3 equiv.), PdCl2(PPh3)2 (10 mol-%) in THF/H2O/EtOH (4/1/2
drops, c = 0.8 molL–1) for 90 min under reflux. Isolated yields after
purification by column chromatography.
enamides (i.e. ene-carbamates) can be isolated in high yields
with only a slight excess of coupling partners. This feature,
Eur. J. Org. Chem. 0000, 0–0
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N. Gigant, A. Honraedt, E. Gras, I. Gillaizeau
FULL PAPER
tert-Butyl
7-[3-(1,3-Dioxolan-2-yl)phenyl]-2,3,4,5-tetrahydro-1H-
in particular, represents a significant advantage relative to
previous methods. Applications of this methodology in the
synthesis of more complex nitrogen-containing molecules
are currently being investigated in our laboratory.
azepine-1-carboxylate (3ab): Title compound 3ab was prepared ac-
cording to the typical procedure using enol phosphate 1a (50 mg,
0.11 mmol). Purification was carried out by flash chromatography
(PE/EtOAc: 9:1 to 8:2) to afford 3ab as a white solid (35 mg, 90%);
R = 0.38 (PE/EtOAc: 8:2); m.p. 115–116 °C. IR (neat): ν = 2934,
˜
f
2882, 1679, 1645, 1442, 1159 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 1.08 (s, 9 H), 1.41–1.66 (m, 4 H), 1.83 (m, 2 H), 2.30 (m, 2 H),
4.00–4.11 (m, 4 H), 5.79 (s, 1 H), 5.88 (t, J = 6.6 Hz, 1 H), 7.29–
7.40 (m, 4 H) ppm. 13C (100 MHz, CDCl3): δ = 24.3 (CH2), 27.7
(CH2), 28.1 (3ϫ CH3), 29.8 (CH2), 48.2 (CH2), 65.5 (2ϫ CH2),
80.0 (C), 103.9 (CH), 123.0 (CH), 123.4 (CH), 125.4 (CH), 126.0
(CH), 128.3 (CH), 138.1 (C), 140.2 (C), 144.3 (C), 154.2 (C) ppm.
MS (IS): m/z = 346.0 [M + H]+, 368.0 [M + Na]+. HRMS (ESI)
m/z [M – C4H9 + 2H]+ calcd. for C16H20NO4 290.13868, found
290.13886.
Experimental Section
General Methods: THF was purified with a dry station GT S100
immediately prior use. The reactions were monitored by thin-layer
chromatography (TLC) analysis using silica gel (60 F254) plates.
Compounds were visualized by UV irradiation and/or spraying
with a solution of potassium permanganate, followed by charring
at 150 °C. Flash column chromatography was performed on silica
gel 60 (230–400 mesh, 0.040–0.063 mm). Melting points (m.p.) were
taken on samples in open capillary tubes and are uncorrected. The
infrared spectra of compounds were recorded with a Thermo Scien-
tific Nicolet iS10. 1H and 13C NMR spectra were recorded at 25 °C
with a spectrometer at 250 MHz (13C, 62.9 MHz) or 400 MHz (13C,
100 MHz). Chemical shifts are given in parts per million relative
to tetramethylsilane (TMS) as an internal standard. The following
abbreviations are used for proton spectra multiplicities: s: singlet,
d: doublet, t: triplet, q: quartet, qt: quintuplet, m: multiplet, br:
broad. Coupling constants (J) are reported in Hertz (Hz). Ionspray
methodology was used to record mass spectra and HRMS spectra
were recorded using a Maxis Bruker 4G instrument.
tert-Butyl 7-[4-(Hydroxymethyl)phenyl]-2,3,4,5-tetrahydro-1H-azep-
ine-1-carboxylate (3ac): Title compound 3ac was prepared accord-
ing to the typical procedure using enol phosphate 1a (50 mg,
0.11 mmol). Purification was carried out by flash chromatography
(PE/EtOAc: 8:2 to 6:4) to afford 3ac as a white solid (30 mg, 89%);
R = = 0.45 (PE/EtOAc: 6:4); m.p. 83–84 °C. IR (neat): ν = 3443,
˜
f
2973, 2930, 1665, 1643, 1438, 1156 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 1.10 (s, 9 H), 1.46–1.76 (m, 4 H), 1.83 (m, 2 H), 2.29
(m, 2 H), 4.68 (s, 2 H), 5.88 (t, J = 6.6 Hz, 1 H), 7.29 (s, 4 H) ppm.
