Cu(II)-mediated aminooxygenation of alkenylimines and alkenylamidines with TEMPO

Article abstract of DOI:10.1055/s-0031-1291157

A method for the synthesis of oxymethyl dihydropyrroles (pyrrolines) and dihydroimidazoles has been developed via Cu(II)-mediated intramolecular aminooxygenation of alkenylimines and alkenylamidines, respectively, with 2,2,6,6-tetramethyl-1-piperidinyloxy radical (TEMPO). Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1291157

LETTER
▌1657
lCettuer (II)-Mediated Aminooxygenation of Alkenylimines and Alkenylamidines
with TEMPO
Aminooxygenation of Alkenylimines and Alkenylamidines
Stephen Sanjaya, Sze Hui Chua, Shunsuke Chiba*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
21 Nanyang Link, 637371 Singapore, Singapore
Fax +6567911961; E-mail: shunsuke@ntu.edu.sg
Received: 12.03.2012; Accepted after revision: 16.04.2012
port the synthesis of oxymethyl dihydropyrroles (pyrro-
Abstract: A method for the synthesis of oxymethyl dihydropyr-
lines) starting from alkenyl carbonitriles and Grignard
roles (pyrrolines) and dihydroimidazoles has been developed via
reagents via Cu(II)-mediated aminooxygenation of the al-
Cu(II)-mediated intramolecular aminooxygenation of alkenylim-
kene of the resulting NH imine with 2,2,6,6-tetramethyl-
1-piperidinyloxy radical (TEMPO, Scheme 1). Moreover,
application of this strategy to N-allylamidines is also pre-
sented for the synthesis of oxymethyldihydroimidazoles
(Scheme 1).
ines and alkenylamidines, respectively, with 2,2,6,6-tetramethyl-1-
piperidinyloxy radical (TEMPO).
Key words: copper, TEMPO, dihydropyrroles (pyrrolines), dihy-
droimidazoles
Nitrogen-containing heterocycles (azaheterocycles) are
an omnipresent component of numerous natural alkaloids
and potent pharmaceutical drugs.1 Diverse approaches to-
ward azaheterocycle synthesis have been developed so
far,2 while there remains a demand for versatile method-
ologies to construct azaheterocycles with selective control
of substitution patterns from readily accessible starting
materials.
N
Cu(OAc)2
NH
O
+
N
N
DMF
X
R
O
R
X
N
C
X =
R' R'
R'
Scheme 1 Cu(II)-mediated synthesis of azaheterocycles from alke-
nylimines and alkenylamidines with TEMPO
We have been interested in the use of readily available
carbonitriles as a precursor of N-H imine by the reaction
with Grignard reagents followed by proper protonation. It
was found that the resulting N-H imines possess a diver-
sity of chemical reactivity towards oxidative C–N bond
formation with an intramolecular aryl C–H bond3 as well
as an alkene tether.4 Moreover, the N-H imines can be
served as an intramolecular directing group for copper-
catalyzed aerobic C–H oxygenation.5
Chemler has developed an elegant strategy of copper-me-
diated/-catalyzed aminooxygenation of alkenes with sul-
fonamide and aniline nitrogens with TEMPO.6,7 We
planned to use an sp2 imino nitrogen for aminooxygen-
ation of alkenes, which has been unprecedented. Based on
this background, suitable reaction conditions were first
explored using 2,2,4-trimethylpent-4-enenitrile (1a) and
p-tolylmagnesium bromide (2a) as starting materials (Ta-
ble 1). Addition of p-tolylmagnesium bromide (2a) to car-
bonitrile 1a occurred smoothly in Et2O at 60 °C (in a
sealed tube). After protonation with MeOH,8 solvent (the
reaction was diluted to 0.1 M) and copper salts as well as
TEMPO (1.5 equiv) were subsequently added. The de-
sired aminooxygenation proceeded smoothly even at
room temperature9 when the reaction mixture was stirred
with one equivalent of Cu(OAc)2 in DMF at room temper-
ature under a N2 atmosphere, affording oxymethyl pyrro-
line 3aa in 68% yield after two hours (Table 1, entry 1),
whereas other Cu(II) complexes such as Cu(OTf)2 and
CuCl2 were not viable for this transformation (Table 1, en-
tries 2 and 3). A catalytic use of Cu(OAc)2 (10 mol%) in
DMF under an O2 atmosphere provided only a trace
amount of 3aa (Table 1, entry 4). It was found that use of
pyridine as a solvent served for enhancement of the cata-
lytic turnover, giving 3aa in 54% yield with 10 mol% of
Cu(OAc)2 (Table 1, entry 5).
