Diaryliodonium Salt-Based Synthesis of N-Alkoxyindolines and Further Insights into the Ishikawa Indole Synthesis

Article abstract of DOI:10.1021/acs.joc.1c00820

A diaryliodonium salt-based strategy enabled the first systematic synthesis of rarely accessible N-alkoxyindolines. Mechanistic analyses suggested that the reaction likely involves reductive elimination of iodobenzene from iodaoxazepine via a four-membered transition state, followed by Meisenheimer rearrangement. Substrates with N-carbamate protection afforded indole in a manner similar to that of the Ishikawa indole synthesis. Preinstallation of a stannyl group as an iodonium salt precursor greatly expanded the substrate scope, and further mechanistic insights are discussed.

Full text of DOI:10.1021/acs.joc.1c00820

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Article
Diaryliodonium Salt-Based Synthesis of N‑Alkoxyindolines and
Further Insights into the Ishikawa Indole Synthesis
Kouhei Shibata, Ken-ichi Takao,* and Akihiro Ogura*
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ABSTRACT: A diaryliodonium salt-based strategy enabled the
first systematic synthesis of rarely accessible N-alkoxyindolines.
Mechanistic analyses suggested that the reaction likely involves
reductive elimination of iodobenzene from iodaoxazepine via a
four-membered transition state, followed by Meisenheimer
rearrangement. Substrates with N-carbamate protection afforded
indole in a manner similar to that of the Ishikawa indole synthesis.
Preinstallation of a stannyl group as an iodonium salt precursor
greatly expanded the substrate scope, and further mechanistic
insights are discussed.
formation. Further examination of this strategy revealed that
indoles could be obtained by changing the substituent on the
nitrogen atom, vastly expanding the utility of the Ishikawa
indole synthesis. We describe the details of these findings
below.
INTRODUCTION
■
Diaryliodonium salts have emerged as precursors for new bond
formation strategies due to their high reactivity, sufficient
stability, and low toxicity.1−10 Various reactions are enabled by
metal catalysts,11−13 whereas diaryliodonium salts are useful for
metal-free carbon−heteroatom bond formation, offering an
attractive metal-free alternative to the Buchwald−Hartwig
reaction.14 A variety of reactions using the iodonium salt have
been developed for O-arylation with aliphatic alcohols,15−19
carboxylic acids,20−23 and phenols,16,23−26 as well as N-
arylation with amines,27−29 amides,30−33 anilines,20,26,34,35
and heteroaromatics.36−40
Intramolecular aryl−heteroatom bond formation is partic-
ularly practical and enables efficient construction of bicyclic
heterocycles. Chemoselectivity is often a problem with
asymmetric diaryliodonium salts41 but can be minimized due
to the strong tendency to give the cyclic product over its linear
counterpart. The Chi group reported the metal-free intra-
molecular N-arylation of diaryliodonium salts (Scheme 1A).42
Copper-mediated intramolecular C−O bond formation from
the diaryliodonium salt generated in situ was achieved by the
Zakarian group (Scheme 1B).43 Very recently, Ishikawa and
co-workers reported an elegant indole synthesis using boron-
masked N-hydroxyamides utilizing the diaryliodonium salt
generated in situ (Scheme 1C).44 Although the substrate scope
of this strategy is limited to electron-rich aromatic derivatives,
this efficient one-pot procedure afforded indoles in good yield.
In this context, we initially intended to synthesize
benzoxazine via diaryliodonium salt-based C−O bond
formation (Scheme 1D). However, treatment of diary-
liodonium salts with a fluorine source resulted in the synthesis
of N-alkoxyindolines, which are rarely synthesized hydro-
genated congeners of N-alkoxyindoles, via C−N bond
RESULTS AND DISCUSSION
■
The substrate was prepared as shown in Scheme 2.
Commercially available 2-(2-bromophenyl)ethyl alcohol (1)
was converted to stannane 2a and condensed with a
hydroxylamine derivative45,46 by the Mitsunobu reaction to
afford 3a after the removal of the Ns group.47 The resulting
amine was benzylated, and 4a was subsequently treated with
the Koser reagent48 to afford iodonium salt 5a as the sole
product.49 Other substrates were similarly synthesized,
although the corresponding iodonium salts are unstable upon
storage even in a freezer and should be used immediately for
the next reaction.
With the substrate in hand, 5a was treated with
tetrabutylammonium fluoride (TBAF). Contrary to our initial
expectation, a small amount of N-benzyloxyindoline 6a was
obtained along with a trace amount of a compound that was
likely benzoxazine 7a (Table 1, entry 1).50 Mild heating of the
reaction mixture improved the yield of 6a to 48% (entry 2).
Solvent and reagent screening revealed that the initially chosen
Received: April 9, 2021
Published: July 1, 2021
https://doi.org/10.1021/acs.joc.1c00820
J. Org. Chem. 2021, 86, 10067−10087
© 2021 American Chemical Society
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Scheme 1. Diaryliodonium Salt-Based Indole/Indoline Synthesis
Scheme 2. Substrate Preparation
combination of TBAF and dimethylformamide (DMF) worked
best (entries 3−9). The addition of molecular sieves (MS) did
not improve the yield (entry 10). Despite their very simple
structure, 2-unsubstituted-N-alkoxyindolines have rarely been
synthesized51,52 as the oxidation of indolines easily leads to
aromatization to indoles or over-oxidation to nitrones and
hydroxamic acids.53 Although N-alkoxyindoline 6a gradually
converted to indole during silica gel purification, isolated 6a
could be stored at room temperature (rt) as a CDCl3 solution
for 1 week or for more than 2 months in a freezer without
decomposition. The reason for the difference in stability
between N-alkoxyindolines and N-hydroxyindolines54 remains
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of N-alkoxyanilines,57−61 our method does not require
electron-withdrawing group incorporation on the nitrogen
atom of the final product.
Table 1. Optimization for N-Alkoxyindoline Synthesis
We propose that the reaction proceeds as described in
Scheme 3A. After deprotection of the hydroxy group, the
oxygen atom attacks the iodine center to afford iodaoxazepine
B. This proposed attack is supported by computational analysis
of a model compound since the corresponding six-membered
iodazine N-oxide (N-attack product) is more unstable by 50
kJ/mol (Scheme 3B, also see the Supporting Information
(SI)). Subsequently, intramolecular ipso-attack by nitrogen
leads to the four-membered ring transition state C, which
undergoes the elimination of iodobenzene to afford the five-
membered N-oxide intermediate D (also, see time-course
analysis in the SI). Calculations using the model compound
suggested that although N-oxide is thermodynamically
unfavorable compared with benzoxazine, a four-membered
ring transition state is strongly advantageous over a three-
membered ring transition state (Scheme 3B).62 Subsequent N-
to-O benzyl migration likely proceeds via a radical-mediated
[1,2]-Meisenheimer rearrangement pathway63,64 since the
addition of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO)
remarkably inhibited the reaction and benzylated TEMPO 8
was obtained instead (Scheme 3A, also the Experimental
Section). [2,3]-Meisenheimer rearrangement of N-allyl or N-
prenyl substrates (5i and 5j) is likely sigmatropic.
With this mechanism in mind, we envisaged that decreasing
the electron density on the nitrogen atom would favor
conversion to the initially expected benzoxazine, and we
therefore synthesized N-Boc-protected diaryliodonium salt 9a
(see the preparation in the Experimental Section). Treatment
with TBAF, however, afforded indole 10a in 73% yield,
without the formation of benzoxazine 11a (Table 3, entry 1),
and a stoichiometric amount of iodobenzene was generated.
Interestingly, a small amount (ca. 10%) of 5-substituted
indoline 12a was detected during each optimization reaction
(discussed below). The solvent screening revealed that DMF is
the optimum solvent, likely due to the good solubility of the
iodonium salt (entries 2−4). We next examined fluoride
reagent
(equiv)
yield of 6a
a
entry
additive (equiv)
solvent
(%)
b
1
TBAF (1.5)
TBAF (1.5)
TBAF (1.5)
TBAF (1.5)
TBAF (1.5)
CsF (1.5)
NH4F (1.5)
TASF (1.5)
PPTS (1.5)
DMF
DMF
THF
toluene
CH2Cl2
DMF
DMF
DMF
DMF
2
48
29
18
18
17
28
45
0
2
3
4
c
5
6
7
8
9
10
TBAF (1.5)
MS 4 Å (500 g/mol) DMF
c
34
a
b
Isolated yield. rt, 6 h. Reflux.
unclear but could be related to known differences between N-
alkoxyindoles and N-hydroxyindoles.55,56
Having optimized the reaction conditions, we moved on to
investigate the substrate scope (Table 2). Substitutions on
benzene were tolerated, but substitution with an electron-
donating methoxy group gave lower yield (entry 4), which
might be attributed to the instability of the product 6d to
oxidation due to the increased electron density of the benzene
ring. The use of a naphthyl ring as the main core leads to
multiple spots on thin-layer chromatography (TLC), possibly
due to complex radical recombination (entry 7; the reaction
mechanism is discussed below). We also screened substitutions
on the nitrogen. The use of a p-nitrobenzyl group led to lower
yield, apparently due to instability of the substrate (entry 8).
N-Allyl substitution worked well and afforded the correspond-
ing product (entry 9). Remarkably, the N-prenylated substrate
afforded O-reverse-prenylated 6j as the sole product (entry
10). In contrast to previous hypervalent iodine-based syntheses
Table 2. Substrate Scope for N-Alkoxyindoline Synthesis
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Scheme 3. Proposed Reaction Mechanism
an excellent yield with TBAF and TASF (entries 8 and 9). For
operational simplicity, we chose a combination of TBAF and
MS 4 Å as the optimal conditions (entry 9).
Table 3. Optimization for Indole Synthesis
With the optimized conditions in hand, we next examined
the substrate scope (Table 4). Various indoles with
substituents at the 4-, 5-, and 6-positions were obtained,
showing the robustness of this transformation. In particular,
the electron-donating methoxy group and electron-with-
drawing fluorine group were both tolerated (entries 4−6).
Interestingly, benzoindole 10g and biaryl-type indole 10h were
also obtained in good yield (entries 7 and 8). 3-Substitution
resulted in lower yield (entry 9). The N-Cbz-protected
substrate afforded indole in moderate yield (entry 10). It is
important to note that while diaryliodonium salt-based indole
synthesis was originally discovered by Ishikawa and co-
workers,44 their substrate scope has been limited to electron-
rich aromatic substrates because in situ nucleophilic aromatic
substitution is required to prepare the diaryliodonium salt. The
stepwise preparation of diaryliodonium salts via stannane
developed herein allowed great expansion of the substrate
scope of the indole synthesis via diaryliodonium salts.
Additionally to note, we were unable to prepare iodonium
salts from acyl-protected substrates (N-Ac or N-Piv), which are
a
yield (%)
entry reagent (equiv)
additive (equiv)
solvent
10a 12a
1
2
3
4
5
6
7
8
9
TBAF (1.2)
TBAF (1.2)
TBAF (1.2)
TBAF (1.2)
CsF (1.5)
NH4F (1.2)
TASF (1.2)
TASF (1.2)
DMF
THF
73
58
60
71
23
62
83
87
89
6
20
2
17
3
toluene
CH2Cl2
DMF
DMF
DMF
DMF
DMF
5
6
−
−
b
MS 4 Å (500 g/mol)
MS 4 Å (500 g/mol)
b
TBAF (1.2)
a
b
Isolated yield. Obtained as an inseparable mixture with unidentified
by-products.
sources and found that tris(dimethylamino)sulfonium difluor-
otrimethylsilicate (TASF) provided the best result (entries 5−
7). The addition of molecular sieves improved the yield, giving
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Table 4. Substrate Scope for Indole Synthesis
a
From the N-Cbz-protected substrate.
Scheme 4. Control Experiments
direct congeners for Ishikawa’s original substrates, likely due to
rapid decomposition during purification.
leads to seven-membered ring intermediate H. The recombi-
nation of the chemical bond is accompanied by reductive
elimination of iodobenzene to afford I,29,62,66,67 which
undergoes N-to-O acyl migration to provide O-Boc inter-
mediate J.57,68 Subsequent intramolecular hydrogen subtrac-
tion affords K, which isomerizes quickly to indole 10a.
Although direct decomposition of N-Boc intermediate I to N-
hydroxyindoline L can also be postulated, successful trans-
formation of Cbz-protected hydroxylamine is inconsistent with
a mechanism involving β-hydrogen elimination. This is further
supported by gas chromatography (GC) analysis: a nearly
equal amount of tert-butyl alcohol was detected in the reaction
mixture, which cannot be generated by a β-elimination
pathway. It should be emphasized that the formation of side
product 12a can be accounted for by sequential [3,3]-
sigmatropic rearrangements via M69 or N,70 which also
strongly indicates the presence of acyl migration intermediate
J.57 The role of molecular sieves can be attributed to the
removal of water, which could hydrolyze intermediates such as
I or J.
We performed several control reactions to clarify the
reaction mechanism (Scheme 4). When protected hydroxyl-
amine 13 was treated with TBAF, 14 was isolated as the sole
product and the corresponding O-Boc product 15 was not
detected (Scheme 4A). One-pot methylation afforded only O-
Me product 16. This is in accord with our brief calculation
with a model compound (see the SI), showing essentially no
equilibrium between the N-carbamate and the corresponding
O-carbonate due to the large energy difference (see the SI).
These results suggest that N-to-O acyl migration65 is unlikely
to be involved in the initiation step of the reaction.
Furthermore, the addition of TEMPO had little effect on
yield and no prominent new by-products were observed,
showing that the reaction is unlikely to be mediated by radical
chemistry (Scheme 4B).
From the above results and comparison with Ishikawa’s
hypothesis,44 we propose the reaction mechanism shown in
Scheme 5. Upon deprotection of the oxygen atom, intra-
molecular attack of the anionic oxygen on the iodine center
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Scheme 5. Proposed Reaction Mechanism
3,3′,5′-Trimethyl-4-nitro-1,1′-biphenyl (S2a).
CONCLUSIONS
■
In conclusion, we have discovered a novel method for the
synthesis of rarely accessible N-alkoxyindolines via diary-
liodonium salt-based transformation. This is the first system-
atic synthetic study of N-alkoxyindolines to date, despite their
simple structures. Further examination greatly expands both
the substrate scope of the Ishikawa indole synthesis and the
understanding of its mechanism. Our method is characterized
by operational simplicity and a broad substrate scope.
Application of this strategy to other heteroaromatics, as well
as further mechanistic analyses, will be reported in due course.
To a stirred solution of S171 (1.61 g, 5.66 mmol), (3,5-
dimethylphenyl)boronic acid (933 mg, 6.22 mmol), and K2CO3
(1.80 g, 13.0 mmol) in 1,2-dimethoxyethane (DME) (50 mL) was
added tetrakis(triphenylphosphine)palladium (144 mg, 0.124 mmol).
After being stirred at 70 °C for 12 h, the mixture was diluted with
H2O (100 mL) and extracted with EtOAc (50 mL × 3). The
combined extracts were washed with saturated brine (50 mL), dried,
and concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (EtOAc/hexane, 1:19−1:2) to
provide 1.39 g (quant.) of S2a as a white solid: TLC Rf 0.74 (EtOAc/
EXPERIMENTAL SECTION
■
General Methods. The reactions were carried out under Ar
unless otherwise noted. Melting points are uncorrected. H HMR
1
spectra were recorded at 400 or 500 MHz with tetramethylsilane as an
internal standard on a JEOL JNM-ECS400 (400 MHz), JEOL JNM-
ECZ400 (400 MHz), or JEOL JNM-ECA500 (500 MHz)
spectrometer unless otherwise noted. 13C{1H} NMR spectra were
recorded at 100 or 125 MHz. High-resolution mass spectra (HRMS)
were measured by the electrospray ionization (ESI) mode (TOF
analyzer) on a Waters LCT Premier XE spectrometer. Thin-layer
chromatography (TLC) was performed on Merck Kieselgel 60 F254
plates. An oil bath was used as the heating source for the reactions
that require heating. The crude reaction mixtures and extracted
materials were purified by chromatography on silica gel (Fuji Silysia,
PSQ-100B) or PTLC (Merck). Combined organic extracts were dried
over anhydrous Na2SO4. Solvents were removed from the reaction
mixture and the combined organic extracts by concentration under
reduced pressure using an evaporator with a water bath at 35−45 °C.
hexane, 1:6); IR (neat) 1584, 1515, 1335, 846, 831, 694 cm−1; H
1
NMR (500 MHz, CDCl3) δ 8.07 (d, 1H, J = 8.0 Hz), 7.52 (d, 1H, J =
8.0 Hz), 7.52 (s, 1H), 7.21 (s, 2H), 7.07 (s, 1H), 2.69 (s, 3H), 2.40 (s,
6H); 13C{1H} NMR (125 MHz, CDCl3) δ 147.9, 146.5, 139.0, 138.8
(2C), 134.4, 131.5, 130.4, 125.6, 125.5, 125.3 (2C), 21.5 (2C), 21.2;
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H15NO2 242.1181;
found 242.1180.
2-(1-Nitronaphthalen-2-yl)ethan-1-ol (S3a).
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To a cooled (0 °C) stirred solution of 2-methyl-1-nitronaphthalene
(S2b) (4.00 g, 21.3 mmol) and formalin (35% solution, 3.80 mL, 36.1
mmol) in dimethyl sulfoxide (DMSO) (40 mL) was added aqueous
KOH (17.9 M solution, 2.02 mL, 36.1 mmol). After being stirred at 0
°C for 30 min and at room temperature for 30 min, the mixture was
quenched with saturated aqueous NH4Cl (40 mL), diluted with H2O
(20 mL), and extracted with EtOAc (70 mL × 4). The combined
extracts were washed with saturated brine (100 mL), dried, and
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (EtOAc/hexane, 1:1) to provide
3.31 g (71%) of S3a as yellow crystals: mp 79−84 °C; TLC Rf 0.32
(EtOAc/hexane, 1:1); IR (neat) 3546, 1523, 1361, 1056, 818, 746
cm−1; 1H NMR (400 MHz, CDCl3) δ 7.94 (d, 1H, J = 8.0 Hz), 7.89
(d, 1H, J = 8.0 Hz), 7.72 (d, 1H, J = 8.4 Hz), 7.63 (td, 1H, J = 8.0, 1.2
Hz), 7.57 (td, 1H, J = 8.0, 1.2 Hz), 7.46 (d, 1H, J = 8.4 Hz), 3.98 (q,
2H, J = 6.4 Hz), 3.03 (t, 2H, J = 6.4 Hz), 1.61 (t, 1H, J = 6.4 Hz);
13C{1H} NMR (100 MHz, CDCl3) δ 148.5, 132.7, 130.8, 128.8,
128.4, 128.1, 127.6, 127.2, 124.7, 121.6, 62.8, 35.2; HRMS (ESI-
TOF) m/z; [M + Na]+ calcd for C12H11NNaO3 240.0637; found
240.0643.