13C (100 MHz, CDCl3): δ = 24.3 (CH2), 27.7 (CH2), 28.2 (3ϫ
CH3), 29.8 (CH2), 48.1 (CH2), 65.2 (CH2), 80.0 (C), 122.8
(CH), 125.3 (2ϫ CH), 126.9 (2ϫ CH), 139.2 (C), 140.2 (C), 144.3
(C), 154.3 (C) ppm. MS (IS): m/z = 304.0 [M + H]+, 326.0
[M + Na]+. HRMS (ESI) m/z [M – C4H9 + 2H]+ calcd. for
C14H18NO3 248.12812, found 248.12829.
Typical Procedure for the Isolation of Dioxazaborocanes: To the
solution of boronic acid in Et2O classically obtained after halogen–
lithium exchange, B(OiPr)3 trapping and saturated NH4Cl wash, is
added dropwise a 3 m solution of diethanolamine (1 equiv. with
respect to the halogen) resulting in the formation of a precipitate.
The pure dioxazaborocane is isolated by filtration, Et2O washing
and drying.[11a]
tert-Butyl
7-(Pyridin-4-yl)-2,3,4,5-tetrahydro-1H-azepine-1-carb-
oxylate (3ad): Title compound 3ad was prepared according to the
typical procedure using enol phosphate 1a (50 mg, 0.11 mmol). Pu-
rification was carried out by flash chromatography (PE/EtOAc: 5:5
to 3:7) to afford 3ad as a orange solid (22 mg, 71%); Rf = = 0.33
Alternatively, when the intermediate boronic acid exhibits low solu-
bility in Et2O, it is first solubilized by addition of MeOH. The
diethanolamine solution (1 equiv. 3 m in iPrOH) is then added and
the mixture stirred vigorously for 0.5 h. After evaporation to dry-
ness, the solid is solubilized in hot CH3CN, and after cooling, 10
vol. of Et2O are added leading to precipitatation. The solid is then
isolated by filtration, washed with Et2O and dried to afford analyti-
cally pure dioxazaborocane.
(PE/EtOAc: 3:7); m.p. 92–93 °C. IR (neat): ν = 2958, 2835, 1698,
˜
1
1647, 1594, 1155 cm–1. H NMR (400 MHz, CDCl3): δ = 1.12 (s,
9 H), 1.15–1.67 (m, 4 H), 1.86 (m, 2 H), 2.34 (m, 2 H), 6.09 (t, J
= 10.3 Hz, 1 H), 7.20 (d, J = 9.8 Hz, 2 H), 8.52 (d, J = 9.7 Hz, 2
H) ppm. 13C (100 MHz, CDCl3): δ = 24.0 (CH2), 27.8 (CH2), 28.1
(3ϫ CH3), 29.6 (CH2), 48.0 (CH2), 80.6 (C), 119.7 (2ϫ CH), 126.4
(CH), 142.6 (C), 147.4 (C), 150.0 (2ϫ CH), 153.8 (C) ppm. MS
(IS): m/z = 275.0 [M + H]+. HRMS (ESI) m/z [M + H]+ calcd. for
C16H23N2O2 275.17540, found 275.17543.
Typical Procedure for the Suzuki–Miyaura Cross-Coupling Reac-
tion: To a solution of the appropriate enol phosphate or enol trifl-
ate 1, 4 or 5[19] (1 equiv.) in THF (0.1 molL–1) under argon was
added PdCl2(PPh3)2 (10 mol-% per phosphate). The flask was evac-
uated and backfilled with argon three times, and the mixture was
stirred for 15 min. Then, dioxazaborocane 2 (1.25 equiv. per enol
phosphate or triflate), aqueous solution of Na2CO3 2 m (3 equiv.
per enol phosphate or triflate), water (0.025 molL–1) and few drops
of EtOH (for the solubility) were added and the mixture was reflux
for 90 min. After cooling, the reaction mixture was filtered through
Celite and was washed with EtOAc. After extraction with EtOAc,
the organic phase was washed with brine, dried with MgSO4 and
concentrated. Flash chromatography (PE/EtOAc) afforded the de-
sired arylated products 3 or 6.
tert-Butyl
7-(Benzofuran-2-yl)-2,3,4,5-tetrahydro-1H-azepine-1-
carboxylate (3ae): Title compound 3ae was prepared according to
the typical procedure using enol phosphate 1a (50 mg, 0.11 mmol).
