Synthesis of indoles and tryptophan derivatives via photoinduced nitrene C-H insertion

Article abstract of DOI:10.1039/c5ob02563j

Functionalized indoles and tryptophans can be obtained from stannylated alkenes and o-iodoanilines via Stille coupling. Subsequent azidation and photochemical nitrene generation results in the formation of the heterocyclic ring systems via C-H insertion.

Full text of DOI:10.1039/c5ob02563j

Organic &
Biomolecular Chemistry
View Article Online
View Journal
PAPER
Synthesis of indoles and tryptophan derivatives via
photoinduced nitrene C–H insertion†
Cite this: DOI: 10.1039/c5ob02563j
Lukas Junk and Uli Kazmaier*
Received 14th December 2015,
Accepted 2nd February 2016
Functionalized indoles and tryptophans can be obtained from stannylated alkenes and o-iodoanilines via
Stille coupling. Subsequent azidation and photochemical nitrene generation results in the formation of
the heterocyclic ring systems via C–H insertion.
DOI: 10.1039/c5ob02563j
www.rsc.org/obc
been developed during the last decades.8 Some of them, such
Introduction
as the Larock protocol9 are based on the coupling of o-iodoani-
Indoles belong to the most important and interesting hetero- lines with alkynes,10 or start directly with o-allylated11 or o-
cycles, not only because of their widespread distribution in alkynylated anilines.12 These approaches give access to
nature, but also from a pharmaceutical point of view.1 The 2- or 2,3-substituted indoles and are especially suitable for the
indole ring system is found in relatively simple compounds synthesis of highly substituted indoles. However, they are
such as the neurotransmitter serotonin, but also in the rather unsuitable for the synthesis of tryptophans and derivatives
complex indole alkaloids, such as the lysergic acid derivatives thereof, where the 2-position is unsubstituted. This problem
(Fig. 1).2 In general, these compounds are formed biosyntheti- can be solved by using silyl-substituted alkynes, followed by
cally from tryptophan, possibly in combination with enzymatic protodesilylation.13
modifications (hydroxylation, halogenation, prenylation).3
For the synthesis of tryptophans, Pd-catalysed annulation
Functionalized tryptophans are also widespread in biologically of o-haloanilines with δ-oxo amino acids can be used
active peptides,4 such as the chondramides5 or the cyclocin- (Scheme 1a),14 or the cyclization of amino acid derived nitro-
amides.6 With respect to that, it is not surprising that a wide styrenes (Scheme 1b).15 The stereogenic α-centre can be intro-
range of synthetic protocols have been developed for the syn- duced by auxiliary control.13 Alternatively, the stereochemical
thesis of the indole nucleus.7
outcome can be controlled by reacting chiral auxiliaries with
In principle, one can differentiate between two major the corresponding 3-substituted indoles,16 or by asymmetric
approaches. The first one starts with an existing indole ring hydrogenation of β-unsaturated amino acid derivatives.17
system, which is modified by substitution. The other one Recent approaches are based on asymmetric cross coupling
generates the indole nucleus, whereby in most cases the five reactions such as Negishi couplings,18 or on stereoselective
membered heterocyclic ring is formed. According to this
approach, most syntheses start with o-substituted nitrobenz-
enes or aniline derivatives. Besides the classical indole synth-
eses a wide range of transition metal catalysed methods have
Fig. 1 Naturally occurring indole derivatives.
Institute of Organic Chemistry, Saarland University, P.O. Box 151150, 66041
Saarbrücken, Germany. E-mail: u.kazmaier@mx.uni-saarland.de
†Electronic supplementary information (ESI) available: Copies of 1H and 13C
Scheme 1 Selected examples of transition metal-catalysed trypto-
NMR spectra. See DOI: 10.1039/c5ob02563j
phane syntheses.
This journal is © The Royal Society of Chemistry 2016
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
additions of azlactones onto vinyl indoles in the presence of
chiral Brønsted acids.19 Regioselective C–H activations allow
the subsequent functionalization at the 2-, 4- and 6-position.20
Our group has been involved in the synthesis of unusual
amino acids21 since a couple of years. As a synthetic tool we
use chelated glycine ester enolates,22 which can be subjected
to a wide range of reactions, such as aldol reactions,23 Michael
additions24 or transition metal catalysed allylic alkylations.25
Stannylated allylic acetates and carbonates provide access to
metallated amino acids that can be subjected to further modi-
fications via Stille couplings.26 Since these cross couplings
proceed under completely neutral conditions, no epimeriza-
tion of stereogenic centres occurs, and therefore, this protocol
is suitable for natural product and drug synthesis.27 Herein,
Table 1 Optimization of the reaction conditions for Stille couplings
Entry
Stannane
PG
“N”
Method
Product
Yield [%]
1
2
3
4
1
1
2
1
TFA
TFA
Bz
N3
A
A
A
B
3a
4a
5a
4a
49
61
91
90
NH2
NH2
NH2
TFA
we describe a new synthetic route toward substituted indoles Method A: Pd(PPh3)4 (5 mol%), CuI (10 mol%), CsF (2.0 equiv.), DMF,
45 °C; Method B: Pd(PPh3)4 (5 mol%), CuI (2.0 equiv.), LiCl (2.0
equiv.), DMF, 80 °C, 18 h.
and tryptophans, based on cross couplings of stannylated
intermediates and subsequent photochemical nitrene C–H
insertion (Scheme 2).
reaction. Therefore, we replaced the TFA protecting group by
the less acidic benzoyl group (entry 3), and indeed, the yield of
the desired coupling product 5a could be increased to 91%. In
Results and discussion
this case, the formation of N-benzoylated allylglycine was not
observed. Since obviously CsF caused the problems in case of
1, we tried to find reaction conditions avoiding such basic
additives. For the coupling of sterically demanding vinylstann-
anes, Corey et al. developed a protocol abstaining CsF com-
pletely, while using 6 equiv. of LiCl and 5 equiv. of CuI in
DMSO.31 This method requires higher reaction temperatures,
but proceeds under completely neutral conditions. In our case,
the best results were obtained with 2 equiv. of LiCl and CuI
each in DMF. Under these conditions, the TFA-derivative 1
could also be coupled in excellent yield (entry 4). Attempts to
use this protocol also for the direct coupling of iodo phenyl-
azide were not successful, the yield under these conditions
was even lower (26%) than in the preciously used method.
Since the azido group obviously is not the best functionality
for Stille couplings, we next focused on its generation and
direct nitrene formation/C–H insertion. Amines can easily be
converted into azides via diazotization and subsequent reac-
tion of the diazonium salt with azide. Use of tert-butylnitrite
In our previous investigations, in general, we obtained the best
results with TFA-protected tert-butyl glycinate as nucleophile,
especially in Pd-catalysed allylic alkylations. Therefore, we
started our investigations with stannylated allyl glycine deriva-
tive 1 (Table 1).28 To gain direct access to the desired azido-
substituted styrene derivative, we subjected 1 to a Stille coup-
ling with o-azidoiodobenzene, evaluating several catalysts and
reaction conditions. In all cases, complex product mixtures
were obtained, resulting, for example, from a decomposition
of the azide. In addition, the formation of allyl glycine was
observed as a result of protodestannation of 1.29 By far the
best results were obtained employing a protocol from Baldwin
et al.,30 which uses an excess of CsF and catalytic amounts of
CuI and Pd(PPh3)4. Under these mild conditions, the expected
coupling product 3a could be obtained in almost 50% yield
(Table 1, entry 1). A slightly better result was obtained in the
coupling of o-iodoaniline (entry 2). The moderate yield in this
case was also caused by protodestannation of 1. We assumed
that under the reaction conditions CsF acts as a base, remov-
ing the proton from the rather acidic trifluoroacetamide. The
HF formed might be the reason for the protodestannation
32
and TMSN3 provided the desired azide 6a in 74% yield. But
33
even better results could be obtained with NaNO2/NaN3 in a
1 : 1 mixture of 0.5 N HCl and MeCN (to increase solubility of
the components) (Scheme 3).
