A general approach to the quinolizidine alkaloids via an intramolecular aza-[3+3] annulation: Synthesis of (±)-2-deoxylasubine II

Article abstract of DOI:10.1055/s-0028-1087661

The first success in constructing a member of quinolizidine family of alkaloids employing an intramolecular aza-[3+3] annulation strategy is described here. The key feature is the usage of vinylogous urethane tethered to a vinyl iminium intermediate with

Full text of DOI:10.1055/s-0028-1087661

LETTER
237
A General Approach to the Quinolizidine Alkaloids via an Intramolecular
Aza-[3+3] Annulation: Synthesis of ( )-2-Deoxylasubine II
Synthesis of
(
)-2-
u
D
eoxylasubine II Zhang, Aleksey I. Gerasyuto, Quincy A. Long, Richard P. Hsung*
Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin, 777 Highland Avenue, Rennebohm Hall,
Madison, WI 53705, USA
Fax +1(608)2625345; E-mail: rhsung@wisc.edu
Received 18 September 2008
Abstract: The first success in constructing a member of quinolizi-
O
O
NR2
X
R2
O
NR2
X
R2
intramol
aza-[3+3]
dine family of alkaloids employing an intramolecular aza-[3+3] an-
nulation strategy is described here. The key feature is the usage of
vinylogous urethane tethered to a vinyl iminium intermediate with
trifluoroacetate serving as the counteranion. The proof-of-concept
is illustrated with the synthesis of 2-deoxylasubine II.
C-1,2
R1
NH
R1
X = Cl or AcO
or O2CCF3
N
N
2a
N
n
n
1
OMe
O
Me
O
O
Key words: intramolecular aza-[3+3] annulation, lasubine I,
lasubine II, quinolizidines, piperidinium trifluoroacetate salt,
Barton’s decarboxylation
O
O
Me
H
N
N
N
Me
N
2b
2c
2d
2e: used
X = O2CCF3
O
O
In the last ten years, we have been developing an aza-
[3+3] annulation reaction1,2 as a general strategy toward
alkaloid synthesis.3,4 The intramolecular variant of this
annulation has been particularly useful in natural product
synthesis. Specifically, reactions of vinylogous amides 1
(Scheme 1) tethered to a vinyl iminium motif through a
tandem sequence of N-1,4-addition and C-1,2-addition3
can lead to a diverse array of nitrogen heterocycles 2a–e,
which have been applied to a number of total syntheses of
alkaloids.5–8 Despite such success, our annulation strategy
has not been useful in approaching simple quinolizidine
and indolizidine structural motifs 3 and 4, which could be
accessed only in low yields. Consequently, this limitation
precluded us from synthesizing any quinolizidine and in-
dolizidine alkaloids, and limited us to the construction of
nitrogen heterocycles 2a–e with quinolizidine and in-
dolizidine motifs embedded therein.
Me
Me
Me
N
Me
N
low-yielding
quinolizidines
indolizidines
3
4
Scheme 1 A deficiency in the aza-[3+3] annulation
decarboxylation
[H]
O
O
X
R2
NR2
R2
R2
a general
approach
aza-[3+3]
X = CF3CO2
MeO
MeO
R1
N
R1
R1
NH
N
[H]
quinolizidines
5: vinylogous urethanes
6
OH
OH
2
2
H
H
H
4
4
4
9a
9a
N
N
N
9a
MeO
MeO
MeO
OMe
lasubine I: C4,9a-anti
OMe
II: C4,9a-syn
OMe
2-deoxylasubine II
It was not until recently did we learn that the counteranion
[X–] in these iminium salts plays a significant role in the
annulation.9 In particular, for the synthesis of 2e,8b while
iminium salts with acetate as the counteranion were com-
pletely ineffective, generating the more reactive trifluoro-
acetate iminium salt9 proved to be the solution, rendering
a vinylogous urethane deployable for the first time in the
aza-[3+3] annulation.8 We had long recognized a distinct
advantage of employing vinylogous urethanes in our aza-
[3+3] annulation being that the resulting methoxy carbon-
yl group in 2e represents an excellent functional handle
for further transformations or removal.8 Therefore, we in-
vestigated annulation reactions of vinylogous urethanes 5
tethered to a trifluoroacetate iminium salt with the intent
to develop a general approach toward the quinolizidine
Scheme 2 Establishing a general approach to quinolizidines
family of alkaloids (Scheme 2). We report here our pre-
liminary success in the synthesis of ( )-2-deoxylasubine
II.10–15
Our efforts commenced with alkyl bromide 7 prepared
from propargyl alcohol in three steps [TBDPS silylation,
alkylation with 1,4-dibromobutane, and Lindlar hydroge-
nation] with an overall yield of 57% (Scheme 3). Dis-
placement of the bromide in 7 with NaN3 gave azide 8,
and azide reduction using Staudinger’s protocol followed
by vinylogous urethane formation using alkynoate 1016
led to vinylogous urethane 1117 in 76% overall yield. Ste-
reochemistry of vinylogous urethane 11 is exclusively Z
[see NOE] likely due to the favorable internal hydrogen
bonding [proton shift of the hydrogen bonded NH: d =
SYNLETT 2009, No. 2, pp 0237–0240
x
x.
