Preparation of heterocyclic amines by an oxidative amination of zinc organometallics mediated by CuI: A new oxidative cycloamination for the preparation of annulated indole derivatives

Article abstract of DOI:10.1002/asia.201000367

Functionalized heterocyclic zinc reagents are easily aminated by an oxidative amination reaction of zinc amidocuprates prepared from various lithium amides. For the oxidation step, PhI(OAc)₂ proved to be the best reagent. The required heterocyc

Full text of DOI:10.1002/asia.201000367

DOI: 10.1002/asia.201000367
Preparation of Heterocyclic Amines by an Oxidative Amination of Zinc
Organometallics Mediated by CuI: A New Oxidative Cycloamination for the
Preparation of Annulated Indole Derivatives
Marcel Kienle, Andreas J. Wagner, Cora Dunst, and Paul Knochel*[a]
Dedicated to Professor Eiichi Nakamura on the occasion of his 60th birthday
Abstract: Functionalized heterocyclic
zinc reagents are easily aminated by an
oxidative amination reaction of zinc
amidocuprates prepared from various
lithium amides. For the oxidation step,
PhIACHTUNGTRENNUNG(OAc)2 proved to be the best re-
agent. The required heterocyclic zinc
organometallics can be prepared either
by direct metalation, by magnesium in-
sertion in the presence of ZnCl2, or by
transmetalation of a suitable magnesi-
um reagent. Furthermore, we report a
new ring-closing reaction involving an
intramolecular oxidative amination re-
action. This reaction allows the prepa-
ration of tetracyclic heterocycles con-
taining furan, thiophene, or indole
rings.
Keywords: amination
·
cross-
coupling · heterocycles · lithium
amides · zinc organometallics
Introduction
these methods. Inspired by the work of Yamamoto and
Ricci,[7] we recently reported an oxidative amination reac-
tion of functionalized amidocuprates.[8] Thus, the prepara-
tion of primary, secondary, and tertiary arylamines was ach-
ieved by the oxidative coupling of polyfunctional aryl and
heteroaryl amidocuprates (Scheme 1). A suitable magnesi-
um reagent 1 is transmetalated to the corresponding copper
species 2 using the complex CuCl·2LiCl. After addition of a
lithium amide 3, a magnesium amidocuprate of type 4 is
formed. Subsequent oxidation using chloranil (5) furnishes
the desired amines of type 6.
Heteroaromatics are important classes of structures in me-
dicinal chemistry.[1] Heteroaromatic amines are widely found
in natural products[2] and are frequent target molecules in
organic synthesis, owing to their potential applications as
pharmaceuticals, xerographic and photographic materials,
conducting polymers, or material precursors.[3] Owing to the
pioneering work of Buchwald, Hartwig, and Beller[4,5] many
functional five- and six-membered heterocyclic amines are
nowadays available.[6] Although much progress has been
made for these transition metal-catalyzed aminations of aryl
and heteroaryl halides, these reactions still have some limi-
tations. Particularly, the mono-functionalization of dihaloar-
enes (e.g., diiodo-, dibromo-, and dichloroarenes) results in
the formation of product mixtures. Some disadvantages for
aminations with sterically hindered amines are the long re-
action times required and the use of strong bases. Finally,
triarylamines cannot always efficiently be prepared by using
More recently, we have reported an extension of this pro-
tocol using functionalized heteroarylzinc reagents for the
[a] M. Kienle, A. J. Wagner, C. Dunst, Prof. Dr. P. Knochel
Department Chemie
Ludwig-Maximilians-Universtꢀt Mꢁnchen
Butenandtstr. 5–13, 81377 Mꢁnchen (Germany)
Fax : (+49)89-2180-77680
E-mail: paul.knochel@cup.uni-muenchen.de
Supporting information for this article is available on the WWW, and
contains experimental procedures, analytical data, and NMR spectra,
under http://dx.doi.org/10.1002/asia.201000367.
Scheme 1. General scheme for the oxidative amination of organomagne-
sium reagents by using chloranil.
