Palladium-Catalyzed Aerobic Oxidative Cyclization of Aliphatic Alkenyl Amides for the Construction of Pyrrolizidine and Indolizidine Derivatives

Article abstract of DOI:10.1055/s-0036-1588502

An efficient palladium-catalyzed aerobic oxidative cyclization has been developed to synthesize a variety of pyrrolizidine and indolizidine derivatives from simple aliphatic alkenyl amides in moderate to good yields. The reaction features the capability of accessing various N-heterocycles and the use of molecular oxygen (1 atm) as the green oxidant.

Full text of DOI:10.1055/s-0036-1588502

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Palladium-Catalyzed Aerobic Oxidative Cyclization of Aliphatic
Alkenyl Amides for the Construction of Pyrrolizidine and Indol-
izidine Derivatives
O
O
Kai-Yip Lo
Pd(II)/ligand
n N
N
n
Liu Ye
H
X
X
R1
O2
R1
Dan Yang*
R2
R2
12 examples
up to 74% yield
Department of Chemistry, The University of Hong Kong,
Pokfulam Road, Hong Kong, P. R. of China
yangdan@hku.hk
aliphatic alkenyl amides
X = C, NTs; n = 1, 2
N-heterocycles
R1 = gem-dimethyl, gem-diphenyl, cyclopentyl
2 = H, cis-Ph, trans-Ph
Published as part of the Cluster Catalytic Aerobic Oxidations
R
Received: 26.06.2017
Accepted after revision: 27.06.2017
Published online: 13.07.2017
alkenyl amides are less favorable for the intramolecular cy-
clization due to their more flexible backbones5 and lower
acidity of aliphatic amide.6 There are only two successful
reports of enantioselective cascade cyclizations of alkene-
tethered aliphatic acrylamides with limited substrate
scope.7a,b On the basis of our continued interest in palladi-
um-catalyzed aerobic oxidative cascade cyclizations, we
herein report a palladium-catalyzed aerobic cyclization of
aliphatic alkenyl amides, allowing for the rapid construc-
tion of various N-heterocycles, including pyrrolizidines, in-
dolizidines, and azatricyclic heterocycles, in moderate to
good yields.
DOI: 10.1055/s-0036-1588502; Art ID: st-2017-r0226-c
Abstract An efficient palladium-catalyzed aerobic oxidative cyclization
has been developed to synthesize a variety of pyrrolizidine and indol-
izidine derivatives from simple aliphatic alkenyl amides in moderate to
good yields. The reaction features the capability of accessing various N-
heterocycles and the use of molecular oxygen (1 atm) as the green oxi-
dant.
Key words palladium catalysis, aerobic oxidation, cascade cyclization,
aminopalladation, N-heterocycles
Our previous work:
Molecular oxygen (O2), as an abundant, inexpensive,
and environmentally friendly oxidant, has been widely em-
ployed as the ideal oxidant in many transition-metal-cata-
lyzed transformations.1 Among them, palladium-catalyzed
aerobic oxidation reactions have evolved as a powerful tool
in organic transformations,2 such as alcohol oxidation,
Wacker oxidation, and oxidative Heck reaction. Although
significant advances in palladium-catalyzed aerobic oxida-
tion reactions have been achieved, the palladium-catalyzed
aerobic oxidative tandem reactions have been less exten-
sively investigated.3 In the past few years, our group has
made many efforts toward the development of palladium-
catalyzed aerobic oxidative cascade cyclizations,4 which
provide synthetically useful approaches for accessing di-
versely functionalized N-heterocycles. For example, an effi-