An elegant protocol to convert aryl azides into the corres-
ponding nitrenes is their treatment with transition metal com-
plexes, e.g., of Rh34 or Ru.35 This approach is well suited for
the synthesis of 2-substituted indoles, but fails in the case of
2-unsubstituted indoles. Treatment of 6a with Rh2(OAc)4 pro-
vided only traces of the desired tryptophan 7a. However, upon
standing during storage in the laboratory, we observed that 6a
was cumulatively contaminated with 7a. Obviously, visible
light was able to “decompose” the azide. Therefore, we sub-
jected 6a to irradiation with a mercury vapour lamp, giving
rise to the desired tryptophan 7a in good yield (Scheme 3).36
Scheme 2 Tryptophan synthesis via Stille coupling/C–H insertion.
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2016

View Article Online
Organic & Biomolecular Chemistry
Paper
Although this procedure was especially developed for the
synthesis of tryptophans, it is of course not limited to this sub-
stance class. Via allylic alkylation also a series of other functio-
nalized vinyl stannanes can be obtained, such as the
corresponding α-hydroxy esters,37 malonates or protected
amines.26b They could all be converted into the corresponding
indole derivatives with comparable success (Table 3).
Table 3 Synthesis of functionalized indoles 10–12
Scheme 3 Photochemical tryptophan synthesis.
To suppress photochemical side reactions by the high-energy
irradiation we next investigated irradiation at 365 nm, using
an adjustable UV-LED lamp. Indeed, under these conditions
the yield could be further increased to 82%.
The optimized reaction conditions found application in the
synthesis of various protected and substituted tryptophan deriva-
tives (Table 2). Both Stille coupling protocols provided compar-
ably good results and also the diazotization/azide formation
delivered good to excellent yields. The yields of the photochemi-
cal C–H insertions were generally in the range of 65–80%. Only
the methoxy-substituted derivatives were found to be less
effective (entries 3 and 4). The application of o-iodonaphthyl-
amine allows the synthesis of benzotryptophans (entry 8).
Yields
Stannane
10
[%]
11
[%]
12
[%]
9a
9b
9c
10a
10b
10c
69
83
69
11a
11b
11c
60
89
69
12a
12b
12c
75
86
77
Table 2 Synthesis of substituted tryptophans
Entry Stannane PG
Method R1
R2
R3
Aniline Yield [%] Azide Yield [%] Tryptophan Yield [%]
1
2
3
4
5
6
7
8
2
2
2
2
2
1
1
1
Bz
Bz
Bz
Bz
A
A
A
A
A
B
B
B
H
H
H
H
H
H
H
H
H
H
OMe
H
H
H
Me
Cl
OMe
H
COOEt 5f
H
5b
5c
5d
5e
70
72
77
71
59
89
74
66
6b
6c
6d
6e
6f
3a
3b
3g
95
89
84
71a
87
87
92
91
7b
7c
7d
7e
7f
8a
8b
8g
78
66
56
34
67
75
81
71
Bz
TFA
TFA
TFA
4a
4b
4g
Me
H
−CHvCH−CHvCH−
Method A: Pd(PPh3)4 (5 mol%), CuI (10 mol%), CsF (2.0 equiv.), DMF, 45 °C, 18 h.; Method B: Pd(PPh3)4 (5 mol%), CuI (2.0 equiv.), LiCl (2.0
equiv.), DMF, 80 °C, 18 h. a (1) NaNO2 (1.6 equiv.), 15 s; (2) NaN3 (1.6 equiv.), 30 min.
This journal is © The Royal Society of Chemistry 2016
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
lation. A Schlenk tube was charged with [(allylPdCl)2] (37 mg,
0.10 mmol) and PPh3 (105 mg, 0.40 mmol), before THF (2 mL)
Conclusions
In conclusion, we could show that Stille couplings of stanny- was added and the solution was stirred for 10 min at room
lated amino acids with iodoanilines generate o-amino styrenes, temperature. 2-(Tributylstannyl)allyl ethyl carbonate (3.35 g,
which can easily be converted into the corresponding azides. 7.27 mmol) was added and the solution was added dropwise
Photochemical C–H insertion of an in situ generated nitrene to the Zn-enolate solution at −78 °C. The reaction mixture was
generates indoles and tryptophans in
a highly efficient slowly warmed to room temperature overnight and stirred for
manner. Applications of this protocol to the stereoselective 18 h. Subsequently, it was diluted with EtOAc (20 mL) before
synthesis of tryptophan-containing peptides are currently 1 M KHSO4 solution (3 mL) was added. The layers were separ-
under investigation.
ated and the aqueous phase was extracted twice with EtOAc.
The combined organic layers were dried over Na2SO4 and con-
centrated. The residue was purified by column chromato-
graphy (hexanes/EtOAc/NEt3 95 : 5 : 1), giving rise to 2 (3.69 g,
6.54 mmol, 90%) as a colorless viscous oil. Rf (2): 0.26
(hexanes/EtOAc 90 : 10). 1H NMR (400 MHz, CDCl3): δ = 0.85 (t,
Experimental
General experimental details
All air- or moisture-sensitive reactions were carried out in J = 7.3 Hz, 9 H), 0.94 (m, 6 H), 1.28 (m, 6 H), 1.42–1.56 (m, 15
dried glassware (>100 °C) under an atmosphere of argon. THF H), 2.60 (dd, J = 14.0, 9.1 Hz, 1 H), 2.92 (dd, J = 14.0, 4.9 Hz, 1
was distilled over Na/benzophenone prior to use. Dichloro- H), 4.58 (m, 1 H), 5.27 (dd, JSn = 59.6 Hz, J = 2.5 Hz, 1 H), 5.81
methane (DCM), MeCN and DMF (anhydrous) were purchased (dd, JSn = 128.5 Hz, J = 2.5 Hz, 1 H), 6.39 (d, J = 7.0 Hz, 1 H),
from Sigma-Aldrich. EtOAc and petroleum ether (PE) were dis- 7.42 (m, 2 H), 7.49 (m, 1 H), 7.77 (m, 2 H) ppm. 13C NMR
tilled prior to use. Reactions were monitored by analytical (100 MHz, CDCl3): δ = 9.7 (d, 1JSn = 333.3 Hz), 13.6, 27.3 (d, 2JSn
3
TLC, which was performed on silica gel on TLC PET-foils by = 57.9), 28.1, 29.0 (d, JSn = 19.8 Hz), 44.0, 52.9, 82.0, 127.0,
Sigma-Aldrich. Visualization was accomplished with UV-light 128.5, 128.7, 131.5, 134.1, 150.6, 166.8, 171.4 ppm. 119Sn NMR
(254 nm), KMnO4 solution or an iodine chamber. Rotary evap- (149.2 MHz, CDCl3): δ = –43.0 ppm. HRMS (CI) m/z calcd for
oration was conducted at 40 °C. The products were purified by C28H47NO3Sn [M]+: 565.2572. Found: 565.2577.