Hz), 7.58 (dd, 1H, J = 7.0, 2.6 Hz), 7.48 (t, 2H, J = 7.0 Hz), 7.42 (tt,
1H, J = 7.0, 2.6 Hz), 4.09 (d, 4H, J = 6.0 Hz), 3.64 (quin, 1H, J = 6.0
Hz), 2.20 (br s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 151.2,
141.3, 138.4, 132.8, 131.2, 129.7, 129.3 (2C), 128.6, 127.1 (2C),
123.0, 65.0 (2C), 43.8; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C15H15NO4 274.1079; found 274.1073.
3-Methoxy-2-(3-nitro-[1,1′-biphenyl]-4-yl)propan-1-ol (S4).
To a cooled (0 °C) stirred solution of S3c (3.08 g, 11.3 mmol) in
DMF (56 mL) was added NaH (60% in oil, 452 mg, 11.3 mmol). The
mixture was stirred at room temperature for 30 min, and MeI was
added. After being stirred at room temperature for 12 h, the mixture
was cooled to 0 °C, quenched with saturated aqueous NH4Cl (5 mL),
diluted with H2O (100 mL), and extracted with EtOAc (100 mL ×
3). The combined extracts were washed with H2O (100 mL) and
saturated brine (100 mL) sequentially, dried, and concentrated under
reduced pressure. The residue was purified by column chromatog-
raphy on silica gel (EtOAc/hexane, 1:2−1:1) to provide 2.06 g (63%)
of S4 as a yellow oil: TLC Rf 0.64 (EtOAc); IR (neat) 3398, 1529,
1356, 1116, 761 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.01 (d, 1H, J
= 2.0 Hz), 7.77 (dd, 1H, J = 8.4, 2.0 Hz), 7.63 (d, 1H, J = 8.4 Hz),
7.58 (dd, 2H, J = 7.2, 1.4 Hz), 7.48 (tt, 2H, J = 7.2, 1.4 Hz), 7.41 (tt,
1H, J = 7.2, 1.4 Hz), 4.07 (m, 1H), 3.99 (m, 1H), 3.81 (m, 2H), 3.73
(m, 1H), 3.40 (s, 3H), 2.66 (t, 1H, J = 6.0 Hz); 13C{1H} NMR (100
MHz, CDCl3) δ 151.1, 141.5, 138.5, 133.1, 131.1, 130.0, 129.3 (2C),
128.6, 127.1 (2C), 122.9, 74.7, 65.2, 59.3, 41.6; HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C16H17NO4 288.1236; found 288.1228.
2-(1-Aminonaphthalen-2-yl)ethan-1-ol (S5a).
2-(3′,5′-Dimethyl-4-nitro-[1,1′-biphenyl]-3-yl)ethan-1-ol (S3b).
To a suspension of S2a (2.03 g, 8.41 mmol) in DMSO (80 mL) were
added formalin (35%, 1.44 mL, 16.8 mmol), aqueous KOH (1.68 M
solution, 5.0 mL, 8.4 mmol), and tetrahydrofuran (THF) (5 mL)
successively under air. After being stirred at room temperature for 12
h, the mixture was quenched with saturated aqueous NH4Cl (10 mL),
diluted with H2O (100 mL), and extracted with EtOAc (100 mL ×
3). The combined extracts were washed with H2O (100 mL) and
saturated brine (100 mL) sequentially, dried, and concentrated under
reduced pressure. The residue was purified by column chromatog-
raphy on silica gel (EtOAc/hexane, 1:9−2:1) to provide 1.41 g (62%)
of S3b as a yellow solid: TLC Rf 0.12 (EtOAc/hexane, 1:6); IR (neat)
3306, 1582, 1517, 1339, 1041, 840 cm−1; 1H NMR (500 MHz,
CDCl3) δ 8.04 (d, 1H, J = 8.0 Hz), 7.60 (d, 1H, J = 2.0 Hz), 7.58 (dd,
1H, J = 8.0, 2.0 Hz), 7.21 (s, 2H), 7.06 (s, 1H), 4.01 (q, 2H, J = 6.0
Hz), 3.27 (t, 2H, J = 6.0 Hz), 2.40 (s, 6H), 1.60 (t, 1H, J = 6.0 Hz);
13C{1H} NMR (125 MHz, CDCl3) δ 148.4, 146.6, 138.9 (2C), 138.8,
134.6, 131.6, 130.6, 126.3, 125.8, 125.4 (2C), 63.0, 36.7, 21.5 (2C);
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H17NO3 272.1287;
found 272.1296.
To a stirred solution of S3a (1.22 g, 5.61 mmol) in EtOH/H2O (4:1,
55 mL) were added iron powder (1.76 g, 31.6 mmol) and NH4Cl
(312 mg, 5.83 mmol). The mixture was stirred at 70 °C for 22 h
under air. The insoluble materials were removed by filtration through
a pad of Celite and washed well with CH2Cl2. The combined filtrate
and washings were concentrated under reduced pressure. The residue
was washed with saturated aqueous NaHCO3 (30 mL) and extracted
with CH2Cl2 (30 mL × 4). The combined extracts were washed with
saturated brine (20 mL), dried, and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel (EtOAc/hexane, 2:1) to provide 784 mg (75%) of S5a as
light brown crystals: mp 75−78 °C; TLC Rf 0.23 (EtOAc/hexane,
2-(3-Nitro-[1,1′-biphenyl]-4-yl)propane-1,3-diol (S3c).
1
1:1); IR (neat) 3406, 3019, 1384, 1217, 771 cm−1; H NMR (400
MHz, CDCl3) δ 7.82 (d, 1H, J = 8.0 Hz), 7.78 (dd, 1H, J = 8.0, 1.6
Hz), 7.46 (td, 1H, J = 8.0, 1.6 Hz), 7.42 (td, 1H, J = 8.0, 1.6 Hz), 7.30
(d, 1H, J = 8.4 Hz), 7.21 (d, 1H, J = 8.4 Hz), 3.99 (t, 2H, J = 6.4 Hz),
2.99 (t, 2H, J = 6.4 Hz), 1.65 (br, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 140.2, 133.5, 129.1, 128.6, 125.4, 125.2, 123.9, 120.6, 118.9,
117.8, 63.4, 35.4; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C12H14NO 188.1075; found 188.1068.
To a cooled (0 °C) stirred solution of S2c72 (4.17 g, 19.6 mmol) in
DMSO (100 mL) and THF (10 mL) were added aqueous KOH
(3.92 M solution, 5.0 mL, 20 mmol) and formalin (35%, 3.3 mL, 39.1
mmol) under air. After being stirred at room temperature for 12 h, the
mixture was quenched with saturated aqueous NH4Cl (10 mL),
diluted with H2O (100 mL), and extracted with EtOAc (100 mL ×
3). The combined extracts were washed with H2O (100 mL) and
saturated brine (100 mL) sequentially, dried, and concentrated under
reduced pressure. The residue was purified by column chromatog-
raphy on silica gel (EtOAc/hexane, 1:1−1:0) to provide 3.08 g (58%)
of S3c as a yellow oil: TLC Rf 0.41 (EtOAc); IR (neat) 3343, 1529,
2-(4-Amino-3′,5′-dimethyl-[1,1′-biphenyl]-3-yl)ethan-1-ol (S5b).
1
1355, 1037, 760, 697 cm−1; H NMR (400 MHz, CDCl3) δ 8.02 (d,
1H, J = 2.0 Hz), 7.79 (dd, 1H, J = 8.2, 2.0 Hz), 7.63 (d, 1H, J = 8.2
10073
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To a stirred solution of S3b (1.42 g, 5.23 mmol) in EtOH (44 mL)
and H2O (12 mL) were added NH4Cl (401 mg, 7.50 mmol) and iron
powder (2.92 g, 52.3 mmol). The mixture was stirred at 70 °C for 2
days under air, and NH4Cl (200 mg, 3.74 mmol) and iron powder
(1.60 g, 28.7 mmol) were added. The mixture was further stirred at 70
°C for 12 h under air. The insoluble materials were removed by
filtration through a pad of Celite and washed well with EtOAc and
H2O. A saturated aqueous solution (5 mL) of NaOH (1 g) and
saturated brine (100 mL) were added to the combined filtrate and
washings, and the mixture was extracted with EtOAc (100 mL × 3).
The combined extracts were washed with saturated brine (50 mL),
dried, and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel (EtOAc/hexane,
1:2−1:0) to provide 409 mg (32%) of S5b as a black oil: TLC Rf 0.38
(EtOAc); IR (neat) 3374, 2921, 1600, 1505, 1384, 1212, 1034, 771
cm−1; 1H NMR (400 MHz, CDCl3) δ 7.32−7.29 (m, 2H), 7.15 (br s,
2H), 6.93 (br s, 1H), 6.76 (d, 1H, J = 8.0 Hz), 3.95 (t, 2H, J = 6.0
Hz), 2.86 (t, 2H, J = 6.0 Hz), 2.36 (s, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 144.6, 141.2, 138.3 (2C), 132.5, 129.5, 128.1, 126.5,
124.5 (3C), 116.7, 63.6, 35.1, 21.6 (2C); HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C16H20NO 242.1545; found 242.1542.
1:2) to provide 2.58 g (75%) of S6a as yellow crystals: mp 110−113
°C; TLC Rf 0.43 (EtOAc/hexane, 1:2); IR (neat) 3280, 2953, 1444,
1384, 1038, 767 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.69 (d, 1H, J
= 7.6 Hz), 7.12 (d, 1H, J = 7.6 Hz), 6.80 (t, 1H, J = 7.6 Hz), 3.81 (t,
2H, J = 7.2 Hz), 3.13 (t, 2H, J = 7.2 Hz), 2.43 (s, 3H), 1.44 (br, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 139.0, 138.5, 137.9, 130.7,
128.4, 102.6, 61.6, 41.0, 21.5; HRMS (ESI-TOF) m/z: [M + Na]+
calcd for C9H11INaO 284.9752; found 284.9763.
2-(2-Iodo-4-methylphenyl)ethan-1-ol (S6b).
As described for the preparation of S6a, compound S5e74 (2.07 g,
13.7 mmol) was converted to 2.88 g (80%) of S6b. Compound S6b
was obtained as an orange oil: TLC Rf 0.37 (EtOAc/hexane, 1:2); IR
(neat) 3357, 2951, 2923, 1486, 1217, 1039, 769 cm−1; 1H NMR (400
MHz, CDCl3) δ 7.68 (s, 1H), 7.13 (d, 1H, J = 7.6 Hz), 7.09 (d, 1H, J
= 7.6 Hz), 3.82 (br s, 2H), 2.97 (t, 2H, J = 6.8 Hz), 2.28 (s, 3H), 1.53
(br, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 140.2, 138.4, 138.0,
130.1, 129.3, 100.8, 62.5, 43.3, 20.5; HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C9H12IO 262.9933; found 262.9942.
2-(3-Amino-[1,1′-biphenyl]-4-yl)-3-methoxypropan-1-ol (S5c).
2-(4-Chloro-2-iodophenyl)ethan-1-ol (S6c).
To a stirred solution of S4 (2.06 g, 7.17 mmol) in EtOH (60 mL) and
H2O (15 mL) were added NH4Cl (384 mg, 7.17 mmol) and iron
powder (4.00 g, 71.7 mmol). The mixture was stirred at 70 °C for 12
h under air. The insoluble materials were removed by filtration
through a pad of Celite and washed well with EtOAc and H2O.
Saturated aqueous NaHCO3 (5 mL) and saturated brine (100 mL)
were added to the combined filtrate and washings, and the mixture
was extracted with EtOAc (100 mL × 3). The combined extracts were
washed with saturated brine (50 mL), dried, and concentrated under
reduced pressure. The residue was purified by column chromatog-
raphy on silica gel (EtOAc/hexane, 1:1−1:0) to provide 1.37 g (74%)
of S5c as pale red crystals: mp 128−130 °C; TLC Rf 0.11 (EtOAc/
hexane, 1:1); IR (neat) 3357, 2925, 1633, 1384, 1212, 1113, 764, 698
cm−1; 1H NMR (400 MHz, CDCl3) δ 7.54 (d, 2H, J = 7.2 Hz), 7.41
(t, 2H, J = 7.2 Hz), 7.32 (t, 1H, J = 7.2 Hz), 7.07 (d, 1H, J = 8.0 Hz),
6.99 (dd, 1H, J = 8.0, 1.6 Hz), 6.93 (d, 1H, J = 2.0 Hz), 4.04 (dd, 1H,
J = 10.4, 9.2 Hz), 3.90 (dd, 1H, J = 11.2, 5.6 Hz), 3.80 (t, 1H, J = 9.2
Hz), 3.70 (dd, 1H, J = 11.2, 5.6 Hz), 3.41 (s, 3H), 3.26 (m, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 145.3, 141.1, 140.9, 128.8 (2C),
127.7, 127.3, 127.1 (2C), 123.9, 118.1, 115.3, 75.8, 65.7, 59.3, 42.0;
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H20NO2 258.1494;
found 258.1493.
As described for the preparation of S6a, compound S5f73 (2.14 g, 12.5
mmol) was converted to 2.61 g (74%) of S6c. Compound S6c was
obtained as a red oil: TLC Rf 0.37 (EtOAc/hexane, 1:2); IR (neat)
1
3332, 2933, 2878, 1579, 1465, 1034, 815, 798 cm−1; H NMR (400
MHz, CDCl3) δ 7.82 (d, 1H, J = 1.6 Hz), 7.27 (dd, 1H, J = 8.0, 1.6
Hz), 7.18 (d, 1H, J = 8.0 Hz), 3.84 (t, 2H, J = 6.8 Hz), 2.98 (t, 2H, J =
6.8 Hz), 1.50 (br, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 139.9,
138.9, 133.0, 130.9, 128.6, 100.6, 62.2, 43.0; HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C8H9ClIO 282.9387; found 282.9380.
2-(4-Fluoro-2-iodophenyl)ethan-1-ol (S6d).
As described for the preparation of S6a, compound S5g73 (1.86 g,
12.0 mmol) was converted to 2.53 g (80%) of S6d. Compound S6d
was obtained as a red oil: TLC Rf 0.37 (EtOAc/hexane, 1:2); IR
(neat) 3364, 2954, 1593, 1482, 1221, 1042, 862, 758 cm−1; 1H NMR
(400 MHz, CDCl3) δ 7.55 (dd, 1H, J = 8.4, 2.8 Hz), 7.22 (dd, 1H, J =
8.4, 6.0 Hz), 7.02 (td, 1H, J = 8.4, 2.8 Hz), 3.82 (t, 2H, J = 6.8 Hz),
2.98 (t, 2H, J = 6.8 Hz), 1.61 (br, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 160.8 (d, J = 249.1 Hz), 137.1 (d, J = 2.9 Hz), 130.8 (d, J =
7.6 Hz), 126.5 (d, J = 23.0 Hz), 115.4 (d, J = 20.1 Hz), 99.7 (d, J =
7.7 Hz), 62.3, 42.7; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C8H9FIO 266.9682; found 266.9669.
2-(2-Iodo-6-methylphenyl)ethan-1-ol (S6a).
2-(1-Iodonaphthalen-2-yl)ethan-1-ol (S6e).
To a stirred solution of TsOH·H2O (7.55 g, 39.7 mmol) in CH3CN
(28 mL) was added S5d73 (1.99 g, 13.2 mmol). The mixture was
stirred at room temperature for 15 min and at 0 °C for 15 min, and
aqueous NaNO2 (6.60 M solution, 4.00 mL, 26.3 mmol) was added.
The mixture was stirred at 0 °C for 40 min, and aqueous KI (8.25 M
solution, 4.00 mL, 33.0 mmol) was added. After being stirred at 0 °C
for 10 min and at room temperature for 4 h, the mixture was
quenched with saturated aqueous NaHCO3 (20 mL), 20 wt %
aqueous Na2S2O3 (20 mL), and extracted with EtOAc (80 mL × 3).
The combined extracts were washed with saturated brine (50 mL),
dried, and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel (EtOAc/hexane,
As described for the preparation of S6a, compound S5a (1.39 g, 7.44
mmol) was converted to 1.82 g (82%) of S6e. Compound S6e was
obtained as orange crystals: mp 72−75 °C; TLC Rf 0.43 (EtOAc/
hexane, 1:2); IR (neat) 3406, 3017, 1499, 1216, 1039, 757 cm−1; 1H
NMR (400 MHz, CDCl3) δ 8.24 (d, 1H, J = 8.4 Hz), 7.76 (d, 2H, J =
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8.0 Hz), 7.57 (t, 1H, J = 8.0 Hz), 7.48 (t, 1H, J = 8.0 Hz), 7.39 (d,
1H, J = 8.4 Hz), 3.97 (q, 2H, J = 6.4 Hz), 3.34 (t, 2H, J = 6.4 Hz),
1.46 (t, 1H, J = 6.4 Hz); 13C{1H} NMR (100 MHz, CDCl3) δ 140.7,
135.3, 133.1, 132.9, 128.9, 128.3, 128.1, 128.0, 126.3, 106.0, 62.7,
45.8; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C12H12IO
298.9933; found 298.9922.
THF (11 mL) was added n-BuLi (2.69 M solution in hexane, 4.10
mL, 11.0 mmol). The mixture was stirred at −78 °C for 0.5 h, and n-
Bu3SnCl (1.75 mL, 6.45 mmol) was added. After being stirred at −78
°C for 30 min and at room temperature for 8 h, the mixture was
quenched with saturated aqueous NH4Cl (5 mL), diluted with H2O
(5 mL), and extracted with EtOAc (10 mL × 3). The combined
extracts were washed with saturated brine (10 mL), dried, and
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (EtOAc/hexane, 1:10) to
provide 875 mg (45%) of 2b as a yellow oil: TLC Rf 0.58 (EtOAc/
hexane, 1:2); IR (neat) 3429, 2958, 2927, 1457, 1216, 1030, 759, 669
2-(4-Iodo-3′,5′-dimethyl-[1,1′-biphenyl]-3-yl)ethan-1-ol (S6f).
