A Catalyzed Aerobic Intramolecular C-O Bond Formation: Facile Access to Ring-Fused Dihydrobenzoxazine Derivatives

Article abstract of DOI:10.1055/s-0036-1588465

A catalyst comprising of catalytic cobalt(II) acetate/copper(II) acetate/ dl -tyrosine with oxygen as the oxidant allows aerobic intramolecular C-O bond construction in [2-(pyrrolidin-1-yl)phenyl]methanol by free-radical promoted intramolecular selective functionalization of an (sp ³)C-H bond by the alcohol, thus providing an environmentally friendly approach to 5 H -benzo[ d ]pyrrolo[2,1- b ][1,3]oxazine derivatives.

Full text of DOI:10.1055/s-0036-1588465

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–E
special topic
A
en
X.-J. Shang, Z.-Q. Liu
Special Topic
Synthesis
A Catalyzed Aerobic Intramolecular C–O Bond Formation: Facile
Access to Ring-Fused Dihydrobenzoxazine Derivatives
Xiao-Jie Shang*a
Zhong-Quan Liu*b,c
H
10 mol% Co(OAc)2
10 mol% Cu(OAc)2
15 mol% DL-tyrosine
N
N
FG
FG
a College of Resources and Environment, Gansu Agricultural
University, Lanzhou, Gansu 730070, P. R. of China
shangxiaojie@yahoo.cn
OH
O
1 atm O2
MeCN, 90 °C
R
R
b College of Pharmacy, Nanjing University of Chinese Medicine,
Nanjing, Jiangsu 210023, P. R. of China
liuzq@njucm.edu.cn
R = alkyl
FG = Me, F, Cl, Br
9 examples
yield: 50–77%
c State Key Laboratory of Applied Organic Chemistry, Lanzhou
University, Lanzhou 730000, P. R. of China
liuzhq@lzu.edu.cn
Published as part of the Special Topic Modern Strategies for
Heterocycles Synthesis
Received: 11.04.2017
Accepted after revision: 20.05.2017
Published online: 27.06.2017
X
H
free-radical
promotion
X
X
+ e–
?
FG
FG
H
FG
DOI: 10.1055/s-0036-1588465; Art ID: ss-2017-c0242-st
O2 or air
R
OH
R
OH
OH
R
X = O, NR
Abstract A catalyst comprising of catalytic cobalt(II) acetate/copper(II)
acetate/DL-tyrosine with oxygen as the oxidant allows aerobic intramo-
lecular C–O bond construction in [2-(pyrrolidin-1-yl)phenyl]methanol
by free-radical promoted intramolecular selective functionalization of
an (sp3)C–H bond by the alcohol, thus providing an environmentally
friendly approach to 5H-benzo[d]pyrrolo[2,1-b][1,3]oxazine derivatives.
Scheme 1 Hypothesis of free-radical promoted intramolecular C–C
bond construction
However, the initial results indicated that it is not C–C
bond construction but C–O bond construction that occurs
under the present conditions (Scheme 2). As a result, ring-
fused heterocycles,7 1,2,3,3a-tetrahydro-5H-benzo[d]pyrro-
lo[2,1-b][1,3]oxazines were isolated as the major product.
This might be a consequence of the distance of the frontier
molecular orbitals. Although an unexpected C–O bond
forming heterocycle was obtained, the present approach to
ring-fused dihydrobenzoxazine derivatives holds advantag-
es over previous methods using excess metal salts.8
Key words free radicals, C–H functionalization, cross-dehydrogena-
tive coupling, aerobic oxidation, heterocycles
Carbon–carbon and/or carbon–heteroatom bond forma-
tion via cross-dehydrogenative coupling (CDC) strategy rep-
resents the most attractive and atom-economic conversion
in synthetic organic chemistry.1 In the past decades, effi-
cient methods for C–X construction through direct (sp3)C–H
functionalization have been achieved.2,3 However, stoichio-
metric oxidants, such as high-valent metal salts and perox-
ides, are generally required to remove the hydrogen atoms
in most previous systems. Therefore, more efficient and
waste-minimizing protocols are highly desirable.
excess MnO2
H
previous work
N
R
N
R
FG
FG
OH
O
this work
Of particular interest is the exploration of novel CDC re-
actions for C–X bond formation; we have accomplished a
series of efficient methods through free-radical promoted
(sp3)C–H functionalization.4 In a continuous study on selec-
tive functionalization of the α-hydroxy-C–H with simple al-
cohols,5 we began to hypothesize whether intramolecular
(sp3)C–C(sp3) bond formation could be realized (Scheme 1).