x
x.
2
0
0
8
Advanced online publication: 15.01.2009
DOI: 10.1055/s-0028-1087661; Art ID: S08708ST
© Georg Thieme Verlag Stuttgart · New York

238
Y. Zhang et al.
LETTER
MeO2C
MeO2C
OMe
N3
Br
NaN3, DMSO, r.t.
96%
H
H
H2, PtO2, MeOH, r.t.
95%
OTBDPS
OTBDPS
7: 57%
N
N
8
from propargyl alcohol
in 3 steps
MeO
MeO
OMe
16
Ph3P
THF–H2O
17: a single isomer
MeO
only Z
NOE
OMe
H
r.t.
O
88%
NOE of 17
MeOH
105 °C
O
OTBDPS
H
H
H
LiI
+
H
H
H
EtOAc
105 °C
36 h
N
H
H
H
H
NH2
OP
MeO
N
H
H
H
Ar
OMe
H
MeO
OMe
CO2Me
11: 86%
10
9: P = TBDPS
HO2C
TBAF, THF, r.t.
OMe
Barton decarboxylation
Z/E = 3.3:1
H
H
i–iii: 39% overall
OMe
N
N
O
OH
pyr-SO3, DMSO
DIPEA, 0 °C
O
O
MeO
MeO
OMe
19: 2-deoxylasubine II
OMe
NH
NH
18: 85%
MeO
MeO
OMe
OMe
Scheme 5 Synthesis of ( )-2-deoxylasubine II. Reagents and con-
ditions: (i) (COCl)2, cat. DMF, 0–25 °C; (ii) 2-mercaptopyridine-1-
oxide sodium salt, DMAP, 0–25 °C; (iii) t-BuSH, hn, tungsten lamp,
2 h.
12: 95%
13: 90%
Scheme 3 Synthesis of the vinylogous urethane precursor 13
8.48 ppm (t, 1 H, J = 5.9 Hz);].4a,7,8 Desilylation and
Parikh–Doering oxidation18 gave annulation precursor 13
with a Z/E ratio of 3.3:1 for the enal.
in 17 was accomplished using NOE experiments. Lithium
iodide promoted demethylation of 17 followed by Bar-
ton’s standard protocol for decarboxylation gave 19 in
39% overall yield for the sequence.
50 mol%
We have described here our first success in constructing a
member of quinolizidine family of alkaloids employing
the intramolecular aza-[3+3] annulation strategy. The key
feature is the usage of vinylogous urethane tethered to a
vinyl iminium ion with trifluoroacetate serving as the
counteranion, and the proof-of-concept is shown with the
synthesis of 2-deoxylasubine II. Efforts in achieving syn-
theses of other quinolizidine family members are ongoing.
N
O2CCF3
OMe
O
MeO
H
H
X
Na2SO4, EtOAc
0 °C to r.t., 16 h
O
O
NR2
NH
NH
MeO
MeO
MeO
MeO
13
14: X = O2CCF3
MeO2C
MeO2C
H
H
H2, Pd/C
N
N
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
MeO
MeO
OMe
16: 54–62%
OMe
15: not isolated
Scheme 4 Sequential aza-[3+3] annulation–hydrogenation
Acknowledgment
Authors thank NIH [NS38049] for financial support.