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CuI-mediated amination.[9] The oxidative amination of zinc
[10]
reagents failed using chloranil, however PhIACTHNUGTRENUNG(OAc)2 gave
much better results and furnished the desired amines in
moderate to good yields. Although the present method re-
quires stoichiometric amounts of CuCl·2LiCl, the procedure
allows the selective amination of various sensitive heterocy-
cles.
Herein, we wish to report the scope and limitations of this
oxidative amination reaction using mostly zinc organometal-
lics. A new ring-closure leading to condensed indoles will
also be reported. Furthermore, the scale-up of this oxidative
cross-coupling reaction will be described in detail.
Scheme 2. CuI-mediated oxidative amination of a zinc reagent obtained
by direct zincation. Conditions: a) [(TMP)2Zn]·2MgCl2·2LiCl
(0.55 equiv), THF, 258C, 45 min; b) CuCl·2LiCl (1.1 equiv), À508C,
30 min; c) LiN (OAc)2
(SiMe3)2, (2.0 equiv), À508C, 1 h; d) PhI
(1.1 equiv), À788C, 1 h.
8
N
ACHTUNGTRENNUNG
Results and Discussion
[(TMP)2Zn]·2MgCl2·2LiCl. The corresponding amidocup-
rates were obtained after transmetalation with CuCl·2LiCl
and the addition of various cyclic and acyclic amines. Subse-
Direct Zincation of Heteroaromatics and Subsequent
Oxidative Amination Reaction
2,4-Dibromothiazole (7a) was zincated within 45 min at
258C by using [(TMP)2Zn]·2MgCl2·2LiCl[11] (8, 0.55 equiv;
TMP=2,2,6,6-tetramethylpiperidyl)[12] furnishing the diaryl-
quent oxidation with PhIACTHNGUTER(NNUG OAc)2 furnished the 5-amino-2-
bromothiazoles 12d–f in 63%–75% yield (entries 3–6).
Using this method, 4-aminothiazoles can also be prepared.
Thus, the zincation and subsequent transmetalation of 2-
bromo-5-trimethylsilylthiazole (7c) gave the corresponding
copper reagents. Oxidative amination with suitable lithium
amides furnished the tertiary amines 12g–h in 73–75% yield
and the triarylamine 12i in 76% yield (entries 7–9). 2-(Phe-
nylthio)thiazole (7d) was also successfully aminated, provid-
ing the amines 12j–k in 72–75% yield (entries 10–11). These
(phenylthio)thiazoles may be further functionalized, since
the phenylthio group can serve as a leaving group in cross-
coupling reactions.[14]
Furthermore, we have applied this method to the amina-
tion of other heteroaromatics, such as benzothiazole (13a),
benzothiophene (13b), benzofuran (13c), and 2,5-dibromo-
thiophene (13d). Benzothiazole (13a) was smoothly zincat-
ed at 258C using [(TMP)2Zn]·2MgCl2·2LiCl (8). Subsequent
oxidative amination with lithium morpholide and LiTMP
furnished the tertiary amines 14a–b in 60%–73% yield
(Table 2, entries 1–2). Remarkably, the steric hindrance of
the TMP moiety did not hamper the oxidative amination.[15]
ACHTUNGTRENNUNGzinc 9a. This zinc reagent was very stable and did not under-
go halogen-dance reactions, as is usual for electron-rich het-
eroaromatic organometallics.[13] After the addition of CuCl·2
LiCl (1.1 equiv), the corresponding copper derivative 10a
was obtained after 30 min at À508C. Further addition of
LiN
G
rate 11a. The subsequent oxidation of 11a by using PhI-
(OAc)2 (1.1 equiv, À788C, 1 h) provided the amino thiazole
12a in 82% yield (Scheme 2). Interestingly, if chloranil (5)
was used for the oxidation step, large amounts of the corre-
sponding homocoupling product of the zinc reagent were
obtained. Of all amination reactions performed with a zinc
reagent, PhIACHTUNGTRENNUNG(OAc)2 was the best oxidant.
A range of thiazoles were aminated in 61–76% yield by
this procedure (Table 1). Thus, the copper derivative 10a
was also reacted with lithium morpholide or lithium N-
methylpiperazide, leading to the tertiary amines 12b and
12c in 61–70% yield (Table 1, entries 1–2). 2-Bromothiazole
(7b) was smoothly zincated within 2 h at 258C by using
Benzothiophene
(13b)
was
metalated
by
using
[(TMP)2Zn]·2MgCl2·2LiCl (8) within 24 h at 258C. The oxi-
dative amination with different lithium amides gave the
amines 14c–d in 67–73% yield (entries 3–4).