flash chromatography on silica gel columns (Macherey-Nagel
General procedures for Stille couplings
60, 0.063–0.2 mm) or by automated flash chromatography
(Grace Reveleris®, Teledyne Isco RediSep Rf silica cartridges). Method A. A dried Schlenk tube was charged with the organo-
Mixtures of EtOAc and hexanes were generally used as eluents. tin compound and the (substituted) o-iodoaniline in DMF
Melting points were determined with a melting point appar- (2 mL mmol−1). CsF (2.0 eq.), CuI (10 mol%) and Pd(PPh3)4
atus IA 9100 by Electrothermal and are uncorrected. 1H, 13C were added and the mixture was stirred at 45 °C. After reaching
and 119Sn spectra were recorded with a Bruker AV II 400 full conversion (TLC) EtOAc and H2O were added. Upon vigor-
[400 MHz (1H), 100 MHz (13C), 149 MHz (119Sn)] spectrometer ous shaking (in the Schlenk tube) a colorless precipitate
in CDCl3 (+0.01% Si(CH3)4) unless otherwise specified. NMR formed and the mixture was filtered through a pad of Celite®
spectra were evaluated using iNMR (Version 5.4.4). Chemical with EtOAc. The filtrate was dried over Na2SO4 and concen-
shifts are reported in ppm relative to Si(CH3)4 and CHCl3 was trated. The residue was purified by (automated) flash
used as the internal standard [δ(1H) = 7.26 ppm, δ(13C) = chromatography.
77.0 ppm]. High resolution mass spectra were recorded with a
Method B. An oven dried Schlenk tube was charged with
Finnigan MAT 95 spectrometer using the CI technique. Photo- LiCl (2.0 eq.) and heated with a heat gun under vacuum
chemical experiments were conducted with a UV-LED [UV-LED (<0.1 mbar). After cooling to r.t. CuI (2.0 eq.), (substituted)
SMART by Opsytec Dr Gröbel GmbH (max. irradiance >25 o-iodoaniline (1.0 eq.) and Pd(PPh3)4 (5 mol%) were added and
W cm−2, λ = 365 nm, beam profile: standard, distance from the flask was evacuated and refilled with Ar three times. DMF
reaction mixture: ca. 5 cm)].
tert-Butyl 2-benzoylamino-4-tributylstannyl-pent-4-enoate with Ar, and the organotin compound (1.2 eq.) was added and
(10 mL mmol−1), which was previously degassed by bubbling
(2). In a 250 mL Schlenk flask HMDS (5.90 mL 4.52 g, the mixture was heated to 80 °C for 18 h. After reaching full
28.0 mmol) was dissolved in THF (20 mL) and a 1.6 M n-BuLi conversion (TLC) the mixture was diluted with EtOAc and
solution (in hexanes) (15.6 mL, 25.0 mmol) was added drop- 5 mL of 1 M KF-solution were added. Upon vigorous shaking
wise at −78 °C. The solution was stirred for 10 min at room (in the Schlenk tube) a colorless precipitate formed and the
temperature and then cooled again to −78 °C. In another mixture was filtered through a pad of Celite® with EtOAc. The
100 mL Schlenk flask ZnCl2 (1.64 g, 12.0 mmol) was carefully layers were separated and the aqueous layer was extracted
dried in vacuum (<0.1 mbar) with a heat gun. tert-Butyl hippu- twice with EtOAc. The combined organic layers were dried over
rate (2.35 g, 10.0 mmol) was added and the flask was evacu- Na2SO4, filtered and concentrated. The residue was purified by
ated and refilled with Ar three times. THF (20 mL) was added, (automated) flash chromatography.
the solution was cooled to −78 °C and transferred to the cold
tert-Butyl
4-(2-aminophenyl)-2-(2,2,2-trifluoroacetamido)
LHMDS solution via cannula. The resulting yellow solution pent-4-enoate (4a). According to method B, 2-iodoaniline
was stirred for 30 min at −78 °C to ensure complete transmeta- (55.9 mg, 0.250 mmol) was reacted with 126 (172 mg,
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2016

View Article Online
Organic & Biomolecular Chemistry
Paper
0.300 mmol), LiCl (21 mg, 0.500 mmol), CuI (95 mg, 1 H), 5.29 (m, 1 H), 6.68 (m, 1 H), 6.71 (ddd, J = 7.2, 7.2, 1.2
0.500 mmol) and Pd(PPh3)4 (14 mg, 12.5 µmol). Automated Hz, 1 H), 6.98 (dd, J = 7.5, 1.6 Hz, 1 H), 7.07 (ddd, J = 9.0, 7.5,
flash chromatography (hexanes/EtOAc 100 : 0 to 80 : 20) 1.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.0, 35.6,
afforded 4a (80 mg, 0.223 mmol, 89%) of 4a as a colorless 50.5, 61.5, 115.5, 116.6, 118.0, 126.8, 128.4, 128.8, 143.6, 144.0,
1
resin. Rf (4a): 0.37 (hexanes/EtOAc 80 : 20). H NMR (400 MHz, 169.0 ppm. HRMS (CI) m/z calcd for C16H22NO4 [M + H]+:
CDCl3): δ = 1.42 (s, 9 H), 2.95 (ddd, J = 14.1, 5.3, 1.4 Hz, 1 H), 292.1543. Found: 292.1581.
3.08 (ddd, J = 14.3, 5.3, 1.0 Hz, 1 H), 3.83 (bs, 2 H), 4.58 (m, 1
2-[2-(2-Aminophenyl)allyl]isoindoline-1,3-dione
(10c).
H), 5.22 (d, J = 1.8 Hz, 1 H), 5.34 (m, 1 H), 6.70 (dd, J = 8.0, 0.9 According to method B 2-iodoaniline (26 mg, 0.119 mmol) was
Hz, 1 H), 6.75 (ddd, J = 7.5, 7.5, 1.1 Hz, 1 H), 6.96 (dd, J = 7.6, reacted with 1726b (68 mg, 0.143 mmol), LiCl (10 mg,
1.4 Hz, 1 H), 7.07 (m, 1 H), 7.43 (d, J = 7.4 Hz, 1 H) ppm. 13C 0.238 mmol), CuI (45 mg, 0.238 mmol) and Pd(PPh3)4 (6.9 mg,
NMR (100 MHz, CDCl3): δ = 27.9, 38.7, 52.6, 83.2, 115.5 (q, JF = 6 µmol). Flash chromatography (hexanes/EtOAc 80 : 20) yielded
296.4 Hz), 116.3, 119.0, 119.6, 127.3, 128.5, 128.6, 142.2, 142.5, 10c (23 mg, 82.6 µmol, 69%) as a brown solid, m.p. 94–95 °C.
146.4 (q, JF = 37.5 Hz), 168.9 ppm. HRMS (CI) m/z calcd for Rf (10c): 0.29 (hexanes/EtOAc 70 : 30).1H NMR (400 MHz,
C17H21F3N2O3 [M]+: 358.1499. Found: 358.1504.