With the vinylogous urethane 13 tethered to the enal in
hand, 50 mol% of piperidinium trifluoroacetate salt was
used to promote the formation of vinyl iminium interme-
diate 14, and an in situ hydrogenation allowed successful
isolation of the annulation product 16 in good yield over
two operations. Although the initial annulation product 15
could be isolated, it is not as stable as 16 (Scheme 4). It is
noteworthy that this work represents the first time our aza-
[3+3] annulation method and has succeeded in construct-
ing a simple quinolizidine structural motif such as 16 in a
synthetically reliable manner.
References and Notes
(1) For reviews, see: (a) Harrity, J. P. A.; Provoost, O. Org.
Biomol. Chem. 2005, 3, 1349. (b) Hsung, R. P.;
Kurdyumov, A. V.; Sydorenko, N. Eur. J. Org. Chem. 2005,
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238.
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Shibata, K. Heterocycles 2006, 68, 2087. (h) Bose, D. S.;
Having established the feasibility of this intramolecular
aza-[3+3] annulation, we were able to complete a facile
synthesis of 2-deoxylasubine II (19) employing 16. As
shown in Scheme 5, hydrogenation of the vinylogous ure-
thane in 16 using Adam’s catalyst gave ester 17 as a single
diastereomer. The assignment of relative stereochemistry
Synlett 2009, No. 2, 237–240 © Thieme Stuttgart · New York

LETTER
Kumar, R. K. Heterocycles 2006, 68, 549. (i) Goodenough,
Synthesis of ( )-2-Deoxylasubine II
239
Kondratenko, M.; Laxmisha, M.; Pache, S.; Ratni, H.;
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Arrayas, R. G.; Adrio, J.; Carretero, J. C. J. Org. Chem.
2007, 72, 10294.
(3) For a leading reference on developing our aza-annulations,
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Wei, L.-L.; Gerasyuto, A. I.; Brennessel, W. W. J. Am.
Chem. Soc. 2002, 124, 10435.
(14) For syntheses of (–)-lasubine II, see: (a) Comins, D. L.;
LaMunyon, D. H. J. Org. Chem. 1992, 57, 5809.
(b) Chalard, P.; Remuson, R.; Gelas-Mialhe, Y.; Gramain,
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M. D.; Lim, V. J. J.; Parvez, M. J. Org. Chem. 2005, 70,
967. (i) Liu, S.; Hua, W.; Haji, A.; Liao, L.; Wang, W.
Zhongguo Yaoke Daxue Xuebao 2007, 38, 193. (j) Kim, G.;
Lim, J. Tetrahedron Lett. 2008, 49, 88.
(15) For syntheses of (+)-lasubine II, see: (a) Yu, R. T.; Rovis, T.
J. Am. Chem. Soc. 2006, 128, 12370. (b) Mancheno, O. G.;
Arrayas, R. G.; Adrio, J.; Carretero, J. C. J. Org. Chem.
2007, 72, 10294.
(16) For a synthesis of 10, see: O’Malley, S. J.; Tan, K. L.;
Watzke, A.; Bergman, R. G.; Ellman, J. A. J. Am. Chem.
Soc. 2005, 127, 13496.
(4) Also see: (a) Ghosh, S. K.; Buchanan, G. S.; Long, Q. A.;
Wei, Y.; Al-Rashid, Z. F.; Sklenicka, H. M.; Hsung, R. P.
Tetrahedron 2008, 63, 883. (b) Sydorenko, N.; Hsung,
R. P.; Vera, E. L. Org. Lett. 2006, 8, 2611. (c) Sydorenko,
N.; Hsung, R. P.; Darwish, O. S.; Hahn, J. M.; Liu, J. J. Org.
Chem. 2004, 69, 6732. (d) McLaughlin, M. J.; Hsung, R. P.;
Cole, K. C.; Hahn, J. M.; Wang, J. Org. Lett. 2002, 4, 2017.
(e) Sklenicka, H. M.; Hsung, R. P.; Wei, L.-L.; McLaughlin,
M. J.; Gerasyuto, A. I.; Degen, S. J.; Mulder, J. A. Org. Lett.
2000, 2, 1161. (f) Hsung, R. P.; Wei, L.-L.; Sklenicka, H.
M.; Douglas, C. J.; McLaughlin, M. J.; Mulder, J. A.; Yao,
L. J. Org. Lett. 1999, 1, 509.
(5) For structural types 2a and 2b, see: Wei, L.-L.; Sklenicka,
H. M.; Gerasyuto, A. I.; Hsung, R. P. Angew. Chem. Int. Ed.
2001, 40, 1516.