Benzofuran (13c), as well as 2,5-dibromothiophene (13d),
was zincated by treatment with [(TMP)2Zn]·2MgCl2·2LiCl
(8) by using microwave irradiation (1008C, 1 h)[16] followed
by an oxidative amination with suitable lithium amides,
yielding the corresponding amines 14e–g in 60–70% yield
(entries 5–7).
Abstract in German: Funktionalisierte heterozyklische
Amine kçnnen durch oxidative Aminierung von Zink-Ami-
docupraten dargestellt warden, welche durch die Reaktion
einer Reihe von Lithiumamiden mit funktionalisierten Zink-
reagenzien zugꢀnglich sind. Dabei hat sich Iodbenzoldiace-
tat PhIACHTUNGTRENNUNG(OAc)2 als optimales Oxidationsmittel herausgestellt.
Die notwendigen Organozinkverbindungen kçnnen durch
direkte Metallierung, Magnesiuminsertion in Gegenwart
von ZnCl2 oder durch Transmetallierung geeigneter Organo-
magnesiumreagenzien dargestellt werden. Darꢁber hinaus
berichten wir von einer neuen Ringschlussreaktion mittels
intramolekularer oxidativer Aminierung. Diese Reaktion er-
mçglicht die Darstellung tetrazyklischer Heterozyklen mit
Furan-, Thiophen-, oder Indolgerꢁsten.
Magnesium Insertion in the Presence of ZnCl2 into Various
Heterocyclic Halides and Subsequent Oxidative Amination
Reaction
Recently, we reported a novel Mg-insertion into aromatic
and heterocyclic bromides and chlorides in the presence of
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Chem. Asian J. 2011, 6, 517 – 523

Preparation of Heterocyclic Amines
Table 1. Oxidative amination of various functionalized thiazoles after
zincation with [(TMP)2Zn]·2MgCl2·2LiCl (8).
Table 2. Oxidative amination of various heterocycles leading to tertiary
and protected secondary amines.
Entry
Substrate
Lithium amide
Product
Entry
Substrate[a]
Lithium amide
Product
(T [8C], t [h])[a]
yield [%][b]
(T [8C], t [h])[b]
yield [%][c]
1
1
13a: 25, 1
14a: 73
7a: 25, 0.75
12b: 70
2
2
13a: 25, 1
14b: 60
14c: 73
14d: 67
14e: 60
7a: 25, 0.75
7b: 25, 2
12c: 61
12d: 75
12e: 71
3
4
5
13b: 25, 24
3
4
5
13b: 25, 24
7b: 25, 2
13c: 100, 1 (MW)
7b: 25, 2
7b: 25, 2
12 f: 63
12g: 65
6
7
6
7
13d: 100, 1 (MW)
13d: 100, 1 (MW)
14 f: 70
14g: 67
[a] Reaction
conditions
for
the
direct
zincation
using
7c: 25, 8
12h: 73
12i: 75
[(TMP)2Zn]·2MgCl2·2LiCl; [b] Yield of analytically pure product.
8
9
(1.1 equiv) and the addition of lithium diphenylamide
(2.0 equiv). Oxidation of 17a by using PhI(OAc)2
ACHTUNGTRENNUNG
7c: 25, 8
(1.1 equiv) led to the desired tertiary amine 18a in 70%
yield (Scheme 3).
In a similar manner, the heterocycle 15a was converted to
the protected secondary amine 18b in 66% yield (Table 3,
7c: 25, 8
7d: 25, 2
7d: 25, 2
12j: 76
12k: 75
10
11
12l: 72
[a] Reaction
conditions
for
the
direct
zincation
using
[(TMP)2Zn]·2MgCl2·2LiCl; [b] Yield of analytically pure product.