CDCl3): δ = 4.13 (bs, 2 H), 4.52 (m, 2 H), 5.18 (m, 2 H),
tert-Butyl 4-(2-aminophenyl)-2-benzoylamino-pent-4-enoate 6.68–6.74 (m, 2 H), 7.07–7.12 (m, 2 H), 7.74 (m, 2 H), 7.88 (m,
(5a). According to method A, 2-iodoaniline (418 mg, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 41.4, 114.6, 115.3,
1.91 mmol) was reacted with 2 (1.08 g, 1.91 mmol), CsF 117.8, 123.4, 124.8, 128.9, 129.3, 132.0, 134.1, 142.0, 144.0,
(580 mg, 3.82 mmol), CuI (36 mg, 0.191 mmol) and Pd(PPh3)4 168.1 ppm. HRMS (CI) m/z calcd for C17H14N2O2 [M]+:
(44 mg, 38 µmol). The reaction was worked up after 2 h. Auto- 278.1050. Found: 278.1080.
mated flash chromatography (hexanes/EtOAc 100 : 0 to 70 : 30)
afforded 5a (628 mg, 1.66 mmol, 87%) as a brown solid, m.p.
General procedure for the diazotation/azidation of anilines33
87–88 °C. Rf (5a): 0.27 (hexanes/EtOAc 70 : 30). 1H NMR The aniline derivative was dissolved in a mixture of MeCN and
(400 MHz, CDCl3): δ = 1.46 (s, 9 H), 2.95 (dd, J = 14.0, 5.4 Hz, 0.5 M HCl (1 : 1, 0.05 M). Subsequently, NaNO2 (1.6 equiv.) was
1 H), 3.16 (ddd, J = 14.0, 5.1, 1.0 Hz, 1 H), 3.88 (bs, 2 H), 4.84 added at 0 °C. After stirring for 5 min NaN3 (1.6 equiv.) was
(ddd, J = 7.5, 5.2, 5.2, Hz, 1 H), 5.23 (d, J = 1.9 Hz, 1 H), 5.38 added. After stirring for another 5 min, saturated NaHCO3
(m, 1 H), 6.64 (dd, J = 8.0, 1.1 Hz, 1 H), 6.72 (ddd, J = 7.5, 7.5, solution was added and the aqueous phase was extracted three
1.1 Hz, 1 H), 6.77 (d, J = 7.5 Hz, 1 H), 6.99–7.04 (m, 2 H), 7.32 times with dichloromethane. The combined organic layers
(m, 2 H), 7.41–7.48 (m, 3 H) ppm. 13C NMR (100 MHz, CDCl3): were dried over Na2SO4, concentrated in vacuo and the residue
δ = 28.1, 39.5, 52.9, 82.3, 116.0, 118.6, 119.2, 126.9, 127.7, was purified by (automated) flash chromatography.
128.2, 128.3, 128.7, 131.3, 133.9, 142.7, 143.0, 166.6,
170.8 ppm. HRMS (CI) m/z calcd for C22H26N2O3 [M]+: pent-4-enoate (3a). According to the general procedure for di-
366.1938. Found: 366.1938. azotation/azidation 4a (74 mg, 0.206 mmol) was reacted with
tert-Butyl
4-(2-azidophenyl)-2-(2,2,2-trifluoroacetamido)
tert-Butyl 4-(2-aminophenyl)-2-hydroxypent-4-enoate (10a). NaNO2 (23 mg, 0.330 mmol) and NaN3 (22 mg, 0.330 mmol).
According to method B 2-iodoaniline (32.4 mg, 0.148 mmol) Flash chromatography (hexanes/EtOAc 90 : 10) afforded azide
was reacted with 1536 (82 mg, 0.178 mmol), LiCl (13 mg, 3a (69 mg, 0.179 mmol, 87%) as a colorless solid, m.
0.296 mmol), CuI (56.4 mg, 0.296 mmol) and Pd(PPh3)4 (9 mg, p. 55–56 °C. Rf (3a): 0.53 (hexanes/EtOAC 80 : 20). 1H NMR
7.4 µmol). Automated flash chromatography (hexanes/EtOAc (400 MHz, CDCl3): δ = 1.39 (s, 9 H), 2.94 (ddd, J = 14.5, 6.2, 0.6
100 : 0 to 80 : 20) yielded 10a (27 mg, 0.103 mmol, 69%) as a Hz, 1 H), 3.27 (ddd, J = 14.5, 5.2, 0.8 Hz, 1 H), 4.47 (m, 1 H),
colorless oil. Rf (10a): 0.26 (hexanes/EtOAc 70 : 30). 1H NMR 5.15 (d, J = 1.5 Hz, 1 H), 5.26 (m, 1 H), 6.79 (d, J = 6.8 Hz, 1 H),
(400 MHz, CDCl3): δ = 1.44 (s, 9 H), 2.64 (ddd, J = 14.3, 8.5, 0.8 7.09–7.16 (m, 3 H), 7.34 (ddd, J = 8.1, 6.8, 2.2 Hz, 1 H) ppm.
Hz, 1 H), 2.88 (m, 1 H), 3.10 (d, J = 5.8 Hz, 1 H), 3.92 (bs, 2 H), 13C NMR (100 MHz, CDCl3): δ = 27.8, 38.1, 52.2, 83.2, 115.6 (d,
4.08 (m, 1 H), 5.21 (m, 1 H), 5.39 (m, 1 H), 6.70 (dd, J = 8.0, 0.9 JF = 292.5 Hz), 118.4, 120.6, 125.0, 129.3, 130.5, 132.9, 137.1,
Hz, 1 H), 6.74 (m, 1 H), 7.02 (dd, J = 7.6, 1.5 Hz, 1 H), 7.07 141.8, 156.3 (d, JF = 37.4 Hz), 169.0 ppm. HRMS (CI) m/z calcd
(ddd, J = 7.9, 7.3, 1.6 Hz, 1 H) ppm. 13C NMR (100 MHz, for C17H19F3N2O3 [M − N2]+: 356.1342. Found: 356.1336.
CDCl3): δ = 28.0, 42.6, 69.1, 82.6, 110.0, 115.8, 118.3, 118.4,
127.7, 128.2, 128.7, 142.8, 143.5, 173.8 ppm. HRMS (CI) m/z (6a). According to the general procedure for diazotation/azida-
calcd for C15H21NO3 [M]+: 263.1516. Found: 263.1510.
tion 5a (113 mg, 0.270 mmol) was reacted with NaNO2 (33 mg,
tert-Butyl 4-(2-azidophenyl)-2-benzoylamino-pent-4-enoate
Diethyl 2-[2-(2-aminophenyl)allyl]malonate (10b). According 0.475 mmol) and NaN3 (31 mg, 0.475 mmol). Automated flash
to method B 2-iodoaniline (130 mg, 0.582 mmol) was reacted chromatography (hexanes/EtOAc 100 : 0, 80 : 20) afforded azide
with 1626b (348 mg, 0.711 mmol), LiCl (50 mg, 1.19 mmol), 6a (107 mg, 0.256 mmol, 95%) as a yellow resin. Rf (6a): 0.21
CuI (227 mg, 1.19 mmol) and Pd(PPh3)4 (31 mg, 27 µmol). (hexanes/EtOAc 80 : 20). 1H NMR (400 MHz, CDCl3): δ = 1.41 (s,
Automated flash chromatography (hexanes/EtOAc 100 : 0, 9 H), 2.98 (ddd, J = 14.4, 6.2, 0.8 Hz, 1 H), 3.31 (ddd, J = 14.4,
80 : 20) afforded 10b (117 mg, 0.402 mmol, 69%) as an orange 5.3, 1.0, Hz, 1 H), 4.71 (ddd, J = 7.6, 6.2, 5.3 Hz, 1 H), 5.12 (d,
1
oil. Rf (10b): 0.23 (hexanes/EtOAc 80 : 20). H NMR (400 MHz, J = 1.7 Hz, 1 H), 5.29 (m, 1 H), 6.52 (d, J = 7.6 Hz, 1 H), 7.05
CDCl3): δ = 1.25 (t, J = 7.1 Hz, 6 H), 2.98 (m, 2 H), 3.52 (t, J = (dd, J = 8.0, 1.2 Hz, 1 H), 7.09 (ddd, J = 7.5, 7.5, 1.2 Hz, 1 H),
7.7 Hz, 1 H), 3.86 (bs, 2 H), 4.17 (q, J = 7.1 Hz, 4 H), 5.14 (m, 7.20 (dd, J = 7.5, 1.6 Hz, 1 H), 7.27 (ddd, J = 8.0, 7.6, 1.6 Hz,
This journal is © The Royal Society of Chemistry 2016
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
1 H), 7.37 (m, 2 H), 7.47 (m, 1 H), 7.57 (m, 2 H) ppm. 13C NMR The solvent was removed in vacuo and the residue was purified
(100 MHz, CDCl3): δ = 28.0, 38.9, 52.3, 82.2, 118.4, 120.0, by (automated) flash chromatography.