(6) For structural type 2c, see: (a) Luo, S.; Zificsak, C. Z.;
Hsung, R. P. Org. Lett. 2003, 5, 4709. (b) Sydorenko, N.;
Zificsak, C. A.; Gerasyuto, A. I.; Hsung, R. P. Org. Biomol.
Chem. 2005, 3, 2140.
(17) Selected Experimental Procedures and
Characterizations
Aza-[3+3] Annulation
(7) For structural type 2d, see: (a) Swidorski, J. J.; Wang, J.;
Hsung, R. P. Org. Lett. 2006, 8, 777. (b) Wang, J.;
Swidorski, J. J.; Sydorenko, N.; Hsung, R. P.; Coverdale,
H. A.; Kuyava, J. M.; Liu, J. Heterocycles 2006, 70, 423.
(8) For structural type 2e, see: (a) Gerasyuto, A. I.; Hsung, R. P.
Org. Lett. 2006, 8, 4899. (b) Gerasyuto, A. I.; Hsung, R. P.
J. Org. Chem. 2007, 72, 2476.
(9) For an asymmetric intramolecular aza-[3+3] annulation, see:
Gerasyuto, A. I.; Hsung, R. P.; Sydorenko, N.; Slafer, B. W.
J. Org. Chem. 2005, 70, 4248.
(10) For isolations of ( )-lasubine I and II, see: (a) Fuji, K.;
Yamada, K.; Fujita, E.; Murata, H. Chem. Pharm. Bull.
1978, 26, 2515. (b) For a leading review in quinolizidine
alkaloids, see: Michael, J. P. Nat. Prod. Rep. 2008, 25, 139;
and references cited therein.
(11) For syntheses of ( )-lasubine I and II, see: (a) Iida, H.;
Tanaka, M.; Kibayashi, C. J. Chem. Soc., Chem. Commun.
1983, 20, 1143. (b) Iida, H.; Tanaka, M.; Kibayashi, C.
J. Org. Chem. 1984, 49, 1909. (c) Ent, H.; De Koning, H.;
Speckamp, W. N. Heterocycles 1988, 27, 237. (d) Bardot,
V.; Gardette, D.; Gelas-Mialhe, Y.; Gramain, J.-C.;
Remuson, R. Heterocycles 1998, 48, 507. (e) Narasaka, K.;
Yamazaki, S.; Ukaji, Y. Chem. Lett. 1985, 1177.
To a stirring heterogeneous suspension of enal 13 (2.81 g,
8.09 mmol) and grounded Na2SO4 (flame-dried, 9.00 g) in
freshly distilled anhyd EtOAc (180 mL) was added
piperidinium trifluoroacetate salt (796.0 mg, 4.00 mmol) at
0 °C. The resulting suspension was allowed to warm up to
r.t. slowly. After 16 h, NMR showed complete consumption
of the aldehyde. To this reaction mixture was added Pd/C
(869.0 mg, 0.81 mmol), and the flask was filled with H2 gas
by five evacuate–back-fill cycles. After which, the mixture
was stirred under H2 at r.t. for 6 h. The mixture was then
filtered through CeliteTM to remove the solid, and the
solution was concentrated in vacuo to give a reddish oil. The
crude product was purified by silica gel flash column
chromatography buffered with Et3N (isocratic eluent:
EtOAc–hexanes, 1:2) to give the desired annulation product
16 (1.65 g, 4.98 mmol) in 62% yield as yellow solid.
Compound 16: Rf = 0.32 (EtOAc–hexanes, 1:2); mp 114–
117 °C. 1H NMR (400 MHz, CDCl3): d = 1.21–1.25 (m, 1
H), 1.36–1.42 (m, 3 H), 1.66–1.75 (m, 2 H), 1.78 (d, 1 H,
J = 6.4 Hz), 1.95 (dd, 1 H, J = 6.5, 13.1 Hz), 2.37–2.54 (m,
3 H), 3.11–3.14 (m, 2 H), 3.36 (s, 3 H), 3.83 (s, 3 H), 3.86 (s,
3 H), 6.63 (s, 1 H), 6.67 (d, 1 H, J = 8.2 Hz), 6.82 (d, 1 H,
J = 8.2 Hz). 13C NMR (100 MHz, CDCl3): d = 21.4, 24.5,
26.5, 29.0, 32.7, 49.5, 50.3, 55.6, 55.8, 57.0, 95.9, 109.7,
110.6, 120.8, 130.9, 148.2, 148.6, 156.1, 168.9. IR (neat):
2940 (s), 1643 (s), 1562 (s), 1511 (s), 1122 (s) cm–1. MS
(APCI): m/e (relative intensity) = 332 (100) [M + H]+; m/e
calcd for C19H25NO4Na: 354.1676; found: 354.1679.