For the case of oxidative C–N bond formation with the in-
tramolecular C=C bond, we recently developed the
PhI(OAc)2-mediated aminobromination to provide func-
tionalized cyclic imines, such as bromomethyl dihydro-
pyrroles and dihydroisoquinolines, with a one-pot
formation of C–C, C–N, and C–Br bonds.4 This transfor-
mation was carried out by a sequence of nucleophilic ad-
dition of Grignard reagents (RMgBr) to alkenyl
carbonitriles to form N-H imines and their iminobromina-
tion by subsequent treatment with PhI(OAc)2, where the
bromine atom of the counteranion of the Grignard re-
agents was incorporated into the final products without
utilizing additional bromine sources.
Inspired by these findings, we have strived to develop the
other types of oxidative functionalization of the C=C bond
with the transient N-H imine intermediates. Herein, we re-
SYNLETT 2012, 23, 1657–1661
Advanced online publication: 11.06.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0031-1291157; Art ID: ST-2012-B0223-L
© Georg Thieme Verlag Stuttgart · New York

1658
S. Sanjaya et al.
LETTER
Table 1 Optimization of the Reaction Conditionsa
Table 3 Scope of Carbonitrilesa
1) p-TolMgBr (2a)
1) p-Tol-MgBr 2a
(1.2 equiv)
Et2O, 60 °C, 4 h
(1.2 equiv)
Et2O, 60 °C, time
(in sealed tube)
then MeOH
R1
R1
Me
R1
O
Me
R2
R2
(in sealed tube)
N
N
R1
O
N
then MeOH
N
CN
p-Tol
CN
2) copper salts
TEMPO (1.5 equiv)
conditions
p-Tol
2) Cu(OAc)2 (1.0 equiv)
TEMPO (1.5 equiv)
DMF (0.1 M), r.t., 2 h
Me
Me
Me
Me
R4
R3
R3 R4
1
3
1a
3aa
Entry Cu salts
(equiv)
Solvent
Temp
(°C)
Time
(h)
Yield
(%)b
Entry Carbonitriles 1
Pyrrolines 3
Yield
(%)b
1
Cu(OAc)2 (1.0)
Cu(OTf)2 (1.0)
DMF
r.t.
80
80
r.t.
60
2
18
5.5
18
18
68
N
O
2
DMF
36
CN
1
N
56
3
CuCl2 (1.0)
DMF
13
Me
Me
p-Tol
4c
5c
Cu(OAc)2 (0.1)
Cu(OAc)2 (0.1)
DMF
trace
54
3ba
1b
Me
Me
pyridine
a All reactions were conducted using 0.4 mmol of carbonitrile 1a with
1.2 equiv of p-tolylmagnesium bromide 2a in Et2O (0.5 mL) at 60 °C
(sealed tube) for 4 h followed by addition of MeOH (60 μL), DMF (4
mL), Cu salts, TEMPO (1.5 equiv), and stirring.
N
O
CN
N
N
N
2
51
p-Tol
b Isolated yield.
c The reaction was performed under an O2 atmosphere.