124.9, 126.8, 128.4, 128.9, 130.6, 131.4, 133.7, 134.0, 137.1,
142.9, 166.4, 170.8 ppm. HRMS (CI) m/z calcd for C22H26N4O3 general procedure for photocylization azide 6a (41 mg,
[M + 2H]+: 394.1999. Found: 394.2002.
0.104 mmol) was irradiated for 9.5 h. Automated flash
tert-Butyl (N-benzoyl)-tryptophanate (7a). According to the
tert-Butyl 4-(2-azidophenyl)-2-hydroxypent-4-enoate (11a). chromatography (hexanes/EtOAc 100 : 0 to 70 : 30) afforded
According to the general procedure for diazotation/azidation tryptophan 7a (31 mg, 85.1 µmol, 82%) as a colorless solid,
10a (26 mg, 98.7 µmol) was reacted with NaNO2 (11 mg, m.p. 125–126 °C. Rf (7a): 0.22 (hexanes/EtOAc 70 : 30). 1H NMR
0.158 mmol) and NaN3 (10 mg, 0.158 mmol). Flash chromato- (400 MHz, CDCl3): δ = 1.41 (s, 9 H), 3.39 (dd, J = 14.9, 5.2 Hz,
graphy (hexanes/EtOAc 80 : 20) afforded azide 11a (17 mg, 1 H), 3.45 (dd, J = 14.9, 5.6 Hz, 1 H), 5.06 (ddd, J = 7.6, 5.4,
58.8 µmol, 60%) as a colorless resin. Rf (11a): 0.47 (hexanes/ 5.4 Hz, 1 H), 6.72 (d, J = 7.6 Hz, 1 H), 7.03–7.08 (m, 2 H), 7.17
EtOAc 90 : 10). 1H NMR (400 MHz, CDCl3): δ = 1.43 (s, 9 H), (m, 1 H), 7.33–7.39 (m, 3 H), 7.47 (m, 1 H), 7.61 (d, J = 7.9 Hz,
2.74 (ddd, J = 14.4, 7.8, 0.7 Hz, 1 H), 2.75 (d, J = 5.9 Hz, 1 H), 1 H), 7.69 (m, 2 H), 8.25 (m, 1 H) ppm. 13C NMR (100 MHz,
3.06 (dd, J = 14.5, 4.3 Hz, 1 H), 4.01 (ddd, J = 7.8, 5.9, 4.4 Hz, CDCl3): δ = 27.6, 28.0, 53.9, 82.3, 110.4, 111.1, 119.0, 119.5,
1 H), 5.12 (d, J = 1.2 Hz, 1 H), 5.31 (m, 1 H), 7.11 (ddd, J = 7.5, 122.1, 122.7, 127.0, 127.9, 128.5, 131.5, 134.1, 136.0, 166.9,
7.5, 1.1 Hz, 1 H), 7.16 (dd, J = 8.0, 0.8 Hz, 1 H), 7.22 (dd, J = 171.1 ppm. HRMS (CI) m/z calcd for C22H24N2O3 [M]+:
7.6, 1.5 Hz, 1 H), 7.33 (ddd, J = 8.0, 8.0, 1.6 Hz, 1 H) ppm. 13C 364.1781. Found: 364.1788.
NMR (100 MHz, CDCl3): δ = 28.0, 41.7, 69.2, 82.5, 118.3, 119.1,
tert-Butyl (N-trifluoroacetyl)-tryptophanate (8a). According
124.8, 128.8, 130.8, 133.9, 137.0, 143.1, 173.7 ppm. HRMS (CI) to the general procedure for photocylization azide 3a (79 mg,
m/z calcd for C15H19NO3 [M
−
N2]+: 261.1359. Found: 0.206 mmol) was irradiated for 12 h. Automated flash
261.1366.
chromatography (hexanes/EtOAc 100 : 0, 80 : 20) afforded
Diethyl 2-[2-(2-azidophenyl)allyl]malonate (11b). According tryptophan 7a (55 mg, 0.154 mmol, 75%) as an off-white solid,
to the general procedure for diazotation/azidation 10a m.p. 130–132 °C. Rf (8a): 0.26 (hexanes/EtOAc 80 : 20). Small
1
(107 mg, (0.367 mmol) was reacted with NaNO2 (41 mg, amounts of azide 3a (6 mg, 16 µmol, 8%) were recovered. H
0.588 mmol) and NaN3 (38 mg, 0.588 mmol). Automated flash NMR (400 MHz, CDCl3): δ = 1.40 (s, 9 H), 3.39 (m, 2 H), 4.83
chromatography (hexanes/EtOAc 100 : 0 to 90 : 10) afforded (m, 1 H), 6.92 (d, J = 6.5 Hz, 1 H), 7.00 (d, J = 2.0 Hz, 1 H), 7.15
azide 11b (104 mg, 0.328 mmol, 89%) as a colorless oil. Rf (dd, J = 7.2, 7.2 Hz, 1 H), 7.23 (dd, J = 7.2, 7.2 Hz, 1 H), 7.36 (d,
(11b): 0.25 (hexanes/EtOAc 90 : 10). 1H NMR (400 MHz, CDCl3): J = 8.1 Hz, 1 H), 7.58 (d, J = 7.9 Hz, 1 H), 8.19 (bs, 1 H) ppm.
δ = 1.24 (t, J = 7.1 Hz, 6 H), 3.08 (m, 2 H), 3.35 (t, J = 7.5 Hz, 1 H), 13C NMR (100 MHz, CDCl3): δ = 27.1, 27.9, 53.9, 83.4, 109.3,
4.15 (q, J = 7.1 Hz, 4 H), 5.03 (m, 1 H), 5.25 (m, 1 H), 7.07–7.16 111.3, 115.6 (d, JF = 287.8 Hz), 118.8, 119.8, 122.4, 122.8, 127.5,
(m, 3 H), 7.32 (ddd, J = 8.0, 7.1, 1.9 Hz, 1 H) ppm. 13C NMR 136.1, 156.7 (d, JF = 37.4 Hz), 169.4 ppm. HRMS (CI) m/z calcd
(100 MHz, CDCl3): δ = 14.0, 35.8, 50.9, 61.4, 118.0, 118.3, for C17H19F3N2O3 [M]+: 356.1342. Found: 356.1346.
124.7, 128.9, 130.8, 133.2, 137.1, 144.0, 168.8 ppm. HRMS (CI)
tert-Butyl
2-hydroxy-3-(1H-indol-3-yl)propanoate
(12a).
m/z calcd for C16H19NO4 [M
−
N2]+: 289.1309. Found: According to the general procedure for photocylization azide
289.1308.