Hydrogenation
(f) Hoffmann, R. W.; Endesfelder, A. Liebigs Ann. Chem.
1986, 1823. (g) Brown, J. D.; Foley, M. A.; Comins, D. L.
J. Am. Chem. Soc. 1988, 110, 7445. (h) Pilli, R. A.; Dias,
L. C.; Maldaner, A. O. Tetrahedron Lett. 1993, 34, 2729.
(i) Pilli, R. A.; Dias, L. C.; Maldaner, A. O. J. Org. Chem.
1995, 60, 717. (j) Ukaji, Y.; Ima, M.; Yamada, T.; Inomata,
K. Heterocycles 2000, 52, 563.
To a flame-dried 100 mL round-bottom flask was added
PtO2 (102.0 mg, 0.45 mmol) and MeOH (10 mL). The flask
was filled with H2 by three evacuate–back-fill cycles and the
resulting suspension was stirred at r.t. for 20 min, and the
original brown powder of PtO2 turned into black sponge. To
this heterogeneous mixture was added via syringe a solution
of the freshly purified annulation product 16 (296.0 mg, 0.89
(12) For syntheses of (–)-lasubine I, see: (a) Chalard, P.;
Remuson, R.; Gelas-Mialhe, Y.; Gramain, J.-C.
Tetrahedron: Asymmetry 1998, 9, 4361. (b) Kundig, P. E.;
Ratni, H. Org. Lett. 1999, 1, 1997. (c) Davis, F. A.; Roa, A.;
Carroll, P. J. Org. Lett. 2003, 5, 3855. (d) Kundig, P. E.;
Cannas, R.; Fabritius, C.-H.; Grossheimann, G.;
Synlett 2009, No. 2, 237–240 © Thieme Stuttgart · New York

240
Y. Zhang et al.
LETTER
mmol) in MeOH (30 mL). The resulting mixture was stirred
at r.t. for 16 h and TLC showed complete conversion of the
starting material. The solution was filtered through CeliteTM
and concentrated in vacuo. The crude product was purified
by silica gel flash column chromatography buffered with
Et3N (isocratic eluent: EtOAc–hexanes, 1:4) to give ester 17
(258.0 mg, 0.77 mmol) in 87% yield as colorless oil.
Compound 17: Rf = 0.26 (EtOAc–hexanes, 1:4). 1H NMR
(400 MHz, CDCl3): d = 1.23 (tq, 1 H, J = 4.3, 12.5 Hz),
1.35–1.44 (m, 3 H), 1.46–1.58 (m, 3 H), 1.61–1.70 (m, 2 H),
1.87 (1 H, tt, J = 4.5, 13.0 Hz), 1.87–1.91 (m, 1 H), 2.11 (1
H, dq, J = 3.6, 13.0 Hz), 2.70 (t, 1 H, J = 4.5 Hz), 2.78–2.81
(m, 1 H), 3.09 (d, 1 H, J = 4.4 Hz), 3.30 (s, 3 H), 3.80 (s, 3
H), 3.81 (s, 3 H), 6.71–6.76 (m, 2 H), 6.86 (s, 1 H). 13C NMR
(125 MHz, CDCl3): d = 24.9, 26.0, 26.7, 28.7, 33.6, 47.3,
50.7, 53.9, 55.7, 55.8, 63.3, 69.9, 110.3, 110.5, 119.7, 134.9,
147.7, 148.6, 173.6. IR (neat): 2929 (s), 1735 (s), 1591 (s),
1259 (s), 1152 (s) cm–1. MS (APCI): m/e (relative intensity)
= 334 (100) [M + H]+; m/e calcd for C19H27NO4Na:
356.1832; found: 356.1848.