cient palladium-catalyzed aerobic oxidative cyclization of
unactivated alkenes bearing pendant unsaturated amide
nucleophiles has been developed for constructing pyrro-
loindoline derivatives (Scheme 1, a).4a–d However, substrate
scope in previous transformations were mostly restricted to
aromatic alkenyl amides, which undoubtedly limited its
wide application in heterocycle synthesis. Compared to aro-
matic ones with fused phenyl ring backbones, aliphatic
O
O
O
Pd(II)/L
(a)
R1
NH
N
PdLn
N
O2
R1
R1
aromatic alkenyl amides
pyrroloindolines
This work:
O
O
O
(b)
n N
N
n
n N
X
X
R1
Pd(II)/L
H
X
PdLn
R1
R1
O2
R2
R2
R2
N-heterocycles
aliphatic alkenyl amides
X = C, NTs; n = 1, 2
Scheme 1 Palladium-catalyzed aerobic oxidative cyclization reactions
The linear aliphatic alkenyl amide 1a was selected as a
model substrate to test the feasibility of this cascade cy-
clization. Due to the lack of Thorpe–Ingold effect8 in linear
substrate 1a, its cyclization is commonly unfavorable. To
our delight, the azabicyclic product 2a could be obtained in
moderate yield when 10 mol% Pd(OAc)2 was used as the
catalyst, 40 mol% pyridine as the ligand, and O2 as the oxi-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

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Table 1 Optimization of Reaction Conditionsa
dant (Table 1, entry 1). The addition of 40 mol% DABCO was
found to accelerate the reaction and give a slightly higher
yield, while the use of stoichiometric amount of DABCO re-
sulted in a decreased yield. It seems that DABCO acts as a
ligand to compete with pyridine and a base to deprotonate
the amido proton (Table 1, entries 2 and 3). Among the in-
vestigated palladium catalysts, Pd(TFA)2 exhibited the best
reactivity (Table 1, entry 4). The reaction temperature also
had impact on the reaction efficiency and the best yield was
obtained at 95 °C (Table 1, entries 4–6). Interestingly, 2.0
equivalents of K2HPO4 in place of DABCO as an additive
could give a comparable yield of 2a when the less expensive
Pd(OAc)2 was employed as the catalyst (Table 1, entry 7).
However, reducing its amount to 40 mol% gave a dimin-
ished yield (Table 1, entry 8). Notably, the olefin isomeriza-
tion product 2a′ was detected under several conditions.
Hence, two optimal conditions were selected. Conditions A:
substrate 1, 10 mol% Pd(TFA)2, 40 mol% pyridine and 40
mol% DABCO in toluene under 1 atm oxygen at 95 °C; Con-
ditions B: substrate 1, 10 mol% Pd(OAc)2, 40 mol% pyridine
and 200 mol% K2HPO4 in toluene under 1 atm oxygen at
95 °C.
O
O
O
Pd source (10 mol%)
pyridine (40 mol%)
N
H
N
N
+
additive, toluene
O2 (1 atm), 70 °C, 48 h
1a
2a
2a'
Entry
Pd source
Additive (mol%)
Conv. (%)b Yield (%)b
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(OAc)2
Pd(OAc)2
–
66
86
52 (4)
56
2
DABCO (40)
DABCO (100)
DABCO (40)
DABCO (40)
DABCO (40)
K2HPO4 (200)
K2HPO4 (40)
3
90
45
4
84
60
5c
6d
7d
8d
91
64
100
100
100
70 (8)
71 (9)
54(5)
a All reactions were carried out with 1a (0.3 mmol), palladium source (0.03
mmol), and pyridine (0.12 mmol) in 3 mL of toluene under oxygen atmo-
sphere at 70 °C for 48 h.
b The conversions and yields were determined by isolation and the values in
parentheses are yields of olefin isomerization products.
c The reaction temperature was 80 °C.
d The reaction temperature was 95 °C. DABCO = 1,4-Diazabicyclo[2.2.2]oc-
tane.