11a (14 mg, 48.4 µmol) was irradiated for 7.5 h. Flash chrom-
2-[2-(2-Azidophenyl)allyl]isoindoline-1,3-dione
(11c). atography (hexanes/EtOAc 80 : 20) afforded indole 12a (9.5 mg,
According to the general procedure for diazotation/azidation 36.4 µmol, 75%) as a colorless resin. Rf (12a): 0.21 (hexanes/
10a (20 mg, 71.9 µmol) was reacted with NaNO2 (7.9 mg, EtOAc 80 : 20). 1H NMR (400 MHz, CDCl3): δ = 1.38 (s, 9 H),
0.115 mmol) and NaN3 (7.5 mg, 0.115 mmol). Column chrom- 2.93 (d, J = 3.6 Hz, 1 H), 3.14 (dd, J = 14.9, 6.2 Hz, 1 H), 3.26
atography (hexanes/EtOAc 90 : 10) afforded azide 11c (15 mg, (dd, J = 14.9, 4.2 Hz, 1 H), 4.41 (m, 1 H), 7.11–7.21 (m, 3 H),
49 µmol, 69%) as a colorless solid, m.p. 88–89 °C. Rf (11c): 7.34 (d, J = 8.0 Hz, 1 H), 7.66 (d, J = 7.8 Hz, 1 H), 8.05 (bs, 1 H)
0.23 (hexanes/EtOAc 90 : 10). 1H NMR (400 MHz, CDCl3): δ = ppm. 13C NMR (100 MHz, CDCl3): δ = 27.9, 30.0, 71.0, 82.4,
4.67 (s, 2 H), 5.17 (d, J = 0.7 Hz, 1 H), 5.33 (d, J = 0.7 Hz, 1 H), 110.8, 111.0, 119.1, 119.3, 122.0, 122.9, 127.8, 136.0,
7.05 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H), 7.15 (dd, J = 8.0, 0.6 Hz, 1 173.7 ppm. HRMS (CI) m/z calcd for C15H19NO3 [M]+:
H), 7.18 (dd, J = 7.6, 1.5 Hz, 1 H), 7.31 (ddd, J = 8.0, 8.0, 1.6 Hz, 261.1359. Found: 261.1361.
1 H), 7.70 (m, 2 H), 7.82 (m, 2 H) ppm. 13C NMR (100 MHz,
Diethyl 2-[(1H-indol-3-yl)methyl]malonate (12b). According
CDCl3): δ = 42.4, 117.2, 118.2, 123.3, 124.7, 129.2, 130.7, 131.7, to the general procedure for photocylization azide 11b (75 mg,
132.0, 133.9, 137.6, 141.8, 167.8 ppm. HRMS (CI) m/z calcd for 0.236 mmol) was irradiated for 12 h. Flash chromatography
C17H11N2O2 [M − N2 − H]+: 275.0815. Found: 275.0833.
(hexanes/EtOAc 80 : 20) afforded indole 12b (59 mg,
0.204 mmol, 86%) as an off-white solid, m.p.: 62–64 °C). Rf
(12b): 0.18 (hexanes/EtOAc 80 : 20). 1H NMR (400 MHz, CDCl3):
δ = 1.22 (t, J = 7.1 Hz, 6 H), 3.42 (d, J = 8.1 Hz, 2 H), 3.80 (t, J =
General procedure for the photocyclization of 2-azidostyrenes
The corresponding azide was dissolved in MeCN (10 mL mmol−1
)
in a round bottom flask, which was then wrapped with 7.6 Hz, 1 H), 4.17 (m, 4 H), 7.02 (d, J = 1.2 Hz, 1 H), 7.14 (td,
aluminium foil and irradiated with an UV-LED lamp at 25% J = 7.1, 1.0 Hz, 1 H), 7.20 (m, 1 H), 7.34 (d, J = 8.0 Hz, 1 H),
(6.25 W cm−2) of the maximum irradiance for the specified 7.63 (d, J = 7.9 Hz, 1 H), 8.16 (s, 1 H) ppm. 13C NMR (100 MHz,
time at room temperature under laboratory atmosphere. CDCl3): δ = 13.9, 24.5, 53.0, 61.4, 111.1, 112.0, 118.5, 119.3,
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2016

View Article Online
Organic & Biomolecular Chemistry
Paper
122.0, 122.5, 127.0, 136.1, 169.3 ppm. HRMS (CI) m/z calcd for
C16H19NO4 [M]+: 289.1309. Found: 289.1313.
Chem. Rev., 2005, 105, 2873–2920; (e) G. R. Humphrey and
J. T. Kuethe, Chem. Rev., 2006, 106, 2875–2911; (f) S. Cacchi
and G. Fabrizi, Chem. Rev., 2011, 111, 2215–2283;
(g) D. F. Taber and P. K. Tirunahari, Tetrahedron, 2011, 67,
7195–7210; (h) M. Inman and C. J. Moody, Chem. Sci., 2013,
4, 29–41; (i) G. Bartoli, R. Dalpozzo and M. Nardi, Chem.
Soc. Rev., 2014, 43, 4728–4750.
8 Ausgewählte Reviews: (a) K. Fujita and R. Yamaguchi,
Synlett, 2005, 560–571; (b) S. Agarwal, S. Caemmerer,
S. Filali, W. Froehner, J. Knoell, M. P. Krahl, K. R. Reddy
and H.-J. Knoelker, Curr. Org. Chem., 2005, 9, 1601–1614;
(c) K. Krüger, A. Tillack and M. Beller, Adv. Synth. Catal.,
2008, 350, 2153–2167; (d) J. Barluenga, F. Rodriguez and
F. J. Fananas, Chem. – Asian J., 2009, 4, 1036–1048;
(e) M. Bandini and A. Eichholzer, Angew. Chem., 2009, 121,
9786–9824, (Angew. Chem., Int. Ed., 2009, 48, 9608–9644);
(f) J. J. Song, J. T. Reeves, D. R. Fandrick, Z. Tan, N. K. Yee
and C. H. Senanayake, ARKIVOC, 2010, (Part 1), 390–449;
(g) S. Cacchi, G. Fabrizi and A. Goggiamani, Org. Biomol.
Chem., 2011, 9, 641–652; (h) R. Vicente, Org. Biomol. Chem.,
2011, 9, 6469–6480; (i) Z. Shi and F. Glorius, Angew. Chem.,
2012, 124, 9354–9356, (Angew. Chem., Int. Ed., 2012, 51,
9220–9222).
2-[(1H-Indol-3-yl)methyl]isoindoline-1,3-dione (20). Accord-
ing to the general procedure for photocylizations azide 11c
(14 mg, 46.0 µmol) was irradiated for 6 h. Automated flash
chromatography (hexanes/EtOAc 100 : 0 to 80 : 20) afforded
indole 12c (9.8 mg, 35.5 µmol, 77%) as a colorless solid, m.p.
180–182 °C. Rf (12c): 0.15 (hexanes/EtOAc 80 : 20). 1H NMR
(400 MHz, CDCl3): δ = 5.03 (s, 2 H), 7.14–7.21 (m, 2 H), 7.34
(m, 1 H), 7.40 (d, J = 2.5 Hz, 1 H), 7.65 (m, 2 H), 7.80 (m, 2 H),
7.94 (m, 1 H), 8.14 (bs, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 32.6, 111.0, 111.4, 119.4, 120.0, 122.3, 123.1, 125.1, 126.5,
132.2, 133.8, 135.9, 168.2 ppm. HRMS (CI) m/z calcd for
C17H13O2N2 [M + H]+: 277.0972. Found: 277.0977.