3ca
1c
Table 2 Scope of Grignard Reagentsa
1) RMgBr 2
(1.2 equiv)
N
O
CN
Et2O, 60 °C, time
(in sealed tube)
then MeOH
Me
Me
3
51
N
N
p-Tol
O
CN
Me
R
2) Cu(OAc)2 (1.0 equiv)
TEMPO (1.5 equiv)
3da
1d
Me
Me
Me
DMF (0.1 M), r.t., 2 h
1a
3
Entry
Grignard reagents 2
Time (h) Yield of 3 (%)b
N
CN
O
1
2
3
4
5
6
4-MeOC6H4MgBr (2b)
4-PhOC6H4MgBr (2c)
2-MeC6H4MgBr (2d)
2-naphthylMgBr (2e)
4-ClC6H4MgBr (2f)
2-thienylMgBr (2g)
3.5
24
3ab 49
3ac 69
3ad 58
3ae 58
3af 51
3ag 42
59%
4
(trans/cis
p-Tol
= 3:1)c
9
7
3ea
1e
Me
44
18
Me
Me
N
Me
Me
O
5
6
CN
N
54
23
a All reactions were conducted using 0.4 mmol of carbonitrile 1a with
1.2 equiv of Grignard reagents 2 in Et2O (0.5 mL) at 60 °C (sealed
tube) for 4 h followed by addition of MeOH (60 μL), DMF (4 mL),
Cu(OAc)2 (1.0 equiv), TEMPO (1.5 equiv), and stirring at r.t.
b Isolated yields.
Me
Me
p-Tol
3fa
Me
1f
N
O
CN
By using one equivalent of Cu(OAc)2 (Table 1, entry 1),
the generality for the synthesis of oxymethyl dihydropyr-
roles 3 was investigated by employing a range of alkenyl
carbonitriles 1 and Grignard reagents 2. The reactions of
1a with various Grignard reagents 2 were summarized in
Table 2. The reactions proceeded with electron-rich aryl
Grignard reagents 2b and 2c (Table 2, entries 1 and 2) as
well as sterically hindered o-tolyl and 2-naphthyl
N
1g
3ga
p-Tol
a All reactions were conducted using 0.4 mmol of carbonitrile 1 with
1.2 equiv of p-tolylmagnesium bromide 2a in Et2O (0.5 mL) at 60 °C
(sealed tube) for 4 h followed by addition of MeOH (60 μL), DMF (4
mL), Cu(OAc)2 (1.0 equiv), TEMPO (1.5 equiv), and stirring at r.t.
b Isolated yields.
c The stereochemistry was determined by NOE measurements.
Synlett 2012, 23, 1657–1661
© Georg Thieme Verlag Stuttgart · New York

LETTER
Aminooxygenation of Alkenylimines and Alkenylamidines
1659
Grignard reagents 2d and 2e (Table 2, entries 3 and 4), tively, after three days (Scheme 2, b). These results
giving oxymethyl pyrrolines 3 in moderate to good yields. indicated that TEMPO might play an important role to fa-
Introduction of 4-chlorophenyl and 2-thienyl groups cilitate the N–C bond forming (cyclization) process.12,13
could be possible (Table 2, entries 5 and 6), while no de- Examination of the substrate scope revealed that several
sired product was observed from alkyl Grignard reagents dihydroimidazoles could be prepared in good to moderate
probably due to the instability of the resulting N-H imine yields through the present aminooxygenation strategy
intermediates.
(Table 4).
The effects of substituents on the alkenyl carbonitriles 1 In summary, an expedient method for the synthesis of
were examined using p-tolylmagnesium bromide (2a, Ta- oxymethyl dihydropyrroles (pyrrolines)14 and oxymethyl-
ble 3). Dimethyl- and 2,2-diallyl-4-pentenenitriles 1b and dihydroimidazoles was developed by the Cu(II)-mediated
1c could be utilized to access 4,4-disubstituted dihydro- reactions of alkenylimines derivatives with TEMPO.15–17
pyrroles (Table 3, entries 1 and 2). A 2-azaspiro[4.5]dec- Further investigation of the scope, detailed mechanisms,
1-ene structure 3da was efficiently constructed from 1- and synthetic applications of the present strategy to other
allylcyclohexanecarbonitrile (1d, Table 3, entry 3). The azaheterocycles is currently under way.
reaction of 2-allyl-2-phenyl-4-pentenenitrile (1e) resulted
in a trans/cis mixture of 3ea in 59% yield, where trans-
Table 4 Synthesis of Dihydroimidazolesa,b
3ea was a major product (3:1 ratio; Table 3, entry 4). From
5,5-dimethyl derivative 1f, only 5-exo-cyclization was
N
observed exclusively (Table 3, entry 5). The reaction of 4-
pentenenitrile (1g) also proceeded to give dihydropyrrole
4ga while the yield was low (23%; Table 3, entry 6).