Table 2 Substrate Scope of Palladium-Catalyzed Oxidative Cascade Cyclizationa
Conditions A: Pd(TFA)2 (10 mol%)
pyridine (40 mol%)
DABCO (40 mol%)
toluene, O2 (1 atm), 95 °C
substrate
product
1a−j
2a−j
Conditions B: Pd(OAc)2 (10 mol%)
pyridine (40 mol%)
K2HPO4 (200 mol%)
toluene, O2 (1 atm), 95 °C
Entry
1
Substrate
Product
Conditions
A
Time (h)
21
Conv. (%)b
100
Yield (%)b,c
74 (9)
O
O
N
N
H
2
3
B
36
24
100
91
74 (4)
58 (9)
1a
2a
A
O
O
N
H
N
4
B
28
100
73
1b
2b
O
O
Me
Me
Me
Me
N
N
H
5
A
20
98
63 (9)
1c
2c
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Table 2 (continued)
Entry
Substrate
Product
Conditions
A
Time (h)
20
Conv. (%)b
98
Yield (%)b,c
O
O
Ph
Ph
Ph
Ph
N
N
6
63 (9)
H
1d
2d
O
O
N
N
7
A
17
100
64 (16)
H
1e
2e
8
9
A
B
A
B
70
66
23
66
83
68
50 (3)ddr = 2:1
27 (3)ddr = 4:1
37 (4)ddr = 4:1
42 (8)ddr = 11:1
O
O
H
H
N
N
H
H
H
H
H
1f
2f
10
11
100
95
O
O
H
H
N
N
H
H
H
1g
2g
O
O
N
N
H
12
13
A
A
43
69
94
87
58
38
N
N
Ts
Ts
2h
1h
O
O
N
N
H
H
Ph
1i
2i
Ph
O
O
N
N
H
14
A
53
95
60
H
Ph
1j
2j
Ph
a Conditions A: substrate 1 (1 mmol), palladium(II) trifluoroacetate (0.1 mmol), pyridine (0.4 mmol) and DABCO (0.4 mmol) in 10 mL of toluene under 1 atm
oxygen at 95 °C; Conditions B: substrate 1 (1 mmol), palladium(II) acetate (0.1 mmol), pyridine (0.4 mmol) and K2HPO4 (2 mmol) in 10 mL of toluene under 1
atm oxygen at 95 °C.
b The yields and conversions were determined by isolation.
c The values in parentheses are yields of olefin isomerization products.
d Products indicated are the major products.
With two optimized reaction conditions in hand, we
then explored the generality of this cascade cyclization. No-
tably, reaction rate under conditions A is generally faster
than that under conditions B (Table 2, entries 1, 2 and 10,
11); however, high diastereoselectivity can be obtained un-
der conditions B. A variety of pyrrolizidine and indolizidine
derivatives can be obtained in moderate to good yields (Ta-
ble 2, entries 1–7, 13, and 14). For the challenging linear
substrates 1a and 1b, cyclizations proceeded smoothly to
afford the pyrrolizidine 2a and indolizidine 2b in good
yields, along with a small amount of olefin isomerization
product (Table 2, entries 1–4). When germinal disubstitut-
ed substrates 1c–e were subjected to the optimal condi-
tions A, the azabicyclic products were obtained in good
yields, with higher reaction rate than linear counterparts
(Table 2, entries 3–5), which might be explained by the
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Thorpe–Ingold effect.8 It is interesting that substrates 1f
and 1g cyclized to afford two diastereomers in moderate
yields, respectively, and the cyclization of trans-configura-
tion substrate 1g gave higher diastereoselectivity (up to
11:1) than cis isomer 1f (up to 4:1). It is noteworthy that
substrate 1h with a tosyl-protected nitrogen group on the
carbon chain can be cyclized in 58% yield to afford 2h (Table
2, entry 12), which contains a pyrazine core widely found in
pharmaceutical molecules.9 The more challenging 1,2-
disubstiuted alkenes 1i and 1j were also applicable in this
transformation. Notably, 2i and 2j were obtained from 1i
and 1j in 38% and 60% yield as single diastereomer, respec-
tively, after oxidative cascade cyclization, indicating that
the aminopalladation of aliphatic unsaturated amides pro-
ceeds via a highly syn-selective pathway.10
The investigation of the applicability of this methodolo-
gy was then focused on the synthesis of more challenging
azatricyclic systems (Table 3). Ring-containing unsaturated
amides 1k,l were tested under conditions A. However, they
are more difficult to undergo cyclization reaction than am-
ides 1a–j. In contrast, the competing β-H elimination as a
major side reaction occurred to deliver bicyclic byproducts
with two diastereomers 2.1k and 2.1k′. For substrate 1k,
the densely fused aza-tricyclic product was only obtained
in 22% yield, whereas spiro aza-tricyclic product 2l was iso-
lated in 24% yield from 1l, accompanied by lots of unidenti-
fied byproducts.