Furthermore, it would be very interesting if C–C bonds
were formed by using oxygen and/or air as the terminal ox-
idant.6
cat. Co(II)
1 atm O2
Scheme 2 Intramolecular C–O bond construction via (sp3)C–H func-
tionalization
Initially, we tested our hypothesis by using [2-(pyrroli-
din-1-yl)phenyl]methanol as the model compound (Table
1). It can be seen from Table 1, factors such as volume of
solvent, catalyst, and oxygen critically affect the reaction
efficiency (entries 1–9). Interestingly, the yield of the de-
sired product was improved to 71% by adding 15 mol% of
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–E

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
B
X.-J. Shang, Z.-Q. Liu
Special Topic
Synthesis
DL-tyrosine (entry 8). The amino acid might act as a ligand,
which could activate the metal catalyst. However, no prod-
uct was observed without O2 (entry 9).
Table 2 Examination of the Substratea
H
10 mol% Co(OAc)2
10 mol% Cu(OAc)2
15 mol% DL-tyrosine
N
N
n
n
Table 1 Modification of the Typical Reaction Conditionsa
FG
FG
OH
O
1 atm O2
MeCN, 90 °C
R
R
cat. Co(II)
1 atm O2
n = 1, 2
N
N
O
OH
MeCN
Entry
Substrate
Product
Yieldb (%)
71
Entry
Catalyst (10 mol%)
MeCN (mL)
Yieldb (%)
N
N
1
2
3
4
5
1
Co(OAc)2
5
5
27
30
39
55
-
O
N
OH
2
Co(OAc)2/Cu(OAc)2
Co(OAc)2/Cu(OAc)2
Co(OAc)2/Cu(OAc)2
Co(OAc)2/Cu(OTf)2
Co(OAc)2/CuCl2
3
15
20
20
20
20
20
20
N
4
77
56
63
61
O
OH
OH
5
6
47
46
71
–
7
Co(OAc)2/CuBr
F
N
F
N
8c
9d
Co(OAc)2/Cu(OAc)2
Co(OAc)2/Cu(OAc)2
O
a Reaction conditions: [2-(pyrrolidin-1-yl)phenyl]methanol (0.2 mmol, 1
equiv), 1 atm. O2 (bubble with an oxygen balloon), 90 °C, 10 h.
b Isolated yield.
Cl
Br
N
Cl
Br
N
O
OH
OH
c 15 mol% of DL-tyrosine was added.
d Without O2.
N
N
Next we examined the scope of substrate. As depicted in
Table 2, ring-fused dihydrobenzoxazine derivatives were
isolated in moderate to good yields (entries 1–9). An array
of substituted [2-(pyrrolidin-1-yl)phenyl]methanols with
alkyl and halogen atoms (F, Cl, Br) in the aromatic core are
amenable to this system (entries 1–5). Other secondary al-
cohols gave the corresponding products in moderate yields
(entries 6–9). However, no reaction occurred with [2-
(piperidin-1-yl)phenyl]methanol or (2-morpholinophe-
nyl)methanol (entries 10 and 11). This might be due to the
mismatching of the HOMO (lone pair of the oxygen atom)
with LUMO (the antibonding π* of imine cation) in space.
O
N
N
N
N
N
N
N
N
6
7
8
9
55c
53c
53c
50c
O
OH
OH
OH
OH
O
O
O
O2
Co(III)OO
Co(II)
+ HOO
N
N
OH
OH
Path I
A
SET[O]
SET[O]
Cu(II)/L, O2
Cu(II)/L, O2
Path II
N
N
HAT
N
OH
OH
O
– H+
Co(III)OO
Co(II)
+ HOO
C
B
O2
Scheme 3 Suggested mechanism
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–E

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
C
X.-J. Shang, Z.-Q. Liu
Special Topic
Synthesis
Table 2 (continued)
1H NMR (400 MHz, CDCl3): δ = 7.16(t, J = 8.0 Hz, 1 H), 6.94 (d, J = 7.2
Hz, 1 H), 6.76 (t, J = 7.2 Hz, 1 H) , 6.71 (d, J = 8.0 Hz, 1 H), 4.94–4.98 (m,
2 H), 4.78 (d, J = 14.0 Hz, 1 H), 3.60–3.65 (m, 1 H), 3.27 (q, J = 8.0 Hz, 1
H), 2.32–2.37 (m, 1 H), 2.04–2.10 (m, 1 H), 1.91–2.00 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 143.15, 127.68, 124.63, 121.58,
117.87, 115.19, 89.43, 68.22, 49.71, 32.41, 22.52.