Purification was carried out by flash chromatography (PE/EtOAc:
95:5 to 9:1) to afford 3ae as a white solid (28 mg, 80%); Rf = 0.57
(PE/EtOAc: 9:1); m.p. 127–128 °C. IR (neat): ν = 2967, 2924, 1698,
˜
1
1650, 1560, 1156 cm–1. H NMR (400 MHz, CDCl3): δ = 1.24 (s,
9 H), 1.47–1.61 (m, 4 H), 1.84 (m, 2 H), 2.32 (m, 2 H), 6.37 (t, J
= 6.8 Hz, 1 H), 6.54 (s, 1 H), 7.16–7.25 (m, 2 H), 7.41 (d, J =
8.0 Hz, 1 H), 7.50 (d, J = 7.4 Hz, 1 H) ppm. 13C (100 MHz,
CDCl3): δ = 24.3 (CH2), 27.3 (CH2), 28.3 (3ϫ CH3), 29.9 (CH2),
46.5 (CH2), 80.3 (C), 101.7 (CH), 111.1 (CH), 120.8 (CH), 122.7
(CH), 124.0 (CH), 124.9 (CH), 136.0 (C), 154.1 (C), 154.9 (C),
154.9 (C) ppm. MS (IS): m/z = 314.0 [M + H]+. HRMS (ESI) m/z
tert-Butyl
7-(4-Methoxyphenyl)-2,3,4,5-tetrahydro-1H-azepine-1-
carboxylate (3aa): Title compound 3aa was prepared according to
the typical procedure using enol phosphate 1a (50 mg, 0.11 mmol).
Purification was carried out by flash chromatography (PE/EtOAc:
[M
214.12265.
– C4H9 +
2H]+ calcd. for C14H16NO 214.12264, found
95:5 to 9:1) to afford 3aa as a white solid (32 mg, 93%); all data Phenyl 6-(4-Methoxyphenyl)-3,4-dihydropyridine-1(2H)-carboxylate
are consistent with the literature.[3a]
(3ba): Title compound 3ba was prepared according to the typical
4
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Cross-Coupling of Dioxazaborocanes with α-Phosphate Enamides
procedure using enol phosphate 1b (50 mg, 0.11 mmol). Purifica-
tion was carried out by flash chromatography (PE/EtOAc: 95:5 to
8:2) to afford 3ba as a white solid (24 mg, 71%); All data are consis-
tent with literature.[3a]
EtOAc: 8:2); m.p. 158–159 °C. IR (neat): ν = 2971, 2932, 1712,
˜
1669, 1606, 1510, 1168 cm–1. 1H NMR (400 MHz, CDCl3): δ =
1.07 (s, 9 H), 2.88 (t, J = 4.6 Hz, 1 H), 3.83 (s, 6 H), 5.70 (t, J =
4.6 Hz, 1 H), 6.91 (d, J = 8.7 Hz, 4 H), 7.46 (d, J = 8.8 Hz, 4
H) ppm. 13C (100 MHz, CDCl3): δ = 24.9 (CH), 27.9 (3ϫ CH3),
55.5 (2ϫ CH3), 81.2 (C), 113.8 (4ϫ CH), 115.7 (2ϫ CH), 126.6
(4ϫ CH), 131.8 (2ϫ C), 142.4 (2ϫ C), 152.6 (C), 159.1 (2ϫ
C) ppm. MS (IS): m/z = 394.0 [M + H]+, 416.0 [M + Na]+. HRMS
(ESI) m/z [M – C4H9 + 2H]+ calcd. for C20H20NO4 338.13868,
found 338.13867.
