Synthesis of unnatural α-amino acid derivatives: Via selective o -C-H functionalization

Article abstract of DOI:10.1039/c7ob02921g

Pd-Catalyzed o-C-H functionalization of α-phenylglycine, 4-hydroxyphenylglycine and phenylalanine using picolinamide as a directing group is reported. We have developed different protocols for the arylation, alkylation, alkynylation, halogenation, alkoxylation, and acyloxylation of these amino acids. The reactions exhibit high selectivity, broad substrate scope, and compatibility with different functional groups in moderate to high yields. They provide a rapid and efficient access to a variety of phenyl based amino acid derivatives which can be further modified and have broad spectrum of applications in medicinal chemistry.

Full text of DOI:10.1039/c7ob02921g

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ARTICLE
Synthesis of Unnatural ræAmino Acid Derivatives via Selective o-C-H
Functionalization
Wanting Zeng, Moldir Nukeyeva, Qiumei Wang and Chao Jiang*
Received 00th January 20xx,
Accepted 00th January 20xx
Pd-catalyzed o-C-H functionalization of r-phenylglycine, 4-hydroxyphenylglycine and phenylalanine using picolinamide as a
directing group is reported. We have developed different protocols for the arylation, alkylation, alkynylation, halogenation,
alkoxylation, and acyloxylation of these amino acids. The reactions exhibit high selectivity, broad substrate scope, and
compatibility with different functional groups in moderate to high yields. They provide a rapid and efficient access to a
variety of phenyl based amino acid derivatives which can be further modified and have broad spectrum of applications in
medicinal chemistry.
DOI: 10.1039/x0xx00000x
www.rsc.org/
Introduction
r-Amino acids (r-AAs) are pivotal structural motifs of peptides,
peptidomimetics and many other pharmaceutically important
compounds.1 The interest in biologics containing non-
proteinogenic amino acids or non-natural linkages has
increased dramatically.2 Coordination-ꢀ]Œꢁꢂšꢁꢀ />I ꢃ}vꢀ
functionalization of nitrogen-ꢂ}všꢄ]v]vP ꢂ}u‰}µvꢀ•U •µꢂZ ꢄ• r-
amino acids, is particularly attractive given their prevalence in
natural products and therapeutic agents.3 Therefore it is
significant to develop new methodologies for the efficient
molecular chemical modifications of amino acids due to the
limited number of natural amino acids and their high potential
application value. In this context, the use of transition-metal
catalysis to modify small molecules in a tailored manner
through C-C or C-X bond formation in aromatic rings could
provide an attractive way to target amino acids that display this
structural motif.4
In recent years, synthetic methods based on transition-
metal catalyzed directed C-H functionalization to access
unnatural counterparts have been investigated. Compared with
traditional cross-coupling reactions, transition-metal catalyzed
directed C-H activation has proven to be a powerful approach
to utilize existing functional groups in a molecule to guide />I
Scheme 1 Pd-catalyzed C-H functionalization of benzylamine and r-phenylglycine.
alkylation,9 borylation,10 alkoxylation,11 alkenylation,12 and
acetoxylation13 reactions for the synthesis of unnatural amino
acids have been published. Considering most work are focused
on phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), and
Z]•š]ꢀ]vꢁ ~I]••U Áꢁ ꢂZ}•ꢁ r-phenylglycine as our substrate and
tried to develop protocols for the synthesis of its derivatives.
Notably, these scaffolds have already been found in many
pharmaceutical drugs (e.g., cephalexin,14 clopidogrel,15
5
cleavage at a particular site in a highly selective manner. In
2
006, Corey et al. first applied the AQ auxiliary for Pd-catalyzed
6
t-CtH acetoxylation of alanine. Inspired by this seminal work,
significant progress has been made in this area. Reports by
7
8,18
several groups on metal-catalyzed halogenation, arylation,
16
ampicillin ), and direct functionalization may expand the scope
of these classes of compounds for further medicinal
investigation. In 2013, Daugulis reported the scope of
palladium-catalyzed, picolinamide-assisted direct arylation and
alkylation of sp2 />I ꢃ}vꢀ• }( ꢃꢁvÌÇo ꢄu]vꢁ• ꢀꢁŒ]Àꢄš]Àꢁ•
a.School of Chemical Engineering, Nanjing University of Science and Technology,
Nanjing 210094, China E-mail: chaojiang@njust.edu.cn
ꢀ
C}}šv}šꢁ• Œꢁoꢄš]vP š} šZꢁ š]šoꢁ ꢄvꢀl}Œ ꢄµšZ}Œ• •Z}µoꢀ ꢄ‰‰ꢁꢄŒ ZꢁŒꢁX
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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Scheme 1a).17 In 2015, Yu and co-workers described the Pd-
Journal Name
a
(
Table 2 C-H arylation of r-phenylglycine
ꢂꢄšꢄoÇÌꢁꢀ />I olefination }( r-phenylglycine, in which a
monoprotected amino acids (MPAA) ligand was employed to
achieve the monoselectivity (Scheme 1b).18 Herein, we report a
variety of o-/>I (µvꢂš]}vꢄo]Ìꢄš]}v• of r-phenylglycine, 4-
hydroxyphenylglycine and phenylalanine including selective bis-
arylation, halogenation, alkoxylation, acyloxylation and
selective mono-alkylation, alkynylation with the yield up to 99%
(Scheme 1c). The site-selectivity in this method was controlled
by a removable bidentate directing group of picolinamide.19
Results and discussion
!
ŒÇoꢀš]}v }( r-phenylglycine, 4-hydroxyphenylglycine and
phenylalanine. Based on one of our previous work of vinylic C-
H arylation of unsubstituted acrylamide,20 we began our
investigation by studying C-H arylation of 1a with phenyl iodide
in the presence of a Pd catalyst under various reaction
conditions (Table 1). The initial optimization experiments were
aimed at varying the equivalence of phenyl iodide (2a), which
plays a crucial role in mono- or di-selectivity (entries 1-4). Next,
we investigated the influence of different solvents including 1,4-
a
Conditions: all reactions were carried on a 0.1 mmol scale. b Isolated yield, mono-
3
dioxane, toluene and CH CN (entries 5-7). Among the solvents
arylated product in the parenthesis. c Conditions: Pd(TFA)
(10 mol %), AgOAc (3.5
2
investigated, the initially used t-AmylOH provided the best
result. The amount of silver acetate is crucial for improving the
yields and selectivity of the di-arylated product. Eventually, the
optimized bis-arylation conditions include 2.5 equiv. of AgOAc
equiv.).
3
k
), methoxyl (3c and 3l), and phenyl (3d), as well as electron-
withdrawing groups such as trifluoromethyl (3h 3p), cyano(3i),
and methoxycarbonyl (3j). Halides including fluoro (3e 3m),
chloro (3f 3n), and bromo (3g 3o) in the meta- or para- position
in t-AmylOH solvent, 10 mol % of Pd(OAc)
2
, and 5 equiv. of aryl
,
iodide at 130 °C.
,
Subsequently, the scope of aryl iodides
2
with diverse
,
,
functional groups was examined under the optimized
conditions (Table 2). As shown in Table 2, we found that a
variety of different functional groups on the arenes were
also worked well and can be used for further synthetic
elaborations. Most of the substrates gave good to excellent
yields even though some of the mono-arylated products were
observed.
tolerated including electron-donating groups such as alkyls (3b
,
Next, we expanded the amino acid substrate scope to 4-
hydroxyphenylglycine (Table 3) and phenylalanine (Table 4). In
Table 3, Aryl iodides bearing methoxyl and phenyl groups gave
moderate to good yields with extended reaction time, while aryl
Table 1 Optimization of the reaction conditions for di-arylation of r-
phenylglycinea
2 3
iodides with electron-withdrawing groups (e.g., 4-CO CF , 3-F,
Table 3 C-H arylation of 4-hydroxyphenylglycinea
a
Unless otherwise noted, all reactions were carried on a 0.1 mmol scale in 0.5 ml
solvent. b Determined by 1HNMR analysis of the crude products which only
contains 3a/ïꢀ[.
a
2
Conditions: 1b/1c (0.1 mmol), ArI (5 equiv.), Pd(OAc) (10 mol %), AgOAc (2.5
equiv.), t-AmylOH (1 mL), 130 C, 24~36 h. b Isolated yield.
o
2
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Table 4 C-H arylation of phenylalaninea
Scheme 3 C-H halogenation of r-phenylglycine. a AgF (3 equiv.) was added.
a
2 2 3
Conditions: substrate 1d (0.1 mmol), ArI (5 equiv.), Pd(OAc) (10 mol %), Ag CO
o
b
(
2.5 equiv.), t-AmylOH (1 mL), 130 C, 24~36 h. Isolated yield.
Scheme 4 C-H alkylation of r-phenylglycine.
4
-CO Me) were not effective. Phenylalanine was also
2
compatible with this protocol when Ag
CO was added instead
2 3
of AgOAc (Table 4). Despite significant progress in the C-H
functionalization of phenylalanine, there are no reports on the
selective o-C-H bis-arylation of phenylalanines.6,8e,21
To further explore the potential application, the C-H
arylation reaction of 1a with 4-bromo-iodobenzene (2g) was
scaled up to 4.0 mmol. 1.43 gram of product 3g was successfully
obtained in 62% yield (Scheme 2a). Then, we attempted the
removal of the picolinamide directing group. Upon treatment
Scheme 5 C-H alkynylation of r-phenylglycine.
with BF
was removed and protected with Boc group to afford
compound
.22
3 2
·Et O in dichloromethane for 48 h, the directing group
AgF was added to achieve the successful chlorination reaction,
otherwise, only trace amount of product was observed. The
fluorination reaction was also attempted with NFSI, but no
fluorinated products were observed.
5
/>I ꢄolÇoꢄš]}v and alkynylation }( r-phenylglycine was also
studied using different alkyl iodides. With extensive
optimization of the conditions, the alkylation reactions were
less efficient, affording moderate yields of the mono-alkylated
3
products 7a, 7b and 7c as shown in Scheme 4. NaHCO was
employed as a base and additive in the reaction, and an oxygen
atmosphere was required for the reaction. Employing a 1-
bromo-alkyne reagent, the mono-selective ortho alkynylated
products 8a
as a promoter (Scheme 5).24
ol}ÆÇoꢀš]}v ꢀvꢁ ꢀꢂÇo}ÆÇoꢀš]}v }( r-phenylglycine and 4-
hydroxyphenylglycine Palladium-catalyzed alkoxylation of r-
, 8b were obtained in moderate yields using NaOAc
!
Scheme 2 (a) Gram-scale synthesis; (b) directing group cleavage.