Entry
Substrate
Product
Yieldb (%)
N
O
N
N
10
–
OH
OH
MS (EI): m/z (%): 176 (10.1), 175 (84.2), 174 (100), 149 (18.3), 146
(23), 144 (20.8), 118 (39.0), 91 (23.1), 77 (17.5), 44 (31.2).
O
O
N
11
–
O
8-Methyl-1,2,3,3a-tetrahydro-5H-benzo[d]pyrrolo[2,1-b][1,3]ox-
azine
a Reaction conditions: substituted [2-(pyrrolidin-1-yl)phenyl]methanol (0.2
mmol, 1 equiv), Co(OAc)2 (10 mol%), Cu(OAc)2 (10 mol%), DL-tyrosine (15
mol%), 1 atm O2 (bubble with an oxygen balloon), 90 °C, 10–20 h.
b Isolated yield.
Colorless oil; yield: 29.1 mg (77%).
1H NMR (400 MHz, CDCl3): δ = 6.84 (d, J = 0.8 Hz, 1 H), 6.60 (d, J = 0.8
Hz, 1 H), 6.55 (s, 1 H), 4.92–4.95 (m, 2 H), 4.76 (d, J = 1.6 Hz, 1 H),
3.59–3.64 (m, 1 H), 3.28 (q, J = 0.8 Hz, 1 H), 2.33 (s, 3 H), 2.30–2.35 (m,
1 H), 2.05–2.11 (m, 1 H), 1.92–2.01 (m, 2 H).
c Diastereomers, ratio 7:3 (1H NMR spectra).
As demonstrated in Scheme 3, two possible pathways
might be involved in this reaction.1c In path I, a hydrogen
atom transfer (HAT) would give radical intermediate A,
which leads to the iminium B by single-electron oxidation.
In contrast, path II might undergo SET first to form a radical
cation C, then followed by HAT to give B. Finally an intramo-
lecular nucleophilic addition followed by deprotonation af-
fords the final product. The steric effect in the nucleophilic
addition would be responsible for the ratio of diastereo-
mers.
In summary, an aerobic intramolecular oxidative dehy-
drogenative C–O bond formation via selective functional-
ization of (sp3)C–H bond with alcohols was developed,
which allowed an environmentally benign access to ring-
fused dihydrobenzoxazine derivatives.
13C NMR (100 MHz, CDCl3): δ = 143.04, 137.43, 124.53, 118.87,
118.78, 115.90, 89.44, 68.17, 49.76, 32.43, 22.56, 21.47.
HRMS (ESI): m/z [M + H]+ calcd for C12H16NO: 190.1226; found:
190.1226.
8-Fluoro-1,2,3,3a-tetrahydro-5H-benzo[d]pyrrolo[2,1-b][1,3]ox-
azine
Colorless oil; yield: 21.6 mg (56%).
1H NMR (400 MHz, CDCl3): δ = 6.88 (td, J = 0.4, 0.8 Hz, 1 H), 6.66–6.71
(m, 2 H), 4.87–7.93 (m, 2 H), 4.73 (d, J = 1.6 Hz, 1 H), 3.59–3.63 (m, 1
H), 3.21 (q, J = 0.8 Hz, 1 H), 2.32–2.39 (m, 1 H), 2.04–2.09 (m, 1 H),
1.91–2.01 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 157.37, 155.01, 139.60, 123.51,
123.45, 117.42, 117.34, 114.35, 114.13, 111.42, 111.20, 89.56, 67.69,
67.67, 50.80, 32.43, 22.66.
HRMS (ESI): m/z [M + H]+ calcd for C11H13NOF: 194.0976; found:
194.0984.
1H and 13C NMR spectra were recorded on a Bruker Avance III 400
spectrometer in CDCl3 with TMS as internal standard. Mass spectra
were determined on a Hewlett Packard 5988A spectrometer by direct
inlet at 70 eV. HRMS data were measured on a Bruker Apex II. All
products were identified by 1H and 13C NMR, MS, HRMS. The starting
materials were purchased from Energy Chemicals, Alfa Aesar, Acros
Organics, J&K Chemicals, Adamas, or Aldrich and used without fur-
ther purification.
8-Chloro-1,2,3,3a-tetrahydro-5H-benzo[d]pyrrolo[2,1-b][1,3]ox-
azine
Colorless oil; yield: 26.3 mg (63%).