Cu(OAc)2 (1.0 equiv)
TEMPO (1.5 equiv)
O
NH
R1
N
R1
N
R2
N
DMF (0.1 M), 80 °C
15 h
R2
(a)
4
5
Cu(OAc)2 (1.0 equiv)
TEMPO (1.5 equiv)
NH
Entry Dihydroimidazoles
Yield
(%)
N
Ph
DMF, 80 °C
24 h
Ph
4a
N
N
5a R = H
5b R = 2-Me 77
5c R = 4-Cl
56
Me
O
O
1
N
N
N
54
+
Ph
R
N
N
Ph
N
Ph
Ph
Ph
5a 56%
Me
6a 6%
(b)
AcO
+
N
Cu(OAc)2
NH
N
N
O
(2.0 equiv)
2
3
5d
43
N
Ph
N
Ph
Ph
N
N
DMF, 80 °C
72 h
Ph
4a
Ph
N
Ph
6a 20%
6a' 7%
Ph
Scheme 2 Reactions of N-allylamidine 4a
N
O
Having developed this Cu(OAc)2-mediated oxyamination
of alkenylimines with TEMPO, we next examined the re-
activity of N-allylamidine 4a towards the intramolecular
aminooxygenation under the present reaction condi-
tions.10 It is noted that amidines could easily be prepared
by addition reactions of amines to the corresponding car-
bonitriles or imidate salts and generally stable to handle.11
Treatment of N-allylamidine 4a with one equivalent of
Cu(OAc)2 and 1.5 equivalents of TEMPO in DMF at
80 °C (for 24 h) afforded the aminooxygenation products,
dihydroimidazoles 5a in 56% yield along with the forma-
tion of 4-methylimidazole 6a in 6% yield (Scheme 2, a).
On the other hand, the reaction of amidine 4a with two
equivalents of Cu(OAc)2 in the absence of TEMPO was
very sluggish, giving 4-methylimidazole 6a and 4-ace-
toxymethylimidazole 6a′ in 20% and 7% yields, respec-
5e
66
N
N
S
Ph
N
O
N
4
5f
47
N
a All reactions were conducted using 0.5 mmol of N-allylamidines 4
with Cu(OAc)2 (1.0 equiv) and TEMPO (1.5 equiv) in DMF at 80 °C.
b Isolated yields were noted above with more than 90% purity of 5.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 1657–1661

1660
S. Sanjaya et al.
LETTER
J.-Y.; Chiba, S. Angew. Chem. Int. Ed. 2011, 50, 5927.
Acknowledgment
(b) Van Humbeck, J. F.; Simonovich, S. P.; Knowles, R. R.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2010, 132, 10012.
(c) Michel, C.; Belanzoni, P.; Gamez, P.; Reedjik, J.;
Baerends, E. J. Inorg. Chem. 2009, 48, 11909. (d) It could
also be proposed that the resulting Cu(III)–TEMPO complex
induces electrophilic cyclization of the imino sp2 nitrogen
with the intramolecular alkene.
This work was supported by funding from Nanyang Technological
University, Singapore Ministry of Education (Academic Research
Fund Tier 2: MOE2010-T2-1-009).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
(14) There have been reported some biologically active natural
alkaloids such as broussonetine and nectrisine bearing
oxymethyl dihydropyrrole or pyrrolidine structures, see:
(a) Merino, P.; Delso, I.; Tejero, T.; Cardona, F.; Marradi,
M.; Faggi, E.; Parmeggiani, C.; Goti, A. Eur. J. Org Chem.
2008, 2929. (b) Hulme, A. N.; Montgomery, C. H.
Tetrahedron Lett. 2003, 44, 7649.
(15) We have tried oxidative and reductive cleavage of the O–N
bond of 3aa (using MCPBA and Zn/MeOH–aq NH4Cl
conditions, respectively), while only decomposed complex
mixtures were obtained.
References and Notes
(1) For recent reviews, see: (a) Thomas, G. L.; Johannes, C. W.