.
phenylglycine with primary or secondary alcohols was also
developed which was rarely studied on r-phenylglycine and
offers a late-stage strategy to synthesize r-phenylglycine
derivatives. Since alcohols can be used as a solvent in palladium-
ꢂꢄšꢄoÇÌꢁꢀ />I ꢃ}vꢀ (µvꢂš]}vꢄo]Ìꢄš]}vU19a,25 we performed the
reaction of 1a with 5 mol % of Pd-catalyst and 3.5 equiv. of
Halogenation, alkylation and alkynylation of r-phenylglycine
and
4-hydroxyphenylglycine.
A
palladium-catalyzed
halogenation of r-phenylglycine with N-halosuccinimides was
also developed to give halo substituted r-phenylglycines, which
provides an efficient and practical entry for further
derivatization.23 With NCS, NBS and NIS as the halogenation
PhI(OAc)
the desired product was obtained in a good yield of 86% when
Pd(OAc) was applied as the catalyst (entry 1). Other palladium
2
in methanol in a sealed tube (Table 5). To our delight,
2
reagents, dihalogenation product 6a, 6b and 6c were obtained
catalysts only led to inferior results (entries 2-4). A mixed
solvent of MeOH: toluene in 4 : 1 gave increased yield and
in 77%, 99% and 70% yields (Scheme 3) using different solvent.
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Table 5 Optimization of the reaction conditions for di-alkoxylationa of r-
phenylglycinea
Scheme 6 C-H acyloxylation and benzoxylation of r-phenylglycine. [a] Ac
equiv.), PhI(OAc) (4 equiv.) were used.
2
O (10
2
In conclusion, palladium-catalyzed picolinamide-assisted
diselective o-C-H arylation, halogenation, alkylation,
alkynylation, alkoxylation and acyl}ÆÇoꢄš]}v }( r-phenylglycine
has been achieved in moderate to good yields. Moreover, the
reaction can be scaled up to gram scale and the picolinamide
group could be removed with Lewis acid. The optimized
protocol provides a valuable tool for the synthesis of unnatural
amino acids which can be further applied in pharmaceutical
chemistry.
a
2 2
Conditions: 1a (0.1 mmol), Pd(OAc) (5 mol %), PhI(OAc) (3.5 equiv.), solvent (1
mL), mixed solvent MeOH: Toluene = 4:1, 3 h. b Isolated yield. No PhI(OAc).
c
higher selectivity of di-methoxylation product (entry 5).
Increasing reaction temperature did not further improve the
yield (entry 6). The alkoxylation did not proceed in the absence
2 2
of either Pd(OAc) or PhI(OAc) (entry 7 and entry 8). We then Experimental
assessed the scope of the reaction with several alcohols under
the optimized reaction conditions with r-phenylglycine
substrate 1a and 4-hydroxyphenylglycine substrate 1b with TBS
protection. As shown in Table 6, the protocol was feasible for
both primary and secondary alcohols, and the desired di-
alkoxylated products were obtained in moderate to good yields.
General remarks
All reagents and metal catalysts were obtained from
commercial sources without further purification. Massspectra
were recorded with an TSQ Quantum-LC/MS/MS of Finnigan
using Electrosprayionization (ESI) techniques. 1H and 13C NMR
spectra were recorded with a Bruker AV-300 and AV-500
!
ꢀꢀ]š]}vꢄooÇU šZꢁ •šµꢀÇ }( šZꢁ ꢄꢂÇo}ÆÇoꢄš]}v }( r-
phenylglycine using PhI(OAc) was carried out with Pd(OAc) as
the catalyst and Ag CO
as the base and promoter (Scheme 6).27
After optimization, the di-acyloxylated products were obtained
in 69% yield with 10 equiv. of Ac O added. Based on the
spectrometer
operating
at
300MHz/500MHz
and
2
2
7
5MHz/125MHz, respectively, with chemical shift values being
1
2
3
Œꢁ‰}Œšꢁꢀ ]v ‰‰u Œꢁoꢄš]Àꢁ š} ꢂZo}Œ}(}Œu ~wAóXîò ‰‰u• (}Œ H
bawU ꢄvꢀ ꢂZo}Œ}(}Œu ~wAóóXíò ‰‰u• (}Œ 13C NMR.
2
General procedure for the o-C-H diarylation. To a 15 mL Schlenk
tube, substrate 1a(1b/1c/1d) (0.1 mmol), aryl iodides (0.5 mmol),
optimized conditions, the ꢃꢁvÌ}ÆÇoꢄš]}v }( r-phenylglycine
with iodobenzene dibenzoate was also achieved as shown in
Scheme 6.
Pd(OAc)
mL) were added under atmospheric air. The mixture was stirred for
2~24 h (for 1b/1c/1d, was stirred for 24~36 h) at 130 °C followed by
2
(2.2 mg, 0.01 mmol), Ag salt (0.25 mmol) and t-AmylOH (1
1
cooling. The mixture was filtered through a celite pad and
concentrated in vacuo. The residue was purified by column
chromatography on silica gel (eluent: petroleum ether /EtOAc) to
afford the desired arylated product (3a~3u, 4a~4i).
Conclusions
Table 6 C-H alkoxylation of r-phenylglycinea
General procedure for the o-C-H dihalogenation. (For chlorination)
To a 15 mL Schlenk tube, 1a (27 mg, 0.1 mmol), NCS (53.4 mg, 0.4
2
mmol), Pd(OAc) (2.2 mg, 0.01 mmol), AgF (38.1 mg, 0.3 mmol) and
p-xylene (1 mL) were added under atmospheric air. The mixture was
stirred for 36 h at 110 °C followed by cooling. The mixture was
filtered through a celite pad and concentrated in vacuo. The residue
was purified by column chromatography on silica gel (eluent:
petroleum ether /EtOAc) to afford the desired arylated product 6a.
(
For bromination) To a 15 mL Schlenk tube, 1a (27 mg, 0.1 mmol),
NBS (71.2 mg, 0.4 mmol), Pd(OAc) (2.2 mg, 0.01 mmol) and DCE (1
mL) were added under atmospheric air. The mixture was stirred for
4 h at 120 °C followed by cooling. The mixture was filtered through
2
2
a celite pad and concentrated in vacuo. The residue was purified by
column chromatography on silica gel (eluent: petroleum ether
/EtOAc) to afford the desired arylated product 6b. (For iodization) To
a
2 2
Conditions: 1a/1b (0.1 mmol), Pd(OAc) (5 mol %), PhI(OAc) (3.5 equiv.), ROH:
o
b
Toluene = 4: 1 (1 mL), 120 C, 3~6 h. Isolated yield.
4
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1
a 15 mL Schlenk tube, substrate 1a (27 mg, 0.1 mmol), NIS (90 mg,
Compound 1c. Light yellow solid, mp 126-127 °C H NMR (500
0
.4 mmol), Pd(OAc)
added under atmospheric air. The mixture was stirred for 24 h at 8.14 (t, J = 8.4 Hz, 1H), 7.83 (dtd, J = 9.4, 7.8, 1.7 Hz, 1H), 7.44 t 7.35
10 °C followed by cooling. The mixture was filtered through a celite (m, 7H), 7.34 t 7.29 (m, 1H), 7.04 t 6.88 (m, 2H), 5.73 (dd, J = 25.9,
pad and concentrated in vacuo. The residue was purified by column 7.4 Hz, 1H), 5.05 (s, 2H), 3.76 (s, 3H). 13C NMR (126 MHz, CDCl
• w
chromatography on silica gel (eluent: petroleum ether /EtOAc) to 171.37, 163.84, 159.06, 149.38, 148.34, 137.33, 136.82, 128.90,
afford the desired arylated product 6c. 128.75, 128.67, 128.09, 127.49, 126.47, 122.39, 115.36, 70.11, 56.11,
General procedure for the o-C-H mono-alkylation. To a 15 mL 52.81. HRMS (EI) calcd. for C22 : 376.1423. Found: 376.1420.
Schlenk tube, 1a (27 mg, 0.1 mmol), RI (0.5 mmol), NaHCO (16.8 mg, Compound 1d. Colorless oil. This compound is known.
2 3
(2.2 mg, 0.01 mmol) and toluene (1 mL) were MHz, CDCl • w ôXõî ~ꢀꢀU J = 46.5, 7.3 Hz, 1H), 8.57 (d, J = 4.3 Hz, 1H),
1
3
20 2 4
H N O
3
0
.2 mmol), Pd(OAc)
2
(2.2 mg, 0.01 mmol), DCE (1 mL) were added (Reference: R. R. Pulimamidi, R. Nomula, R. Pallepogu and H. Shaik,
1
under oxygen atmospheric . The mixture was stirred for 24 h at Eur. J. Med. Chem., 2014, 79, 117.) H NMR (500 MHz, CDCl
3
• w ôXñî
corresponding temperature followed by cooling. The mixture was (d, J = 4.7 Hz, 1H), 8.48 (d, J = 8.1 Hz, 1H), 8.13 (d, J = 7.8 Hz, 1H), 7.80
filtered through a celite pad and concentrated in vacuo. The residue (td, J = 7.7, 1.5 Hz, 1H), 7.48 t 7.36 (m, 1H), 7.26 (t, J = 7.2 Hz, 2H),
was purified by column chromatography on silica gel (eluent: 7.21 (t, J = 7.2 Hz, 1H), 7.17 (d, J = 7.2 Hz, 2H), 5.15 t 4.94 (m, 1H),
petroleum ether /EtOAc) to afford the desired arylated product 3.70 (s, 3H), 3.23 (qd, J = 13.9, 6.2 Hz, 2H).
1
7
a~7c.
Compound 3a. Yellow oil, yield 82 %. H NMR (300 MHz, CDCl
3
)
General procedure for the o-C-H mono-alkynylation. To a 15 mL w ôXðô ~ꢀU J = 4.6 Hz, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 7.8 Hz,
Schlenk tube, 1a/1c (0.1 mmol), bromoalkyne (0.4 mmol), Pd(OAc) 1H), 7.74 (d, J = 1.5 Hz, 1H), 7.47 t 7.31 (m, 12H), 7.26 (d, J = 7.5 Hz,
2.2 mg, 0.01 mmol), NaOAc (16.4 mg, 0.2 mmol) and dioxane (1 mL) 2H), 6.09 (d, J = 8.6 Hz, 1H), 3.59 (s, 3H). 13C NMR (75 MHz, CDCl
• w
2
(
3
were added under atmospheric air. The mixture was stirred for 48 h 171.31, 162.78, 149.34, 147.89, 143.00, 140.90, 136.94, 134.28,
at 120 °C followed by cooling. The mixture was filtered through a 133.24, 130.12, 129.54, 128.09, 127.58, 127.32, 125.99, 122.08,
celite pad and concentrated in vacuo. The residue was purified by 52.80, 52.52. HRMS (ESI) calcd. for C27
H
22 2
N O
3
: 422.1630. Found
column chromatography on silica gel (eluent: petroleum ether 422.1632.
1
/EtOAc) to afford the desired arylated product 8a/8b.