1
cm−1; H NMR (400 MHz, CDCl3) δ 7.30 (m, 1H), 7.16−7.14 (m,
2H), 3.72 (br q, 2H, J = 8.0 Hz), 2.97 (t, 2H, J = 8.0 Hz), 2.41 (s,
3H), 1.62−1.49 (m, 6H), 1.43−1.31 (m, 6H), 1.21−1.04 (m, 6H),
0.93 (t, 9H, J = 7.6 Hz); 13C{1H} NMR (100 MHz, CDCl3) δ 143.9,
142.8, 136.5, 135.0, 130.9, 126.3, 63.1, 40.2, 29.2 (3C), 27.6 (3C),
20.5, 13.8 (3C), 10.9 (3C); HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C21H39OSn 427.2023; found 427.2028.
As described for the preparation of S6a, compound S5b (427 mg,
1.77 mmol) was converted to 328 mg (62%) of S6f. Compound S6f
was obtained as a light brown oil: TLC Rf 0.41 (EtOAc/hexane, 1:2);
2-[4-Methyl-2-(tributylstannyl)phenyl]ethan-1-ol (2c). As de-
scribed for the preparation of 2b, compound S6b (877 mg, 3.35
mmol) was converted to 481 mg (34%) of 2c. Compound 2c was
obtained as a yellow oil: TLC Rf 0.58 (EtOAc/hexane, 1:2); IR (neat)
1
IR (neat) 3381, 2919, 1604, 1384, 1042, 900, 772 cm−1; H NMR
(400 MHz, CDCl3) δ 7.86 (d, 1H, J = 8.4 Hz), 7.46 (d, 1H, J = 2.4
Hz), 7.17 (br s, 2H), 7.14 (dd, 1H, J = 8.4, 2.0 Hz), 7.01 (br s, 1H),
3.91 (q, 2H, J = 6.4 Hz), 3.08 (t, 2H, J = 6.8 Hz), 2.38 (s, 6H), 1.42
(t, 1H, J = 6.0 Hz); 13C{1H} NMR (100 MHz, CDCl3) δ 141.9,
141.4, 140.0 (2C), 138.6 (2C), 129.5, 129.2, 127.3, 125.0 (2C), 99.3,
62.5, 43.9, 21.5 (2C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C16H18IO 353.0402; found 353.0397.
1
3421, 2958, 2929, 1464, 1381, 1216, 1044, 758, 669 cm−1; H NMR
(400 MHz, CDCl3) δ 7.21 (br s, 1H), 7.15 (d, 1H, J = 8.0 Hz), 7.08
(d, 1H, J = 8.0 Hz), 3.80 (t, 2H, J = 7.2 Hz), 2.84 (t, 2H, J = 7.2 Hz),
2.31 (s, 3H), 1.56−1.46 (m, 6H), 1.37−1.30 (m, 6H), 1.11−1.02 (m,
6H), 0.89 (t, 9H, J = 7.2 Hz); 13C{1H} NMR (100 MHz, CDCl3) δ
142.6, 141.9, 138.0, 135.2, 129.4, 128.6, 64.3, 41.7, 29.3 (3C), 27.6
(3C), 21.1, 13.8 (3C), 10.6 (3C); HRMS (ESI-TOF) m/z: [M + H]+
calcd for C21H39OSn 427.2023; found 427.2014.
2-(3-Iodo-[1,1′-biphenyl]-4-yl)-3-methoxypropan-1-ol (S6g).
2-[4-Methoxy-2-(tributylstannyl)phenyl]ethan-1-ol (2d).
As described for the preparation of S6a, compound S5c (1.27 g, 4.95
mmol) was converted to 1.67 g (92%) of S6g. Compound S6g was
obtained as a yellow oil: TLC Rf 0.27 (EtOAc/hexane, 1:2); IR (neat)
3406, 2926, 2878, 1596, 1538, 1474, 1376, 1116, 1033, 762, 697
To a cooled (0 °C) stirred solution of 2-bromo-4-methoxyphenyl-
acetic acid (S7) (1.12 g, 4.76 mmol) in THF (15 mL) were added
NaBH4 (437 mg, 11.6 mmol) and BF3·OEt2 (0.720 mL, 5.73 mmol).
After being stirred at 60 °C for 1 h, the mixture was quenched with
MeOH (5 mL) and stirred at room temperature for 30 min. The
mixture was diluted with H2O (10 mL) and extracted with EtOAc (25
mL × 4). The combined extracts were washed with saturated brine
(25 mL), dried, and concentrated under reduced pressure to provide
crude S8, which was used in the next step without further purification.
To a cooled (−78 °C) stirred solution of crude S8 obtained above
in THF (13 mL) was added n-BuLi (2.69 M solution in hexane, 3.60
mL, 9.68 mmol). The mixture was stirred at −78 °C for 40 min, and
n-Bu3SnCl (1.50 mL, 5.53 mmol) was added. After being stirred at
−78 °C for 20 min and at room temperature for 2.5 h, the mixture
was quenched with saturated aqueous NH4Cl (10 mL), diluted with
H2O (10 mL), and extracted with EtOAc (20 mL × 4). The
combined extracts were washed with saturated brine (20 mL), dried,
and concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (EtOAc/hexane, 1:8) to provide
1.25 g (60% for two steps from S7) of 2d as a yellow oil: TLC Rf 0.67
(EtOAc/hexane, 1:2); IR (neat) 3445, 2958, 2928, 1589, 1465, 1216,
1041, 758, 669 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.18 (d, 1H, J =
8.6 Hz), 6.98 (d, 1H, J = 2.6 Hz), 6.82 (dd, 1H, J = 8.6, 2.6 Hz), 3.80
(s, 3H), 3.78 (q, 2H, J = 6.8 Hz), 2.82 (t, 2H, J = 6.8 Hz), 1.59−1.48
(m, 6H), 1.40−1.27 (m, 6H), 1.18−1.00 (m, 6H), 0.89 (t, 9H, J = 7.2
Hz); 13C{1H} NMR (100 MHz, CDCl3) δ 157.5, 144.4, 136.9, 129.5,
122.9, 113.3, 64.4, 55.3, 41.2, 29.2 (3C), 27.5 (3C), 13.8 (3C), 10.7
(3C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H39O2Sn
443.1972; found 443.1986.
1
cm−1; H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.53 (d, 3H, J =
8.0 Hz), 7.44 (t, 2H, J = 7.6 Hz), 7.36 (t, 1H, J = 7.6 Hz), 7.29 (d,
1H, J = 8.0 Hz), 4.04−3.91 (m, 2H), 3.78−3.71 (m, 2H), 3.60 (tt,
1H, J = 7.6, 6.4 Hz), 3.43 (s, 3H), 2.50 (t, 1H, J = 5.2 Hz); 13C{1H}
NMR (100 MHz, CDCl3) δ 141.9, 140.8, 139.2, 138.5, 129.0 (2C),
127.9 (2C), 127.3, 127.1 (2C), 102.7, 75.3, 65.4, 59.3, 50.5; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C16H18IO2 369.0352; found
369.0366.
2-(2-Tributylstannylphenyl)ethan-1-ol (2a). To a cooled (−78
°C) stirred solution of 2-(2-bromophenyl)ethyl alcohol (1) (2.70 mL,
20.0 mmol) in THF (50 mL) was added n-BuLi (2.6 M solution in
hexane, 19.5 mL, 50.7 mmol). The mixture was stirred at −78 °C for
1 h, and n-Bu3SnCl (7.50 mL, 27.6 mmol) was added. After being
stirred at −78 °C for 1 h and at room temperature for 5.5 h, the
mixture was quenched with saturated aqueous NH4Cl (25 mL),
diluted with H2O (25 mL), and extracted with EtOAc (50 mL × 3).
The combined extracts were washed with saturated brine (50 mL),
dried, and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel (EtOAc/hexane,
1:10) to provide 6.44 g (78%) of 2a as a colorless oil: TLC Rf 0.46
(EtOAc/hexane, 1:10); IR (neat) 3356, 2957, 2926, 1464, 1377,
1217, 1045, 757, 667 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.42 (dd,
1H, J = 6.8, 0.9 Hz), 7.30−7.24 (m, 2H), 7.19 (td, 1H, J = 7.2, 2.0
Hz), 3.83 (q, 2H, J = 6.8 Hz), 2.87 (t, 2H, J = 6.8 Hz), 1.54−1.44 (m,
6H), 1.39−1.29 (m, 6H), 1.16−0.99 (m, 6H), 0.89 (t, 9H, J = 7.2
Hz); 13C{1H} NMR (100 MHz, CDCl3) δ 145.0, 143.0, 137.3, 128.7,
128.6, 126.1, 64.2, 42.3, 29.3 (3C), 27.6 (3C), 13.8 (3C), 10.6 (3C);
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C20H37OSn 413.1866;
found 413.1873.
2-[4-Chloro-2-(tributylstannyl)phenyl]ethan-1-ol (2e). As de-
scribed for the preparation of 2b, compound S6c (1.50 g, 5.32
mmol) was converted to 651 mg (27%) of 2e. Compound 2e was
obtained as a red oil: TLC Rf 0.43 (EtOAc/hexane, 1:2); IR (neat)
2-[2-Methyl-6-(tributylstannyl)phenyl]ethan-1-ol (2b). To a
cooled (−78 °C) stirred solution of S6a (1.21 g, 4.60 mmol) in
10075
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3375, 2957, 2926, 1462, 1377, 1046, 760 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.34 (d, 1H, J = 2.0 Hz), 7.24−7.17 (m, 2H), 3.80 (q, 2H, J
= 6.8 Hz), 2.83 (t, 2H, J = 6.8 Hz), 1.55−1.48 (m, 6H), 1.38−1.29
(m, 6H), 1.18−1.01 (m, 6H), 0.90 (t, 9H, J = 7.2 Hz); 13C{1H} NMR
(100 MHz, CDCl3) δ 145.6, 143.3, 136.4, 132.4, 129.9, 128.4, 64.0,
41.5, 29.2 (3C), 27.5 (3C), 13.8 (3C), 10.7 (3C); HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C20H36ClOSn 447.1477; found 447.1479.
2-[4-Fluoro-2-(tributylstannyl)phenyl]ethan-1-ol (2f). As de-
scribed for the preparation of 2b, compound S6d (1.50 g, 5.63
mmol) was converted to 733 mg (30%) of 2f. Compound 2f was
obtained as a red oil: TLC Rf 0.43 (EtOAc/hexane, 1:2); IR (neat)
To a cooled (0 °C) stirred solution of hydroxylamine hydrochloride
(S9) (1.45 g, 22.5 mmol) in DMF (50 mL) were added tert-
butyldimethylchlorosilane (3.40 g, 22.5 mmol) and Et3N (10.5 mL,
75.0 mmol). The mixture was stirred at room temperature for 11 h
and 2-nitrobenzenesulfonyl chloride (3.34 g, 15.1 mmol) was added
at 0 °C. After being stirred at room temperature for 6.5 h, the mixture
was quenched with H2O (50 mL) and extracted with EtOAc/hexane
(1:4, 100 mL × 4). The combined extracts were washed with H2O
(100 mL × 2) and saturated brine (60 mL), dried, and concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel (EtOAc/hexane, 1:10) to provide 3.20
g (64%) of S1075 as white crystals: TLC Rf 0.33 (EtOAc/hexane,
1:3); H NMR (400 MHz, CDCl3) δ 8.16 (dd, 1H, J = 6.8, 2.0 Hz),
7.90 (dd, 1H, J = 7.2, 1.6 Hz), 7.84−7.76 (m, 2H), 7.65 (br s, 1H),
0.88 (s, 9H), 0.25 (s, 6H).
N-(tert-Butyldimethylsilyloxy)-2-nitro-N-[2-(tributyl-stannyl)-
phenethyl]benzenesulfonamide (S11a).
1
3375, 2957, 2927, 1577, 1474, 1214, 1045, 875, 760 cm−1; H NMR
(400 MHz, CDCl3) δ 7.22 (dd, 1H, J = 8.4, 5.2 Hz), 7.11 (dd, 1H, J =
8.4, 2.4 Hz), 6.94 (td, 1H, J = 8.4, 2.4 Hz), 3.80 (t, 2H, J = 6.8 Hz),
2.85 (t, 2H, J = 6.8 Hz), 1.62−1.43 (m, 6H), 1.39−1.27 (m, 6H),
1.19−1.00 (m, 6H), 0.90 (t, 9H, J = 7.2 Hz); 13C{1H} NMR (100
MHz, CDCl3) δ 161.3 (d, J = 247.2 Hz), 145.6 (d, J = 1.9 Hz), 140.5
(d, J = 2.8 Hz), 129.9 (d, J = 5.8 Hz), 123.1 (d, J = 17.3 Hz), 115.1
(d, J = 21.8 Hz), 64.2, 41.3, 29.2 (3C), 27.5 (3C), 13.8 (3C), 10.7
(3C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C20H36FOSn
431.1772; found 431.1771.
1
2-[1-(Tributylstannyl)naphthalen-2-yl]ethan-1-ol (2g). As de-
scribed for the preparation of 2b, compound S6e (988 mg, 3.31
mmol) was converted to 404 mg (26%) of 2g. Compound 2g was
obtained as a yellow oil: TLC Rf 0.68 (EtOAc/hexane, 1:2); IR (neat)
To a cooled (0 °C) stirred solution of 2a (5.88 g, 14.3 mmol), S10
(3.73 g, 11.2 mmol), and PPh3 (5.87 g, 22.4 mmol) in THF/toluene
(1:3, 44 mL) was slowly added diethyl azodicarboxylate (2.2 M
solution in toluene, 7.70 mL, 16.9 mmol). After being stirred at 0 °C
for 1 h and at room temperature for 2 h, the mixture was concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel (CH2Cl2/hexane, 1:8) to provide 7.06
g (87% from S10) of S11a as pale yellow crystals: mp 39−41 °C;
TLC Rf 0.31 (EtOAc/hexane, 1:6); IR (neat) 2956, 2929, 1550, 1464,
1378, 1180, 845, 758, 600 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.08,
(dd, 1H, J = 8.0, 1.6 Hz), 7.76 (td, 1H, J = 8.0, 1.6 Hz), 7.68 (td, 1H,
J = 8.0, 1.6 Hz), 7.55 (dd, 1H, J = 8.0, 1.6 Hz), 7.38 (d, 1H, J = 7.2
Hz), 7.24 (m, 1H), 7.19−7.15 (m, 2H), 3.37 (t, 2H, J = 8.0 Hz), 2.96
(t, 2H, J = 8.0 Hz), 1.53−1.40 (m, 6H), 1.36−1.27 (m, 6H), 1.14−
1.02 (m, 6H), 0.98 (s, 9H), 0.87 (t, 9H, J = 7.6 Hz), 0.23 (s, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 149.8, 144.9, 142.6, 137.2,
1
3428, 2958, 2927, 1457, 1383, 1216, 1043, 816, 758, 669 cm−1; H
NMR (400 MHz, CDCl3) δ 7.90 (dd, 1H, J = 8.4, 1.6 Hz), 7.81 (dd,
1H, J = 8.4, 1.6 Hz), 7.77 (d, 1H, J = 8.4 Hz), 7.46 (td, 1H, J = 8.4,
1.6 Hz), 7.42 (td, 1H, J = 8.4, 1.6 Hz), 7.35 (d, 1H, J = 8.4 Hz), 3.86
(q, 2H, J = 6.8 Hz), 3.08 (t, 2H, J = 6.8 Hz), 1.62−1.45 (m, 6H),
1.38−1.29 (m, 6H), 1.27−1.15 (m, 6H), 0.87 (t, 9H, J = 7.2 Hz);
13C{1H} NMR (100 MHz, CDCl3) δ 144.4, 142.7, 139.7, 132.5,
129.8, 129.2, 128.9, 127.7, 125.7, 125.0, 64.7, 42.3, 29.3 (3C), 27.5
(3C), 13.8 (3C), 13.3 (3C); HRMS (ESI-TOF) m/z: [M + Na]+
calcd for C24H38NaOSn 485.1842; found 485.1853.
2-(3′,5′-Dimethyl-4-(tributylstannyl)-[1,1′-biphenyl]-3-yl)ethan-
1-ol (2h). As described for the preparation of 2b, compound S6f (272
mg, 0.773 mmol) was converted to 151 mg (38%) of 2h. Compound
2h was obtained as a pale yellow oil: TLC Rf 0.54 (EtOAc/hexane,
1:2); IR (neat) 3332, 2956, 2925, 1604, 1463, 1383, 1217, 1045, 823,
1
759, 669 cm−1; H NMR (400 MHz, CDCl3) δ 7.49−7.40 (m, 3H),
7.21 (br s, 2H), 6.99 (br s, 1H), 3.87 (q, 2H, J = 6.8 Hz), 2.94 (t, 2H,
J = 6.8 Hz), 2.38 (s, 6H), 1.62−1.49 (m, 6H), 1.44−1.28 (m, 6H),
1.19−1.02 (m, 6H), 0.90 (t, 9H, J = 7.2 Hz); 13C{1H} NMR (100
MHz, CDCl3) δ 145.4, 141.60, 141.55, 141.2, 138.4 (2C), 137.6,
129.1, 127.5, 125.2 (2C), 124.8, 64.3, 42.3, 29.3 (3C), 27.6 (3C),
21.6 (2C), 13.8 (3C), 10.7 (3C); HRMS (ESI-TOF) m/z: [M + H]+
calcd for C28H45OSn 517.2492; found 517.2488.
134.8, 133.0, 130.8, 128.6, 128.5, 126.4, 126.1, 123.8, 57.1, 37.0, 29.3
(3C), 27.5 (3C), 26.2 (3C), 18.5, 13.8 (3C), 10.5 (3C), −4.1 (2C);
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H55N2O5SSiSn
727.2623; found 727.2603.
N-(tert-Butyldimethylsilyloxy)-N-[2-methyl-6-(tributyl-stannyl)-
phenethyl]-2-nitrobenzenesulfonamide (S11b).
3-Methoxy-2-{3-(tributylstannyl)-[1,1′-biphenyl]-4-yl}propan-1-
ol (2i). As described for the preparation of 2b, compound S6g (1.67 g,
4.55 mmol) was converted to 792 mg (33%) of 2i. Compound 2i was
obtained as a yellow oil: TLC Rf 0.71 (EtOAc/hexane, 1:2); IR (neat)
1
3448, 2956, 2925, 1466, 1376, 1115, 1081, 1034, 765, 698 cm−1; H
NMR (400 MHz, CDCl3) δ 7.63 (br s, 1H), 7.55 (d, 2H, J = 8.4 Hz),
7.50−7.42 (m, 3H), 7.34 (td, 1H, J = 7.6, 0.8 Hz), 7.25 (d, 1H, J = 8.4
Hz), 4.05 (m, 1H), 3.83 (m, 1H), 3.78 (t, 1H, J = 8.8 Hz), 3.65 (dd,
1H, J = 8.8, 4.4 Hz), 3.41 (s, 3H), 3.11 (m, 1H), 2.72 (dd, 1H, J = 8.0,
3.6 Hz), 1.66−1.47 (m, 6H), 1.40−1.28 (m, 6H), 1.23−1.05 (m, 6H),
0.90 (t, 9H, J = 7.2 Hz); 13C{1H} NMR (100 MHz, CDCl3) δ 145.1,
144.6, 141.3, 139.3, 136.0, 128.9 (2C), 127.5, 127.2 (3C), 126.4, 77.9,
67.7, 59.4, 50.8, 29.3 (3C), 27.6 (3C), 13.8 (3C), 10.7 (3C); HRMS
(ESI-TOF) m/z [M + H]+ calcd for C28H45O2Sn 533.2442; found
533.2448.