1H NMR (400 MHz, CDCl3): δ = 7.10 (dd, J = 0.4, 0.8 Hz, 1 H), 6.91 (d, J =
0.4 Hz, 1 H), 6.61 (d, J = 0.80 Hz, 1 H), 4.87–4.92 (m, 2 H), 4.72 (d, J =
1.6 Hz, 1 H), 3.56–5.61 (m, 1 H), 3.20–3.26 (m, 1 H), 2.31–2.38 (m, 1
H), 2.07–2.09 (m, 1 H), 1.93–1.98 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 141.75, 127.60, 124.54, 123.01,
122.76, 116.19, 89.47, 67.80, 49.76, 32.33, 22.48.
5H-Benzo[d]pyrrolo[2,1-b][1,3]oxazines; General Procedure
A
solution of [2-(pyrrolidin-1-yl)phenyl]methanol (0.2 mmol, 1
HRMS (ESI): m/z [M + H]+ calcd for C11H13NOCl: 210.0680; found:
equiv), Co(OAc)2 (0.02 mmol, 10 mol%), Cu(OAc)2 (0.02 mmol, 10
mol%), and DL-tyrosine (0.03 mmol, 15 mol%) in MeCN (20 mL) was
stirred at 90 °C and bubbled with O2 (equipped with an O2 balloon)
for 10–20 h. Sat. brine (15 mL) was added, and the mixture was ex-
tracted with CH2Cl2 (3 × 10 mL). The combined organic phases were
dried (MgSO4), filtered, and concentrated. The residue was purified by
column chromatography (hexane/EtOAc 20:1) to give the product.
210.0685.
8-Bromo-1,2,3,3a-tetrahydro-5H-benzo[d]pyrrolo[2,1-b][1,3]ox-
azine
Colorless oil; yield: 30.9 mg (61%).
1H NMR (400 MHz, CDCl3): δ = 7.23 (d, J = 0.8 Hz, 1 H), 7.04 (s, 1 H),
6.55 (d, J = 0.8 Hz, 1 H), 4.87–4.90 (m, 2 H), 4.72 (d, J = 1.6 Hz, 1 H),
3.55–3.60 (m, 1 H), 3.23 (q, J = 0.8 Hz, 1 H), 2.30–2.38 (m, 1 H), 2.04–
2.09 (m, 1 H), 1.90–1.99 (m, 2 H).
1,2,3,3a-Tetrahydro-5H-benzo[d]pyrrolo[2,1-b][1,3]oxazine
Colorless oil; yield: 24.8 mg (71%).
13C NMR (100 MHz, CDCl3): δ = 142.18, 130.47, 127.37, 123.39,
116.43, 109.83, 89.45, 67.74, 49.57, 32.32, 22.46.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–E

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
D
X.-J. Shang, Z.-Q. Liu
Special Topic
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C11H13NOBr: 254.1075; found:
254.1085.
J = 4, 8 Hz, 0.33 H), 3.55–3.65 (m, 1 H), 3.25–3.35 (m, 1 H), 2.29–2.36
(m, 1 H), 2.05–2.12 (m, 2 H), 1.92–2.00 (m, 2 H), 1.73–1.80 (m, 1 H),
1.58–1.67 (m, 1 H), 1.35–1.46 (m, 1 H), 0.91–0.97 (m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 143.78, 142.46, 127.51, 127.45,
125.60, 125.52, 125.17, 124.16, 117.75, 117.34, 114.94, 114.91, 88.66,
81.43, 75.88, 49.59, 49.33, 34.63, 34.11, 33.87, 32.58, 32.33, 32.32,
28.27, 27.94, 22.87, 22.82, 22.44, 22.34.
HRMS (ESI): m/z [M + H]+ calcd for C16H24NO: 246.1852; found:
246.1855.
5-Ethyl-1,2,3,3a-tetrahydro-5H-benzo[d]pyrrolo[2,1-b][1,3]ox-
azine
Colorless oil; yield: 22.3 mg (55%); diastereomers, ratio 7:3.