Compound 3b. White solid, yield 70 %, mp 139-140 °C. H NMR
General procedure for the o-C-H dialkoxylation. To a 15 mL Schlenk ~ïìì aIÌU /5/oï• w ôXðõ ~ꢀU W A ðXí IÌU íI•U ôXðì ~ꢀU J = 8.3 Hz, 1H),
tube, 1a/1b (0.1 mmol), PhI(OAc) (0.35 mmol, 112 mg), Pd(OAc) 8.04 (d, J= 7.7 Hz, 1H), 7.75 (t, J= 7.6 Hz, 1H), 7.44 t7.15 (m, 12H),6.12
1.1 mg, 0.005 mmol), ROH and toluene (4:1, 1 mL) were added (d, J = 8.7 Hz, 1H), 3.61 (s, 3H), 2.43 (s, 6H). 13C NMR (75 MHz, CDCl
2
2
(
3
)
under atmospheric air. The mixture was stirred for 3 h (for 1b was w íóíXïõU íòîXóîU íðõXïñU íðóXó9, 142.95, 138.02, 137.16, 137.03,
stirred for 3~6 h) at 120 °C followed by cooling. The mixture was 133.41, 130.14, 129.38, 128.83, 127.31, 126.00, 122.18, 52.81, 52.51,
filtered through a celite pad and concentrated in vacuo. The residue 21.29. HRMS (ESI) calcd. for C29
was purified by column chromatography on silica gel (eluent:
petroleum ether /EtOAc) to afford the desired arylated product (300 MHz, CDCl
9a~9h). 6.8 Hz, 1H), 7.75 (s, 1H), 7.35 (t, J = 7.5 Hz, 6H), 7.24 (t, J = 7.5 Hz, 2H),
DꢃvꢃŒꢀo ‰Œ}ꢂꢃꢁµŒꢃ (}Œ šZꢃ or/rI ꢁ]ꢀꢂÇo}ÆÇoꢀš]}vX To a 15 mL Schlenk 6.97 (d, J = 8.3 Hz, 4H), 6.14 (d, J = 8.5 Hz, 1H), 3.86 (s, 6H), 3.62 (s,
tube, 1a (27 mg, 0.1 mmol), PhI(OR) (0.5 mmol), Pd(OAc) • w íóíXíîU íòîXñì, 158.70, 149.04,
(2.2 mg, 3H). 13C NMR (75 MHz, CDCl
.01 mmol), Ag CO (27.6 mg, 0.1 mmol) and toluene (1 mL) were 147.57, 142.35, 136.70, 133.51, 132.97, 130.33, 129.99, 126.99,
added under atmospheric air. (For acetoxylaion, PhI(OAc) (0.4 125.73, 121.81, 113.22, 54.91, 52.54, 52.23. HRMS (EI) calcd. for
mmol), Ac O (1mmol) were added.) The mixture was stirred for 12 h : 482.1842. Found: 482.1843.
at 120 °C followed by cooling. The mixture was filtered through a Compound 3d. White solid, yield 72 %. mp 166-167 °C. H NMR
celite pad and concentrated in vacuo. The residue was purified by (300 MHz, CDCl • w ôXðð ~ꢀꢀU J = 11.7, 6.3 Hz, 2H), 8.05 (d, J = 7.7 Hz,
column chromatography on silica gel (eluent: petroleum ether 1H), 7.76 (t, J = 7.7 Hz, 1H), 7.69 (d, J = 7.4 Hz, 8H), 7.57 t 7.43 (m,
EtOAc) to afford the desired arylated product 10a~10c.
8H), 7.42 t 7.30 (m, 6H), 6.21 (d, J = 8.4 Hz, 1H), 3.67 (s, 3H). 13C NMR
Compound 1a. White solid, mp 67-68 °C. This compound is (75 MHz, CDCl • w íóíXðîU íòîXôñU íðõXîòU íðóXõîU íðîXòôU íðìXóïU
H
26 2
N O
3
: 450.1943. Found 450.1941.
1
Compound 3c. Yellow solid, yield 70 %, mp 135-136 °C. H NMR
3
• w ôXñì ~•U íI•U ôXðî ~ꢀU J = 8.3 Hz, 1H), 8.04 (d, J =
(
2
2
3
0
2
3
2
2
29 26 2 5
C H N O
1
3
/
3
known. (Reference: A. V. Malkov, L. Gouriou, G. C. Lloydjones, I. Starý, 140.31, 140.05, 136.99, 133.37, 130.31, 129.97, 128.77, 127.49,
V. Langer, P. Spoor, V. Vinader and P. Kocovský, Chem. Eur. J., 2006, 127.34, 127.11, 126.84, 126.05, 122.06, 53.13, 52.69. HRMS (EI) calcd.
1
1
2, 6910-6929.) I baw ~ïìì aIÌU /5/oï• w ôXõð ~ꢀU W A òXí IÌU íI•U for C39
H
30 2
N O
3
: 574.2256. Found: 574.2257.
1
8
.59 (d, J = 4.1 Hz, 1H), 8.16 (d, J = 7.8 Hz, 1H), 7.83 (td, J = 7.7, 1.6
Compound 3e. Yellow oil, yield 55 %. H NMR (300 MHz, CDCl
3
)
Hz, 1H), 7.58 t 7.29 (m, 6H), 5.78 (d, J = 7.6 Hz, 1H), 3.77 (s, 3H).
w ôXñì ~ꢀU J = 4.4 Hz, 1H), 8.36 (d, J = 8.2 Hz, 1H), 8.03 (d, J = 7.8 Hz,
1
Compound 1b. Yellow oil. H NMR (300 MHz, CDCl
3
• w ôXôï ~ꢀU J 1H), 7.76 (td, J = 7.7, 1.4 Hz, 1H), 7.48 t 7.29 (m, 6H), 7.23 (d, J = 7.6
=
7
6
9
1
5
4
7.1 Hz, 1H), 8.57 (d, J = 4.6 Hz, 1H), 8.16 (d, J = 7.8 Hz, 1H), 7.98 t Hz, 2H), 7.13 (t, J = 8.7 Hz, 4H), 6.03 (d, J = 8.4 Hz, 1H), 3.63 (s, 3H).
.67 (m, 1H), 7.42 (dd, J = 6.5, 4.9 Hz, 1H), 7.32 (d, J = 8.5 Hz, 2H), 13C NMR (126 MHz, CDCl
• w íóíXïíU íòîXðó ~ꢀU WCF = 246.7 Hz), 162.90,
.82 (d, J = 8.5 Hz, 2H), 5.69 (d, J = 7.5 Hz, 1H), 3.76 (s, 3H), 0.96 (s, 149.24, 148.10, 142.13, 137.18, 136.88, 133.74, 131.35(d, JCF = 5.2
H), 0.18 (s, 6H). 13C NMR (126 MHz, CDCl
• w íóíXîôU íòïXóìU íññXõïU Hz), 130.58, 127.54, 126.29, 122.17, 115.17 (d, JCF = 21.4 Hz), 52.95,
49.29, 148.27, 137.25, 129.16, 128.64, 126.42, 122.27, 120.43, 52.79. HRMS (EI) calcd. for C27
3
3
H
20 2
F N
2
O
3
: 458.1442. Found: 458.1440.
1
6.05, 52.60, 25.61, 18.10, -4.46. HRMS (EI) calcd. for C21
H
28 2
N O
4
Si:
Compound ïꢃ[. Yellow oil, yield 16 %. H NMR (300 MHz, CDCl
3
)
00.1818. Found: 400.1815.
w ôXôñ ~ꢀU J = 6.2 Hz, 1H), 8.58 (d, J = 3.9 Hz, 1H), 8.11 (d, J = 7.7 Hz,
1
H), 7.82 (t, J = 7.7 Hz, 1H), 7.57 t 7.35 (m, 6H), 7.29 (dd, J = 6.9, 4.0
J. Name., 2013, 00, 1-3 | 5
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DOI: 10.1039/C7OB02921G
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Journal Name
1
Hz, 1H), 7.14 (t, J = 8.7 Hz, 2H), 5.80 (d, J = 7.0 Hz, 1H), 3.70 (s, 3H).
Compound 3k. Yellow solid, yield 72 %, mp 123-124 °C. H NMR
13C NMR (75 MHz, CDCl
49.16, 148.18, 141.51, 137.18, 136.12, 134.43, 131.13 (d, JCF = 7.4 8.08 (d, J = 7.8 Hz, 1H), 7.77 (td, J = 7.7, 1.5 Hz, 1H), 7.38 (dd, J = 15.9,
Hz), 130.79, 128.29 (d, JCF = 8.2 Hz), 126.86, 126.34, 122.18, 117.58, 8.2 Hz, 4H), 7.32 t 7.20 (m, 8H), 6.18 (t, J = 12.6 Hz, 1H), 3.61 (s, 3H),
3 3
• w íóíXîðU íòîXïì ~ꢀU WCF = 246.1 Hz), 163.52, (300 MHz, CDCl • w ôXñï ~ꢀU J = 4.5 Hz, 1H), 8.46 (d, J = 8.7 Hz, 1H),
1
1
C
15.14 (d, JCF = 21.5 Hz), 53.47, 52.67. HRMS (EI) calcd. for 2.43 (s, 6H). 13C NMR (126 MHz, CDCl
3
• w íóíXðóU íòîXôòU íðõXòñU
21
H
2
17FN O
3
: 364.1223. Found: 364.1227.
148.06, 143.24, 140.92, 137.82, 137.09, 133.28, 130.48, 130.08,
1
Compound 3f. Yellow oil, yield 80 %. H NMR (300 MHz, CDCl
3
• w 128.45, 128.13, 127.41, 126.67, 126.09, 122.35, 52.89, 52.57, 21.60.
8
7
2
1
1
.51 (d, J = 4.6 Hz, 1H), 8.33 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 7.8 Hz, 1H), HRMS (EI) calcd. for C29
.76 (td, J = 7.7, 1.5 Hz, 1H), 7.50 t 7.29 (m, 10H), 7.21 (d, J = 7.6 Hz,
H), 6.00 (d, J = 8.2 Hz, 1H), 3.64 (s, 3H). 13C NMR (75 MHz, CDCl
H
26
N
2
O
3
: 450.1943. Found: 450.1941.
1
Compound 3l. Yellow oil, yield 70 %. H NMR (300 MHz, CDCl
3
• w
3
• w 8.47 (d, J = 4.1 Hz, 1H), 8.38 (d, J = 8.6 Hz, 1H), 8.03 (d, J = 7.8 Hz, 1H),
71.06, 162.67, 148.94, 147.94, 141.81, 139.27, 137.17, 133.72, 7.75 (td, J = 7.7, 1.2 Hz, 1H), 7.44 t 7.31 (m, 4H), 7.27 (d, J = 7.5 Hz,
33.19, 130.85, 130.37, 128.31, 127.52, 126.23, 122.05, 52.91, 52.74. 2H), 6.97 (d, J = 7.8 Hz, 6H), 6.16 (d, J = 8.8 Hz, 1H), 3.79 (s, 6H), 3.61
HRMS (EI) calcd. for C27
H
2
20Cl N
2
O
3
: 490.0851. Found: 490.0851.