As described for the preparation of S11a, compounds 2b and S10
(357 mg, 1.07 mmol) were converted to 421 mg (53% from S10) of
S11b. Compound S11b was obtained as a yellow oil: TLC Rf 0.56
(EtOAc/hexane, 1:2); IR (neat) 2957, 2929, 1550, 1380, 1258, 1181,
827, 753, 562 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.07 (d, 1H, J =
8.0 Hz), 7.75 (t, 1H, J = 8.0 Hz), 7.67 (td, 1H, J = 8.0, 1.2 Hz), 7.51
(dd, 1H, J = 8.0, 1.2 Hz), 7.25 (m, 1H), 7.13−7.08 (m, 2H), 3.16 (t,
2H, J = 8.0 Hz), 2.97 (t, 2H, J = 8.0 Hz), 2.25 (s, 3H), 1.57−1.40 (m,
6H), 1.37−1.27 (m, 6H), 1.18−1.05 (m, 6H), 1.03 (s, 9H), 0.89 (t,
9H, J = 7.6 Hz), 0.34 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ
149.8, 143.5, 142.7, 136.3, 135.2, 134.8, 132.6, 131.1, 130.8, 126.6,
126.2, 123.8, 55.2, 35.6, 29.3 (3C), 27.5 (3C), 26.4 (3C), 20.5, 18.6,
13.8 (3C), 10.7 (3C), −3.6 (2C); HRMS (ESI-TOF) m/z: [M + H]+
calcd for C33H57N2O5SSiSn 741.2779; found 741.2743.
N-(tert-Butyldimethylsilyloxy)-2-nitrobenzenesulfon-amide
(S10).
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N-(tert-Butyldimethylsilyloxy)-N-[4-methyl-2-(tributyl-stannyl)-
phenethyl]-2-nitrobenzenesulfonamide (S11c).
N-(tert-Butyldimethylsilyloxy)-N-[4-fluoro-2-(tributyl-stannyl)-
phenethyl]-2-nitrobenzenesulfonamide (S11f).
As described for the preparation of S11a, compounds 2f and S10
(341 mg, 1.03 mmol) were converted to 996 mg (quant. from S10) of
S11f. Compound S11f was obtained as pale red crystals: mp 68−71
°C; TLC Rf 0.72 (EtOAc/hexane, 1:3); IR (neat) 2957, 2930, 1578,
As described for the preparation of S11a, compounds 2c and S10
(329 mg, 0.989 mmol) were converted to 682 mg (93% from S10) of
S11c. Compound S11c was obtained as white crystals: mp 83−85 °C;
TLC Rf 0.45 (EtOAc/hexane, 1:3); IR (neat) 2957, 2929, 1550, 1379,
1
1474, 1379, 1255, 1180, 845, 749, 583 cm−1; H NMR (400 MHz,
1
1181, 829, 758, 579 cm−1; H NMR (400 MHz, CDCl3) δ 8.07 (dd,
CDCl3) δ 8.07 (dd, 1H, J = 8.0, 1.2 Hz), 7.77 (td, 1H, J = 8.0, 1.2
Hz), 7.69 (td, 1H, J = 8.0, 1.2 Hz), 7.55 (dd, 1H, J = 8.0, 1.2 Hz),
7.15 (dd, 1H, J = 8.4, 5.2 Hz), 7.07 (dd, 1H, J = 8.4, 2.8 Hz), 6.91 (td,
1H, J = 8.4, 2.8 Hz), 3.33 (t, 2H, J = 8.0 Hz), 2.93 (t, 2H, J = 8.0 Hz),
1.52−1.44 (m, 6H), 1.36−1.27 (m, 6H), 1.15−1.00 (m, 6H), 0.97 (s,
9H), 0.88 (t, 9H, J = 7.6 Hz), 0.21 (s, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 161.3 (d, J = 247.2 Hz), 149.8, 145.4 (J = 1.9 Hz),
140.4 (J = 2.9 Hz), 134.9, 133.2, 130.8, 129.8 (d, J = 6.7 Hz), 126.1,
123.7, 123.0 (d, J = 17.3 Hz), 115.2 (d, J = 20.1 Hz), 57.2, 36.1, 29.2
(3C), 27.5 (3C), 26.2 (3C), 18.4, 13.8 (3C), 10.5 (3C), −4.2 (2C);
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H54FN2O5SSiSn
745.2529; found 745.2492.
1H, J = 8.0, 0.9 Hz), 7.75 (td, 1H, J = 8.0, 0.9 Hz), 7.67 (td, 1H, J =
8.0, 0.9 Hz), 7.54 (dd, 1H, J = 8.0, 0.9 Hz), 7.18 (br s, 1H), 7.09−
7.07 (m, 2H), 3.35 (t, 2H, J = 8.0 Hz), 2.92 (t, 2H, J = 8.0 Hz), 2.29
(s, 3H), 1.53−1.40 (m, 6H), 1.37−1.28 (m, 6H), 1.15−1.01 (m, 6H),
0.98 (s, 9H), 0.88 (t, 9H, J = 7.2 Hz), 0.25 (s, 6H); 13C{1H} NMR
(100 MHz, CDCl3) δ 149.8, 142.4, 141.7, 137.8, 135.3, 134.8, 133.0,
130.8, 129.4, 128.3, 126.5, 123.8, 57.2, 36.4, 29.3 (3C), 27.5 (3C),
26.3 (3C), 21.2, 18.5, 13.8 (3C), 10.4 (3C), −4.1 (2C); HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C33H57N2O5SSiSn 741.2779; found
741.2806.
N-(tert-Butyldimethylsilyloxy)-N-[4-methoxy-2-(tributyl-stannyl)-
phenethyl]-2-nitrobenzenesulfonamide (S11d).
O-(tert-Butyldimethylsilyl)-N-[2-(tributylstannyl)phenethyl]-
hydroxylamine (3a). To a cooled (0 °C) stirred solution of S11a
(3.21 g, 4.42 mmol) in DMF (25 mL) were added 2-mercaptoethanol
(0.930 mL, 13.3 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) (2.00 mL, 13.4 mmol). After being stirred at room
temperature for 3 h, the mixture was quenched with H2O (30 mL)
and extracted with EtOAc/hexane (1:4, 50 mL × 3). The combined
extracts were washed with saturated brine (50 mL), dried, and
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (EtOAc/hexane, 1:20) to
provide 1.83 g (77%) of 3a as a yellow oil: TLC Rf 0.66 (EtOAc/
hexane, 1:8); IR (neat) 2956, 2928, 1464, 1252, 864, 837, 780, 666
cm−1; 1H NMR (400 MHz, CDCl3) δ 7.39 (d, 1H, J = 7.2 Hz), 7.26−
7.22 (m, 2H), 7.16 (m, 1H), 5.10 (br s, 1H), 3.10 (t, 2H, J = 8.0 Hz),
2.82 (t, 2H, J = 8.0 Hz), 1.53−1.42 (m, 6H), 1.37−1.28 (m, 6H),
1.16−0.99 (m, 6H), 0.93 (s, 9H), 0.88 (t, 9H, J = 7.2 Hz), 0.12 (s,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 146.4, 142.5, 137.1, 128.5
(2C), 125.7, 56.2, 36.8, 29.3 (3C), 27.6 (3C), 26.5 (3C), 18.2, 13.8
(3C), 10.6 (3C), −5.2 (2C); HRMS (ESI-TOF) m/z: [M + H]+
calcd for C26H52NOSiSn 542.2840; found 542.2855.
O-(tert-Butyldimethylsilyl)-N-[2-methyl-6-(tributyl-stannyl)-
phenethyl]hydroxylamine (3b). As descried for the preparation of
3a, compound S11b (120 mg, 0.162 mmol) was converted to 101 mg
(quant.) of 3b (a mixture of rotamer). Compound 3b was obtained as
a yellow oil: TLC Rf 0.65 (EtOAc/hexane, 1:10); IR (neat) 2957,
2928, 1463, 1253, 838, 759, 667 cm−1; 1H NMR (400 MHz, CDCl3)
δ 7.24 (dd, 1H, J = 6.0, 2.8 Hz), 7.17−7.09 (m, 2H), 5.09 (br s, 1H),
3.09 (t, 2H × 1/6, J = 7.2 Hz), 3.00−2.96 (m, 2H × 5/6), 2.87−2.83
(m, 2H), 2.36 (s, 3H × 5/6), 2.33 (s, 3H × 1/6), 1.60−1.44 (m, 6H),
1.40−1.29 (m, 6H), 1.16−0.99 (m, 6H), 0.94 (s, 9H × 5/6), 0.93 (s,
9H × 1/6), 0.89 (t, 9H, J = 7.2 Hz), 0.13 (s, 6H × 5/6), 0.11 (s, 6H
× 1/6); 13C{1H} NMR (100 MHz, CDCl3) for major rotamer δ
144.6, 143.1, 136.3, 134.9, 130.9, 126.1, 55.1, 35.4, 29.3 (3C), 27.6
(3C), 26.5 (3C), 20.3, 18.2, 13.8 (3C), 10.8 (3C), −5.2 (2C); HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C27H54NOSiSn 556.2997; found
556.2997.
As described for the preparation of S11a, compounds 2d and S10
(858 mg, 2.58 mmol) were converted to 1.82 g (93% from S10) of
S11d. Compound S11d was obtained as white crystals: mp 85−87
°C; TLC Rf 0.30 (EtOAc/hexane, 1:6); IR (neat) 2956, 2930, 1550,
1379, 1180, 828, 748, 585 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.07
(dd, 1H, J = 8.0, 0.9 Hz), 7.76 (td, 1H, J = 8.0, 0.9 Hz), 7.68 (td, 1H,
J = 8.0, 0.9 Hz), 7.54 (dd, 1H, J = 8.0, 0.9 Hz), 7.12 (d, 1H, J = 8.4
Hz), 6.94 (d, 1H, J = 2.8 Hz), 6.78 (dd, 1H, J = 8.4, 2.8 Hz), 3.78 (s,
3H), 3.33 (t, 2H, J = 8.0 Hz), 2.90 (t, 2H, J = 8.0 Hz), 1.56−1.40 (m,
6H), 1.36−1.27 (m, 6H), 1.15−1.04 (m, 6H), 0.98 (s, 9H), 0.88 (t,
9H, J = 7.6 Hz), 0.24 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ
157.5, 149.6, 144.0, 136.8, 134.8, 133.0, 130.8, 129.3, 126.3, 123.8,
122.7, 113.4, 57.3, 55.2, 36.0, 29.3 (3C), 27.5 (3C), 26.2 (3C), 18.5,
13.8 (3C), 10.5 (3C), −4.1 (2C); HRMS (ESI-TOF) m/z: [M + H]+
calcd for C33H57N2O6SSiSn 757.2729; found 757.2739.
N-(tert-Butyldimethylsilyloxy)-N-[4-chloro-2-(tributyl-stannyl)-
phenethyl]-2-nitrobenzenesulfonamide (S11e).
As described for the preparation of S11a, compounds 2e and S10
(300 mg, 0.901 mmol) were converted to 759 mg (quant. from S10)
of S11e. Compound S11e was obtained as pale red crystals: mp 75−
77 °C; TLC Rf 0.72 (EtOAc/hexane, 1:3); IR (neat) 2956, 2929,
1
1550, 1381, 1180, 827, 770, 583, 563 cm−1; H NMR (400 MHz,
CDCl3) δ 8.07 (dd, 1H, J = 8.0, 1.2 Hz), 7.77 (td, 1H, J = 8.0, 1.2
Hz), 7.69 (td, 1H, J = 8.0, 1.2 Hz), 7.55 (dd, 1H, J = 8.0, 1.2 Hz),
7.31 (d, 1H, J = 2.4 Hz), 7.20 (dd, 1H, J = 8.0, 2.4 Hz), 7.11 (d, 1H, J
= 8.0 Hz), 3.34 (t, 2H, J = 7.2 Hz), 2.93 (t, 2H, J = 7.2 Hz), 1.54−
1.40 (m, 6H), 1.36−1.27 (m, 6H), 1.16−0.99 (m, 6H), 0.97 (s, 9H),
0.88 (t, 9H, J = 7.6 Hz), 0.21 (s, 6H); 13C{1H} NMR (100 MHz,
CDCl3) δ 149.8, 145.3, 143.1, 136.4, 134.9, 133.2, 132.5, 130.8, 129.7,
128.5, 126.1, 123.8, 56.9, 36.2, 29.2 (3C), 27.5 (3C), 26.2 (3C), 18.4,
13.8 (3C), 10.6 (3C), −4.2 (2C); HRMS (ESI-TOF) m/z: [M + H]+
calcd for C32H54ClN2O5SSiSn 761.2233; found 761.2262.
O-(tert-Butyldimethylsilyl)-N-[4-methyl-2-(tributyl-stannyl)-
phenethyl]hydroxylamine (3c). As described for the preparation of
3a, compound S11c (575 mg, 0.778 mmol) was converted to 355 mg
(82%) of 3c. Compound 3c was obtained as a yellow oil: TLC Rf 0.59
(EtOAc/hexane, 1:10); IR (neat) 2956, 2928, 1463, 1250, 837, 779
1
666 cm−1; H NMR (400 MHz, CDCl3) δ 7.20 (d, 1H, J = 1.4 Hz),
7.16 (d, 1H, J = 8.0 Hz), 7.09 (dd, 1H, J = 8.0, 1.4 Hz), 5.11 (br s,
1H), 3.10 (t, 2H, J = 7.2 Hz), 2.79 (t, 2H, J = 7.2 Hz), 2.32 (s, 3H),
1.62−1.43 (m, 6H), 1.39−1.30 (m, 6H), 1.17−0.99 (m, 6H), 0.94 (s,
9H), 0.90 (t, 9H, J = 7.2 Hz), 0.13 (s, 6H); 13C{1H} NMR (100
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MHz, CDCl3) δ 143.3, 142.2, 137.8, 134.9, 129.3, 128.3, 56.3, 36.2,
29.3 (3C), 27.6 (3C), 26.5 (3C), 21.2, 18.2, 13.8 (3C), 10.5 (3C),
−5.2 (2C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C27H54NOSiSn 556.2997; found 556.2978.
N-Benzyl-O-(tert-butyldimethylsilyl)-N-[2-methyl-6-
(tributylstannyl)phenethyl]hydroxylamine (4b). As described for the
preparation of 4a, compound 3b (48.8 mg, 88.0 μmol) was converted
to 47.8 mg (84%) of 4b (a mixture of rotamer). Compound 4b was
obtained as a yellow oil: TLC Rf 0.40 (EtOAc/hexane, 1:50); IR
O-(tert-Butyldimethylsilyl)-N-[4-methoxy-2-(tributyl-stannyl)-
phenethyl]hydroxylamine (3d). As described for the preparation of
3a, compound S11d (1.74 g, 2.30 mmol) was converted to 1.05 g
(80%) of 3d. Compound 3d was obtained as a yellow oil: TLC Rf 0.67
(EtOAc/hexane, 1:10); IR (neat) 2956, 2928, 1590, 1464, 1385,
1241, 1044, 837, 759, 667 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.19
(d, 1H, J = 8.8 Hz), 6.97 (d, 1H, J = 2.8 Hz), 6.81 (dd, 1H, J = 8.8,
2.8 Hz), 5.10 (br s, 1H), 3.80 (s, 3H), 3.07 (t, 2H, J = 7.2 Hz), 2.78
(t, 2H, J = 7.2 Hz), 1.63−1.44 (m, 6H), 1.39−1.30 (m, 6H), 1.18−
1.01 (m, 6H), 0.94 (s, 9H), 0.90 (t, 9H, J = 7.2 Hz), 0.13 (s, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 157.3, 143.9, 138.3, 129.2,
1
(neat) 2956, 2928, 2855, 1462, 1254, 891, 836, 759, 697 cm−1; H
NMR (400 MHz, CDCl3) δ 7.36−7.22 (m, 5H), 7.18 (dd, 1H, J =
5.6, 2.8 Hz), 7.10−7.02 (m, 2H), 4.10 (br, 1H), 3.66 (br, 1H), 3.07
(br, 1H), 2.78 (br, 3H), 2.28 (s, 3H × 5/6), 2.26 (s, 3H × 1/6),
1.52−1.35 (m, 6H), 1.32−1.23 (m, 6H), 0.97 (s, 9H), 0.88 (t, 9H, J =
7.6 Hz), 0.95−0.86 (m, 6H), 0.22 (br, 3H), 0.12 (br, 3H); 13C{1H}
NMR (100 MHz, CDCl3) for major rotamer δ 145.0, 143.1, 137.3,
136.4, 134.8, 130.9, 129.7 (2C), 128.4 (2C), 127.5, 126.0, 66.3, 60.1,
35.5, 29.3 (3C), 27.5 (3C), 26.4 (3C), 20.3, 18.0, 13.9 (3C), 10.7
(3C), −3.8 (br), −4.5 (br); HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C34H60NOSiSn 646.3466; found 646.3435.
122.6, 113.3, 56.3, 55.2, 35.7, 29.3 (3C), 27.6 (3C), 26.5 (3C), 18.2,
13.8 (3C), 10.6 (3C), −5.2 (2C); HRMS (ESI-TOF) m/z: [M + H]+
calcd for C27H54NO2SiSn 572.2946; found 572.2930.
N-Benzyl-O-(tert-butyldimethylsilyl)-N-[4-methyl-2-
(tributylstannyl)phenethyl]hydroxylamine (4c). As described for the
preparation of 4a, compound 3c (224 mg, 0.404 mmol) was
converted to 262 mg (quant.) of 4c (a mixture of rotamer).