Pd(II)
O2
O
Pd(0)
Base
HN
H
O
R
1
Pd(II)H
R
O
N
H
N
2
Pd(II)
H
R
I
O
R
O
R
Pd(II)
N
H
O
N
H
H
Pd(II)
N
Pd(II)
IV
III
O
R
H
−Pd(II)H
R
2.1k
II
N
H
2'
Scheme 2 A proposed mechanism for the palladium-catalyzed aerobic
oxidative cascade cyclization and competing pathways
On the basis of previous reports4,10 and above results, a
proposed reaction mechanism is shown in Scheme 2. The
initial coordination of amide and olefin to palladium(II)
center forms complex I, followed by intramolecular amino-
palladation to afford alkylpalladium(II) complex II. This C–N
bond-formation step is proposed to proceed in a highly syn-
selective fashion,10 of which the R group is on the same face
Table 3 Substrate Scope of Azatricyclic Productsa
Pd(TFA)2 (10 mol%)
pyridine (40 mol%)
DABCO (40 mol%)
monocyclization
product
substrate
byproduct
+
1k−l
2k−l
2.1k
toluene, O2, 95 °C
Entry
Substrate
Product
Monocyclization product Time (h)
Conv. (%)b
Yield (%)b,c
22 (29, 23)
O
O
O
N
H
N
N
H
1
24
100
H
H
H
H
2k
1k
2.1k & 2.1k'
O
O
N
NH
2
–
86
80
24
H
2l
1l
a Reaction conditions: substrate 1 (1 mmol), palladium(II) trifluoroacetate (0.1 mmol), pyridine (0.4 mmol), and DABCO (0.4 mmol) in 10 mL of toluene under 1
atm oxygen at 95 °C.
b Isolated yield unless otherwise indicated.
c The values in parenthesis are yields of two inseparable monocyclized diastereomers, which were determined by 1HNMR spectrum using 4-nitrobenzene as the
internal standard.
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as the angular hydrogen, as evidenced by the observed ste-
reochemistry of 2i and 2j. This is different from our prece-
dent work7b where a high anti selectivity was observed,11
which might be resulted from different ligands employed in
the two reaction systems. Olefin insertion of complex II de-
livers σ-organopalladium(II) complex III and subsequent β-
hydride elimination gives the final product 2 and palladi-
um(II) hydride species. The active palladium(II) species is
recycled through the reoxidation of palladium(II) hydride
by molecular oxygen.12 For ring-containing amide 1k, the
conversion of alkylpalladium(II) complex II into complex III
is unfavorable due to large ring strain. Therefore, the com-
peting β-hydride elimination predominantly occurred to
produce bicyclic side products and their corresponding di-
astereomers. On the other hand, re-insertion of Pd-H spe-
cies to product 2 is likely to proceed to deliver complex IV,
which was transformed into isomeric product 2′ via β-hy-
dride elimination.
In conclusion, we have developed an aerobic oxidative
cascade cyclization of aliphatic alkenyl amides for rapid as-
sembly of various N-heterocycles, including pyrrolizidine
and indolizidine derivatives as well as azatricyclic heterocy-
cles in moderate to good yields, using molecular oxygen as
the green oxidant.13 The observed stereochemistry indi-
cates the aminopalladation step proceeds via a syn manner.
This cascade cyclization may be applied in the synthesis of
related natural products.
Mizugaki, T.; Ebitani, K.; Kaneda, K. Angew. Chem. Int. Ed. 2006,
45, 481. (i) Zhu, J.; Liu, J.; Ma, R.; Xie, H.; Li, J.; Jiang, H.; Wang,
W. Adv. Synth. Catal. 2009, 351, 1229. (j) Campbell, A. N.; White,
P. B.; Guzei, I. A.; Stahl, S. S. J. Am. Chem. Soc. 2010, 132, 15116.
(k) Izawa, Y.; Pun, D.; Stahl, S. S. Science 2011, 333, 209.
(l) White, P. B.; Jaworski, J. N.; Zhu, G. H.; Stahl, S. S. ACS Catal.
2016, 6, 3340.
(3) For selected reviews, see: (a) McDonald, R. I.; Liu, G.; Stahl, S. S.