(d, J = 8.8 Hz, 3H). 13C NMR (126 MHz, CDCl
3
• w íóíXññU íòîXôõU íñõXïðU
1
Compound 3g. white solid, yield 87 %, mp 149-150 °C. H NMR 149.50, 148.01, 142.91, 142.30, 137.05, 133.16, 130.11, 129.29,
(
300 MHz, CDCl
.01 (d, J = 7.8 Hz, 1H), 7.77 (td, J = 7.7, 1.7 Hz, 1H), 7.55 (d, J = 8.3 HRMS (EI) calcd. for C29
Hz, 4H), 7.46 t 7.30 (m, 2H), 7.33 t 7.13 (m, 6H), 5.99 (d, J = 8.2 Hz, Compound 3m. White solid, yield 85 %, mp 135-136 °C. H NMR
• w íóíXìðU íòîXòõU íðôXõñU (300 MHz, CDCl • w ôXññ t 8.46 (m, 1H), 8.41 (d, J = 8.3 Hz, 1H), 8.07
47.99, 141.78, 139.77, 137.10, 133.07, 131.25, 130.31, 127.52, t 8.00 (m, 1H), 7.79 t 7.69 (m, 1H), 7.48 t 7.33 (m, 4H), 7.28 t 7.06
3
• w ôXñî ~ꢀU J = 4.0 Hz, 1H), 8.31 (d, J = 7.9 Hz, 1H), 127.43, 126.08, 122.22, 121.90, 114.92, 113.81, 55.19, 52.93, 52.68.
8
26 2 5
H N O : 482.1842. Found: 482.1853.
1
1
1
1
5
H), 3.65 (s, 3H). 13C NMR (75 MHz, CDCl
3
3
26.20, 121.94, 52.92, 52.74. HRMS (EI) calcd. for C27
H
20Br N
2 2
O
3
:
(m, 8H), 6.07 (d, J = 8.5 Hz, 1H), 3.67 (s, 3H). 13C NMR (75 MHz, CDCl
w íóíXíðU íòîXïô ~ꢀU WCF = 247.5 Hz), 162.79, 149.06, 148.06, 142.82
3
)
77.9841. Found: 577.9840.
1
Compound 3h. White solid, yield 66 %, mp 145-146 °C. H NMR (d, JCF = 7.52 Hz), 141.71, 137.02, 133.17, 130.23, 129.69 (d, JCF = 8.04
(
300 MHz, CDCl
3
• w ôXðî ~ꢀU J = 4.3 Hz, 1H), 8.22 (d, J = 7.6 Hz, 1H), Hz), 127.50, 126.13, 125.30, 121.98, 116.85 (d, JCF = 21.14 Hz), 114.64
8
.00 (d, J = 7.8 Hz, 1H), 7.75 (ddd, J = 22.3, 14.2, 4.4 Hz, 5H), 7.52 (d, (d, JCF = 21.04 Hz), 52.71. HRMS (EI) calcd. for C27 : 458.1442.
20 2 2 3
H F N O
J = 7.9 Hz, 4H), 7.46 t 7.35 (m, 2H), 7.25 (d, J = 7.6 Hz, 2H), 5.93 (d, J Found: 458.1449.
7.8 Hz, 1H), 3.66 (d, J = 10.8 Hz, 3H). 13C NMR (126 MHz, CDCl
1
=
1
1
3
• w
3
Compound 3n. Yellow oil. Yield 73 %. H NMR (300 MHz, CDCl )
71.05, 162.88, 148.92, 148.09, 144.73, 141.77, 137.17, 132.99, w ôXññ ~ꢀU J = 3.9 Hz, 1H), 8.38 (d, J = 8.1 Hz, 1H), 8.03 (d, J = 7.8 Hz,
30.56, 129.97, 129.90 (q, JCF3 = 32.51 Hz), 127.76, 126.37, 125.20 (q, 1H), 7.76 (td, J = 7.7, 1.5 Hz, 1H), 7.44 t 7.35 (m, 8H), 7.31 (d, J = 5.9
J
CF3 = 3.31 Hz), 124.28 (q, JCF3 = 273.22 Hz), 121.96, 53.19, 52.97. Hz, 2H), 7.24 (d, J = 7.6 Hz, 2H), 6.00 (d, J = 8.3 Hz, 1H), 3.69 (s, 3H).
HRMS (EI) calcd. for C29
H
F
20 6
2
N O
3
: 558.1378. Found: 558.1375.
13C NMR (75 MHz, CDCl
3
• w íóíXìðU íòîXóðU íðõXìîU íðôXíõU íðîXðïU
1
Compound 3i. White solid, yield 67 %, mp 125-126 °C. H NMR 141.60, 137.04, 134.04, 133.21, 130.30, 129.79, 129.37, 127.86,
(
300 MHz, CDCl
3
• w ôXðõ ~ꢀU J = 4.2 Hz, 1H), 8.22 (d, J = 7.4 Hz, 1H), 127.70, 127.52, 126.10, 122.03, 52.79. HRMS (EI) calcd. for
.99 (d, J = 7.8 Hz, 1H), 7.77 (ddd, J = 19.2, 12.6, 4.5 Hz, 5H), 7.56 t : 490.0851. Found: 490.0857.
.40 (m, 6H), 7.24 (t, J = 7.6 Hz, 2H), 5.83 (d, J = 7.5 Hz, 1H), 3.68 (s, Compound 3o. Yellow solid, yield 73 %, mp 101-102 °C. H NMR
H). 13C NMR (75 MHz, CDCl
• w íóìXòìU íòîXòõU íðôXñôU íðôXìíU (300 MHz, CDCl • w ôXñó ~•U íI•U ôXïó ~ꢀU J = 8.1 Hz, 1H), 8.03 (d, J =
7
7
3
1
1
C
27 2 2 3
C H20Cl N O
1
3
3
45.54, 141.31, 137.28, 132.53, 131.88, 130.43, 130.33, 127.83, 7.8 Hz, 1H), 7.76 (td, J = 7.7, 1.5 Hz, 1H), 7.56 (d, J = 7.7 Hz, 4H), 7.42
26.49, 121.97, 118.64, 111.66, 52.99. HRMS (EI) calcd. for t 7.27 (m, 6H), 7.24 (t, J = 6.4 Hz, 2H), 5.98 (d, J = 8.3 Hz, 1H), 3.70 (s,
: 472.1535. Found: 472.1536.
Compound 3j. White solid, yield 70 %, mp 166-167 °C. H NMR 142.70, 141.49, 137.04, 133.19, 132.61, 130.77, 130.35, 129.67,
300 MHz, CDCl • w ôXðð ~ꢀU J = 4.5 Hz, 1H), 8.28 (d, J = 8.1 Hz, 1H), 128.17, 127.56, 126.15, 122.28, 122.00, 52.89, 52.78. HRMS (EI) calcd.
.10 (d, J = 8.3 Hz, 4H), 7.98 (d, J = 7.8 Hz, 1H), 7.73 (td, J = 7.7, 1.5 for C27
Hz, 1H), 7.48 (d, J = 8.4 Hz, 5H), 7.43 t 7.32 (m, 2H), 7.23 (d, J = 7.6
3H). 13C NMR (75 MHz, CDCl
3
• w íóíXìíU íòîXóóU íðõXììU íðôXïñU
29
H
20
4
N O
3
1
(
3
8
H
2
20Br N
2
O
3
: 577.9841. Found: 577.9846.
1
Compound 3p. Yellow oil, yield 63 %. H NMR (300 MHz, CDCl
3
)
Hz, 1H), 5.96 (d, J = 8.2 Hz, 1H), 3.93 (s, 6H), 3.62 (s, 3H). 13C NMR (75 w ôXðô ~ꢀU J = 4.0 Hz, 1H), 8.35 (d, J = 7.5 Hz, 1H), 8.05 (d, J = 7.8 Hz,
MHz, CDCl • w íóìXõïU íòòXôìU íòîXóïU íðôXõíU íðôXììU íðñXñóU 1H), 7.83 t 7.56 (m, 9H), 7.49 t 7.35 (m, 2H), 7.34 t 7.26 (m, 2H), 5.93
42.08, 137.03, 132.81, 130.17, 129.61, 129.40, 128.64, 127.52, (d, J = 7.8 Hz, 1H), 3.72 (s, 3H). 13C NMR (126 MHz, CDCl
• w íóìXõòU
162.99, 149.01, 148.23, 141.82, 141.59, 137.12, 133.41, 132.99,
130.71, 130.54 (q, JCF3 = 32.2 Hz), 128.81, 127.82, 126.56, 126.31,
3
1
1
5
3
26.17, 121.95, 52.84, 52.74, 52.06. HRMS (EI) calcd. for C31
H
26 2 7
N O :
38.1740. Found: 538.1742.
1
Compound ïi[. White solid, yield 20 %, mp 124-125 °C. H NMR 124.69(d, JCF3 = 3.11 Hz), 124.18(q, JCF3 = 272.50 Hz), 122.06, 53.12,
(
300 MHz, CDCl
3
• w ôXôô ~ꢀU J = 6.7 Hz, 1H), 8.55 (d, J = 4.2 Hz, 1H), 52.81. (CF
3
peak is overlapping with other peaks.) HRMS (EI) calcd.
8
.11 (t, J = 9.4 Hz, 3H), 7.87 t 7.72 (m, 1H), 7.68 t 7.52 (m, 3H), 7.40 for C29
H
F
20 6
2
N O
3
: 558.1378. Found: 558.1384.