Compound 4c was obtained as a yellow oil: TLC Rf 0.37 (EtOAc/
hexane, 1:50); IR (neat) 2956, 2928, 2855, 1462, 1384, 1253, 890,
O-(tert-Butyldimethylsilyl)-N-[4-chloro-2-(tributyl-stannyl)-
phenethyl]hydroxylamine (3e). As described for the preparation of
3a, compound S11e (317 mg, 0.417 mmol) was converted to 177 mg
(74%) of 3e. Compound 3e was obtained as a yellow oil: TLC Rf 0.67
(EtOAc/hexane, 1:10); IR (neat) 2958, 2929, 1463, 1384, 1216, 839,
1
836, 779, 759, 697 cm−1; H NMR (400 MHz, CDCl3) δ 7.32−7.24
1
(m, 5H), 7.14 (br s, 1H), 7.08−7.03 (m, 2H), 4.01 (br, 1H), 3.76 (br,
1H), 2.81 (br, 4H), 2.31 (s, 3H × 1/6), 2.28 (s, 3H × 5/6), 1.55−
1.41 (m, 6H), 1.37−1.26 (m, 6H), 1.16−0.94 (m, 6H), 0.94 (s, 9H),
0.88 (t, 9H, J = 7.6 Hz), 0.10 (br, 6H); 13C{1H} NMR (100 MHz,
CDCl3) for major rotamer δ 144.0, 142.1, 137.5, 137.3, 134.7, 129.9
(2C), 129.3, 128.5, 128.3 (2C), 127.5, 65.7, 62.3, 36.4, 29.3 (3C),
27.5 (3C), 26.4 (3C), 21.2, 18.0, 13.9 (3C), 10.4 (3C), −4.3 (br,
2C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C34H60NOSiSn
646.3466; found 646.3481.
758, 669 cm−1; H NMR (400 MHz, CDCl3) δ 7.32 (d, 1H, J = 2.4
Hz), 7.22 (dd, 1H, J = 8.4, 2.4 Hz), 7.17 (d, 1H, J = 8.4 Hz), 5.08 (br
s, 1H), 3.08 (t, 2H, J = 7.2 Hz), 2.80 (t, 2H, J = 7.2 Hz), 1.59−1.42
(m, 6H), 1.39−1.28 (m, 6H), 1.18−1.03 (m, 6H), 0.93 (s, 9H), 0.90
(t, 9H, J = 7.6 Hz), 0.12 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3)
δ 145.1, 144.6, 136.3, 132.0, 129.8, 128.4, 56.0, 36.1, 29.2 (3C), 27.5
(3C), 26.4 (3C), 18.2, 13.8 (3C), 10.6 (3C), −5.2 (2C); HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C26H51ClNOSiSn 576.2450;
found 576.2439.
N-Benzyl-O-(tert-butyldimethylsilyl)-N-[4-methoxy-2-
(tributylstannyl)phenethyl]-hydroxylamine (4d). As described for
the preparation of 4a, compound 3d (466 mg, 0.816 mmol) was
converted to 621 mg (quant.) of 4d. Compound 4d was obtained as a
yellow oil: TLC Rf 0.71 (MeOH/CH2Cl2/hexane, 1:5:320); IR (neat)
2956, 2929, 2855, 1590, 1473, 1230, 1044, 909, 891, 837, 780, 734,
O-(tert-Butyldimethylsilyl)-N-[4-fluoro-2-(tributyl-stannyl)-
phenethyl]hydroxylamine (3f). As described for the preparation of
3a, compound S11f (310 mg, 0.417 mmol) was converted to 165 mg
(71%) of 3f. Compound 3f was obtained as a yellow oil: TLC Rf 0.62
(EtOAc/hexane, 1:10); IR (neat) 2958, 2929, 1577, 1473, 1384,
1
1216, 872, 838, 759, 669 cm−1; H NMR (400 MHz, CDCl3) δ 7.21
1
666 cm−1; H NMR (400 MHz, CDCl3) δ 7.37−7.28 (m, 5H), 7.13
(dd, 1H, J = 8.4, 5.2 Hz), 7.08 (dd, 1H, J = 8.4, 2.8 Hz), 6.93 (td, 1H,
J = 8.4, 2.8 Hz), 5.08 (br s, 1H), 3.08 (t, 2H, J = 7.2 Hz), 2.80 (t, 2H,
J = 7.2 Hz), 1.61−1.42 (m, 6H), 1.38−1.29 (m, 6H), 1.18−1.01 (m,
6H), 0.93 (s, 9H), 0.89 (t, 9H, J = 7.2 Hz), 0.12 (s, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 161.2 (d, J = 246.2 Hz), 145.1 (d, J = 2.0
Hz), 141.8 (d, J = 2.9 Hz), 129.7 (d, J = 6.7 Hz), 122.9 (d, J = 17.2
Hz), 115.1 (d, J = 21.1 Hz), 56.2, 35.9, 29.2 (3C), 27.5 (3C), 26.4
(3C), 18.2, 13.8 (3C), 10.6 (3C), −5.2 (2C); HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C26H51FNOSiSn 560.2746; found 560.2751.
N-Benzyl-O-(tert-butyldimethylsilyl)-N-[2-(tributyl-stannyl)-
phenethyl]hydroxylamine (4a). To a stirred solution of 3a (873 mg,
1.62 mmol) in DMF (8 mL) were added BnBr (0.290 mL, 2.42
mmol) and N,N-diisopropylethylamine (0.560 mL, 3.22 mmol). After
being stirred at 60 °C for 34 h, the mixture was quenched with H2O
(10 mL) and extracted with EtOAc/hexane (1:4, 20 mL × 4). The
combined extracts were washed with saturated brine (20 mL), dried,
and concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (MeOH/CH2Cl2/hexane,
1:5:200) to provide 775 mg (76%) of 4a as a yellow oil. A small
amount of 4a was further purified by preparative TLC (EtOAc/
hexane, 1:50): TLC Rf 0.82 (MeOH/CH2Cl2/hexane, 1:5:160), 0.62
(EtOAc/hexane, 1:50); IR (neat) 2957, 2928, 2855, 1463, 1254,
1217, 890, 837, 759, 698 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.35−
7.29 (m, 5H), 7.24−7.11 (m, 4H), 4.02 (br, 1H), 3.76 (br, 1H), 2.83
(br, 4H), 1.50−1.36 (m, 6H), 1.34−1.25 (m, 6H), 0.94 (s, 9H),
1.09−0.92 (m, 6H), 0.87 (t, 9H, J = 6.8 Hz), 0.08 (br, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 147.1, 142.3, 137.3, 136.9, 129.9 (2C),
128.7, 128.5, 128.4 (2C), 127.5, 125.5, 65.7, 62.1, 36.9, 29.2 (3C),
27.5 (3C), 26.4 (3C), 18.0, 13.9 (3C), 10.4 (3C), −4.4 (br, 2C);
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H58NOSiSn
632.3310; found 632.3297.
(d, 1H, J = 8.8 Hz), 6.95 (d, 1H, J = 2.4 Hz), 6.80 (dd, 1H, J = 8.8,
2.4 Hz), 4.06 (br, 1H), 3.80 (br, 1H), 3.80 (s, 3H), 2.85 (br, 4H),
1.61−1.42 (m, 6H), 1.39−1.30 (m, 6H), 1.16−1.02 (m, 6H), 0.99 (s,
9H), 0.92 (t, 9H, J = 8.0 Hz), 0.13 (br, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 157.2, 143.6, 139.0, 137.3, 129.9 (2C), 129.4, 128.3
(2C), 127.5, 122.3, 113.3, 65.7, 62.4, 55.2, 35.9, 29.3 (3C), 27.5 (3C),
26.4 (3C), 18.0, 13.9 (3C), 10.5 (3C), −4.2 (br, 2C); HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C34H60NO2SiSn 662.3415; found
662.3446.
N-Benzyl-O-(tert-butyldimethylsilyl)-N-[4-chloro-2-
(tributylstannyl)phenethyl]hydroxylamine (4e). As described for the
preparation of 4a, compound 3e (103 mg, 0.179 mmol) was
converted to 106 mg (89%) of 4e. Compound 4e was obtained as a
yellow oil: TLC Rf 0.43 (EtOAc/hexane, 1:50); IR (neat) 3020, 2958,
1
2929, 1463, 1384, 1216, 891, 837, 758, 669 cm−1; H NMR (400
MHz, CDCl3) δ 7.32−7.25 (m, 6H), 7.16 (dd, 1H, J = 8.0, 2.4 Hz),
7.07 (d, 1H, J = 8.0 Hz), 4.02 (br, 1H), 3.74 (br, 1H), 2.77 (br, 4H),
1.53−1.39 (m, 6H), 1.35−1.25 (m, 6H), 1.12−0.98 (m, 6H), 0.94 (s,
9H), 0.88 (t, 9H, J = 7.2 Hz), 0.09 (br, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 145.3, 144.9, 137.1, 136.0, 131.7, 129.9, 129.8 (2C),
128.4 (2C), 128.3, 127.6, 65.7, 61.9, 36.2, 29.2 (3C), 27.4 (3C), 26.3
(3C), 18.0, 13.8 (3C), 10.5 (3C), −4.4 (br, 2C); HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C33H57ClNOSiSn 666.2920; found
666.2900.
N-Benzyl-O-(tert-butyldimethylsilyl)-N-[4-fluoro-2-
(tributylstannyl)phenethyl]hydroxylamine (4f). As described for the
preparation of 4a, compound 3f (95.7 mg, 0.171 mmol) was
converted to 111 mg (100%) of 4f. Compound 4f was obtained as a
yellow oil: TLC Rf 0.46 (EtOAc/hexane, 1:50); IR (neat) 2957, 2928,
1
2855, 1577, 1473, 1361, 1216, 877, 837, 759 cm−1; H NMR (400
MHz, CDCl3) δ 7.33−7.25 (m, 5H), 7.11 (dd, 1H, J = 8.4, 0.9 Hz),
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7.02 (dd, 1H, J = 8.4, 2.8 Hz), 6.88 (td, 1H, J = 8.4, 2.8 Hz), 4.04 (br,
1H), 3.74 (br, 1H), 2.80 (br, 4H), 1.55−1.36 (m, 6H), 1.34−1.25 (m,
6H), 1.13−0.98 (m, 6H), 0.94 (s, 9H), 0.88 (t, 9H, J = 7.2 Hz), 0.10
(br, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.0 (d, J = 236.7
Hz), 144.9 (d, J = 1.9 Hz), 142.5 (d, J = 2.8 Hz), 137.2, 129.9 (2C),
129.8, 128.4 (2C), 127.6, 122.5 (d, J = 17.3 Hz), 115.0 (d, J = 21.1
Hz), 65.7, 62.1, 36.1, 29.2 (3C), 27.5 (3C), 26.3 (3C), 18.0, 13.8
(3C), 10.5 (3C), −4.2 (br, 2C); HRMS (ESI-TOF) m/z: [M + H]+
calcd for C33H57FNOSiSn 650.3215; found 650.3245.
To a stirred solution of S13 (884 mg, 2.07 mmol) in DMF (20 mL)
were added BnBr (0.380 mL, 3.18 mmol) and N,N-diisopropylethyl-
amine (0.720 mL, 4.13 mmol). After being stirred at 60 °C for 38 h,
the mixture was quenched with H2O (30 mL) and extracted with
EtOAc/hexane (1:4, 75 mL × 4). The combined extracts were dried
and concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (EtOAc/hexane, 1:40) to
provide 1.12 g (quant.) of S14 as white crystals: mp 65−67 °C; TLC
Rf 0.31 (EtOAc/hexane, 1:50); IR (neat) 3030, 2954, 2855, 1461,
1
1385, 1253, 884, 836, 780, 750, 698 cm−1; H NMR (400 MHz,
N-(tert-Butyldimethylsilyloxy)-N-[2-(1-iodonaphthalen-2-yl)-
ethyl]-2-nitrobenzenesulfonamide (S12).
CDCl3) δ 8.21 (br d, 1H, J = 8.4 Hz), 7.72 (t, 2H, J = 8.8 Hz), 7.55
(td, 1H, J = 8.0, 1.2 Hz), 7.46 (td, 1H, J = 8.0, 1.2 Hz), 7.39 (d, 2H, J
= 6.8 Hz), 7.36−7.27 (m, 4H), 4.00 (br, 2H), 3.31 (br, 2H), 2.99 (br,
2H), 0.96 (s, 9H), 0.09 (br, 6H); 13C{1H} NMR (100 MHz, CDCl3)
δ 142.6, 137.4, 135.2, 132.9, 132.8, 130.1 (2C), 128.9, 128.34 (2C),
128.24, 127.8, 127.7, 127.5, 126.1, 105.6, 64.6, 59.3, 39.5, 26.4 (3C),
18.0, −4.6 (br, 2C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C25H33INOSi 518.1376; found 518.1401.
To a cooled (0 °C) stirred solution of S6e (1.11 g, 3.71 mmol), S10
(1.12 g, 3.37 mmol), and PPh3 (1.31 g, 5.01 mmol) in THF/toluene
(1:3, 11 mL) was slowly added diethyl azodicarboxylate (2.2 M
solution in toluene, 2.30 mL, 5.06 mmol). After being stirred at 0 °C
for 30 min and at room temperature for 4.5 h, the mixture was
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (CH2Cl2/hexane, 1:2) to
provide 1.80 g (87%) of S12 as yellow crystals: mp 150−152 °C;
TLC Rf 0.42 (EtOAc/hexane, 1:2); IR (neat) 2954, 2930, 1547, 1383,
1179, 827, 772 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.20 (d, 1H, J =
8.0 Hz), 8.12 (d, 1H, J = 8.0 Hz), 7.78−7.75 (m, 3H), 7.70 (t, 1H, J =
8.0 Hz), 7.56 (t, 2H, J = 8.4 Hz), 7.47 (t, 2H, J = 8.4 Hz), 3.54 (t, 2H,
J = 6.8 Hz), 3.38 (t, 2H, J = 6.8 Hz), 0.97 (s, 9H), 0.19 (s, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 140.5, 135.2, 134.9, 133.3,
133.1, 132.9, 130.9, 129.2, 128.4, 128.04, 127.96 (2C), 126.40,
126.37, 123.7, 105.9, 55.2, 40.4, 26.2 (3C), 18.3, −4.3 (2C); HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C24H30IN2O5SSi 613.0689;
found 613.0681.
O-(tert-Butyldimethylsilyl)-N-[2-(1-iodonaphthalen-2-yl)ethyl]-
hydroxylamine (S13).
O-(tert-Butyldimethylsilyl)-N-(4-nitrobenzyl)-N-[2-
(tributylstannyl)phenethyl]hydroxylamine (S15).
To a stirred solution of 3a (273 mg, 0.505 mmol) in DMF (3 mL)
were added 4-nitrobenzyl bromide (163 mg, 0.756 mmol) and N,N-
diisopropylethylamine (0.175 mL, 1.00 mmol). The mixture was
stirred at 60 °C for 16.5 h, and 4-nitrobenzyl bromide (122 mg, 0.566
mmol) and N,N-diisopropylethylamine (0.130 mL, 0.746 mmol) were
added. After being stirred at 60 °C for 13.5 h, the mixture was
quenched with H2O (5 mL) and extracted with EtOAc/hexane (1:4, 5
mL × 6). The combined extracts were dried and concentrated under
reduced pressure. The residue was purified by column chromatog-
raphy on silica gel (EtOAc/hexane, 1:50) to provide 280 mg (82%) of
S15 as a yellow oil. A small amount of S15 was further purified by
preparative TLC (EtOAc/hexane, 1:50): TLC Rf 0.62 (EtOAc/
hexane, 1:50); IR (neat) 2957, 2928, 2856, 1607, 1525, 1464, 1347,
1
1255, 893, 851, 758 cm−1; H NMR (400 MHz, CDCl3) δ 8.18 (d,
To a cooled (0 °C) stirred solution of S12 (1.60 g, 2.61 mmol) in
DMF (9 mL) were added 2-mercaptoethanol (0.550 mL, 7.88 mmol)
and DBU (1.17 mL, 7.84 mmol). After being stirred at room
temperature for 3.5 h, the mixture was quenched with H2O (20 mL)
and extracted with EtOAc/hexane (1:4, 50 mL × 6). The combined
extracts were washed with H2O (100 mL × 2) and saturated brine
(100 mL), dried, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel (EtOAc/
hexane, 1:60) to provide 958 mg (86%) of S13 as a yellow oil: TLC Rf
0.50 (EtOAc/hexane, 1:10); IR (neat) 3255, 3051, 2954, 2928, 2855,
1620, 1471, 1252, 1048, 881, 838, 780, 747 666 cm−1; 1H NMR (400
MHz, CDCl3) δ 8.24 (br d, 1H, J = 8.4 Hz), 7.75 (br d, 2H, J = 8.4
Hz), 7.56 (td, 1H, J = 8.4, 1.6 Hz), 7.48 (td, 1H, J = 8.4, 1.6 Hz), 7.39
(d, 1H, J = 8.4 Hz), 5.11 (br s, 1H), 3.29 (t, 2H, J = 6.8 Hz), 3.21 (t,
2H, J = 6.8 Hz), 0.94 (s, 9H), 0.13 (s, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 141.9, 135.3, 132.94, 132.88, 128.8, 128.3, 127.93,
127.89, 126.2, 105.7, 54.2, 40.4, 26.5 (3C), 18.2, −5.2 (2C); HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C18H27INOSi 428.0907; found
428.0893.
2H, J = 8.4 Hz), 7.50 (d, 2H, J = 8.4 Hz), 7.36 (d, 1H, J = 7.6 Hz),
7.27−7.23 (m, 1H), 7.18−7.13 (m, 2H), 3.98 (br, 2H), 2.85 (br, 4H),
1.56−1.38 (m, 6H), 1.36−1.26 (m, 6H), 1.12−0.99 (m, 6H), 0.94 (s,
9H), 0.88 (t, 9H, J = 7.2 Hz), 0.07 (br, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 147.5, 146.5, 144.8, 142.1, 137.0, 130.7 (2C), 128.7,
128.6, 125.8, 123.6 (2C), 64.7, 62.6, 36.9, 29.3 (3C), 27.5 (3C), 26.2
(3C), 17.9, 13.8 (3C), 10.5 (3C), −4.4 (br, 2C); HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C33H57N2O3SiSn 677.3160; found 677.3188.
N-Allyl-O-(tert-butyldimethylsilyl)-N-[2-(tributyl-stannyl)-
phenethyl]hydroxylamine (S16).