tert-Butyl 2-(4-Methoxyphenyl)azacyclotridec-2-ene-1-carboxylate
(3ca): Title compound 3ca was prepared according to the typical
procedure using enol phosphate 1c (60 mg, 0.11 mmol). Purifica-
tion was carried out by flash chromatography (PE/EtOAc: 97:3 to
9:1) to afford 3ca as a white solid (32 mg, 75%); All data are consis-
tent with literature.[3a]
tert-Butyl 3,5-Bis(4-methoxyphenyl)-4H-1,4-oxazine-4-carboxylate
(3ha): Title compound 3ha was prepared according to the typical
procedure using enol phosphate 1h (90 mg, 0.13 mmol). Purifica-
tion was carried out by flash chromatography (PE/EtOAc: 95:5 to
8:2) to afford 3ha as a white solid (42 mg, 82%); Rf = 0.56 (PE/
tert-Butyl
3-(4-Methoxyphenyl)-4H-benzo[b][1,4]oxazine-4-carb-
oxylate (3da): Title compound 3da was prepared according to the
typical procedure using enol phosphate 1d (60 mg, 0.12 mmol). Pu-
rification was carried out by flash chromatography (PE/EtOAc:
95:5 to 85:15) to afford 3da as a white solid (38 mg, 93%); Rf =
EtOAc: 8:2); m.p. 128–129 °C. IR (neat): ν = 2979, 1707, 1606,
˜
0.69 (PE/EtOAc: 8:2); m.p. 128–129 °C. IR (neat): ν = 2976, 2921,
˜
1
1511, 1122 cm–1. H NMR (400 MHz, CDCl3): δ = 1.12 (s, 9 H),
1704, 1611, 1509, 1159 cm–1. 1H NMR (400 MHz, CDCl3): δ =
1.19 (s, 9 H), 3.81 (s, 3 H), 6.53 (s, 1 H), 6.86 (d, J = 6.8 Hz, 2 H),
6.91 (dd, J = 5.8, J = 3.6 Hz, 1 H), 7.10 (dd, J = 6.0, J = 3.6 Hz,
2 H), 7.27 (d, J = 8.8 Hz, 2 H), 7.67 (dd, J = 6.1, J = 3.4 Hz, 1
H) ppm. 13C (100 MHz, CDCl3): δ = 27.9 (3ϫ CH3), 55.5 (CH3),
82.0 (C), 114.0 (2ϫ CH), 116.0 (CH), 123.5 (CH), 124.8 (CH),
126.1 (2ϫ CH), 126.2 (CH), 126.9 (C), 128.1 (C), 129.4 (C), 134.8
(CH), 151.2 (C), 152.3 (C), 159.2 (C) ppm. MS (IS): m/z = 340.0
[M + H]+, 362.0 [M + Na]+. HRMS (ESI) m/z [M – C4H9 + 2H]+
calcd. for C16H14NO4 284.09173, found 284.09184.
3.82 (s, 6 H), 6.69 (s, 2 H), 6.90 (d, J = 8.8 Hz, 4 H), 7.46 (d, J =
8.8 Hz, 4 H) ppm. 13C (100 MHz, CDCl3): δ = 27.9 (3ϫ CH3), 55.5
(2ϫ CH3), 81.6 (C), 114.2 (4ϫ CH), 125.8 (4ϫ CH), 126.7 (2ϫ
C), 127.4 (2ϫ C), 137.0 (2ϫ CH), 152.9 (C), 159.1 (2ϫ C) ppm.
MS (IS): m/z = 396.0 [M + H]+, 418.0 [M + Na]+. HRMS (ESI)
m/z [M – C4H9 + 2H]+ calcd. for C18H18NO3 296.12812, found
296.12819.
Di-tert-butyl 2,5-Bis(4-methoxyphenyl)pyrazine-1,4-dicarboxylate
(3ia): Title compound 3ia was prepared according to the typical
procedure using enol phosphate 1i (80 mg, 0.10 mmol). Purification
was carried out by flash chromatography (PE/EtOAc: 95:5 to 85:15)
to afford 3ia as a white solid (32 mg, 68%); Rf = 0.79 (PE/EtOAc:
tert-Butyl
3-(4-Methoxyphenyl)-4H-pyrido[3,2-b][1,4]oxazine-4-
carboxylate (3ea): Title compound 3ea was prepared according to
the typical procedure using enol phosphate 1e (60 mg, 0.12 mmol).
Purification was carried out by flash chromatography (PE/EtOAc:
7:3 to 5:5) to afford 3ea as a white solid (34 mg, 83%); Rf = 0.47
8:2); m.p. 56–57 °C. IR (neat): ν = 2973, 1694, 1608, 1510,
˜
1
1121 cm–1. H NMR (400 MHz, CDCl3): δ = 1.22 (s, 18 H), 3.81
(s, 6 H), 6.45 (s, 2 H), 6.85 (d, J = 8.8 Hz, 4 H), 7.23 (d, J = 8.8 Hz,
4 H) ppm. 13C (100 MHz, CDCl3): δ = 28.0 (6ϫ CH3), 55.6 (2ϫ
CH3), 81.9 (2ϫ C), 113.8 (4ϫ CH), 116.2 (2ϫ C), 117.5 (2ϫ CH),
127.4 (4ϫ CH), 131.7 (2ϫ C), 150.7 (2ϫ C), 159.4 (2ϫ C) ppm.