1
(
dd, J = 7.8, 4.9 Hz, 3H), 7.35 t 7.22 (m, 1H), 5.79 (d, J = 7.0 Hz, 1H),
Compound ï‰[. Yellow oil, yield 21 %. H NMR (300 MHz, CDCl
3
)
3
.93 (d, J = 5.1 Hz, 3H), 3.68 (d, J = 5.2 Hz, 3H). 13C NMR (75 MHz, w ôXôõ ~ꢀU J = 6.5 Hz, 1H), 8.59 (d, J = 4.6 Hz, 1H), 8.12 (d, J = 7.8 Hz,
3
CDCl • w íóíXìõU íòòXôñU íòïXðñU íðõXìðU íðôXíïU íððXõõU íðíXðóU 1H), 7.89 t 7.75 (m, 3H), 7.71 t 7.56 (m, 3H), 7.48 t 7.38 (m, 3H), 7.35
1
1
4
37.27, 134.19, 130.40, 129.54, 129.16, 128.59, 128.42, 126.95, t 7.29 (m, 1H), 5.73 (d, J = 7.0 Hz, 1H), 3.72 (s, 3H). 13C NMR (126 MHz,
26.39, 122.22, 53.47, 52.71, 52.03. HRMS (EI) calcd. for C23
H
20
N
2
O
5
:
CDCl
134.61, 132.86, 130.69, 130.61(q, JCF3 = 32.4 Hz), 128.83, 128.80È
28.57, 127.23, 126.68(d, JCF3 = 3.28 Hz), 126.49, 126.86(q, JCF3
3
• w íóíXíôU íòïXòîU íðõXîïU íðôXïïU íðíXíîÈ141.08È137.31,
04.1372. Found: 404.1378.
1
=
6
| J. Name., 2012, 00, 1-3
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ARTICLE
2
72.08 Hz), 124.41(d, JCF3 = 3.10 Hz), 122.29, 53.69, 52.82. (CF
is overlapping with other peaks.) HRMS (EI) calcd. for C22
14.1191. Found: 414.1192.
Compound 3q. Yellow oil. yield 75 %. H NMR (300 MHz, CDCl
w ôXñî ~ꢀU J = 4.3 Hz, 1H), 8.34 (d, J = 7.9 Hz, 1H), 8.02 (d, J = 7.6 Hz, t 7.35 (m, 11H), 7.26 (dd, J = 6.1, 1.8 Hz, 1H), 7.16 (d, J = 7.5 Hz, 2H),
3
peak 127.22, 126.95, 126.39, 126.09, 122.17, 116.61, 70.15, 52.80, 52.72.
H
17
F
3
N
2
O
3
:
HRMS (EI) calcd. for C46
H
36 2
N O
4
: 680.2675. Found: 680.2669.
1
4
Compound 4a. Colorless oil, yield 78 %. H NMR (500 MHz, CDCl
3
)
1
3
)
w ôXñô t 8.51 (m, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.80 t 7.74 (m, 2H), 7.46
1
7
8
1
1
1
H), 7.79 (t, J = 7.4 Hz, 1H), 7.61 (t, J = 7.6 Hz, 2H), 7.40 (dd, J = 14.7, 4.44 (ddd, J = 10.8, 9.1, 4.3 Hz, 1H), 3.47 (dd, J = 14.2, 4.3 Hz, 1H),
.4 Hz, 2H), 7.25 t 7.14 (m, 4H), 7.08 (d, J = 8.1 Hz, 2H), 5.97 (d, J = 3.42 (s, 3H), 3.15 (dd, J = 14.2, 10.9 Hz, 1H). 13C NMR (126 MHz, CDCl
.0 Hz, 1H), 3.70 (s, 3H). 13C NMR (75 MHz, CDCl
• w íóìXôõU íòîXòóU w íóíXôðU íòïXôõU íðõXïòU íðóXõìU íðïXóîU íðíXóíU íïóXíðU íïíXóñU
58.59 (d, J = 249 Hz), 148.69, 148.14, 141.98 (d, J = 6.91 Hz), 140.77, 129.76, 129.71, 128.41, 127.19, 126.52, 126.20, 122.28, 52.28, 52.07,
3
)
3
37.25, 136.74, 133.20, 132.99, 130.41, 127.70, 126.36, 121.99, 31.98. HRMS (EI) calcd. for C28
H
24 2
N O
3
: 436.1787. Found: 436.1793.
1
17.94 (d, J = 22.58 Hz), 108.57 (d, J = 20.60 Hz), 52.93, 52.88. HRMS
Compound 4b. Yellow oil, yield 70 %. H NMR (500 MHz, CDCl
3
)
(
EI) calcd. for C27
H
18Br
2
F
2
N
2
O
3
: 613.9652. Found: 613.9649.
w ôXññ ~ꢀꢀꢀU J = 4.7, 1.5, 0.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.77 (td,
3
• w J = 7.7, 1.7 Hz, 2H), 7.40 (ddd, J = 7.6, 4.7, 1.2 Hz, 1H), 7.24 (ddd, J =
1
Compound 3r. Yellow oil, yield 53 %. H NMR (500 MHz, CDCl
8
7
8
1
.49 (d, J = 4.6 Hz, 1H), 8.38 (d, J = 8.8 Hz, 1H), 8.03 (d, J = 7.8 Hz, 1H), 9.2, 8.0, 6.4 Hz, 9H), 7.13 (d, J = 7.5 Hz, 2H), 4.43 (ddd, J = 10.9, 8.9,
.74 (td, J = 7.7, 1.5 Hz, 1H), 7.36 (dd, J = 7.2, 5.0 Hz, 1H), 7.31 (d, J = 4.2 Hz, 1H), 3.48 (dt, J = 11.6, 5.8 Hz, 1H), 3.43 (s, 3H), 3.17 (dd, J =
.2 Hz, 4H), 6.95 (d, J = 8.8 Hz, 4H), 6.70 (s, 2H), 6.03 (d, J = 8.8 Hz, 14.1, 10.9 Hz, 1H), 2.42 (s, 6H). 13C NMR (126 MHz, CDCl
H), 3.85 (s, 6H), 3.58 (s, 3H), 0.95 (s, 9H), 0.19 (s, 6H). 13C NMR (126 163.94, 149.40, 147.87, 143.66, 138.82, 137.13, 136.73, 131.93,
• w íóíXóóU íòîXõìU íñõXííU íñðXíïU íðõXñôU íðóXõõU 129.72, 129.56, 129.11, 126.47, 126.18, 122.27, 52.32, 52.04, 31.80,
3
• w íóíXõóU
MHz, CDCl
3
1
1
C
44.14, 137.08, 133.36, 130.64, 127.04, 126.08, 122.25, 121.69, 21.30. HRMS (EI) calcd. for C30
13.62, 55.31, 52.54, 52.43, 25.65, 18.16, -4.34. HRMS (EI) calcd. for
Si: 612.2656. Found: 612.2649.
H
28
N
2
O
3
: 464.2100. Found: 464.2106.
1
Compound 4c. Yellow oil, yield 86 %. H NMR (500 MHz, CDCl
3
• w
35
H
40
2
N O
6
8.55 (d, J = 4.7 Hz, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.76 (td, J = 7.7, 1.5
Hz, 2H), 7.41 t 7.37 (m, 1H), 7.30 (t, J = 5.7 Hz, 4H), 7.24 t 7.17 (m,
1
3
Compound ïŒ[. Yellow oil, yield 36 %. H NMR (500 MHz, CDCl )
w ôXòñ ~ꢀU J = 6.7 Hz, 1H), 8.55 (d, J = 4.7 Hz, 1H), 8.12 (d, J = 7.8 Hz, 1H), 7.12 (d, J = 7.5 Hz, 2H), 6.97 (t, J = 5.7 Hz, 4H), 4.54 t 4.33 (m,
H), 7.80 (td, J = 7.7, 1.2 Hz, 1H), 7.50 t 7.32 (m, 4H), 6.96 (d, J = 8.6 1H), 3.86 (s, 6H), 3.53 t 3.40 (m, 4H), 3.18 (dd, J = 14.1, 11.0 Hz, 1H).
Hz, 2H), 6.81 (dt, J = 13.4, 6.7 Hz, 1H), 6.76 (d, J = 2.5 Hz, 1H), 5.73 (d, 13C NMR (126 MHz, CDCl
• w íóíXõóU íòïXõòU íñôXóôU íðõXïðU íðóXôôU
J = 6.9 Hz, 1H), 3.84 (s, 3H), 3.68 (s, 3H), 0.97 (s, 9H), 0.20 (s, 6H). 13
143.34, 137.16, 134.16, 132.22, 130.77, 129.80, 126.49, 126.22,
NMR (126 MHz, CDCl • w íóíXôîU íòïXòôU íñõXíìU íññXñîU íðõXðïU 122.27, 113.85, 55.35, 52.27, 52.11, 31.85. HRMS (EI) calcd. for
48.27, 143.82, 137.28, 132.52, 130.52, 128.28, 127.00, 126.39, : 496.1998. Found: 496.2003.
22.36, 122.30, 119.44, 113.81, 55.31, 53.25, 52.66, 25.66, 18.19, - Compound 4d. Light yellow oil, yield 85 %. H NMR (500 MHz,
• w ôXñï ~ꢀꢀU J = 4.0, 0.7 Hz, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.85 (d,
1
3
C
3
1
1
4
30 28 2 5
C H N O
1
.32. HRMS (EI) calcd. for C28
H
34 2
N O
5
Si: 506.2237. Found: 506.2230. CDCl
3
1
Compound 3s. White solid, yield 50 %, mp 130-131 °C. H NMR J = 9.0 Hz, 1H), 7.77 (td, J = 7.7, 1.7 Hz, 1H), 7.71 t 7.65 (m, 8H), 7.51
~
ñìì aIÌU /5/oï• w ôXðò t 8.38 (m, 2H), 8.04 (d, J = 7.8 Hz, 1H), 7.74 t 7.46 (m, 8H), 7.41 t 7.36 (m, 3H), 7.31 (dd, J = 8.2, 6.8 Hz, 1H), 7.24
td, J = 7.7, 1.6 Hz, 1H), 7.66 (t, J = 7.9 Hz, 8H), 7.53 t 7.44 (m, 8H), (t, J = 6.5 Hz, 2H), 4.56 (ddd, J = 10.8, 9.2, 3.9 Hz, 1H), 3.59 (dd, J =
(
7
1
.35 (ddd, J = 10.4, 7.5, 4.2 Hz, 3H), 6.80 (s, 2H), 6.10 (d, J = 8.6 Hz, 14.2, 3.9 Hz, 1H), 3.41 (s, 3H), 3.27 (dd, J = 14.2, 10.9 Hz, 1H). 13C NMR
H), 3.61 (s, 3H), 0.98 (s, 9H), 0.23 (s, 6H). 13C NMR (126 MHz, CDCl
(126 MHz, CDCl • w íóíXôõU íòïXõôU íðõXïïU íðóXõðU íðïXðíU íðìXõíU
3
)
3
w íóíXóïU íòîXôôU íñðXîõU íðõXñðU íðôXìîU íððXíõU íðìXôôU íðìXððU 140.74, 140.01, 137.18, 132.08, 130.20, 129.90, 128.88, 127.40,
1
1
40.09, 137.06, 129.96, 128.83, 127.41, 127.22, 126.93, 126.56, 127.19, 127.16, 126.70, 126.24, 122.29, 52.50, 52.15, 32.05. HRMS
26.07, 122.18, 121.69, 52.67, 52.64, 25.66, 18.19, -4.30. HRMS (EI) (EI) calcd. for C40 : 588.2413. Found: 588.2419.
Compound 4e. Yellow solid, yield 58 %, mp 128-129 °C. H NMR
• w (500 MHz, CDCl • w ôXñò ~ꢀU J = 4.6 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H),
32 2 3
H N O
1
calcd. for C45
H
44
N
2
O
4
Si: 704.3070. Found: 704.3078.