To a stirred solution of 3a (264 mg, 0.489 mmol) in DMF (2 mL)
were added 3-bromopropene (54 μL, 0.64 mmol) and N,N-
diisopropylethylamine (0.130 mL, 0.746 mmol). After being stirred
at 60 °C for 39.5 h, the mixture was quenched with H2O (8 mL) and
extracted with EtOAc/hexane (1:4, 10 mL × 8). The combined
extracts were dried and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel (EtOAc/
hexane, 1:50) to provide 138 mg (49%) of S16 as a yellow oil. A small
amount of S16 was further purified by preparative TLC (EtOAc/
hexane, 1:50): TLC Rf 0.58 (EtOAc/hexane, 1:50); IR (neat) 3053,
2957, 2928, 2856, 1723, 1464, 1253, 1217, 992, 889, 837, 759, 668
N-Benzyl-O-(tert-butyldimethylsilyl)-N-[2-(1-iodonaphthalen-2-
yl)ethyl]hydroxylamine (S14).
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cm−1; 1H NMR (400 MHz, CDCl3) δ 7.39 (dd, 1H, J = 6.8, 0.8 Hz),
7.29−7.22 (m, 2H), 7.16 (td, 1H, J = 6.8, 2.0 Hz), 5.93 (m, 1H), 5.18
(br d, 1H, J = 14.8 Hz), 5.13 (br d, 1H, J = 8.0 Hz), 3.42 (br, 2H),
2.87 (br, 4H), 1.62−1.43 (m, 6H), 1.39−1.30 (m, 6H), 1.18−1.01
(m, 6H), 0.95 (s, 9H), 0.90 (t, 9H, J = 7.2 Hz), 0.17 (s, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 147.2, 142.2, 136.9, 133.8, 128.8, 128.5,
125.6, 118.5, 64.3, 62.0, 37.2, 29.3 (3C), 27.6 (3C), 26.3 (3C), 18.0,
13.8 (3C), 10.5 (3C), −4.3 (br, 2C); HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C29H56NOSiSn 582.3153; found 582.3167.
1240, 1016, 746, 698 cm−1; H NMR (400 MHz, CDCl3) δ 7.48 (d,
2H, J = 6.8 Hz), 7.41−7.32 (m, 3H), 7.12 (d, 2H, J = 8.0 Hz), 6.91 (t,
2H, J = 8.0 Hz), 5.02 (s, 2H), 3.48 (t, 2H, J = 8.0 Hz), 2.88 (t, 2H, J =
8.0 Hz); 13C{1H} NMR (100 MHz, CDCl3) δ 153.0, 138.0, 129.2
(2C), 128.6 (2C), 128.2, 128.1, 127.4, 124.7, 122.8, 113.6, 77.1, 58.1,
27.9; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H16NO
226.1232; found 226.1226.
1-(Benzyloxy)-4-methylindoline (6b). As described for the
preparation of 5a, compound 4b (47.8 mg, 74.1 μmol) was converted
to 37.5 mg (69%) of 5b. Since compound 5b was unstable and
difficult to store even in the freezer, the obtained 5b was immediately
used in the next step.
O-(tert-Butyldimethylsilyl)-N-(3-methylbut-2-en-1-yl)-N-[2-
(tributylstannyl)phenethyl]-hydroxylamine (S17).
As described for the preparation of 6a, compound 5b (25.5 mg,
34.9 μmol) was converted to 2.4 mg (29%) of 6b. Compound 6b was
obtained as a yellow oil: TLC Rf 0.43 (EtOAc/hexane, 1:10); IR
(neat) 3011, 2924, 2854, 1599, 1455, 1379, 1216, 1025, 757, 698
cm−1; 1H NMR (400 MHz, CDCl3) δ 7.47 (d, 2H, J = 7.6 Hz), 7.40−
7.32 (m, 3H), 7.04 (t, 1H, J = 8.0 Hz), 6.74 (dd, 2H, J = 8.0, 2.4 Hz),
5.00 (s, 2H), 3.47 (t, 2H, J = 7.6 Hz), 2.80 (t, 2H, J = 7.6 Hz), 2.21 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 152.7, 138.0, 134.1, 129.2
(2C), 128.5 (2C), 128.2, 127.5, 126.8, 123.8, 111.0, 77.2, 57.8, 26.6,
18.4; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H18NO
240.1388; found 240.1395.
1-(Benzyloxy)-6-methylindoline (6c). As described for the
preparation of 5a, compound 4c (189 mg, 0.293 mmol) was
converted to 158 mg (74%) of 5c. Since compound 5c was unstable
and difficult to store even in the freezer, the obtained 5c was
immediately used in the next step.
As described for the preparation of 6a, compound 5c (31.3 mg,
42.9 μmol) was converted to 6.4 mg (62%) of 6c. Compound 6c was
obtained as a yellow oil: TLC Rf 0.48 (EtOAc/hexane, 1:10); IR
(neat) 3012, 2925, 2855, 1591, 1454, 1216, 1024, 757, 697 cm−1; 1H
NMR (400 MHz, CDCl3) δ 7.48 (d, 2H, J = 6.8 Hz), 7.41−7.32 (m,
3H), 6.99 (d, 1H, J = 7.6 Hz), 6.72 (d, 1H, J = 7.6 Hz), 6.72 (br s,
1H), 5.02 (s, 2H), 3.45 (t, 2H, J = 7.6 Hz), 2.82 (t, 2H, J = 7.6 Hz),
2.30 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 153.1, 138.0,
137.3, 129.1 (2C), 128.5 (2C), 128.2, 125.2, 124.4, 123.6, 114.2, 77.2,
58.4, 27.6, 21.6; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C16H18NO 240.1388; found 240.1387.
1-(Benzyloxy)-6-methoxyindoline (6d). As described for the
preparation of 5a, compound 4d (301 mg, 0.455 mmol) was
converted to 210 mg (62%) of 5d. Since compound 5d was unstable
and difficult to store even in the freezer, the obtained 5d was
immediately used in the next step.
As described for the preparation of 6a, compound 5d (27.3 mg,
36.6 μmol) was converted to 2.5 mg (27%) of 6d. Compound 6d was
obtained as a yellow oil: TLC Rf 0.40 (EtOAc/hexane, 1:10); IR
(neat) 2918, 2850, 1595, 1493, 1384, 1283, 1208, 1027, 754, 613
cm−1; 1H NMR (400 MHz, CDCl3) δ 7.48 (d, 2H, J = 7.6 Hz), 7.41−
7.34 (m, 3H), 6.98 (d, 1H, J = 8.4 Hz), 6.45 (dd, 1H, J = 8.4, 2.0 Hz),
6.36 (br s, 1H), 4.99 (s, 2H), 3.71 (s, 3H), 3.48 (t, 2H, J = 8.0 Hz),
2.81 (t, 2H, J = 8.0 Hz); 13C{1H} NMR (100 MHz, CDCl3) δ 159.9,
154.2, 137.9, 129.3 (2C), 128.6 (2C), 128.2, 125.0, 120.0, 108.7, 99.4,
77.2, 58.6, 55.6, 27.1; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C16H18NO2 256.1338, found 256.1335.
1-(Benzyloxy)-6-chloroindoline (6e). As described for the
preparation of 5a, compound 4e (69.8 mg, 0.104 mmol) was
converted to 19.2 mg (24%) of 5e. Since compound 5e was unstable
and difficult to store even in the freezer, the obtained 5e was
immediately used in the next step.
To a stirred solution of 3a (172 mg, 0.319 mmol) in DMF (2 mL)
were added 1-bromo-3-methyl-2-butene (57 μL, 0.49 mmol) and
N,N-diisopropylethylamine (0.110 mL, 0.631 mmol). After being
stirred at 60 °C for 42 h, the mixture was quenched with H2O (2 mL)
and extracted with EtOAc/hexane (1:4, 5 mL × 4). The combined
extracts were dried and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel (EtOAc/
hexane, 1:50) to provide 65.3 mg (34%) of S17 as a yellow oil. A
small amount of S17 was further purified by preparative TLC
(EtOAc/hexane, 1:50): TLC Rf 0.37 (EtOAc/hexane, 1:50); IR
1
(neat) 2958, 2929, 1463, 1384, 1256, 1216, 893, 836, 759 cm−1; H
NMR (400 MHz, CDCl3) δ 7.38 (d, 1H, J = 6.8 Hz), 7.26−7.22 (m,
2H), 7.15 (td, 1H, J = 6.8, 2.0 Hz), 5.26 (t, 1H, J = 7.2 Hz), 3.36 (br,
2H), 2.79 (br, 4H), 1.71 (s, 3H), 1.62 (s, 3H), 1.58−1.43 (m, 6H),
1.38−1.29 (m, 6H), 1.17−1.00 (m, 6H), 0.94 (s, 9H), 0.89 (t, 9H, J =
7.6 Hz), 0.15 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 147.4,
142.3, 136.9, 135.5, 128.8, 128.5, 125.5, 120.0, 62.1, 59.1, 37.3, 29.3
(3C), 27.6 (3C), 26.4 (3C), 26.1, 18.4, 18.0, 13.9 (3C), 10.5 (3C),
−4.2 (2C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C31H60NOSiSn 610.3466; found 610.3447.
1-(Benzyloxy)indoline (6a). To a stirred solution of 4a (192 mg,
0.305 mmol) in CH2Cl2 (3 mL) was added PhI(OH)OTs (Koser
reagent, 180 mg, 0.460 mmol). After being stirred at room
temperature in the dark for 15 h, the mixture was concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel (MeOH/CH2Cl2, 1:10) to provide 5a,
containing a small amount of tin-derived impurities, as a yellow oil.
To remove impurities, the obtained oil was treated with hexane (50
mL), sonicated for 30 min, and filtered through a filter paper to afford
white crystals, which were recrystallized from Et2O (50 mL),
sonicated for 30 min, and filtered through a filter paper to give 131
mg (60%) of pure 5a as white crystals: mp 132−134 °C
(decomposition); TLC Rf 0.13 (MeOH/CH2Cl2, 1:10); IR (neat)
2954, 2978, 1471, 1194, 1131, 1044, 1015, 887, 836, 753, 691, 573
cm−1; 1H NMR (400 MHz, CDCl3) δ 8.02 (d, 1H, J = 8.4 Hz), 7.68
(dd, 2H, J = 8.4, 0.9 Hz), 7.57−7.55 (m, 2H), 7.49−7.44 (m, 2H),
7.34−7.25 (m, 8H), 7.17 (t, 1H, J = 7.6 Hz), 7.03 (d, 2H, J = 8.0 Hz),
3.86 (br, 2H), 3.08 (t, 2H, J = 7.6 Hz), 2.78 (br, 2H), 2.30 (s, 3H),
0.88 (s, 9H), −0.03 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ
143.7, 142.9, 139.4, 138.0, 136.7, 134.2 (2C), 133.1, 131.9 (2C),
131.7, 131.5, 130.0 (2C), 129.9, 128.7 (2C), 128.6 (2C), 127.8, 126.1
(2C), 120.3, 115.0, 64.4, 59.3, 35.4, 26.3 (3C), 21.4, 17.9, −4.7 (br,
2C); HRMS (ESI-TOF) calcd for m/z: [M-OTs]+ C27H35INOSi
544.1533; found 544.1545.
As described for the preparation of 6a, compound 5e (15.8 mg,
21.1 μmol) was converted to 2.8 mg (51%) of 6e. Compound 6e was
obtained as a yellow oil: TLC Rf 0.50 (EtOAc/hexane, 1:10); IR
(neat) 3031, 2958, 2858, 1725, 1603, 1476, 1216, 1023, 884, 756, 698
cm−1; 1H NMR (400 MHz, CDCl3) δ 7.46 (d, 2H, J = 7.2 Hz), 7.41−
7.33 (m, 3H), 7.00 (d, 1H, J = 7.6 Hz), 6.85 (d, 1H, J = 7.6 Hz), 6.82
(br s, 1H), 4.98 (s, 2H), 3.47 (t, 2H, J = 7.6 Hz), 2.82 (t, 2H, J = 7.6
Hz); 13C{1H} NMR (100 MHz, CDCl3) δ 154.1, 137.6, 133.1, 129.2
(2C), 128.6 (2C), 128.4, 126.5, 125.5, 122.6, 113.7, 77.2, 58.5, 27.4;
To a stirred solution of 5a (44.7 mg, 63.3 μmol) in DMF (1 mL)
was added TBAF (1.0 M solution in THF, 95 μL, 95 μmol). After
being stirred at 60 °C for 2 h, the mixture was quenched with
saturated aqueous NH4Cl (2 mL), diluted with H2O (6 mL), and
extracted with EtOAc/hexane (1:4, 8 mL × 6). The combined
extracts were dried and concentrated under reduced pressure. The
residue was purified by preparative TLC (EtOAc/hexane, 1:10) to
provide 6.9 mg (48%) of 6a as a brown oil: TLC Rf 0.57 (EtOAc/
hexane, 1:10); IR (neat) 3030, 2954, 2919, 2859, 1608, 1476, 1365,
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HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H15ClNO 260.0842;
found 260.0831.
1-(Benzyloxy)-6-fluoroindoline (6f). As described for the prepara-
tion of 5a, compound 4f (60.5 mg, 93.3 μmol) was converted to 28.7
mg (42%) of 5f. Since compound 5f was unstable and difficult to store
even in the freezer, the obtained 5f was immediately used in the next
step.
As described for the preparation of 6a, compound 5f (23.2 mg,
31.6 μmol) was converted to 3.3 mg (43%) of 6f. Compound 6f was
obtained as a yellow oil: TLC Rf 0.47 (EtOAc/hexane, 1:10); IR
(neat) 3017, 2923, 2858, 1615, 1488, 1216, 1022, 887, 756, 698 cm−1;
1H NMR (400 MHz, CDCl3) δ 7.46 (dd, 2H, J = 8.0, 1.2 Hz), 7.41−
7.35 (m, 3H), 7.00 (dd, 1H, J = 8.0, 5.2 Hz), 6.60−6.52 (m, 2H), 4.98
(s, 2H), 3.49 (t, 2H, J = 7.6 Hz), 2.82 (t, 2H, J = 7.6 Hz); 13C{1H}
NMR (100 MHz, CDCl3) δ 164.2, 154.5 (d, J = 15.3 Hz), 137.6,
129.2 (2C), 128.6 (2C), 128.4, 125.2 (d, J = 9.5 Hz), 123.1, 109.0 (d,
J = 23.0 Hz), 101.2 (d, J = 26.8 Hz), 77.2, 58.7, 27.2; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C15H15FNO 244.1138; found
244.1145.
1-(4-Nitrobenzyloxy)indoline (6h). As described for the prepara-
tion of 5a, compound S15 (185 mg, 0.274 mmol) was converted to
185 mg (89%) of 5h. Since compound 5h was unstable and difficult
to store even in the freezer, the obtained 5h was immediately used in
the next step.
mg, 45 μmol). After being stirred at 60 °C for 2 h, the mixture was
quenched with saturated aqueous NH4Cl (2 mL), diluted with H2O
(2 mL), and extracted with EtOAc/hexane (1:4, 5 mL × 6). The
combined extracts were dried and concentrated under reduced
pressure. The residue was purified by preparative TLC (EtOAc/
hexane, 1:10) to provide 0.6 mg (9%) of 6a and 1.3 mg (18%) of 8.76
Compound 8 was obtained as a yellow oil: TLC Rf 0.71 (EtOAc/
hexane, 1:10); H NMR (400 MHz, CDCl3) δ 7.38−7.32 (m, 5H),
4.82 (s, 2H), 1.52−1.49 (m, 6H), 1.26 (s, 6H), 1.15 (s, 6H).
tert-Butyl (tert-Butyldimethylsilyloxy)carbamate (S18).
1
To a cooled (0 °C) stirred solution of hydroxylamine hydrochloride
(S9) (1.03 g, 15.6 mmol) in DMF (30 mL) were added tert-
butyldimethylchlorosilane (2.80 g, 18.6 mmol) and Et3N (12.0 mL,
86.0 mmol). The mixture was stirred at room temperature for 2.5 h,
and tert-butyldimethylchlorosilane (498 mg, 3.31 mmol) was added.
The mixture was stirred at room temperature for 1 h, and Boc2O
(4.06 g, 18.6 mmol) was added at 0 °C. After being stirred at room
temperature for 4 h, the mixture was quenched with H2O (30 mL)
and extracted with EtOAc/hexane (1:4, 30 mL × 4). The combined
extracts were washed with saturated brine (60 mL), dried, and
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (EtOAc/hexane, 1:10) to
provide 3.67 g (92%) of S1877 as a colorless oil: TLC Rf 0.82
As described for the preparation of 6a, compound 5h (23.8 mg,
31.3 μmol) was converted to 1.2 mg (14%) of 6h. Compound 6h was
obtained as a yellow oil: TLC Rf 0.46 (EtOAc/hexane, 1:6); IR (neat)
1
2926, 2855, 1523, 1347, 1216, 853, 758, 667 cm−1; H NMR (400
1
(EtOAc/hexane, 1:2); H NMR (400 MHz, CDCl3) δ 6.66 (br s,
MHz, CDCl3) δ 8.24 (d, 2H, J = 8.8 Hz), 7.64 (d, 2H, J = 8.8 Hz),
7.17−7.13 (m, 2H), 6.95 (t, 1H, J = 7.2 Hz), 6.88 (d, 1H, J = 7.2 Hz),
5.10 (s, 2H), 3.49 (t, 2H, J = 7.6 Hz), 2.90 (t, 2H, J = 7.6 Hz);
13C{1H} NMR (100 MHz, CDCl3) δ 158.7, 152.5, 145.4, 129.5 (2C),
128.2, 127.5, 124.9, 123.8 (2C), 123.3, 113.5, 75.6, 58.2, 27.9; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C15H15N2O3 271.1083; found
271.1090.
1-(Allyloxy)indoline (6i). As described for the preparation of 5a,
compound S16 (73.1 mg, 0.126 mmol) was converted to 71.0 mg
(85%) of 5i. Since compound 5i was unstable and difficult to store
even in the freezer, the obtained 5i was immediately used in the next
step.
As described for the preparation of 6a, compound 5i (25.1 mg, 37.7
μmol) was converted to 3.2 mg (48%) of 6i. Compound 6i was
obtained as a brown oil: TLC Rf 0.47 (EtOAc/hexane, 1:8); IR (neat)
2923, 2852, 1723, 1384, 1262, 1022, 759 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.17 (t, 1H, J = 7.8 Hz), 7.13 (br d, 1H, J = 7.8 Hz), 6.99
(d, 1H, J = 7.8 Hz), 6.93 (td, 1H, J = 7.8, 0.8 Hz), 6.11 (m, 1H), 5.37
(dd, 1H, J = 17.2, 1.6 Hz), 5.27 (dd, 1H, J = 10.4, 0.8 Hz), 4.50 (d,
2H, J = 6.0 Hz), 3.56 (t, 2H, J = 7.6 Hz), 2.92 (t, 2H, J = 7.6 Hz);
13C{1H} NMR (100 MHz, CDCl3) δ 153.0, 134.8, 128.2, 127.5,
124.7, 122.8, 118.5, 113.5, 75.9, 58.1, 27.9; HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C11H14NO 176.1075; found 176.1081.