was stirred at 0 °C for 2 min before oxalyl chloride (104.0
mg, 0.82 mmol) was added via syringe. The resulting
solution was allowed to warm up to r.t. over 30 min, and was
stirred at r.t. for an additional 1 h. After which, a high
vacuum (0.665–1.33 mbar) was slowly applied to remove
solvent and volatile materials. The residual material was
then further dried under high vacuum for 30 min, before it
was dissolved in anhyd CH2Cl2 (8 mL) and transferred via
syringe to a chilled solution of 2-mercaptopyridine-1-oxide
sodium salt (122.0 mg, 0.82 mmol) and DMAP (10 mg, 0.08
mmol) in anhyd CH2Cl2 (8 mL). The resulting suspension
was stirred at 0 °C with the flask shielded from light using
Al foil. It was then slowly warmed up to r.t. and stirred at r.t.
for 1.5 h.
After which, t-BuSH (587.0 mg, 6.50 mmol) was added via
syringe all at once and the yellowish suspension was then
irradiated with a 300 W tungsten lamp for 3 h with the
solution cooled by a water bath. Solvent and excess of
t-BuSH was then removed in vacuo, and 5% aq NaHCO3
(30 mL) solution was added. The aqueous layer was
extracted with Et2O (3 × 30 mL). The combined organic
layers were washed with sat. aq NaCl (10 mL), dried over
MgSO4, filtered, and concentrated in vacuo. The crude
material was purified by silica gel flash column
Demethylation of Ester 17
To a solution of ester 17 (112 mg, 0.336 mmol) in freshly
distilled EtOAc (7 mL) was added LiI (270 mg, 2.02 mmol).
The resulting solution was deoxygenated via purging with
Argon gas for 15 min, and then the reaction vessel was
sealed under Argon, wrapped with aluminum foil, and
heated in a 105 °C oil bath. After heating for 36 h, the
solution was cooled down to r.t. and filtered. The light brown
solid filter cake was washed with EtOAc (3 mL) and Et2O (2
mL), and dried in vacuo to give a brown solid. The solid salt
was then dissolved in H2O (10 mL), and acidified via
dropwise addition of 1.0 N aq HCl solution until the pH
value of the aqueous solution reached 3–4. The aqueous
solution was then saturated with solid NaCl, and extracted
with CHCl3 (6 × 8 mL). The combined organic layers were
dried over Na2SO4, filtered, and concentrated in vacuo to
give product acid 18 (91.0 mg, 0.29 mmol) in 85% yield as
a light brown solid. Acid 18 was used immediately for
decarboxylation.
chromatography buffered with Et3N (isocratic eluent:
EtOAc–hexanes, 1:4) to give product ( )-2-deoxylasubine II
(19, 44.0 mg, 0.16 mmol) in 39% yield as colorless oil,
which solidified upon standing.
Compound 19: Rf = 0.29 (EtOAc–hexanes, 1:4); mp 68–
70 °C. 1H NMR (500 MHz, CDCl3): d = 1.25 (tt, 1 H, J = 4.3,
11.5 Hz), 1.33–1.47 (m, 5 H), 1.54–1.61 (m, 4 H), 1.63–1.75
(m, 3 H), 1.87–1.92 (t, 1 H, J = 10.5 Hz), 2.66 (d, 1 H,
J = 9.3 Hz), 2.82 (dd, 1 H, J = 2.9, 10.9 Hz), 3.85 (s, 3 H),
3.88 (s, 3 H), 6.76–6.89 (m, 3 H). 13C NMR (125 MHz,
CDCl3): d = 24.8, 24.9, 26.2, 33.7, 33.8, 36.5, 53.5, 55.7,
55.9, 63.4, 70.2, 110.3, 110.7, 119.5, 138.2, 147.6, 148.9. IR
(neat): 2926 (s), 1502 (s), 1147 (s) cm–1. MS (APCI): m/e
(relative intensity) = 276 (100) [M + H]+; m/e calcd for
C17H26NO2: 276.1958; found: 276.1958.
Barton’s Decarboxylation
To a solution of acid 18 (130.0 mg, 0.41 mmol) in anhyd
CH2Cl2 (10 mL) was added one drop of DMF. The solution
(18) See: Parikh, J. R.; von Doering, W. E. J. Am. Chem. Soc.
1967, 89, 5505; this is the only oxidation in which the
Z-geometry of the vinylogous urethane does not scramble.
Synlett 2009, No. 2, 237–240 © Thieme Stuttgart · New York

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