LiCl and ZnCl2, leading to aromatic and heteroaromatic
zinc organometallics.[17] We have applied this method to the
zincation of several heterocycles followed by an oxidative
amination. Thus, 4-bromo-1,3,5-trimethyl-1H-pyrazole (15a)
was treated with Mg turnings (2.5 equiv) in the presence of
LiCl (2.5 equiv) and ZnCl2 (1.0 equiv), furnishing the zinc
species 16a within 30 min at 258C. The amidocuprate 17a
was obtained after transmetalation with CuCl·2LiCl
Scheme 3. Mg-insertion to the 4-bromopyrazole (15a) in the presence of
LiCl and ZnCl2 followed by an oxidative amination with PhIACTHNUTRGNEUNG(OAc)2.
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519

P. Knochel et al.
FULL PAPERS
controlled K channels in eukaryotic cells[22] explaining our
interest for preparing their undescribed [2,3-b]-fused ana-
logs.
Table 3. Oxidative amination of zinc reagents obtained by magnesium in-
sertion in the presence of LiCl and ZnCl2.
Entry
Substrate
Lithium amide
Product
(T [8C], t [min])[a]
yield [%][b]
Thus, a Br/Mg-exchange on 3-bromobenzofuran (19) with
iPrMgCl·LiCl (À558C, 24 h) provided the corresponding
magnesium reagent. A higher temperature for the exchange
reaction resulted in the decomposition of the metalated spe-
cies. This magnesium reagent was transmetalated to the zinc
species 20a using ZnCl2 (1.1 equiv, À558C to 258C, 20 min).
A subsequent Negishi cross-coupling with the bromoaniline
1
15a: 25, 15
18b: 66
21a in the presence of PdACHTNUTGRNEUNG
(OAc)2 (1 mol%) and S-Phos[18]
(2 mol%) furnished the desired benzofuran derivative 22a
within 5 h at 258C in 75% yield (Scheme 4).
2
15b: 25, 15
15b: 25, 15
15c: 25, 60
15c: 25, 60
18c: 66
18d: 60
18e: 67
18 f: 57
3
4
5
Scheme 4. Negishi cross-coupling of the zinc reagent 20a with the bro-
moaniline 21a.
[a] Reaction conditions for the Mg insertion in the presence of LiCl and
ZnCl2 [b] Yield of analytically pure product.
Using the same conditions, the zinc reagent 20a was cou-
pled with various bromoanilines to give the corresponding
biaryls 22b–d in 86–91% yield (Table 4, entries 1–3). The re-
lated 3-bromobenzothiophene was converted to the corre-
sponding zinc reagent 20b. Thus, treatment of 3-bromoben-
zothiophene with iPrMgCl·LiCl (1.1 equiv, À558C, 24 h) and
subsequent addition of ZnCl2 (1.1 equiv) furnished the zinc
species 20b. This reagent reacted with various bromoani-
entry 1). Other chloro- or bromo-N-heterocycles, such as
15b and 15c, led to the corresponding zinc compounds by
using the previously described Mg insertion in the presence
of ZnCl2. These zinc reagents were then aminated by using
the oxidative amination, yielding the protected secondary
and tertiary amines 18c–f in 57–67% yield (entries 2–5).
lines under Pd-catalysis ([PdACHTNUTRGNEUNG(OAc)2] (1 mol%) and S-
Oxidative Cycloamination
Phos[18] (2 mol%)) providing the corresponding coupling
products 22e–h in 43–81% yield (entries 4–7).
We have found that the oxidative amination can also be
used for performing an oxidative ring closure leading to
These primary amines 22d and 22h were then protected
with various protecting groups. Thus, deprotonation of 22d
and 22h with nBuLi (1.1 equiv, À308C, 30 min) gave the
corresponding lithium species. Subsequent addition of an
electrophile (e.g., MeI, allyl bromide, or TIPS-Cl (ClSi-
indole derivatives. Furo
ring structural motifs in natural products[19] and thieno
b]indoles of type B find application in treating diseases of
the human central nervous system.[20] Benzofuro
[2,3-
b]indole derivatives, such as C, have not been described and
only the unsubstituted benzothieno[2,3-b]indole D has been
prepared (Figure 1).[21] The inversely condensed benzofuro-
[3,2-b]indoles of type E show high activity in opening Ca-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
(iPr)3), 1.1 equiv, À308C to 258C, 30 min) gave the desired
G
secondary amines 22i–n in 30–96 yield (Table 5, entries 1–6).