1-[(2-Methylbut-3-en-2-yl)oxy]indoline (6j). As described for the
preparation of 5a, compound S17 (63.3 mg, 0.104 mmol) was
converted to 42.7 mg (59%) of 5j. Since compound 5j was unstable
and difficult to store even in the freezer, the obtained 5j was
immediately used in the next step.
1H), 1.48 (s, 9H), 0.95 (s, 9H), 0.17 (s, 6H).
Benzyl (tert-Butyldimethylsilyloxy)carbamate (S19).
To a cooled (0 °C) stirred solution of hydroxylamine hydrochloride
(S9) (203 mg, 3.14 mmol) in DMF (16 mL) were added tert-
butyldimethylchlorosilane (575 mg, 3.81 mmol) and Et3N (2.40 mL,
17.2 mmol). The mixture was stirred at room temperature for 12 h,
and benzyl chloroformate (0.500 mL, 3.56 mmol) was added at 0 °C.
After being stirred at room temperature for 9.5 h, the mixture was
quenched with H2O (50 mL) and extracted with EtOAc/hexane (1:4,
50 mL × 4). The combined extracts were washed with H2O (50 mL)
and saturated brine (50 mL), dried, and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel (EtOAc/hexane, 1:20) to provide 144 mg (16%) of S1977 as
a yellow oil: TLC Rf 0.32 (EtOAc/hexane, 1:10); H NMR (400
MHz, CDCl3) δ 7.37−7.32 (m, 5H), 6.89 (br s, 1H), 5.17 (s, 2H),
0.94 (s, 9H), 0.16 (s, 6H).
tert-Butyl (tert-Butyldimethylsilyloxy)-[2-(tributyl-stannyl)-
phenethyl]carbamate (S20a).
1
To a cooled (0 °C) stirred solution of 2a (2.18 g, 5.30 mmol), S18
(1.00 g, 4.04 mmol), and PPh3 (2.12 g, 8.08 mmol) in THF/toluene
(1:3, 14 mL) was slowly added diethyl azodicarboxylate (2.2 M
solution in toluene, 3.70 mL, 8.14 mmol). After being stirred at 0 °C
for 1 h and at room temperature for 6 h, the mixture was concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel (EtOAc/hexane, 1:60) to provide 805
mg (44% from S18) of S20a as a colorless oil: TLC Rf 0.68 (EtOAc/
hexane, 1:10); IR (neat) 2957, 2857, 1705, 1463, 1367, 1254, 1164,
As described for the preparation of 6a, compound 5j (23.5 mg, 33.9
μmol) was converted to 3.9 mg (57%) of 6j. Compound 6j was
obtained as a brown oil: TLC Rf 0.50 (EtOAc/hexane, 1:10); IR
(neat) 2979, 2930, 2859, 1609, 1477, 1359, 1237, 1145, 995, 923, 754
1
cm−1; H NMR (400 MHz, CDCl3) δ 7.14 (t, 1H, J = 7.6 Hz), 7.10
(d, 1H, J = 7.6 Hz), 6.94 (d, 1H, J = 7.6 Hz), 6.89 (t, 1H, J = 7.6 Hz),
6.14 (dd, 1H, J = 17.6, 10.8 Hz), 5.37 (d, 1H, J = 17.6 Hz), 5.13 (d,
1H, J = 10.8 Hz), 3.52 (br, 2H), 2.90 (br, 2H), 1.44 (s, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 153.9, 144.1, 128.0, 127.3, 124.5, 122.2,
113.7, 113.5, 80.3, 60.3, 27.9 (2C), 25.6 (br); HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C13H18NO 204.1388; found 204.1380.
1-(Benzyloxy)-2,2,6,6-tetramethylpiperidine (8). To a stirred
solution of 5a (20.6 mg, 28.8 μmol) in DMF (0.6 mL) were added
TBAF (1.0 M solution in THF, 44 μL, 44 μmol) and TEMPO (7.0
1
1074, 839, 757, 668 cm−1; H NMR (400 MHz, CDCl3) δ 7.38 (d,
1H, J = 6.4 Hz), 7.25−7.23 (m, 2H), 7.15 (td, 1H, J = 7.2, 1.6 Hz),
3.63 (t, 2H, J = 7.6 Hz), 2.93 (t, 2H, J = 7.6 Hz), 1.53−1.47 (m, 6H),
1.46 (s, 9H), 1.37−1.28 (m, 6H), 1.17−1.05 (m, 6H), 0.99 (s, 9H),
0.88 (t. 9H, J = 7.2 Hz), 0.17 (s, 6H); 13C{1H} NMR (100 MHz,
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CDCl3) δ 157.9, 146.1, 142.4, 136.9, 128.7, 128.6, 125.8, 81.3, 54.6,
35.2, 29.3 (3C), 28.4 (3C), 27.5 (3C), 26.1 (3C), 18.0, 13.9 (3C),
10.5 (3C), −4.9 (2C); HRMS (ESI-TOF) m/z: [M + K]+ calcd for
C31H59KNO3SiSn 680.2923; found 680.2953.
(2C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H62NO4SiSn
672.3470; found 672.3484.
tert-Butyl (tert-Butyldimethylsilyloxy)-[4-chloro-2-
(tributylstannyl)phenethyl]carbamate (S20e).
tert-Butyl (tert-Butyldimethylsilyloxy)-[2-methyl-6-
(tributylstannyl)phenethyl]carbamate (S20b).
As described for the preparation of S20b, compounds 2e and S18
(57.6 mg, 0.233 mmol) were converted to 85.9 mg (55% from S18)
of S20e. Compound S20e was obtained as a yellow oil: TLC Rf 0.47
(EtOAc/hexane, 1:10); IR (neat) 2957, 2929, 2857, 1704, 1463,
To a stirred solution of 2b (92.4 mg, 0.217 mmol) and S18 (48.1 mg,
0.194 mmol) in toluene (2 mL) was added cyanomethylenetributyl-
phosphorane (80 μL, 0.31 mmol). After being stirred at 100 °C for 15
h, the mixture was concentrated under reduced pressure. The residue
was purified by column chromatography on silica gel (EtOAc/hexane,
1:70) to provide 57.3 mg (45% from S18) of S20b (a mixture of
rotamer) as a yellow oil: TLC Rf 0.56 (EtOAc/hexane, 1:10); IR
(neat) 2957, 2929, 2857, 1703, 1462, 1367, 1253, 1164, 1071, 893,
1
1368, 1252, 1162, 1079, 840, 759, 668 cm−1; H NMR (400 MHz,
CDCl3) δ 7.30 (d, 1H, J = 2.4 Hz), 7.20 (dd, 1H, J = 8.0, 2.4 Hz),
7.15 (d, 1H, J = 8.0 Hz), 3.59 (t, 2H, J = 7.6 Hz), 2.88 (t, 2H, J = 7.6
Hz), 1.56−1.47 (m, 6H), 1.43 (s, 9H), 1.37−1.28 (m, 6H), 1.19−
1.04 (m, 6H), 0.98 (s, 9H), 0.89 (t. 9H, J = 7.2 Hz), 0.17 (s, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 157.8, 144.9, 144.3, 136.0,
132.1, 130.0, 128.4, 81.4, 54.2, 34.3, 29.2 (3C), 28.4 (3C), 27.5 (3C)
26.1 (3C), 17.9, 13.8 (3C), 10.6 (3C), −4.8 (2C); HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C31H59ClNO3SiSn 676.2975; found
676.3005.
1
841, 759, 670 cm−1; H NMR (400 MHz, CDCl3) δ 7.23 (m, 1H),
7.13−7.09 (m, 2H), 3.56 (t, 2H × 1/6, J = 8.0 Hz), 3.47 (t, 2H × 5/6,
J = 8.0 Hz), 2.97 (t, 2H, J = 8.0 Hz), 2.39 (s, 3H × 5/6), 2.35 (s, 3H
× 1/6), 1.50 (s, 9H), 1.53−1.45 (m, 6H), 1.37−1.28 (m, 6H), 1.20−
1.03 (m, 6H), 0.99 (s, 9H), 0.88 (t. 9H, J = 7.2 Hz), 0.16 (s, 6H);
13C{1H} NMR (100 MHz, CDCl3) for major rotamer δ 158.3, 143.9,
tert-Butyl (tert-Butyldimethylsilyloxy)-[4-fluoro-2-
(tributylstannyl)phenethyl]carbamate (S20f).
143.3, 136.7, 135.0, 131.0, 126.2, 81.5, 53.4, 33.0, 29.3 (3C), 28.4
(3C), 27.6 (3C), 26.1 (3C), 20.4, 18.0, 13.9 (3C), 10.9 (3C), −4.8
(2C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H62NO3SiSn
656.3521; found 656.3551.
tert-Butyl (tert-Butyldimethylsilyloxy)-[4-methyl-2-
(tributylstannyl)phenethyl]carbamate (S20c).
As described for the preparation of S20b, compounds 2f and S18
(52.7 mg, 0.213 mmol) were converted to 81.6 mg (58% from S18)
of S20f. Compound S20f was obtained as a yellow oil: TLC Rf 0.54
(EtOAc/hexane, 1:10); IR (neat) 2957, 2929, 2857, 1704, 1474,
1
1368, 1253, 1215, 1163, 1078, 840, 759, 667 cm−1; H NMR (400
MHz, CDCl3) δ 7.19 (dd, 1H, J = 8.4, 5.2 Hz), 7.06 (dd, 1H, J = 8.4,
2.0 Hz), 6.91 (td, 1H, J = 8.4, 2.0 Hz), 3.59 (t, 2H, J = 7.6 Hz), 2.89
(t, 2H, J = 7.6 Hz), 1.56−1.46 (m, 6H), 1.43 (s, 9H), 1.37−1.28 (m,
6H), 1.18−1.01 (m, 6H), 0.98 (s, 9H), 0.88 (t. 9H, J = 7.2 Hz), 0.17
(s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 157.8, 145.1, 141.5,
130.0 (d, J = 5.7 Hz), 122.8, 122.6, 115.2 (d, J = 21.1 Hz), 81.3, 54.5,
34.3, 29.2 (3C), 28.4 (3C), 27.5 (3C), 26.1 (3C), 18.0, 13.8 (3C),
10.6 (3C), −4.8 (2C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C31H59FNO3SiSn 660.3270, found 660.3256.
As described for the preparation of S20a, compounds 2c and S18
(144 mg, 0.581 mmol) were converted to 51.1 mg (14% from S18) of
S20c. Compound S20c was obtained as a colorless oil: TLC Rf 0.64
(EtOAc/hexane, 1:10); IR (neat) 2957, 2929, 2857, 1705, 1463,
1
1368, 1254, 1163, 1080, 841, 759, 668 cm−1; H NMR (400 MHz,
CDCl3) δ 7.17−7.07 (m, 3H), 3.60 (t, 2H, J = 8.0 Hz), 2.89 (t, 2H, J
= 8.0 Hz), 2.30 (s, 3H), 1.53−1.47 (m, 6H), 1.46 (s, 9H), 1.37−1.30
(m, 6H), 1.17−1.02 (m, 6H), 0.98 (s, 9H), 0.88 (t. 9H, J = 7.2 Hz),
0.17 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 158.0, 143.0,
142.2, 137.6, 134.9, 129.5, 128.5, 81.3, 54.8, 34.7, 29.3 (3C), 28.4
(3C), 27.5 (3C), 26.1 (3C), 21.2, 18.0, 13.9 (3C), 10.5 (3C), −4.9
(2C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H62NO3SiSn
656.3521; found 656.3549.
tert-Butyl (tert-Butyldimethylsilyloxy)-{3-methoxy-2-[3-(tributyl-
stannyl)-[1,1′-biphenyl]-4-yl]propyl}carbamate (S20i).
tert-Butyl (tert-Butyldimethylsilyloxy)-[4-methoxy-2-
(tributylstannyl)phenethyl]carbamate (S20d).
As described for the preparation of S20b, compounds 2i and S18
(79.8 mg, 0.323 mmol) were converted to 63.8 mg (26% from S18)
of S20i. Compound S20i was obtained as a yellow oil: TLC Rf 0.64
(EtOAc/hexane, 1:10); IR (neat) 2956, 2928, 2857, 1730, 1703,
1
1464, 1366, 1251, 1170, 1108, 840, 763, 698 cm−1; H NMR (400
As described for the preparation of S20a, compounds 2d and S18
(404 mg, 1.63 mmol) were converted to 341 mg (31% from S18) of
S20d. Compound S20d was obtained as a yellow oil: TLC Rf 0.66
(EtOAc/hexane, 1:10); IR (neat) 2957, 2930, 2857, 1704, 1591,
MHz, CDCl3) δ 7.56 (d, 2H, J = 8.0 Hz), 7.53 (br s, 1H), 7.48 (d,
1H, J = 8.0 Hz), 7.45−7.37 (m, 3H), 7.32 (t, 1H, J = 6.8 Hz), 3.98
(dd, 1H, J = 14.8, 6.4 Hz), 3.80 (dd, 1H, J = 14.8, 6.0 Hz), 3.60 (t,
1H, J = 8.0 Hz), 3.52 (t, 1H, J = 8.0 Hz), 3.28 (m, 1H), 3.28 (s, 3H),
1.55−1.51 (m, 6H), 1.39−1.31 (m, 6H), 1.31 (s, 9H), 1.22−1.05 (m,
6H), 0.94 (s, 9H), 0.89 (t. 9H, J = 7.2 Hz), 0.17 (s, 3H), 0.15 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 156.8, 146.6, 144.5, 141.8,
138.8, 135.6, 128.8 (2C), 127.5, 127.2 (3C), 127.0, 80.7, 76.0, 59.1,
53.6, 46.9, 29.4 (3C), 28.2 (3C), 27.6 (3C), 26.1 (3C), 18.0, 13.9
(3C), 10.8 (3C), −4.6, −4.9; HRMS (ESI-TOF) m/z: [M + H]+
calcd for C39H68NO4SiSn 762.3940; found 762.3911.
1
1464, 1368, 1251, 1164, 1079, 841, 759, 668 cm−1; H NMR (400
MHz, CDCl3) δ 7.17 (d, 1H, J = 8.4 Hz), 6.94 (d, 1H, J = 2.8 Hz),
6.80 (dd, 1H, J = 8.4, 2.8 Hz), 3.78 (s, 3H), 3.59 (t, 2H, J = 7.6 Hz),
2.87 (t, 2H, J = 7.6 Hz), 1.54−1.47 (m, 6H), 1.45 (s, 9H), 1.37−1.28
(m, 6H), 1.17−1.03 (m, 6H), 0.99 (s, 9H), 0.88 (t. 9H, J = 7.2 Hz),
0.17 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 157.9, 157.3,
143.8, 138.0, 129.5, 122.5, 113.4, 81.2, 55.3, 54.8, 34.2, 29.3 (3C),
28.4 (3C), 27.5 (3C), 26.1 (3C), 18.0, 13.9 (3C), 10.6 (3C), −4.9
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Article
Benzyl (tert-Butyldimethylsilyloxy)-[2-(tributylstannyl)-
phenethyl]carbamate (S21).
As described for the preparation of 10a, compound 9b (30.0 mg,
40.6 μmol) was converted to 4.8 mg (90%) of 10b.78 Compound 10b
was obtained as a brown oil: TLC Rf 0.25 (EtOAc/hexane, 1:4); H
1
NMR (400 MHz, CDCl3) δ 8.16 (br, 1H), 7.25 (d, 1H, J = 7.2 Hz),
7.21 (t, 1H, J = 2.8 Hz), 7.11 (t, 1H, J = 7.2 Hz), 6.92 (d, 1H, J = 7.2
Hz), 6.58 (br s, 1H), 2.57 (s, 3H).
6-Methyl-1H-indole (10c). As described for the preparation of 9a,
compound S20c (50.3 mg, 76.8 μmol) was converted to 43.1 mg
(76%) of 9c. Since compound 9c was unstable and difficult to store
even in the freezer, the obtained 9c was immediately used in the next
step.
As described for the preparation of 10a, compound 9c (22.6 mg,
30.5 μmol) was converted to 2.5 mg (62%) of 10c.79 Compound 10c
was obtained as brown crystals: TLC Rf 0.39 (EtOAc/hexane, 1:4);
1H NMR (400 MHz, CDCl3) δ 8.02 (br, 1H), 7.52 (d, 1H, J = 8.4
Hz), 7.20 (br s, 1H), 7.14 (t, 1H, J = 2.8 Hz), 6.95 (d, 1H, J = 8.4
Hz), 6.50 (br s, 1H), 2.47 (s, 3H).
To a cooled (0 °C) stirred solution of 2a (678 mg, 1.64 mmol), S19
(388 mg, 1.38 mmol), and PPh3 (867 mg, 3.31 mmol) in THF/
toluene (1:3, 5 mL) was slowly added diethyl azodicarboxylate (2.2 M
solution in toluene, 31.5 mL, 3.30 mmol). After being stirred at 0 °C
for 1 h and at room temperature for 3 h, the mixture was concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel (EtOAc/hexane, 1:70) to provide 539
mg (58% from S19) of S21 as a colorless oil: TLC Rf 0.56 (EtOAc/
hexane, 1:10); IR (neat) 2956, 2929, 2857, 1709, 1463, 1390, 1252,
1
1075, 836, 756, 697 cm−1; H NMR (400 MHz, CDCl3) δ 7.37 (dd,
6-Methoxy-1H-indole (10d). As described for the preparation of
9a, compound S20d (233 mg, 0.347 mmol) was converted to 134 mg
(51%) of 9d. Since compound 9d was unstable and difficult to store
even in the freezer, the obtained 9d was immediately used in the next
step.
As described for the preparation of 10a, compound 9d (26.6 mg,
35.2 μmol) was converted to 4.2 mg (81%) of 10d.80 Compound 10d
was obtained as brown crystals: TLC Rf 0.40 (EtOAc/hexane, 1:3);
1H NMR (400 MHz, CDCl3) δ 8.02 (br, 1H), 7.51 (d, 1H, J = 8.8
Hz), 7.10 (t, 1H, J = 2.8 Hz), 6.89 (d, 1H, J = 2.4 Hz), 6.80 (dd, 1H, J
= 8.8, 2.4 Hz), 6.48 (br s, 1H), 3.85 (s, 3H).
6-Chloro-1H-indole (10e). As described for the preparation of 9a,
compound S20e (78.3 mg, 0.116 mmol) was converted to 47.5 mg
(54%) of 9e. Since compound 9e was unstable and difficult to store
even in the freezer, the obtained 9e was immediately used in the next
step.