Acknowledgements
Financial support from the Deutsche Forschungsgemeinschaft
was gratefully acknowledged.
References
9 (a) R. C. Larock and E. K. Yum, J. Am. Chem. Soc., 1991,
113, 6689–6690; (b) R. C. Larock, E. K. Yum and
M. D. Refvik, J. Org. Chem., 1998, 63, 7652–7662.
1 (a) W. Gul and M. T. Hamann, Life Sci., 2005, 78, 442–453;
(b) C. V. Galliford and K. A. Scheidt, Angew. Chem., 2007,
119, 8902–8912, (Angew. Chem., Int. Ed., 2007, 46, 8748– 10 (a) L. Ackermann, L. T. Kaspar and C. J. Gschrei, Chem.
8758);
(c)
A.
J.
Kochanowska-Karamyan
and
Commun., 2004, 2824–2825; (b) L. Ackermann,
R. Sandmann, A. Villar and L. T. Kaspar, Tetrahedron, 2008,
64, 769–777; (c) D. Gao and T. G. Back, Chem. – Eur. J.,
2012, 18, 14828–14840.
M. T. Harmann, Chem. Rev., 2010, 110, 4489–4497;
(d) S. M. Bronner, G. Y. J. Im and N. K. Garg, in Heterocycles
in Natural Product Synthesis, ed. K. C. Majumdar and
S. K. Chattopadhyay, Wiley-VCH, Weinheim, 2011, pp. 11 (a) L. S. Hegedus, G. F. Allen, J. J. Bozell and
221–265.
E. L. Waterman, J. Am. Chem. Soc., 1978, 100, 5800–5807;
(b) L. S. Hegedus, P. M. Winton and S. Varaprath, J. Org.
Chem., 1981, 46, 2215–2221; (c) P. J. Harrington and
L. S. Hegedus, J. Org. Chem., 1984, 49, 2657–2662.
2 D. Jakubczyk, J. Z. Cheng and S. E. O’Connor, Nat. Prod.
Rep., 2014, 31, 1328–1338.
3 (a) C. D. Murphy, Nat. Prod. Rep., 2006, 23, 147–152;
(b) T. Rauhut and E. Glawischnig, Phytochemistry, 2009, 70, 12 (a) S. Cacchi, G. Fabrizi and A. Goggiamani, Adv. Synth.
1638–1644; (c) M. S. Pedras, E. E. Yaya and E. Glawischnig,
Nat. Prod. Rep., 2011, 28, 1381–1405; (d) W. Xu, D. J. Gavia
and Y. Tang, Nat. Prod. Rep., 2014, 31, 1474–1487.
4 N. Fusetani and S. Matsunaga, Chem. Soc. Rev., 1963, 93,
1793–1808.
Catal., 2006, 348, 1301–1305; (b) B. M. Trost and
A. McClory, Angew. Chem., 2007, 119, 2120–2123, (Angew.
Chem., Int. Ed., 2007, 46, 2074–2077); (c) Z. Shi, C. Zhang,
S. Li, D. Pan, S. Ding, Y. Cui and N. Jiao, Angew. Chem.,
2009, 121, 4642–4646, (Angew. Chem., Int. Ed., 2009, 48,
4572–4576).
5 (a) B. Kunze, R. Jansen, F. Sasse, G. Höfle and
H. Reichenbach, J. Antibiot., 1995, 48, 1262–1266; 13 (a) C. Ma, X. Liu, S. Yu, S. Zhao and J. M. Cook, Tetrahedron
(b) R. Jansen, B. Kunze, H. Reichenbach and G. Höfle,
Liebigs Ann., 1996, 285–290.
6 (a) W. D. Clark, T. Corbett, F. Valeriote and P. Crews, J. Am.
Chem. Soc., 1997, 119, 9285–9286; (b) B. K. Rubio,
S. J. Robinson, C. E. Avalos, F. A. Valeriote, N. J. de Voogd
Lett., 1999, 40, 657–660; (b) C. Ma, X. Liu, X. Li, J. Flippen-
Anderson, S. Yu and J. M. Cook, J. Org. Chem., 2001, 66,
4525–4542; (c) H. Zhou, X. Liao and J. M. Cook, Org. Lett.,
2004, 6, 249–252; (d) J. Ma, W. Yin, H. Zhou and
J. M. Cook, Org. Lett., 2007, 9, 3491–3494.
and P. Crews, J. Nat. Prod., 2008, 71, 1475–1478; 14 (a) Y. Jia and J. Zhu, Synlett, 2005, 2469–2472;
(c) J. M. Garcia, S. S. Curzon, K. R. Watts and
J. P. Konopelski, Org. Lett., 2012, 14, 2054–2057.
7 (a) R. J. Sundberg, The Chemistry of Indoles, Academic
Press, New York, 1970; (b) R. J. Sundberg, Indoles, Academic
Press, London, 1996; (c) G. W. Gribble, J. Chem. Soc., Perkin
Trans. 1, 2000, 1045–1075; (d) S. Cacchi and G. Fabrizi,
(b) P. S. Baran, C. A. Guerrero, N. B. Ambhaikar and
B. D. Hafensteiner, Angew. Chem., 2005, 117, 3960–3963,
(Angew. Chem., Int. Ed., 2005, 44, 606–609); (c) P. S. Baran,
B. D. Hafensteiner, N. B. Ambhaikar, C. A. Guerrero and
J. D. Gallagher, J. Am. Chem. Soc., 2006, 128, 8678–8693;
(d) Y. Jia and J. Zhu, J. Org. Chem., 2006, 71, 7826–7834;
This journal is © The Royal Society of Chemistry 2016
Org. Biomol. Chem.

View Article Online
Paper
Organic & Biomolecular Chemistry
(e) J. Michaux, P. Retailleau and J.-M. Campagne, Synlett,
2008, 1532–1536.
(b) U. Kazmaier and F. L. Zumpe, Angew. Chem., 2000, 112,
805–807, (Angew. Chem., Int. Ed., 2000, 39, 802–804);
(c) U. Kazmaier and T. Lindner, Angew. Chem., 2005, 117,
3368–3371, (Angew. Chem., Int. Ed., 2005, 44, 3303–3306);
(d) U. Kazmaier and D. Stolz, Angew. Chem., 2006, 118,
3143–3146, (Angew. Chem., Int. Ed., 2006, 45, 3072–3075);
(e) U. Kazmaier, D. Stolz, K. Krämer and F. Zumpe, Chem. –
Eur. J., 2008, 14, 1322–1329.
15 C. A. Dacko, N. G. Akhmedov and B. C. G. Söderberg, Tetra-
hedron: Asymmetry, 2008, 19, 2775–2783.
16 (a) M. Gander-Coquoz and D. Seebach, Helv. Chim. Acta,
1988, 71, 224–236; (b) L. Zhang and J. M. Finn, J. Org.
Chem., 1995, 60, 5719–5720; (c) T. Gan, R. Liu, P. Yu,
S. Zhao and J. M. Cook, J. Org. Chem., 1997, 62, 9298–9304;
(d) H. D. Jain, C. Zhang, S. Zhou, H. Zhou, J. Ma, X. Liu, 26 (a) U. Kazmaier, D. Schauß, S. Raddatz and M. Pohlman,
X. Liao, A. M. Deveau, C. M. Dieckhaus, M. A. Johnson,
K. S. Smith, T. L. Macdonald, H. Kakeya, H. Osada and
J. M. Cook, Bioorg. Med. Chem., 2008, 16, 4626–4651;
Chem. – Eur. J., 2001, 7, 456–464; (b) C. Bukovec,
A. O. Wesquet and U. Kazmaier, Eur. J. Org. Chem., 2011,
1047–1056.