MS (IS): m/z = 495.5 [M + H]+, 517.5 [M + Na]+. HRMS (ESI)
m/z [M + H]+ calcd. for C28H35N2O6 495.24896, found 495.24820.
(PE/EtOAc: 6:4); m.p. 151–152 °C. IR (neat): ν = 3093, 2973, 1720,
˜
1
1610, 1511, 1082 cm–1. H NMR (400 MHz, CDCl3): δ = 1.19 (s,
9 H), 3.81 (s, 3 H), 6.56 (s, 1 H), 6.85 (d, J = 8.8 Hz, 2 H), 7.08
(dd, J = 8.0, J = 4.8 Hz), 7.23 (dd, J = 8.0, J = 1.4 Hz, 1 H), 7.36
(d, J = 6.9 Hz, 2 H), 8.29 (dd, J = 4.8, J = 1.5 Hz, 1 H) ppm. 13C
(100 MHz, CDCl3): δ = 27.9 (3ϫ CH3), 55.5 (CH3), 82.5 (C), 114.0
(2ϫ CH), 122.1 (CH), 123.8 (CH), 126.3 (2ϫ CH), 127.3 (C), 127.7
(C), 133.9 (CH), 142.7 (C), 143.5 (CH), 147.2 (C), 151.5 (C), 159.4
(C) ppm. MS (IS): m/z = 341.0 [M + H]+, 363.0 [M + Na]+. HRMS
(ESI) m/z [M – C4H9 + 2H]+ calcd. for C15H13N2O4 285.08698,
found 285.08719.
7-(4-Methoxyphenyl)-2,3,4,5-tetrahydrooxepine (6aa): Title com-
pound 6aa was prepared according to the typical procedure using
lactone-derived enol phosphate 4a (60 mg, 0.17 mmol). Purification
was carried out by flash chromatography (PE/EtOAc/Et3N: 95:4:1)
to afford 6aa as a white solid (25 mg, 72%); Rf = 0.69 (PE/EtOAc:
95:5); m.p. Ͻ 50 °C. IR (neat): ν = 2935, 2857, 1667, 1600, 1510,
˜
tert-Butyl
3-(4-Methoxyphenyl)-4H-benzo[b][1,4]thiazine-4-carb-
1
1178 cm–1. H NMR (400 MHz, CDCl3): δ = 1.69 (qt, J = 6.1 Hz,
oxylate (3fa): Title compound 3fa was prepared according to the
typical procedure using enol phosphate 1f (60 mg, 0.12 mmol). Pu-
rification was carried out by flash chromatography (PE/EtOAc:
95:5 to 9:1) to afford 3fa as a white solid (37 mg, 87%); Rf = 0.65
1 H), 1.72 (qt, J = 5.8 Hz, 1 H), 2.31 (q, J = 6.0 Hz, 1 H), 3.82 (s,
3 H), 4.10 (t, J = 5.1 Hz, 1 H), 5.56 (t, J = 6.2 Hz, 1 H), 6.85 (d,
J = 8.8 Hz, 2 H), 7.48 (d, J = 8.8 Hz, 2 H) ppm. 13C (100 MHz,
CDCl3): δ = 25.7 (CH2), 26.5 (CH2), 32.2 (CH2), 55.5 (CH3), 72.9
(CH2), 106.9 (CH), 113.7 (2ϫ CH), 126.3 (2ϫ CH), 130.2 (C),
158.2 (C), 159.5 (C) ppm. MS (IS): m/z = 205.0 [M + H]+. HRMS
(PE/EtOAc: 9:1); m.p. 134–135 °C. IR (neat): ν = 2973, 1706,
˜
1134 cm–1. H NMR (400 MHz, CDCl3): δ = 1.21 (s, 9 H), 3.81 (s,
1
3 H), 6.36 (s, 1 H), 6.86 (d, J = 8.8 Hz, 2 H), 7.16 (t, J = 8.0 Hz,
1 H), 7.28 (m, 2 H), 7.36 (d, J = 8.7 Hz, 2 H), 7.67 (d, J = 8.0 Hz,
1 H) ppm. 13C (100 MHz, CDCl3): δ = 28.0 (3ϫ CH3), 55.5 (CH3),
81.9 (C), 112.3 (CH), 114.0 (2ϫ CH), 126.2 (CH), 126.5 (2ϫ CH),
126.8 (CH), 126.8 (CH), 126.9 (CH), 130.6 (C), 133.5 (C), 138.2
(C), 141.4 (C), 152.2 (C), 159.6 (C) ppm. MS (IS): m/z = 356.0 [M
+ H]+, 378.0 [M + Na]+. HRMS (ESI) m/z [M – C4H9 + 2H]+
calcd. for C15H14NOS 256.07906, found 256.07918.