1H NMR (400 MHz, CDCl3): δ = 7.15–7.20 (m, 1 H), 7.04 (d, J = 0.80 Hz,
0.70 H), 7.00 (d, J = 0.8 Hz, 0.30 H), 6.69–6.80 (m, 2 H), 5.00–5.06 (m, 1
H), 4.89 (dd, J = 0.4, 0.8 Hz, 0.70 H), 4.66 (dd, J = 0.4, 1.2 Hz, 0.30 H),
3.56–3.66 (m, 1 H), 3.26–3.36 (m, 1 H), 2.29–2.37 (m, 1 H), 2.06–2.18
(m, 2 H), 1.91–1.99 (m, 2 H), 1.73–1.86 (m, 1 H), 1.13 (t, J = 0.8 Hz, 1
H), 1.04 (t, J = 0.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 143.91, 142.49, 127.49, 127.46,
125.68, 125.27, 125.08, 124.21, 117.85, 117.36, 115.12, 114.95, 88.55,
81.43, 49.59, 49.44, 32.57, 32.35, 28.90, 27.23, 22.45, 22.37, 10.16,
9.40.
Funding Information
This project is supported by the National Natural Science Foundation
of China (Nos. 21662001, 21472080, 21672089).
N
oaitn
a
l
N
a
utarl
Secince
F
o
u
n
d
oaitn
of
C
h
n
i
a
2(
1
6
6
2
0
0
1
N)oaitn
a
l
N
a
utra
l
S
ecin
c
e
F
o
u
n
d
oaitn
of
C
h
n
i
a
2(
1
4
7
2
0
8
0
N)oaitn
a
l
N
a
utarl
Secince
F
o
u
n
d
oaitn
of
C
h
n
i
a
2(
1
6
7
2
0
8
9)
HRMS (ESI): m/z [M + H]+ calcd for C13H18NO: 204.1383; found:
204.1380.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588465.
S
u
p
p
o
nrtogI
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
5-Propyl-1,2,3,3a-tetrahydro-5H-benzo[d]pyrrolo[2,1-b][1,3]ox-
azine
Colorless oil; yield: 23.0 mg (53%); diastereomers, ratio 7:3.
References
1H NMR (400 MHz, CDCl3): δ = 7.14–7.19 (m, 1 H), 7.05 (d, J = 7.6 Hz,
0.69 H), 6.98 (d, J = 7.2 Hz, 0.31 H), 6.83–6.79 (m, 2 H), 5.06 (t, J = 4.8
Hz, 0.32 H), 5.01 (t, J = 4.8 Hz, 0.67 H), 4.92 (dd, J = 2.8, 8.0 Hz, 0.68 H),
4.78 (dd, J = 3.2, 10 Hz, 0.30 H), 3.56–5.65 (m, 1 H), 3.26–3.34 (m, 1 H),
2.32–2.35 (m, 1 H), 1.93–2.11 (m, 1 H), 1.51–1.76 (m, 3 H), 0.98–1.06
(m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.75, 142.50, 127.50, 127.41,
125.60, 125.54, 125.17, 124.16, 117.77, 117.36, 115.00, 114.97, 88.63,
81.45, 75.24, 49.62, 49.40, 38.11, 36.59, 32.56, 32.35, 22.46, 22.36,
18.68, 18.41, 14.23, 13.97.
(1) For selected recent reviews on CDC reactions, see: (a) Li, C.-J.
Acc. Chem. Res. 2009, 42, 335. (b) Yeung, C. S.; Dong, V. M. Chem.
Rev. 2011, 111, 1215. (c) Girard, S. A.; Knauber, T.; Li, C.-J.
Angew. Chem. Int. Ed. 2014, 53, 74. (d) Jia, F.; Li, Z. Org. Chem.
Front. 2014, 1, 194. (e) Guo, X.; Li, Z.; Li, C. Prog. Chem. 2010, 22,
1434.
(2) For reviews on selective functionalization of sp3-α-C–H bond in
simple aliphatic alcohols, see: (a) Zhang, S.; Zhang, F.; Tu, Y.-Q.
Chem. Soc. Rev. 2011, 40, 1937. (b) Shang, X.; Liu, Z.-Q. Huaxue
Xuebao 2015, 73, 1275. For selected reviews on (sp3)C–H func-
tionalization, see: (c) Bergman, R. G. Nature (London) 2007, 446,
391. (d) Liu, C.; Zhang, H.; Shi, W.; Lei, A. Chem. Rev. 2011, 111,
1780. (e) Davies, H. M. L.; Morton, D. Chem. Soc. Rev. 2011, 40,
1857. (f) Newhouse, T.; Baran, P. S. Angew. Chem. Int. Ed. 2011,
50, 3362. (g) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q. Acc.