1
Compound 3t. Yellow oil, yield 81 %. H NMR (500 MHz, CDCl
3
3
8
.49 (dd, J = 4.0, 0.6 Hz, 1H), 8.40 (d, J = 8.5 Hz, 1H), 8.04 (d, J = 7.8 7.84 t 7.74 (m, 2H), 7.45 t 7.40 (m, 1H), 7.33 (dd, J = 8.2, 5.5 Hz, 4H),
Hz, 1H), 7.75 (td, J = 7.7, 1.6 Hz, 1H), 7.43 t 7.28 (m, 10H), 7.01 t 6.93 7.28 t 7.22 (m, 1H), 7.16 t 7.08 (m, 6H), 4.47 (td, J = 10.8, 4.0 Hz, 1H),
m, 4H), 6.88 (d, J = 1.4 Hz, 2H), 6.05 (d, J = 8.6 Hz, 1H), 5.04 (s, 2H), 3.47 (d, J = 0.4 Hz, 3H), 3.41 (dd, J = 14.2, 4.0 Hz, 1H), 3.10 (dd, J =
(
3
1
1
1
5
.85 (s, 6H), 3.61 (s, 3H). 13C NMR (126 MHz, CDCl
59.18, 157.28, 149.56, 148.00, 144.24, 137.09, 136.79, 133.37, 162.19 (d, J
30.64, 128.63, 128.08, 127.64, 126.90, 126.10, 122.25, 116.61, 132.04, 131.31 (d, J
3
• w íóíXóòU íòîXõîU 14.2, 11.0 Hz, 1H). 13C NMR (126 MHz, CDCl
= 246.17 Hz), 149.18, 147.95, 142.73, 137.53, 137.28,
= 7.85 Hz), 130.02, 126.67, 126.37, 122.31,
3
• w íóíXóîU íòïXôðU
F
F
13.67, 70.07, 55.33, 52.61, 52.56. HRMS (EI) calcd. for C36
H
32 2
N O
6
:
115.36 (d, J
F
= 21.23 Hz), 52.23, 52.14, 32.04. HRMS (EI) calcd. for
88.2260. Found: 588.2255.
C
28
H
22
2
F N
2
O
3
: 472.1598. Found: 472.1601.
1
1
Compound 3u. White solid, yield 68 %, mp 264-265 °C. H NMR
Compound 4f. Yellow oil, yield 75 %. H NMR (500 MHz, CDCl
3
• w
(
500 MHz, CDCl
3
• w ôXðó t 8.39 (m, 2H), 8.08 t 8.02 (m, 1H), 7.75 (td, 8.56 (d, J = 3.1 Hz, 1H), 7.98 (d, J = 7.6 Hz, 1H), 7.78 (dd, J = 14.8, 7.9
J = 7.7, 1.7 Hz, 1H), 7.68 (d, J = 8.1 Hz, 8H), 7.52 (d, J = 8.3 Hz, 4H), Hz, 2H), 7.53 (d, J = 8.2 Hz, 4H), 7.48 t 7.39 (m, 1H), 7.30 t 7.17 (m,
7
4
1
1
1
.48 (dd, J = 10.6, 4.8 Hz, 4H), 7.45 t 7.42 (m, 2H), 7.38 (ddd, J = 7.4, 5H), 7.12 (d, J = 7.6 Hz, 2H), 4.46 (td, J = 10.7, 3.7 Hz, 1H), 3.47 (s, 3H),
.4, 1.9 Hz, 4H), 7.36 t 7.33 (m, 2H),6.97 (s, 2H) 6.11 (d, J = 8.4 Hz, 3.40 (dd, J = 14.3, 3.7 Hz, 1H), 3.08 (dd, J = 14.2, 11.0 Hz, 1H). 13C NMR
H), 5.09 (s, 2H), 3.65 (s, 3H). 13C NMR (126 MHz, CDCl
62.91, 157.41, 149.50, 148.03, 144.26, 140.84, 140.51, 140.10, 137.30, 131.74, 131.60, 131.39, 129.92, 126.82, 126.43, 122.31,
37.07, 136.74, 129.94, 128.85, 128.65, 128.12, 127.64, 127.44, 121.54, 52.31, 52.25, 32.00. HRMS (EI) calcd. for C28
91.9997. Found: 591.9999.
3 3
• w íóíXóîU (126 MHz, CDCl • w íóíXòìU íòïXôóU íðõXìóU íðôXìíU 142.56, 140.42,
H
2 2 3
22Br N O :
5
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DOI: 10.1039/C7OB02921G
ARTICLE
Journal Name
1
Compound 4g. Yellow solid, yield 52 %, mp 121-122 °C. H NMR 163.74, 149.08, 148.33, 137.20, 136.23, 132.86, 130.47, 126.38,
(
500 MHz, CDCl
.87 t 7.72 (m, 2H), 7.68 (d, J = 7.9 Hz, 4H), 7.49 (d, J = 7.7 Hz, 4H), Found: 425.9213.
.47 t 7.41 (m, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.18 (d, J = 7.6 Hz, 2H),
.45 (td, J = 10.3, 3.3 Hz, 1H), 3.42 (s, 3H), 3.38 (dd, J = 11.2, 4.9 Hz, (300 MHz, CDCl
H), 3.05 (dd, J = 14.3, 11.0 Hz, 1H). 13C NMR (126 MHz, CDCl
• w 1H), 8.17 (d, J = 7.8 Hz, 1H), 7.95 t 7.77 (m, 3H), 7.47 t 7.39 (m, 1H),
71.44, 163.82, 149.04, 148.03, 145.13, 142.48, 137.33, 131.80, 6.76 t 6.53 (m, 2H), 3.81 (s, 3H). 13C NMR (126 MHz, CDCl
• w íòõXòóU
30.13, 129.55(q, JCF3 = 33.24 Hz), 126.99, 126.47, 125.43(q, JCF3 163.74, 149.18, 148.53, 141.11, 140.94, 137.35, 131.09, 126.54,
.31 Hz), 124.30 (q, JCF3 = 271.55 Hz), 123.21, 122.29, 52.29, 52.19, 122.51, 64.98, 53.51. HRMS (EI) calcd. for C15 : 521.8937.
2.14. (CF peak is overlapping with other peaks.) HRMS (EI) calcd. Found: 521.8936.
3
• w ôXñð ~ꢀU J = 4.7 Hz, 1H), 7.99 (d, J = 7.8 Hz, 1H), 122.41, 56.99, 53.21. HRMS (EI) calcd. for C15
H
12Br
2
N
2
O
3
: 425.9215.
7
7
4
1
1
1
3
3
1
Compound 6c. Yellow solid, yield 70 %, mp 118-119 °C. H NMR
3
• w õXñî ~ꢀU J = 7.6 Hz, 1H), 8.61 (dt, J = 11.3, 5.7 Hz,
3
3
=
12 2 2 3
H I N O
3
1
for C30
H
F
22 6
2
N O
3
: 572.1535. Found: 572.1538.
Compound 7a. Colorless oil, yield 50 %. H NMR (500 MHz, CDCl
3
)
1
Compound 4h. Yellow oil, yield 34 %. H NMR (300 MHz, CDCl
3
)
w ôXóõ ~ꢀU J = 7.2 Hz, 1H), 8.55 (d, J = 4.5 Hz, 1H), 8.16 (d, J = 7.7 Hz,
w ôXññ ~ꢀU J = 4.5 Hz, 1H), 8.09 (d, J = 8.2 Hz, 4H), 7.97 (d, J = 7.8 Hz, 1H), 7.82 (dd, J = 10.3, 5.0 Hz, 1H), 7.46 t 7.35 (m, 2H), 7.26 (ddd, J =
H), 7.77 (ddd, J = 14.1, 10.1, 5.3 Hz, 2H), 7.43 (t, J = 6.6 Hz, 6H), 7.28 16.9, 11.6, 7.1 Hz, 3H), 6.03 (d, J = 7.6 Hz, 1H), 3.75 (d, J = 1.5 Hz, 3H),
dd, J = 13.3, 5.3 Hz, 1H), 7.16 (d, J = 7.4 Hz, 2H), 4.42 (td, J = 10.8, 3.8 2.98 t 2.86 (m, 2H), 1.32 (t, J = 7.6 Hz, 3H). 13C NMR (126 MHz, CDCl
1
(
3
)
Hz, 1H), 3.96 (s, 6H), 3.41 (s, 3H), 3.08 (dd, J = 14.1, 11.1 Hz, 1H). 13
C
w íóíXóðU íòïXôòU íðõXïìU íðôXïïU íðîXõìU íïóXïðU 134.40, 129.43,
3
NMR (126 MHz, CDCl • w íóíXðñU íòóXìñU íòïXôíU íðõXìñU íðôXìñU 128.88, 126.94, 126.70, 126.49, 122.38, 52.79, 52.69, 25.90, 15.51.
1
1
C
46.30, 142.89, 137.28, 131.43, 129.93, 129.83, 129.79, 129.08, HRMS (EI) calcd. for C17
26.86, 126.41, 122.28, 52.25, 52.19, 32.09. HRMS (EI) calcd. for
: 552.1897. Found: 552.1900.
Compound ðZ[. Yellow oil, yield 25 %. H NMR (500 MHz, CDCl
H
18
N
2
O
3
: 298.1317. Found: 298.1321.
1
Compound 7b. Colorless oil, yield 45 %. H NMR (500 MHz, CDCl
3
)
32
H
28
2
N O
7
w ôXóó ~ꢀU J = 7.0 Hz, 1H), 8.55 (d, J = 4.4 Hz, 1H), 8.16 (d, J = 7.8 Hz,
1
3
)
1H), 7.82 (t, J = 7.2 Hz, 1H), 7.41 (dd, J = 7.0, 5.2 Hz, 1H), 7.38 (d, J =
w ôXñð ~ꢀU J = 4.6 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.00 (t, J = 8.2 Hz, 7.6 Hz, 1H), 7.30 t 7.19 (m, 3H), 6.02 (d, J = 7.6 Hz, 1H), 3.75 (s, 3H),
H), 7.79 (td, J = 7.7, 1.5 Hz, 1H), 7.41 (dd, J = 6.9, 4.9 Hz, 1H), 7.33 2.83 (dd, J = 18.1, 8.2 Hz, 2H), 1.72 (dd, J = 15.0, 7.5 Hz, 2H), 1.02 (t,
dd, J = 12.9, 8.1 Hz, 3H), 7.29 (ddd, J = 14.1, 7.0, 1.4 Hz, 2H), 7.19 t J = 7.3 Hz, 3H). 13C NMR (126 MHz, CDCl
• w íóíXóñU íòïXôñU íðõXïíU
3
(
3
7
3
.14 (m, 1H), 4.84 (td, J = 8.3, 5.6 Hz, 1H), 3.93 (s, 3H), 3.61 (s, 3H), 148.32, 141.48, 137.32, 134.53, 130.29, 128.65, 126.95, 126.74,
.36 (dd, J = 14.2, 5.5 Hz, 1H), 3.13 (dd, J = 14.2, 8.2 Hz, 1H). 13C NMR 126.47, 122.38, 52.77, 35.03, 24.51, 14.23. HRMS (EI) calcd. for
(
126 MHz, CDCl
3
• w íóíXóóU íòòXõõU íòïXôòU íðõXíðU íðôXíñU íðòXìõU
41.79, 137.26, 133.64, 130.17, 129.89, 129.59, 128.85, 128.41,
28.13, 127.11, 126.41, 122.31, 53.39, 52.40, 52.19, 35.09. HRMS (EI) w ôXóñ ~ꢀU J = 7.0 Hz, 1H), 8.55 (d, J = 4.4 Hz, 1H), 8.17 (d, J = 7.8 Hz,
C
18
H
20
N
2
O
3
: 312.1474. Found: 312.1473.