Chem. Rev. 2011, 111, 2981. For representative examples, see:
(b) Schultz, M. J.; Sigman, M. S. J. Am. Chem. Soc. 2006, 128,
1460. (c) Zhu, M.-K.; Zhao, J.-F.; Loh, T.-P. J. Am. Chem. Soc. 2010,
132, 6284. (d) Scarborough, C. C.; Stahl, S. S. Org. Lett. 2006, 8,
3251. (e) Wang, A.; Jiang, H.; Chen, H. J. Am. Chem. Soc. 2009,
131, 3846. (f) Shi, Z.; Ding, S.; Cui, Y.; Jiao, N. Angew. Chem. Int.
Ed. 2009, 48, 7895. (g) Ji, X.; Huang, H.; Wu, W.; Jiang, H. J. Am.
Chem. Soc. 2013, 135, 5286. (h) Li, J.; Grubbs, R. H.; Stoltz, B. M.
Org. Lett. 2016, 18, 5449.
(4) (a) Yip, K. T.; Yang, M.; Law, K. L.; Zhu, N. Y.; Yang, D. J. Am.
Chem. Soc. 2006, 128, 3130. (b) Yip, K. T.; Zhu, N. Y.; Yang, D.
Org. Lett. 2009, 11, 1911. (c) He, W.; Yip, K. T.; Zhu, N. Y.; Yang,
D. Org. Lett. 2009, 11, 5626. (d) Yip, K. T.; Yang, D. Chem. Asian J.
2011, 6, 2166. (e) Yip, K.-T.; Yang, D. Org. Lett. 2011, 13, 2134.
(f) Xing, D.; Yang, D. Org. Lett. 2013, 15, 4370. (g) Du, W.; Gu, Q.;
Li, Z.; Yang, D. J. Am. Chem. Soc. 2015, 137, 1130. (h) Ye, L.; Lo, K.-
Y.; Gu, Q.; Yang, D. Org. Lett. 2017, 19, 308.
(5) (a) Larock, R. C.; Hightower, T. R.; Hasvold, L. A.; Peterson, K. P.
J. Org. Chem. 1996, 61, 3584. (b) Cacchi, S.; Fabrizi, G. Chem. Rev.
2005, 105, 2873.
(6) The pKaof the anilido proton is about 21.5, see: (a) Bordwell, F.
G.; Ji, G. Z. J. Am. Chem. Soc. 1991, 113, 8398. The pKαof the ali-
phatic amide proton is about 26.5; see: (b) Bordwell, F. G.; Fried,
H. E. J. Org. Chem. 1991, 56, 4218.
(7) (a) Ramalingan, C.; Takenaka, K.; Sasai, H. Tetrahedron 2011, 67,
2889. (b) Du, W.; Gu, Q.; Li, Y.; Lin, Z.; Yang, D. Org. Lett. 2017,
19, 316.
Funding Information
Financial support was provided by the University of Hong Kong and
the Hong Kong Research Grants Council (HKU 706109P and HKU
(8) Jung, M. E.; Piizzi, G. Chem. Rev. 2005, 105, 1735.
(9) Romanelli, M. N.; Galeotti, N.; Ghelardini, C.; Manetti, D.;
Martini, E.; Gualtieri, F. CNS Drug Reviews 2006, 12, 39.
(10) For examples of cis-aminopalladation, see: (a) Negishi, E.-I.
Handbook of Organopalladium Chemistry for Organic Synthesis;
Wiley: New York, 2002. (b) Kočovsy, P.; Bäckvall, J.-E. Chem. Eur.
J. 2015, 21, 36. (c) Neukom, J. D.; Perch, N. S.; Wolfe, J. P. J. Am.
Chem. Soc. 2010, 132, 6276. (d) Neukom, J. D.; Perch, N. S.;
Wolfe, J. P. Organometallics 2011, 30, 1269. (e) Liu, G.; Stahl, S. S.
J. Am. Chem. Soc. 2007, 129, 6328. (f) Mai, D. N.; Wolfe, J. P. J. Am.
Chem. Soc. 2010, 132, 12157.
(11) For examples of trans-aminopalladation, see: (a) Weinstein, A.
B.; Stahl, S. S. Angew. Chem. Int. Ed. 2012, 51, 11505. (b) Mai, D.
N.; Wolfe, J. P. J. Am. Chem. Soc. 2006, 128, 2893.
(12) (a) Konnick, M. M.; Gandhi, B. A.; Guzei, I. A.; Stahl, S. S. Angew.