(ESI) m/z [M
+
H]+ calcd. for C13H17O2 205.12231, found
205.12231.
Ethyl 2-(4-Methoxyphenyl)-1H-indole-1-carboxylate (6bc): Title
compound 6bc was prepared according to the typical procedure
using enol phosphate 5b (50 mg, 0.13 mmol). Purification was car-
ried out by flash chromatography (PE/EtOAc: 7:3 to 6:4) to afford
6bc as a colourless oil (34 mg, 89%); Rf = 0.50 (PE/EtOAc: 6:4).
1
tert-Butyl
2,6-Bis(4-methoxyphenyl)pyridine-1(4H)-carboxylate
IR (neat): ν = 3349, 2983, 1730, 1452, 1393, 1041 cm–1. H NMR
˜
(3ga): Title compound 3ga was prepared according to the typical
procedure using enol phosphate 1g (82 mg, 0.12 mmol). Purifica-
tion was carried out by flash chromatography (PE/EtOAc: 9:1 to
(400 MHz, CDCl3): δ = 1.15 (t, J = 7.1 Hz, 3 H), 2.00 (br., 1 H),
4.26 (q, J = 7.1 Hz, 2 H), 4.73 (s, 2 H), 6.58 (s, 1 H), 7.23–7.33 (m,
4 H), 7.41 (d, J = 7.6 Hz, 1 H), 8.16 (d, J = 8.3 Hz, 1 H) ppm. 13C
8:2) to afford 3ga as a white solid (32 mg, 68%); Rf = 0.51 (PE/ (100 MHz, CDCl3): δ = 14.0 (CH3), 63.2 (CH2), 65.2 (CH2), 110.9
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O42927
/KAP1
Date: 28-10-14 11:25:30
Pages: 7
N. Gigant, A. Honraedt, E. Gras, I. Gillaizeau
FULL PAPER
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(CH), 115.7 (2ϫ CH), 120.7 (CH), 123.4 (CH), 124.7 (CH), 126.4
(2ϫ CH), 129.1 (CH), 129.6 (C), 133.8 (C), 137.3 (C), 140.5
(C), 140.7 (C), 151.9 (C) ppm. MS (IS): m/z = 296.0 [M + H]+,
318.0 [M + Na]+. HRMS (ESI) m/z [M + H]+ calcd. for
C18H18NO3 296.12812, found 296.12817.
4Ј-Methoxy-3,5-dimethylbiphenyl (6ca): Title compound 6ca was
prepared according to the typical procedure using enol phosphate
5c (50 mg, 0.20 mmol). Purification was carried out by flash
chromatography (PE/EtOAc: 98:2) to afford 6ca as a white solid
(41 mg, 98%); All data are consistent with literature.[20]
Supporting Information (see footnote on the first page of this arti-
1
cle): H NMR spectra, 13C NMR spectra, for all new compounds.
Acknowledgments
Financial support from the Ministère de l’Enseignement Supérieur
et de la Recherche (MESR) to N. G., from Minakem to A. H. and
the LABEX SynOrg (ANR-11-LABX-0029) are gratefully ac-
knowledged. H. Bonin is thanked for preliminary experiments.
[11]
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Received: July 18, 2014
Published Online: ᭿
6
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42927
/KAP1
Date: 28-10-14 11:25:30
Pages: 7
Cross-Coupling of Dioxazaborocanes with α-Phosphate Enamides
Arylenamide Synthesis
N. Gigant,* A. Honraedt, E. Gras,*
I. Gillaizeau* .................................... 1–7
Efficient Cross-Coupling of Dioxazaboro-
canes with α-Phosphate Enamides
A
series of α-(hetero)arylenamides has
stable dioxazaborocanes, high yields were
obtained through application of a slight ex-
cess of coupling partners.
Keywords: Homogeneous catalysis / Cross-
coupling / Palladium / Boron heterocycles /
Nitrogen heterocycles / Enols
been synthesized by Suzuki–Miyaura cross-
couplings. Starting from simple α-phos-
phate enamides and air- and moisture-
Eur. J. Org. Chem. 0000, 0–0
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