1
1
1
Compound 7c. Colorless oil, yield 42 %. H NMR (500 MHz, CDCl
3
)
calcd. for C24
H
22 2
N O
5
: 418.1529. Found: 418.1533.
1H), 7.83 (td, J = 7.7, 1.4 Hz, 1H), 7.42 (dd, J = 7.0, 5.2 Hz, 1H), 7.38
1
Compound 4i. Yellow oil, yield 65 %. H NMR (500 MHz, CDCl
3
• w (d, J = 7.6 Hz, 1H), 7.24 (dt, J = 14.5, 6.9 Hz, 3H), 6.01 (d, J = 7.6 Hz,
8
9
.62 (d, J = 4.5 Hz, 1H), 7.98 (t, J = 10.4 Hz, 1H), 7.79 (ddd, J = 11.8, 1H), 3.75 (s, 3H), 2.93 t 2.76 (m, 2H), 1.71 t 1.62 (m, 2H), 1.44 (dd, J
.3, 5.4 Hz, 2H), 7.44 t 7.39 (m, 1H), 7.37 (d, J = 4.7 Hz, 6H), 7.27 (dd, = 14.8, 7.4 Hz, 2H), 0.94 (t, J = 7.3 Hz, 3H). 13C NMR (126 MHz, CDCl
3
)
J = 7.1, 2.9 Hz, 3H), 7.14 (d, J = 7.6 Hz, 2H), 4.49 (td, J = 11.0, 3.8 Hz, w íóíXóòU íòïXôðU íðõXïîU íðôXïíU íðíXóïU íïóXïîU íïðXðòU íïìXîðU
H), 3.49 (s, 3H), 3.37 (dd, J = 16.1, 8.9 Hz, 1H), 3.10 (dd, J = 14.2, 11.1 128.68, 127.03, 126.68, 126.46, 122.39, 52.84, 52.77, 33.57, 32.68,
1
Hz, 1H). 13C NMR (126 MHz, CDCl
• w íóíXòðU íòïXôôU íðõXíìU íðôXïòU 22.80, 14.04. HRMS (EI) calcd. for C19
H
3
22
2
N O
3
: 326.1630. Found:
1
1
43.29, 142.41, 137.21, 134.32, 131.66, 130.05, 129.72, 129.67, 326.1635.
1
28.08, 127.49, 126.83, 126.28, 122.22, 52.31, 52.12, 32.20. HRMS
Compound 8a. Yellow oil, yield 51 %. H NMR (500 MHz, CDCl
3
• w
(
EI) calcd. for C28
H
2
22Cl N
2
O
3
: 504.1007. Found: 504.1010.
9.06 (d, J = 7.5 Hz, 1H), 8.54 (d, J = 4.3 Hz, 1H), 8.15 (d, J = 7.8 Hz, 1H),
1
Compound 5. White solid, yield 84 %, mp 63-64 °C. H NMR (300 7.81 (td, J = 7.7, 1.6 Hz, 1H), 7.54 (dt, J = 4.1, 2.0 Hz, 1H), 7.46 (dd, J =
MHz, CDCl
J = 8.4 Hz, 6H), 5.50 (d, J = 7.8 Hz, 1H), 4.70 (s, 1H), 3.55 (s, 3H), 1.33 1.5 Hz, 1H), 7.28 (td, J = 7.5, 1.3 Hz, 1H), 6.16 (d, J = 7.7 Hz, 1H), 3.75
s, 9H). 13C NMR (126 MHz, CDCl • w íóíXðíU íñïXõóU íðíXóîU íïõXõîU (s, 3H), 1.16 (dd, J = 8.3, 3.8 Hz, 21H). 13C NMR (126 MHz, CDCl
• w
33.54, 131.29, 131.14, 130.45, 127.42, 122.00, 79.63, 54.16, 52.66, 170.75, 163.82, 149.49, 148.17, 138.35, 137.20, 133.97, 128.96,
8.34. HRMS (EI) calcd. for C26 NO : 573.0150. Found: 573.0153. 128.44, 128.28, 126.35, 123.07, 122.39, 103.94, 97.16, 55.60, 52.76,
Compound 6a. Yellow oil, yield 77 %. H NMR (300 MHz, CDCl
.27 (d, J = 8.4 Hz, 1H), 8.59 (dd, J = 4.7, 0.6 Hz, 1H), 8.17 (d, J = 7.8 450.2333.
3
• w óXñð ~ꢀU J = 8.3 Hz, 4H), 7.36 (t, J = 7.5 Hz, 1H), 7.19 (t, 7.6, 1.0 Hz, 1H), 7.40 (ddd, J = 7.5, 4.8, 1.0 Hz, 1H), 7.33 (td, J = 7.6,
(
3
3
1
2
H
25Br
2
4
1
3
• w 18.68, 11.39. HRMS (EI) calcd. for C26
H
34
N
2
O
3
Si: 450.2339. Found:
9
1
Hz, 1H), 7.42 (ddd, J = 7.6, 4.8, 1.1 Hz, 1H), 7.34 (d, J = 7.7 Hz, 2H),
.20 (dd, J = 8.6, 7.4 Hz, 2H), 6.80 (d, J = 8.5 Hz, 1H), 3.78 (s, 3H). 13
NMR (126 MHz, CDCl • w íòõXôñU íòïXõñU íðõXîðU íðôXðñU íïóXïïU 1H), 7.81 (td, J = 7.7, 1.4 Hz, 1H), 7.43 t 7.36 (m, 6H), 7.33 (t, J = 7.0
35.80, 133.62, 129.93, 128.91, 126.51, 122.55, 53.30, 52.58. HRMS Hz, 1H), 7.15 (d, J = 2.7 Hz, 1H), 6.94 (dd, J = 8.6, 2.7 Hz, 1H), 6.09 (d,
EI) calcd. for C15 : 338.0225. Found: 338.0229. J = 7.5 Hz, 1H), 5.04 (s, 2H), 3.74 (s, 3H), 1.15 (dd, J = 8.5, 3.8 Hz, 21H).
Compound 6b. White solid, yield 99 %, mp 101-102 °C. H NMR 13C NMR (126 MHz, CDCl
• w íóíXìíU íòïXóõU íñôXðîU íðõXñóU íðôXíòU
300 MHz, CDCl • w õXïô ~ꢀU J = 8.2 Hz, 1H), 8.60 (dd, J = 4.0, 0.7 Hz, 137.18, 136.54, 130.92, 129.66, 128.70, 128.19, 127.61, 126.29,
H), 8.33 t 8.03 (m, 1H), 7.83 (td, J = 7.8, 1.6 Hz, 1H), 7.57 (d, J = 8.0 124.16, 122.39, 119.95, 115.70, 103.76, 97.03, 70.26, 55.03, 52.75,
Hz, 2H), 7.43 (ddd, J = 7.6, 4.8, 1.1 Hz, 1H), 7.03 (t, J = 8.0 Hz, 1H), 18.68, 11.38. HRMS (EI) calcd. for C33 Si: 556.2757. Found:
Compound 8b. Yellow oil, yield 55 %. H NMR (500 MHz, CDCl
3
)
7
C
w ôXõô ~ꢀU J = 7.4 Hz, 1H), 8.53 (d, J = 4.7 Hz, 1H), 8.15 (d, J = 7.8 Hz,
3
1
(
2 2 3
H12Cl N O
1
3
(
3
1
40 2 4
H N O
6
.85 (d, J = 8.5 Hz, 1H), 3.79 (s, 3H). 13C NMR (75 MHz, CDCl
3
• w íòõXòîU 556.2753.
8
| J. Name., 2012, 00, 1-3
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DOI: 10.1039/C7OB02921G
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ARTICLE
Compound 9a. White solid, yield 89 %, mp 131-132 °C. H NMR 0.06 (s, 6H). 13C NMR (126 MHz, CDCl
1
3
• w íóîXíñU íòïXòïU íñôXíõU
~
ïìì aIÌU /5/oï• w ôXõõ ~ꢀU W A õXì IÌU íI•U ôXññ ~ꢀU W A ïXõ IÌU íI•U 157.18, 150.24, 148.05, 137.09, 125.97, 122.52, 107.70, 97.30, 68.36,
8
4
.20 (d, J = 7.8 Hz, 1H), 7.80 (td, J = 7.7, 1.6 Hz, 1H), 7.38 (ddd, J = 7.4, 52.37, 46.25, 31.29, 25.72, 19.23, 18.21, 13.95, -4.25. HRMS (EI) calcd.
.8, 1.1 Hz, 1H), 7.26 (dd, J = 9.9, 6.8 Hz, 1H), 6.62 (dd, J = 13.3, 9.0 for C29
H
44 2
N O
6
Si: 544.2969. Found: 544.2972.