(e) M. Okada, I. Sato, S. J. Cho, Y. Suzuki, M. Ojika, 27 (a) J. Deska and U. Kazmaier, Angew. Chem., 2007, 119,
D. Dubnau and Y. Sakagami, Biosci., Biotechnol., Biochem.,
2004, 68, 2374–2387; (f) P. Zhang, R. Liu and J. M. Cook,
Tetrahedron Lett., 1995, 36, 9133–9136; (g) S. Bittner,
4654–4657, (Angew. Chem., Int. Ed., 2007, 46, 4570–4573);
(b) J. Deska and U. Kazmaier, Chem. – Eur. J., 2007, 13,
6204–6211.
R. Scherzer and E. Harlev, Amino Acids, 2007, 33, 19–42; 28 U. Kazmaier, D. Schauß, M. Pohlman and S. Raddatz, Syn-
(h) C. R. Edwankar, R. V. Edwankar, O. A. Namjoshi,
X. Liao and J. M. Cook, J. Org. Chem., 2013, 78, 6471–6487.
17 (a) U. Schmidt and J. Wild, Liebigs Ann. Chem., 1985, 1882–
1894; (b) Y. Yokoyama, T. Matsumoto and Y. Murakami, J.
thesis, 2000, 914–916.
29 (a) G. T. Crisp and P. T. Glink, Tetrahedron Lett., 1992, 33,
4649–4652; (b) G. T. Crisp and P. T. Glink, Tetrahedron Lett.,
1994, 50, 3213–3234.
Org. Chem., 1995, 60, 1486–1487; (c) Y. Yokoyama, 30 (a) S. P. H. Mee, V. Lee and J. E. Baldwin, Angew. Chem.,
H. Hikawa, M. Mitsuhashi, A. Uyama, Y. Hiroki and
Y. Murakami, Eur. J. Org. Chem., 2004, 1244–1253.
18 M. Tanaka, H. Hikawa and Y. Yokoyama, Tetrahedron, 2011,
67, 5897–5901.
2004, 116, 1152–1156, (Angew. Chem., Int. Ed., 2004, 43,
1132–1136); (b) S. P. H. Mee, V. Lee and J. E. Baldwin,
Chem. – Eur. J., 2005, 11, 3294–3308.
31 Xi. Han, B. M. Stoltz and E. J. Corey, J. Am. Chem. Soc.,
1999, 121, 7600–7605.
19 M. Terada, K. Moriya, K. Kanomata and K. Sorimachi,
Angew. Chem., 2011, 123, 12794–12798, (Angew. Chem., Int. 32 K. Barral, A. D. Moorhouse and J. E. Moses, Org. Lett.,
Ed., 2011, 50, 12586–12590). 2007, 9, 1809–1811.
20 (a) Q. Liu, Q. Li, Y. Ma and Y. Jia, Org. Lett., 2013, 15, 4528– 33 K. Nakanishi, X. Huang, H. Jiang, Y. Liu, K. Fang,
4531; (b) S. Preciado, L. Mendive-Tapia, F. Alberico and
R. Lavilla, J. Org. Chem., 2013, 78, 8129–8135;
D. Huang, S. K. Choi, E. Katz and M. Eldefrawi, Bioorg.
Med. Chem., 1997, 5, 1969–1988.
(c) H. K. Potukuchi and T. Bach, J. Org. Chem., 2013, 78, 34 (a) M. Shen, B. E. Leslie and T. G. Driver, Angew. Chem.,
12263–12267; (d) Y. Feng, D. Holte, J. Zoller, S. Umemiya,
L. R. Simke and P. S. Baran, J. Am. Chem. Soc., 2015, 137,
10160–10163.
2008, 120, 5134–5137, (Angew. Chem., Int. Ed., 2008, 47,
5056–5059); (b) B. J. Stokes, K. J. Richert and
T. G. Driver, J. Org. Chem., 2009, 74, 6442–6451;
(c) K. Sun, S. Liu, P. M. Bec and T. G. Driver, Angew.
Chem., 2011, 123, 1740–1744, (Angew. Chem., Int. Ed.,
2011, 50, 1702–1706); (d) C. Kong and T. G. Driver, Org.
Lett., 2015, 17, 802–805.
21 U. Kazmaier, in Frontiers in Asymmetric Synthesis and Appli-
cation of alpha-Amino Acids, ed. Hrsg.: V. A. Soloshonok and
K. Izawa, ACS Books, Washington, 2009, pp. 157–176.
22 (a) U. Kazmaier, J. Deska and A. Watzke, Angew. Chem.,
2006, 118, 4973–4976, (Angew. Chem., Int. Ed., 2006, 45, 35 E. P. Farney and T. P. Yoon, Angew. Chem., 2014, 126, 812–
4855–4858); (b) K. Krämer, J. Deska, C. Hebach and 816, (Angew. Chem., Int. Ed., 2014, 53, 793–797).
U. Kazmaier, Org. Biomol. Chem., 2009, 7, 103–111; 36 For photochemical indole syntheses using aryl azides see:
(c) S. Datta and U. Kazmaier, Org. Biomol. Chem., 2011, 9,
872–880; (d) S. Datta, A. Bayer and U. Kazmaier, Org.
Biomol. Chem., 2012, 10, 8268–8275; (e) U. Kazmaier,
A. Bayer and J. Deska, Synthesis, 2013, 1462–1468.
(a) P. A. S. Smith and B. B. Brown, J. Am. Chem. Soc., 1952,
73, 2435–2437; (b) R. J. Sundberg, H. F. Russell, W. V. Ligon
Jr. and L.-S. Lin, J. Org. Chem., 1972, 37, 719–724;
(c) P. Molina, J. Alcantara and C. Lopez-Leonardo, Tetrahe-
dron Lett., 1995, 36, 953–956; (d) O. Leogane and H. Lebel,
Angew. Chem., 2008, 120, 356–358, (Angew. Chem., Int. Ed.,
2008, 47, 350–352); (e) D. R. Bobeck, S. France,
C. A. Leverett, F. Sánchez-Cantalejo and A. Padwa, Tetra-
hedron Lett., 2009, 50, 3145–3147; X. D. Xia, J. Xuan,
Q. Wang, L.-Q. Lu, J. R. Chen and W. J. Xiao, Adv. Synth.
Catal., 2014, 356, 2807–2812.
23 (a) R. Grandel and U. Kazmaier, Tetrahedron Lett., 1997, 38,
8009–8012; (b) R. Grandel, U. Kazmaier and F. Rominger,
J. Org. Chem., 1998, 63, 4524–4528.
24 (a) M. Pohlman and U. Kazmaier, Org. Lett., 2003, 5, 2631–
2633; (b) M. Pohlman, U. Kazmaier and T. Lindner, J. Org.
Chem., 2004, 69, 6909–6912; (c) B. Mendler and
U. Kazmaier, Org. Lett., 2005, 7, 1715–1718.
25 (a) U. Kazmaier and F. L. Zumpe, Angew. Chem., 1999, 111, 37 A. Kiefer, D. Gawas and U. Kazmaier, Eur. J. Org. Chem.,
1572–1574, (Angew. Chem., Int. Ed., 1999, 38, 1468–1470);
2015, 5810–5816.
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2016