Having the secondary amines 22a–n in hand, we exam-
ined the oxidative ring closure of these compounds for the
formation of annulated indole derivatives. Thus, the benzo-
furan derivative 22a was deprotonated by using nBuLi
(2.0 equiv, À788C to À308C, 5 h) to give the corresponding
bis-metalated species. After transmetalation with CuCl·2
LiCl (1.1 equiv, À508C, 20 min), the resulting copper species
underwent a ring closure mediated by chloranil (5, 1.1 equiv,
À788C, 1 h) furnishing the desired indole derivative 23a in
80% yield (Scheme 5). The best results for this ring closure
ACHTUNGTRENNUNG
Figure 1. Condensed indole derivatives of type A–E.
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Preparation of Heterocyclic Amines
Table 4. Negishi cross-coupling of zinc reagents with various bromoani-
lines.
Table 5. Monoprotection of the primary amines 22d and 22h.
Entry
Substrate[a]
Electrophile
Product yield [%][b]
Entry
Substrate[a]
Lithium amide
Product yield [%][b]
1
MeI
1
22d
22d
22d
22h
22h
22h
22i: 62
22j: 94
22k: 48
22l: 96
22m: 91
22n: 30
20a
22b: 86
2
3
4
5
6
allyl bromide
TIPS-Cl
2
20a
20a
20b
20b
22c: 91
22d: 89
22e: 43
22 f: 62
3
4
5
MeI
allyl bromide
TIPS-Cl
6
7
[a] Reaction conditions for the protection step; i) nBuLi (1.1 equiv,
À308C, 30 min); ii) electrophile (1.1 equiv, À308C to 258C, 30 min).
[b] Yield of analytically pure product.
20b
20b
22g: 68
22h: 81
[a] Reaction conditions for the cross-coupling reaction: 258C, 5 h;
[b] Yield of analytically pure product.
were obtained, when the precursors were diluted in THF
(0.1m). By running the oxidation cross-coupling reaction at
a 1.0m concentration in THF, large amounts of undesired
by-products were obtained.
Scheme 5. Oxidative cycloamination for the synthesis of annulated indole
derivatives.
The reaction conditions detailed above proved to be gen-
eral for such ring closing reactions, both for non-donating
and donating substituents on the aniline nitrogen. Also,
steric factors seemed to play a negligible role even with
bulky substituents, such as TIPS. Thus, deprotonation of the
benzofuran derivatives 22b–c and 22i–k was achieved with
nBuLi (2.0 equiv, À788C, 1 h, then À308C, 3 h). After trans-
metalation with CuCl·2 LiCl, the corresponding copper spe-
cies were oxidized with chloranil leading to the indole deriv-
atives 23b–f in 50–84% yield (Table 6, entries 1–5). Similar-
ly, the related benzothiophene derivatives 22e–g and 22l–n
gave the corresponding tetracyclic heterocycles 23g–l in 51–
89% yield (entries 6–11).
Conclusions
In summary, we have shown that amidocuprates obtained
from organozinc reagents can be smoothly oxidized by PhI-
AHCTUNGRTEG(NNUN OAc)2. A range of heterocycles was successfully aminated
by this protocol. The organozinc reagents required for the
amination show a remarkable thermal stability and are supe-
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521

P. Knochel et al.
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Table 6. CuI-mediated oxidative cycloamination.
rior to the corresponding magnesium reagents. Furthermore,
we applied the oxidative amination reaction to the synthesis
of indole derivatives. A range of tetracyclic heterocycles was
synthesized by a new oxidative ring closing reaction. Further
extensions of this methodology, as well as applications in
natural material chemistry, are currently underway in our
laboratories.