Chem. Int. Ed. 2006, 45, 2904. (b) Popp, B. V.; Stahl, S. S. J. Am.
Chem. Soc. 2007, 129, 4410. (c) Popp, B. V.; Stahl, S. S. Chem. Eur.
J. 2009, 15, 2915.
706112P).
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588502.
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References and Notes
(1) For selected reviews of transition-metal-catalyzed aerobic oxi-
dation, see: (a) Punniyamurthy, T.; Velusamy, S.; Iqbal, J. Chem.
Rev. 2005, 105, 2329. (b) Piera, J.; Bäckvall, J.-E. Angew. Chem.
Int. Ed. 2008, 47, 3506. (c) Shi, Z.; Zhang, C.; Tang, C.; Jiao, N.
Chem. Soc. Rev. 2012, 41, 3381. (d) McCann, S. D.; Stahl, S. S. Acc.
Chem. Res. 2015, 48, 1756.
(2) For selected reviews, see: (a) Stahl, S. S. Angew. Chem. Int. Ed.
2004, 43, 3400. (b) Stahl, S. S. Science 2005, 309, 1824.
(c) Sigman, M. S.; Jensen, D. R. Acc. Chem. Res. 2006, 39, 221.
(d) Gligorich, K. M.; Sigman, M. S. Chem. Commun. 2009, 3854.
For representative examples, see: (e) Nishimura, T.; Onoue, T.;
Ohe, K.; Uemura, S. J. Org. Chem. 1999, 64, 6750. (f) Fix, S. R.;
Brice, J. L.; Stahl, S. S. Angew. Chem. Int. Ed. 2002, 41, 164.
(g) Andappan, M. M. S.; Nilsson, P.; Larhed, M. Chem. Commun.
2004, 218. (h) Mitsudome, T.; Umetani, T.; Nosaka, N.; Mori, K.;
(13) General Procedure
To a well-stirred solution of Pd(TFA)2(33.2 mg, 0.1 mmol) in
toluene (5 mL) were added pyridine (32.3 μL, 0.4 mmol) and
DABCO (44.9 mg, 0.4 mmol). The mixture was stirred continu-
ously until the solid dissolved. The reaction solution was oxy-
genated for 15 min, then amide 1a (139.2 mg, 1.0 mmol) and
toluene (5 mL) were added. The resulting solution was stirred
under an O2 atmosphere for 15 min, then heated at 95 °C with
an air condenser under an O2 atmosphere for 21 h. The reaction
mixture was filtered through a short pad of Celite, then concen-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F

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trated in vacuo. The residue was purified by flash column chro-
matography to afford 2a (101.5 mg, 0.74 mmol, 74% yield) as a
yellow oil.
2-Methylenehexahydro-3H-pyrrolizin-3-one (2a)
Yellow liquid; analytical TLC (silica gel 60), 50% EtOAc in n-
hexane, Rf = 0.18. 1H NMR (400 MHz, CDCl3): δ = 5.93 (t, J = 2.7
Hz, 1 H), 5.28 (t, J = 2.2 Hz, 1 H), 3.77 (tt, J = 7.2, 4.9 Hz, 1 H),
3.67 (dt, J = 12.0 Hz, 8.1 Hz, 1 H), 3.21 (ddd, J = 12.3, 9.6, 3.0 Hz,
1 H), 3.00 (ddt , J = 17.0 Hz, 7.4 Hz, 2.1 Hz, 1 H), 2.50 (ddd, J =
17.0 Hz, 7.4 Hz, 3.1 Hz, 1 H), 2.26–1.93 (m, 3 H), 1.30–1.21 (m, 1
H). 13C NMR (100 MHz, CDCl3): δ = 168.3 (C), 143.0 (C), 115.2
(CH2), 58.5 (CH), 41.4 (CH2), 31.9 (CH2), 31.4 (CH2), 25.9 (CH2);
IR (CH2Cl2) 3048, 2981, 2888, 1692, 1659, 1445, 1244, 1208,
1156 cm–1. LRMS (EI, 20 eV): m/z = 137 (100) [M+]. HRMS (EI):
m/z calcd for C8H11NO [M+]: 137.0841; found: 137.0843.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F