Chem. Res. 2012, 45, 788. (h) Roizen, J. L.; Harvey, M. E.; Du Bois,
J. Acc. Chem. Res. 2012, 45, 911. (i) White, M. C. Science (Wash-
ington, D. C.) 2012, 335, 807. (j) Rouquet, G.; Chatani, N. Angew.
Chem. Int. Ed. 2013, 52, 11726. (k) Hartwig, J. F. J. Am. Chem. Soc.
2016, 138, 2. (l) He, J.; Wasa, M.; Chan, K. S. L.; Shao, Q.; Yu, J.-Q.
Chem. Rev. 2017, in press; DOI: 10.1021/acs.chemrev.6b00622.
(3) For selected recent reviews on general C–H functionalization,
see: (a) Le Bras, J.; Muzart, J. Chem. Rev. 2011, 111, 1170.
(b) Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Chem. Rev. 2011, 111, 1293.
(c) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011,
40, 5068. (d) Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. Angew.
Chem. Int. Ed. 2012, 51, 8960. (e) Zhang, C.; Tang, C.; Jiao, N.
Chem. Soc. Rev. 2012, 41, 3464. (f) Shang, X.; Liu, Z.-Q. Chem. Soc.
Rev. 2013, 42, 3253. (g) Liu, C.; Yuan, J.; Gao, M.; Tang, S.; Li, W.;
Shi, R.; Lei, A. Chem. Rev. 2015, 115, 12138. (h) Yang, L.; Huang,
H. Chem. Rev. 2015, 115, 3468. (i) Guo, X.-X.; Gu, D.-W.; Wu, Z.;
Zhang, W. Chem. Rev. 2015, 115, 1622. (j) Zheng, Q.-Z.; Jiao, N.
Chem. Soc. Rev. 2016, 45, 4590. (k) Qin, Y.; Zhu, L.; Luo, S. Chem.
Rev. 2017, in press; DOI: 10.1021/acs.chemrev.6b00657. For
selected recent examples, see: (l) Huo, C.; Yuan, Y.; Wu, M.; Jia,
X.; Wang, X.; Chen, F.; Tang, J. Angew. Chem. Int. Ed. 2014, 53,
HRMS (ESI): m/z [M + H]+ calcd for C14H20NO: 218.1539; found:
218.1540.
5-Butyl-1,2,3,3a-tetrahydro-5H-benzo[d]pyrrolo[2,1-b][1,3]ox-
azine
Colorless oil; yield: 24.5 mg (53%); diastereomers, ratio 7:3.
1H NMR (400 MHz, CDCl3): δ = 7.144–7.190 (m, 1 H), 7.05 (d, J = 7.6
Hz, 0.70 H), 6.99 (d, J = 7.6 Hz, 0.30 H), 6.74 (m, 2 H), 5.06 (t, J = 4.8 Hz,
0.3 H), 5.01 (t, J = 4.8 Hz, 0.70 H), 4.91 (dd, J = 2.8, 8 Hz, 0.71 H), 4.76
(dd, J = 4.0, 10.4 Hz, 0.3 H), 3.62–3.66 (m, 0.28 H), 3.56–3.61 (m, 0.7
H), 3.26–3.36 (m, 1 H), 2.11–2.35 (m, 1 H), 2.05–2.10 (m, 1.84 H),
1.93–2.00 (m, 2.32 H), 1.750–1.785 (m, 1 H), 1.39–1.55 (m, 4 H), 0.98
(m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.72, 142.47, 127.49, 127.41,
125.60, 125.24, 124.16, 117.85, 117.40, 115.05, 114.98, 88.65, 81.48,
76.48, 75.54, 49.61, 49.41, 35.72, 34.21, 32.55, 32.33, 27.69, 27.30,
22.89, 22.56, 22.43, 22.34, 14.09.
HRMS (ESI): m/z [M + H]+ calcd for C15H22NO: 232.1696; found:
232.1704.
5-Isopentyl-1,2,3,3a-tetrahydro-5H-benzo[d]pyrrolo[2,1-
b][1,3]oxazine
Colorless oil; yield: 24.5 mg (50%); diastereomers, ratio 7:3.
1H NMR (400 MHz, CDCl3): δ = 7.14–7.19 (m, 1 H), 7.05 (d, J = 8 Hz,
0.70 H), 6.99 (d, J = 8 Hz, 0.30 H), 6.68–6.79 (m, 2 H), 5.05 (t, J = 8 Hz,
0.33 H), 5.00 (t, J = 8 Hz, 0.66 H), 4.90 (dd, J = 4, 8 Hz, 0.67 H), 4.73 (dd,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–E