Entry
Substrate
Product yield [%][a]
1
22b
23b: 84
2
Experimental Section
2,4-Dibromo-N,N-bis(trimethylsilyl)-1,3-thiazol-5-amine (12a)
22c
22i
22j
22k
23c: 50
23d: 50
23e: 70
23 f: 81
A dry and argon-flushed Schlenk-flask, equipped with a magnetic stirring
bar and
a septum, was charged with 2,4-dibromo-1,3-thiazole (7a)
(243 mg, 1.0 mmol) and THF (1 mL). To the resulting mixture was added
dropwise [(TMP)2Zn]·2MgCl2·2 LiCl (8, 1.30 mL, 1.68m in THF,
0.55 mmol) and the reaction mixture was stirred for 45 min. CuCl·2 LiCl
(1.1 mL, 1.0m in THF, 1.1 mmol) was added dropwise to 9a at À508C
3
4
5
under argon and the mixture was stirred for 30 min. LiNACHTUNGTRENNUNG(SiMe3)2
(2 mmol, 1m in THF) was added dropwise to the resulting cuprate 10a,
and the mixture was stirred for 1 h at À508C. The reaction mixture was
cooled to À788C, then a solution of PhI
ACHTUNGRTEN(NUNG OAc)2 (354 mg, 1.1 mmol) in dry
THF (10 mL) was added slowly over a period of 60 min. The reaction
mixture was then warmed to À508C and stirred for an additional 3 h.
Et2O (100 mL) was poured into the crude reaction mixture. The organic
phase was washed with 2ꢃ10 mL portions of aqueous NH4OH (2.0m)
and extracted with Et2O. The combined organic layers were dried
(Na2SO4), filtered, and concentrated under reduced pressure. Purification
by flash chromatography (pentane; Al2O3 III) yielded 12a (331 mg,
80%) as a colorless oil. IR (ATR): n˜ =2950, 1499, 1412, 1251, 1204, 1154,
1
1009, 909, 869, 837, 816, 790, 753, 684, 666, 632 cmÀ1; H NMR (300 MHz,
CDCl3): d=0.17 ppm (s, 18H); 13C NMR (150 MHz, CDCl3): d=147.3,
127.7, 119.8, 1.5 ppm; MS (70 eV, EI): m/z (%)=402 (18), 399 (18), 387
(32), 385 (14), 323 (15), 321 (14), 125 (12), 123 (11), 97 (11), 83 (11), 73
(100); HRMS (EI): m/z calc. for [C9H1879Br2N2SSi2] 399.9096, found:
399.9086.
6
7
8
22e
22 f
23g: 81
23h: 58
2-(1-Benzo[b]furan-3-yl)-N-phenylaniline (22a)
A dry and argon-flushed Schlenk-flask, equipped with a magnetic stirring
bar and a septum, was charged with 3-bromobenzofuran (22a) (295 mg,
1.5 mmol) and THF (0.75 mL). The solution was cooled to À558C, then
iPrMgCl·LiCl (1.65 mmol, 1.30m in THF, 1.27 mL) was added and the re-
sulting mixture was stirred for 24 h. Then, ZnCl2 (1.5 mmol, 1m in THF,
1.5 mL) was added and the solution was warmed up to À108C within
20 min. A dry and argon-flushed Schlenk-flask, equipped with a magnetic
stirring bar and a septum, was charged with 2-bromoaniline (172 mg,
1.0 mmol), PdACTHUNRGTNEUNG(OAc)2 (2.3 mg, 0.01 mmol) and S-Phos (8.2 mg,
22g
22l
23i: 70
23j: 89
23k: 62
23l: 71
0.02 mmol) in THF (1 mL). To this mixture, the freshly prepared zinc re-
agent was added within 10 min at 258C. The resulting solution was stirred
at 258C for additional 5 h to obtain full conversion. The reaction mixture
was quenched by the addition of sat. NH4Cl-solution (5 mL) and the
product was extracted with EtOAc (3ꢃ25 mL). The combined organic
phases were successively washed with sat. thiourea solution (2ꢃ10 mL)
and sat. NaCl solution (20 mL), dried (MgSO4) and concentrated under
reduced pressure. Purification by flash chromatography (pentane/Et2O;
9:1) yielded 22a (213 mg, 75%) as white solid. IR (ATR): n˜ =3392, 3036,
1588, 1500, 1452, 1420, 1336, 1304, 1220, 1200, 1164, 1100, 1080, 964, 856,
9
10
11
800, 740, 700 cmÀ1 1H NMR (300 MHz, CDCl3): d=7.77 (s, 1H), 7.56 (t,
;
3J=9.3 Hz, 2H), 7.42 (ddd, 3J=15.7 Hz, 3J=7.7 Hz, 4J=1.3 Hz, 2H),
7.36–7.33 (m, 1H), 7.31–7.29 (m, 1H), 7.27–7.22 (m, 3H), 7.06–7.04 (m,
2H), 7.00 (td, 3J=7.5 Hz, 4J=1.3 Hz, 1H), 6.94 (tt, 3J=7.5 Hz, 4J=
1.1 Hz, 1H), 5.69 ppm (br. s, 1H, NH); 13C NMR (150 MHz, CDCl3): d=
155.6, 143.1, 142.9, 141.8, 131.5, 129.6, 129.0, 127.2, 125.0, 123.3, 121.7,
121.0, 120.8, 120.5, 119.0, 116.7, 112.0, 105.0 ppm; MS (70 eV, EI): m/z
(%)=286 (21), 285 (100), 284 (14), 256 (12), 254 (11); HRMS (EI): m/z
calc. for [C20H15NO] 285.1154, found: 285.1145.