Hz, 3H), 3.89 (s, 6H), 3.69 (s, 3H). 13/ baw ~óñ aIÌU /5/oï• w íóíXóñU
Compound 9h. Yellow oil, yield 82 %. H NMR (500 MHz, CDCl
1
3
)
1
1
3
63.71, 158.10, 149.78, 148.10, 137.01, 129.70, 126.01, 122.35, w õXíì ~ꢀU J = 9.8 Hz, 1H), 8.49 (d, J = 4.5 Hz, 1H), 8.19 (d, J = 7.8 Hz,
14.04, 104.25, 56.04, 52.37, 46.15. HRMS (EI) calcd. for C17
H
N
8 2
O
5
:
1H), 7.79 (td, J = 7.7, 1.6 Hz, 1H), 7.36 (ddd, J = 7.5, 4.7, 1.0 Hz, 1H),
6.61 (d, J = 9.8 Hz, 1H), 6.01 (s, 2H), 3.72 (ddd, J = 33.6, 8.7, 6.4 Hz,
30.1216. Found: 330.1220.
1
Compound 9b. White solid, yield 91 %, mp 104-105 °C. H NMR 4H), 3.65 (s, 3H), 2.16 (dt, J = 13.2, 6.6 Hz, 2H), 1.08 (dd, J = 6.7, 3.7
300 MHz, CDCl • w íóîXíóU
• w õXíô ~ꢀU J = 9.5 Hz, 1H), 8.52 (d, J = 4.7 Hz, 1H), Hz, 12H), 0.97 (s, 9H), 0.20 (s, 6H). 13C NMR (126 MHz, CDCl
(
3
3
8
7
4
.20 (d, J = 7.7 Hz, 1H), 7.80 (t, J = 7.7 Hz, 1H), 7.43 t 7.32 (m, 1H), 163.64, 158.20, 157.19, 150.18, 148.00, 137.08, 125.97, 122.51,
.20 (t, J = 8.3 Hz, 1H), 6.71 (d, J = 9.8 Hz, 1H), 6.55 (d, J = 8.3 Hz, 2H), 107.51, 97.12, 75.01, 52.39, 46.10, 28.40, 25.72, 19.37, 18.20, -4.23.
.13 t 3.85 (m, 4H), 3.68 (s, 3H), 2.04 t 1.75 (m, 4H), 1.10 (t, J = 7.4 HRMS (EI) calcd. for C29
H
44 2
N O
6
Si: 544.2969. Found: 544.2973.
Hz, 6H). 13C NMR (75 MHz, CDCl
• w íóíXôïU íòïXñòU íñóXññU íðõXõðU
Compound 10a. Yellow oil, yield 69 %. H NMR (500 MHz, CDCl
1
3
3
)
1
4
47.95, 136.97, 129.46, 125.91, 122.32, 114.26, 104.67, 70.22, 52.27, w ôXõô ~ꢀU J = 9.1 Hz, 1H), 8.58 (d, J = 4.2 Hz, 1H), 8.14 (d, J = 7.8 Hz,
6.19, 22.53, 10.51. HRMS (EI) calcd. for C21
H
26
2
N O
5
: 386.1842. 1H), 7.81 (td, J = 7.7, 1.6 Hz, 1H), 7.55 t 7.29 (m, 2H), 7.08 (d, J = 8.2
Hz, 2H), 6.30 (d, J = 9.2 Hz, 1H), 3.70 (s, 3H), 2.40 (s, 6H). 13C NMR
Found: 386.1848.
Compound 9c. Yellow oil, yield 89 %. H NMR (300 MHz, CDCl
.17 (d, J = 9.5 Hz, 1H), 8.53 (d, J = 4.4 Hz, 1H), 8.21 (d, J = 7.8 Hz, 1H), 137.25, 129.35, 126.45, 122.50, 122.45, 120.89, 52.93, 46.93, 20.96.
.81 (t, J = 7.7 Hz, 1H), 7.43 t 7.34 (m, 1H), 7.20 (t, J = 8.3 Hz, 1H), HRMS (EI) calcd. for C19 : 386.1114. Found: 386.1118.
.69 (d, J = 9.8 Hz, 1H), 6.56 (d, J = 8.3 Hz, 2H), 4.21 t 3.89 (m, 4H), Compound 10b. White solid, yield: 54 %, mp 105-106 °C. H NMR
.68 (s, 3H), 1.94 t 1.77 (m, 4H), 1.64 t 1.51 (m, 4H), 0.99 (t, J = 7.4 (300 MHz, CDCl • w õXîô ~ꢀU J = 8.8 Hz, 1H), 8.42 (d, J = 4.3 Hz, 1H),
• w íóíXóõU íòïXñôU íñóXñóU íðõXõôU 8.37 t 8.28 (m, 4H), 8.11 (d, J = 7.8 Hz, 1H), 7.78 (t, J = 7.7 Hz, 1H),
47.92, 136.97, 129.44, 125.90, 122.36, 114.24, 104.66, 68.34, 52.27, 7.67 (t, J = 7.3 Hz, 2H), 7.55 (t, J = 7.5 Hz, 4H), 7.51 t 7.44 (m, 1H),
6.23, 31.20, 19.08, 13.78. HRMS (EI) calcd. for C23 : 414.2155. 7.38 (dd, J = 7.0, 5.3 Hz, 1H), 7.29 t 7.24 (m, 2H), 6.48 (d, J = 8.9 Hz,
1H), 3.58 (s, 3H). 13C NMR (126 MHz, CDCl
• w íóìXìíU íòðXðñU íòïXòìU
149.83, 149.31, 148.11, 137.27, 133.97, 130.55, 129.32, 128.98,
w õXíô ~ꢀU J = 9.8 Hz, 1H), 8.63 t 8.34 (m, 1H), 8.19 (d, J = 7.8 Hz, 1H), 128.79, 126.39, 122.73, 122.42, 121.01, 52.97, 47.46. HRMS (EI) calcd.
.78 (td, J = 7.7, 1.7 Hz, 1H), 7.36 (ddd, J = 7.5, 4.7, 1.1 Hz, 1H), 7.19 for C29 : 510.1427. Found: 510.1430.
t, J = 8.3 Hz, 1H), 6.74 (d, J = 9.9 Hz, 1H), 6.54 (d, J = 8.4 Hz, 2H), 3.84 Compound 10c. White solid, yield 67 %, mp 114-115 °C. H NMR
dd, J = 8.7, 6.4 Hz, 2H), 3.77 (dd, J = 8.7, 6.3 Hz, 2H), 3.67 (s, 3H), 2.19 (500 MHz, CDCl • w õXîì ~ꢀU J = 8.8 Hz, 1H), 8.45 (d, J = 4.6 Hz, 1H),
dp, J = 13.2, 6.6 Hz, 2H), 1.09 (dd, J = 6.7, 3.3 Hz, 12H). 13C NMR (126 8.27 (d, J = 8.6 Hz, 4H), 8.11 (d, J = 7.8 Hz, 1H), 7.81 (t, J = 7.7 Hz, 1H),
1
3 3
• w (126 MHz, CDCl • w íóìXòîU íòôXõîU íòïXôìU íðõXñïU íðõXîôU íðôXðíU
9
7
6
3
18 2 7
H N O
1
3
Hz, 6H). 13C NMR (75 MHz, CDCl
3
1
4
30 2 5
H N O
Found: 414.2159.
Compound 9d. Colorless oil, yield 82 %. H NMR (500 MHz, CDCl
3
1
3
)
7
22 2 7
H N O
1
(
(
(
3
MHz, CDCl
3
• w íóíXõñU íòïXóíU íñóXóïU íñìXìõU íðôXìíU íïóXíìU 7.54 (d, J = 8.5 Hz, 4H), 7.48 (t, J = 8.3 Hz, 1H), 7.42 (dd, J = 7.5, 4.7
1
1
29.58, 126.02, 122.49, 114.23, 104.63, 75.17, 52.44, 46.21, 28.43, Hz, 1H), 7.26 (d, J = 8.1 Hz, 2H), 6.43 t 6.37 (m, 1H), 3.58 (s, 3H). 13
C
9.36. HRMS (EI) calcd. for C23
H
30 2
N O
5
: 414.2155. Found: 414.2158. NMR (126 MHz, CDCl
3
• w íòõXõòU íòïXòîU íòïXññU íðõXòïU íðõXîìU
1
Compound 9e. Colorless oil, yield 93 %. H NMR (300 MHz, CDCl
3
)
148.12, 140.61, 137.37, 131.91, 129.43, 129.20, 127.39, 126.52,
w ôXõì ~ꢀU J = 9.3 Hz, 1H), 8.54 (d, J = 4.4 Hz, 1H), 8.19 (d, J = 7.8 Hz, 122.62, 122.48, 121.09, 53.05, 47.38. HRMS (EI) calcd. for
H), 7.79 (td, J = 7.7, 1.4 Hz, 1H), 7.37 (dd, J = 7.5, 4.8 Hz, 1H), 6.50 : 578.0648. Found: 578.0655.
d, J = 9.5 Hz, 1H), 6.06 (s, 2H), 3.82 (s, 6H), 3.67 (s, 3H), 0.97 (s, 9H),
1
29 2 2 7
C H20Cl N O
(
0
1
5
4
.21 (s, 6H). 13C NMR (126 MHz, CDCl
57.47, 150.03, 148.24, 137.16, 126.10, 122.59, 107.43, 96.88, 56.07,
3
• w íóîXíôU íòïXôñU íñôXôíU
Conflicts of interest
Si: There are no conflicts to declare.
2.53, 46.20, 25.70, 18.21, -4.25. HRMS (EI) calcd. for C23
H
32 2
N O
6
60.2030. Found: 460.2035.
1
Compound 9f. Yellow oil, yield 91 %. H NMR (300 MHz, CDCl
3
• w
9
7
1
1
.10 (d, J = 9.8 Hz, 1H), 8.52 (d, J = 4.7 Hz, 1H), 8.18 (t, J = 8.7 Hz, 1H), Acknowledgements
.79 (td, J = 7.7, 1.5 Hz, 1H), 7.40 t 7.30 (m, 1H), 6.57 (d, J = 9.8 Hz,
This work was supported by the National Natural Science
H), 6.03 (s, 2H), 4.01 t 3.83 (m, 4H), 3.66 (s, 3H), 1.94 t 1.76 (m, 4H),
.08 (t, J = 7.4 Hz, 6H), 0.97 (d, J = 2.0 Hz, 9H), 0.20 (s, 6H). 13C NMR
Foundation of China (NSFC) (Grant No. 21402092, 21772092),
Natural Science Foundation of Jiangsu Province t China (Grant
No. BK20140775), the Priority Academic Program development
of Jiangsu Higher Education Institutions t China (PAPD). We
thank Dr. Jianwei Bian for helpful discussions.
(
126 MHz, CDCl
3
• w íóîXîíU íòïXòóU íñôXíóU íñóXîíU íñìXíóU íðôXìõU
1
2
5
37.11, 126.00, 122.51, 107.67, 97.31, 70.24, 52.40, 46.22, 25.72,
2.62, 18.21, 10.66, -4.25. HRMS (EI) calcd. for C27
H
40 2
N O
6
Si:
16.2656. Found: 516.2661.
1
Compound 9g. Yellow oil, yield 85 %. H NMR (500 MHz, CDCl
3
• w
9
7
.09 (d, J = 9.8 Hz, 1H), 8.52 (d, J = 4.2 Hz, 1H), 8.20 (d, J = 7.8 Hz, 1H),
.79 (td, J = 7.7, 1.6 Hz, 1H), 7.37 (ddd, J = 7.5, 4.8, 1.0 Hz, 1H), 6.55
Notes and references
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(
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t 1.70 (m, 4H), 1.57 (tq, J = 14.8, 7.3 Hz, 4H), 0.97 (s, 9H), 0.20 (s, 6H),
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
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ARTICLE
Journal Name
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