As described for the preparation of 10a, compound 9e (26.2 mg,
34.5 μmol) was converted to 4.4 mg (84%) of 10e.81 Compound 10e
was obtained as brown crystals: TLC Rf 0.37 (EtOAc/hexane, 1:4);
1H NMR (400 MHz, CDCl3) δ 8.15 (br, 1H), 7.54 (d, 1H, J = 8.4
Hz), 7.40 (br s, 1H), 7.21 (t, 1H, J = 2.8 Hz), 7.09 (dd, 1H, J = 8.4,
2.0 Hz), 6.54 (br s, 1H).
6-Fluoro-1H-indole (10f). As described for the preparation of 9a,
compound S20f (73.3 mg, 0.111 mmol) was converted to 43.6 mg
(53%) of 9f. Since compound 9f was unstable and difficult to store
even in the freezer, the obtained 9f was immediately used in the next
step.
As described for the preparation of 10a, compound 9f (27.1 mg,
36.4 μmol) was converted to 4.3 mg (87%) of 10f.78 Compound 10f
was obtained as brown crystals: TLC Rf 0.34 (EtOAc/hexane, 1:4);
1H NMR (400 MHz, CDCl3) δ 8.14 (br, 1H), 7.55 (dd, 1H, J = 8.8,
6.2 Hz), 7.19 (t, 1H, J = 2.0 Hz), 7.08 (dd, 1H, J = 9.6, 2.4 Hz), 6.89
(td, 1H, J = 8.8, 2.4 Hz), 6.53 (br s, 1H).
1H, J = 6.8, 2.0 Hz), 7.35−7.30 (m, 5H), 7.24−7.19 (m, 2H), 7.15
(td, 1H, J = 6.8, 2.0 Hz), 5.06 (s, 2H), 3.67 (t, 2H, J = 7.6 Hz), 2.94
(t, 2H, J = 7.6 Hz), 1.52−1.41 (m, 6H), 1.35−1.26 (m, 6H), 1.14−
1.00 (m, 6H), 0.96 (s, 9H), 0.87 (t, 9H, J = 7.2 Hz), 0.13 (s, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 158.5, 145.8, 142.4, 137.0,
136.0, 128.9, 128.5 (4C), 128.3 (2C), 125.9, 67.9, 54.5, 35.3, 29.3
(3C), 27.5 (3C), 26.0 (3C), 18.0, 13.8 (3C), 10.5 (3C), −4.9 (2C);
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C34H58NO3SiSn
676.3208; found 676.3242.
1H-Indole (10a). To a stirred solution of S20a (538 mg, 0.839
mmol) in CH2Cl2 (8 mL) was added PhI(OH)OTs (Koser reagent,
498 mg, 1.27 mmol). After being stirred at room temperature in the
dark for 14 h, the mixture was concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel
(MeOH/CH2Cl2, 1:10) to provide 404 mg (67%) of 9a as a yellow
amorphous: TLC Rf 0.13 (MeOH/CH2Cl2, 1:10); IR (neat) 2956,
1
2929, 1699, 1384, 1201, 1130, 1044, 755, 689, 572 cm−1; H NMR
(400 MHz, CDCl3) δ 7.95 (d, 3H, J = 8.0 Hz), 7.65 (d, 2H, J = 7.6
Hz), 7.55−7.50 (m, 3H), 7.39 (t, 2H, J = 8.0 Hz), 7.22 (m, 1H), 7.08
(d, 2H, J = 8.0 Hz), 3.74 (t, 2H, J = 6.8 Hz), 3.19 (t, 2H, J = 6.8 Hz),
2.32 (s, 3H), 1.31 (s, 9H), 0.96 (s, 9H), 0.16 (s, 6H); 13C{1H} NMR
(100 MHz, CDCl3) δ 157.5, 143.0, 141.9, 139.1, 138.1, 134.5 (2C),
132.7, 132.1, 131.6 (2C), 131.4, 130.0, 128.4 (2C), 126.1 (2C),
120.6, 115.9, 81.6, 51.9, 35.2, 28.2 (3C), 25.9 (3C), 21.3, 17.8, −5.0
(2C); HRMS (ESI-TOF) m/z: [M − OTs]+ calcd for C25H37INO3Si
554.1587; found 554.1598.
To a stirred solution of 9a (25.9 mg, 35.7 μmol) and dried
molecular sieves 4 Å powder (17.8 mg) in DMF (0.7 mL) was added
TBAF (1.0 M solution in THF, 44 μL, 44 μmol). After being stirred
at room temperature for 4 h, the mixture was quenched with saturated
aqueous NH4Cl (2 mL), diluted with H2O (2 mL), and extracted with
EtOAc/hexane (1:4, 6 mL × 5). The combined extracts were dried
and concentrated under reduced pressure. The residue was purified by
preparative TLC (EtOAc/hexane, 1:4) to provide 4.1 mg (89%) of
1H-Benzo[g]indole (10g).
10a78 as light brown crystals; TLC Rf 0.30 (EtOAc/hexane, 1:4); H
1
NMR (400 MHz, CDCl3) δ 8.16 (br, 1H), 7.65 (d, 1H, J = 8.0 Hz),
7.41 (dd, 1H, J = 8.0, 0.8 Hz), 7.23 (td, 1H, J = 8.0, 0.8 Hz), 7.23−
7.18 (m, 2H), 6.57 (br s, 1H).
Data for a trace amount of by-product 12a: brown crystals; mp 58−
60 °C; TLC Rf 0.18 (EtOAc/hexane, 1:4); IR (neat) 3383, 2928,
1
2852, 1754, 1493, 1370, 1275, 1154, 886, 755 cm−1; H NMR (400
As described for the preparation of S20b, compounds 2g and S18
(66.2 mg, 0.268 mmol) were converted to 120 mg (65% from S18) of
S20g. Since compound S20g was unstable due to protodestanylation,
the obtained S20g was immediately used in the next step.
As described for the preparation of 9a, compound S20g (43.7 mg,
63.2 μmol) was converted to 34.1 mg (69%) of 9g. Since compound
9g was unstable and difficult to store even in the freezer, the obtained
9g was immediately used in the next step.
As described for the preparation of 10a, compound 9g (20.3 mg,
26.2 μmol) was converted to 3.8 mg (87%) of 10g.82 Compound 10g
was obtained as yellow crystals: TLC Rf 0.33 (EtOAc/hexane, 1:4);
1H NMR (400 MHz, CDCl3) δ 8.90 (br, 1H), 8.01 (d, 1H, J = 8.0
MHz, CDCl3) δ 6.92 (br d, 1H, J = 0.8 Hz), 6.78 (dd, 1H, J = 8.0, 0.8
Hz), 6.57 (d, 1H, J = 8.0 Hz), 3.57 (t, 2H, J = 8.0 Hz), 3.03 (t, 2H, J =
8.0 Hz), 1.54 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 153.0,
149.5, 143.9, 130.7, 119.9, 118.1, 109.3, 83.2, 48.0, 30.1, 27.9 (3C);
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C13H18NO3 236.1287;
found 236.1294.
4-Methyl-1H-indole (10b). As described for the preparation of 9a,
compound S20b (80.2 mg, 0.123 mmol) was converted to 61.8 mg
(68%) of 9b. Since compound 9b was unstable and difficult to store
even in the freezer, the obtained 9b was immediately used in the next
step.
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Hz), 7.93 (d, 1H, J = 8.6 Hz), 7.73 (d, 1H, J = 8.6 Hz), 7.54 (t, 1H, J
= 8.0 Hz), 7.52 (d, 1H, J = 8.0 Hz), 7.43 (t, 1H, J = 8.0 Hz), 7.29 (t,
1H, J = 2.4 Hz), 6.71 (br s, 1H).
To a cooled (0 °C) stirred solution of 3a (50.3 mg, 93.1 μmol) in
CH2Cl2 (1 mL) were added Ac2O (18 μL, 0.19 mmol) and 4-
dimethylaminopyridine (DMAP) (2.6 mg, 21 μmol). After being
stirred at room temperature for 2 h, the mixture was quenched with
H2O (2 mL) and extracted with EtOAc (2 mL × 4). The combined
extracts were dried and concentrated under reduced pressure. The
residue was purified by preparative TLC (EtOAc/hexane, 1:20) to
provide 33.2 mg (61%) of S23 as a yellow oil: TLC Rf 0.35 (EtOAc/
hexane, 1:20); IR (neat) 2956, 2929, 2857, 1678, 1464, 1383, 1254,
5-(3,5-Dimethylphenyl)-1H-indole (10h).
1
1071, 836, 784, 755, 667 cm−1; H NMR (400 MHz, CDCl3) δ 7.40
(dd, 1H, J = 7.2, 1.2 Hz), 7.25−7.15 (m, 3H), 3.80 (br, 2H), 2.94 (t,
2H, J = 7.2 Hz), 2.07 (br, 3H), 1.57−1.42 (m, 6H), 1.38−1.29 (m,
6H), 1.20−1.05 (m, 6H), 1.01 (s, 9H), 0.88 (t, 9H, J = 7.2 Hz), 0.24
(s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.7, 142.5, 137.1
(2C), 128.5, 125.9, 51.8 (br), 35.2 (br), 29.3 (3C), 27.5 (3C), 26.0
(3C), 21.4, 18.0, 13.8 (3C), 10.5 (3C), −4.4 (2C); HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C28H54NO2SiSn 584.2946; found
584.2957.
As described for the preparation of S20b, compounds 2h (110 mg,
0.213 mmol) and S18 were converted to 121 mg (76% from 2h) of
S20h. Since compound S20h was unstable due to protodestanylation,
the obtained S20h was immediately used in the next step.
As described for the preparation of 9a, compound S20h (121 mg,
0.162 mmol) was converted to 107 mg (79%) of 9h. Since compound
9h was unstable and difficult to store even in the freezer, the obtained
9h was immediately used in the next step.
N-(tert-Butyldimethylsilyloxy)-N-[2-(tributylstannyl)-phenethyl]-
pivalamide (S24).
As described for the preparation of 10a, compound 9h (30.6 mg,
36.9 μmol) was converted to 6.3 mg (77%) of 10h. Compound 10h
was obtained as a yellow oil: TLC Rf 0.37 (EtOAc/hexane, 1:4); IR
(neat) 3415, 3019, 2918, 1601, 1458, 1413, 1307, 1217, 1094, 882,
To a cooled (0 °C) stirred solution of 3a (186 mg, 0.344 mmol) in
CH2Cl2 (4 mL) were added PivCl (64 μL, 0.53 mmol) and Et3N (72
μL, 0.52 mmol). After being stirred at room temperature for 23 h, the
mixture was quenched with H2O (4 mL) and extracted with CH2Cl2
(4 mL × 4). The combined extracts were dried and concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel (CH2Cl2/hexane, 1:2) to provide 177
mg (82%) of S24 as a yellow oil: TLC Rf 0.30 (MeOH/CH2Cl2/
hexane, 1:5:60); IR (neat) 2957, 2929, 1652, 1464, 1254, 1168, 838,
1
850, 762, 727 cm−1; H NMR (400 MHz, CDCl3) δ 8.15 (br, 1H),
7.85 (s, 1H), 7.44 (s, 2H), 7.28 (br s, 2H), 7.24 (br s, 1H), 6.97 (br s,
1H), 6.60 (br s, 1H), 2.40 (s, 6H); 13C{1H} NMR (100 MHz,
CDCl3) δ 142.7, 138.2 (2C), 135.4, 133.8, 128.5, 128.1, 125.5 (2C),
124.8, 122.2, 119.4, 111.2, 103.1, 21.6 (2C); HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C16H16N 222.1283; found, 222.1292.
3-(Methoxymethyl)-6-phenyl-1H-indole (10i). As described for
the preparation of 9a, compound S20i (46.0 mg, 60.5 μmol) was
converted to 31.7 mg (62%) of 9i. Since compound 9i was unstable
and difficult to store even in the freezer, the obtained 9i was
immediately used in the next step.
1
784, 756 cm−1; H NMR (400 MHz, CDCl3) δ 7.41 (d, 1H, J = 7.2
Hz), 7.29−7.16 (m, 3H), 3.91 (t, 2H, J = 8.0 Hz), 3.00 (t, 2H, J = 8.0
Hz), 1.61−1.45 (m, 6H), 1.39−1.30 (m, 6H), 1.21 (s, 9H), 1.12−
1.06 (m, 6H), 1.02 (s, 9H), 0.89 (t, 9H, J = 7.2 Hz), 0.25 (s, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 178.8, 145.4, 142.7, 137.1,
128.6, 127.9, 125.9, 53.8, 39.1, 35.4, 29.3 (3C), 27.9 (3C), 27.5 (3C),
26.4 (3C), 18.6, 13.8 (3C), 10.5 (3C), −4.0 (2C); HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C31H60NO2SiSn 626.3415; found
626.3385.
As described for the preparation of 10a, compound 9i (28.0 mg,
33.1 μmol) was converted to 6.3 mg (38%) of 10i. Compound 10i
was obtained as pale yellow crystals: mp 105−108 °C; TLC Rf 0.36
(EtOAc/hexane, 1:2); IR (neat) 3378, 2924, 2858, 1446, 1384, 1091,
1
1055, 822, 752, 690, 545 cm−1; H NMR (400 MHz, CDCl3) δ 8.15
(br, 1H), 7.77 (d, 1H, J = 8.4 Hz), 7.64 (d, 2H, J = 7.6 Hz), 7.58 (s,
1H), 7.46−7.41 (m, 3H), 7.32 (br t, 1H, J = 8.4 Hz), 7.23 (br s, 1H),
4.70 (s, 2H), 3.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
142.4, 137.1, 136.1, 128.8 (2C), 127.5 (2C), 126.8, 126.6, 124.4,
120.1, 119.6, 113.5, 109.8, 66.6, 57.7; HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C16H16NO 238.1232; found 238.1236.
tert-Butyl (tert-Butyldimethylsilyloxy)(3-phenylpropyl)-carba-
mate (13).
1H-Indole (10a) from the Diaryliodonium Salt (S22).
To a cooled (0 °C) stirred solution of 3-phenylpropion-aldehyde
(S25) (0.265 mL, 2.01 mmol) in MeOH (20 mL) was added NaBH4
(117 mg, 3.09 mmol) under air. After being stirred at 0 °C for 5 min,
the mixture was quenched with saturated aqueous NH4Cl (10 mL)
and extracted with EtOAc (20 mL × 2). The combined extracts were
washed with saturated brine (40 mL), dried, and concentrated under
reduced pressure to provide crude S26, which was used in the next
step without further purification.
As described for the preparation of 9a, compound S21 (251 mg, 0.373
mmol) was converted to 251 mg (89%) of S22. Since compound S22
was unstable and difficult to store even in the freezer, the obtained
S22 was immediately used in the next step.
As described for the preparation of 10a, compound S22 (26.7 mg,
35.1 μmol) was converted to 2.5 mg (61%) of 10a.
N-(tert-Butyldimethylsilyloxy)-N-[2-(tributylstannyl)-phenethyl]-
acetamide (S23).
To a cooled (0 °C) stirred solution of crude S26 obtained above,
S18 (395 mg, 1.60 mmol), and PPh3 (1.05 g, 4.00 mmol) in THF/
toluene (1:3, 8 mL) was slowly added diethyl azodicarboxylate (2.2 M
solution in toluene, 1.55 mL, 3.41 mmol). After being stirred at 0 °C
for 1 h and at room temperature for 1 h, the mixture was concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel (EtOAc/hexane, 1:20) to provide 158
mg (27%) of 13 as a yellow oil: TLC Rf 0.57 (EtOAc/hexane, 1:8); IR
(neat) 2953, 2931, 2858, 1702, 1455, 1367, 1252, 1164, 1098, 1024,
1
894, 840, 784, 699 cm−1; H NMR (400 MHz, CDCl3) δ 7.29−7.26
(m, 2H), 7.20−7.18 (m, 3H), 3.45 (t, 2H, J = 7.6 Hz), 2.62 (t, 2H, J =
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Article
7.6 Hz), 1.98 (quint, 2H, J = 7.6 Hz), 1.46 (s, 9H), 0.93 (s, 9H), 0.12
(s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 158.1, 141.8, 128.4
(3C), 125.9 (2C), 81.2, 52.1, 33.1, 28.4 (3C), 27.5, 26.0 (3C), 17.9,
−5.0 (2C); HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C20H36NO3Si 366.2464, found 366.2461.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
tert-Butyl Hydroxy(3-phenylpropyl)carbamate (14). To a stirred
solution of 13 (18.4 mg, 50.3 μmol) in DMF (1 mL) was added
TBAF (1.0 M solution in THF, 61 μL, 61 μmol). After being stirred
at room temperature for 1 h, the mixture was quenched with saturated
aqueous NH4Cl (2 mL) and extracted with EtOAc/hexane (1:4, 4 mL
× 3). The combined extracts were dried and concentrated under
reduced pressure. The residue was purified by preparative TLC
(EtOAc/hexane, 1:4) to provide 10.7 mg (85%) of 14 as a pale yellow
oil: TLC Rf 0.23 (EtOAc/hexane, 1:4); IR (neat) 3279, 2930, 1693,
This research was supported by JSPS KAKENHI Grant
number 19K15571 and Keio Gijuku Academic Development
Funds. We acknowledge Prof. Fumitoshi Kakiuchi, Prof.
Takuya Kochi, and Shota Kanno at Keio University for GC
measurements.
REFERENCES
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ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00820.
Supporting experimental procedures; computational
methods; and spectral data of new compounds (PDF)
AUTHOR INFORMATION
■
Corresponding Authors
Ken-ichi Takao − Department of Applied Chemistry, Keio
University, Yokohama 223-8522, Japan; orcid.org/0000-
0001-8629-1002; Email: takao@applc.keio.ac.jp
Akihiro Ogura − Department of Applied Chemistry, Keio
University, Yokohama 223-8522, Japan; orcid.org/0000-
0002-4793-5706; Email: ogura@applc.keio.ac.jp
Author
Kouhei Shibata − Department of Applied Chemistry, Keio
University, Yokohama 223-8522, Japan
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Alkyl-Aryl Ethers from the Reaction of Aliphatic Alcohols and
Unsymmetric Diaryliodonium Salts. J. Org. Chem. 2015, 80, 6456−
6466.
(19) Seidl, T. L.; Sundalam, S. K.; McCullough, B.; Stuart, D. R.
Unsymmetrical Aryl(2,4,6-Trimethoxyphenyl)Iodonium Salts: One-
Pot Synthesis, Scope, Stability, and Synthetic Studies. J. Org. Chem.
2016, 81, 1998−2009.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00820
Author Contributions
This manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
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