22m
22n
[a] Yield of analytically pure product.
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Preparation of Heterocyclic Amines
6-Phenyl-6H-[1]benzo
G
E
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A dry and argon-flushed Schlenk-flask, equipped with a magnetic stirring
bar and a septum, was charged with 2-(1-benzofuran-3-yl)-N-phenylani-
line (285 mg, 1 mmol) and THF (10 mL). The solution is cooled to
À788C and nBuLi (0.87 mL, 2.30m in pentane, 2.0 mmol) was added
dropwise. The mixture was stirred for 1 h at À788C and for additional 3 h
at À308C. Then, the mixture was cooled to À508C and CuCl·2 LiCl
(1.1 mL, 1.0m in THF, 1.1 mmol) was added and stirred for 20 min. After
cooling to À788C, THF (9 mL) was added followed by the dropwise addi-
tion of chloranil (270 mg, 0.1m in THF, 1.1 mmol). Diethyl ether was
added to the crude reaction mixture and it was filtered through Celite,
washed with ether thoroughly, and the filtrate was washed with 2ꢃ10 mL
portions of aqueous NH4OH (2.0m). The organic extract was dried over
MgSO4, filtered and concentrated under reduced pressure. Purification
by flash chromatography (pentane) afforded 23a (192 mg, 68%) as color-
less solid. IR (ATR): n˜ =3184, 3052, 2920, 2852, 1912, 1872, 1624, 1592,
1560, 1500, 1448, 1400, 1328, 1300, 1204, 1176, 1148, 1108, 1076, 1012,
960, 916, 852, 784, 748, 724, 696, 676 cmÀ1 1H NMR (300 MHz, CDCl3):
;
d=7.90 (t, 3J=7.8 Hz, 1H), 7.82 (d, 3J=7.8 Hz, 1H), 7.72 (d, 3J=7.8 Hz,
2H), 7.64–7.60 (m, 3H), 7.53 (d, 3J=7.8 Hz, 1H), 7.45 (t, 3J=7.5 Hz,
3
1H), 7.38–7.32 (m, 2H), 7.28–7.26 (m, 1H), 7.22 ppm (t, J=8.1 Hz, 1H);
13C NMR (150 MHz, CDCl3): d=157.0, 156.0, 137.5, 136.0, 130.1, 127.4,
125.0, 124.7, 124.0, 121.9, 121.8, 121.7, 121.2, 119.6, 119.0, 112.1, 111.6,
99.5 ppm; MS (70 eV, EI): m/z (%)=284 (21), 283 (100), 254 (32), 179
(8); HRMS (EI): m/z calc. for [C20H13NO] 283.0997, found: 283.0987.
We thank the Fonds der chemischen Industrie, the ERC (European Re-
search Council), the DFG, and SFB749 for financial support. We also
thank Chemetall GmbH (Frankfurt), W. C. Heraeus GmbH, and BASF
AG (Ludwigshafen) for generous gifts of chemicals.
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Received: May 14, 2010
Published online: August 2, 2010
Chem. Asian J. 2011, 6, 517 – 523
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
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