Curr. Opin. Chem. Biol. 2011, 15, 516. (b) Tohme, R.;
Darwiche, N.; Gali-Muhtasib, H. Molecules 2011, 16, 9665.
(c) Dandapani, S.; Marcaurelle, L. A. Curr. Opin. Chem.
Biol. 2010, 14, 362. (d) Welsch, M. E.; Snyder, S. A.;
Stockwell, B. R. Curr. Opin. Chem. Biol. 2010, 14, 347.
(e) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T.
Org. Biomol. Chem. 2006, 4, 2337.
(2) For selected reviews, see: (a) Joule, J. A.; Mills, K.
Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell:
Chichester, 2010. (b) Progress in Heterocyclic Chemistry;
Vol. 20; Gribble, G. W.; Joule, J. A., Eds.; Elsevier: Oxford,
2008, and others in this series. (c) Comprehensive
Heterocyclic Chemistry III; Katritzky, A. R.; Ramsden,
C. A.; Scriven, E. F. V.; Taylor, R. J. K., Eds.; Pergamon:
Oxford, 2008. (d) Comprehensive Heterocyclic Chemistry
II; Katritzky, A. R.; Rees, C. A.; Scriven, E. F. V.; Taylor,
R. J. K., Eds.; Pergamon: Oxford, 1996. (e) Eicher, T.;
Hauptmann, S. The Chemistry of Heterocycles; Wiley-VCH:
Weinheim, 2003.
(3) Zhang, L.; Ang, G. Y.; Chiba, S. Org. Lett. 2010, 12, 3682.
(4) Sanjaya, S.; Chiba, S. Tetrahedron 2011, 67, 590.
(5) Zhang, L.; Ang, G. Y.; Chiba, S. Org. Lett. 2011, 13, 1622.
(6) (a) Paderes, M. C.; Belding, L.; Fanovic, B.; Dudding, T.;
Keister, J. B.; Chemler, S. R. Chem. Eur. J. 2012, 18, 1711.
(b) Paderes, M. C.; Chemler, S. R. Eur. J. Org. Chem. 2011,
3679. (c) Chemler, S. R. J. Organomet. Chem. 2011, 696,
150. (d) Sherman, E. S.; Chemler, S. R. Adv. Synth. Catal.
2009, 351, 467. (e) Paderes, M. C.; Chemler, S. R. Org. Lett.
2009, 11, 1915. (f) Fuller, P. H.; Kim, J.-W.; Chemler, S. R.
J. Am. Chem. Soc. 2008, 130, 17638.
(16) General Procedure for the Synthesis of 2,2,6,6-
Tetramethyl-1-[(2,4,4-trimethyl-5-p-tolyl-3,4-dihydro-
2H-pyrrol-2-yl)methoxy]piperidine (3aa)
To a 10 mL Schlenk tube with a Teflon valve was added
carbonitrile 1a (48.2 mg, 0.39 mmol) in Et2O (0.4 mL) and
p-tolylmagnesium bromide (2a, 0.53 mL, 0.47 mmol, 0.88
M in Et2O) was added slowly. The reaction was then heated
at 60 °C under sealed conditions for 4 h. The mixture was
quenched with distilled MeOH (60 μL) at 0 °C, and DMF (4
mL), Cu(OAc)2 (72.2 mg, 0.40 mmol), and TEMPO (91.7
mg, 0.59 mmol) were added immediately. The mixture was
further stirred at r.t. for 2 h under an inert atmosphere. The
reaction was quenched with ammonium buffer solution (pH
9) and extracted three times with Et2O. The organic phase
was then washed with H2O and brine and dried over MgSO4.
The solvent was evaporated to give a crude mixture, which
was purified by flash column chromatography (hexane–
EtOAc = 95:5) to provide 3aa (98.7 mg, 0.27 mmol) in 68%
yield.
Analytical Data
Colorless oil. IR (NaCl): 2968, 2932, 2870, 1609, 1468,
1360, 1312, 1244, 1132, 1070, 1053, 752, 731 cm–1. 1H
NMR (400 MHz, CDCl3): δ = 1.07 (3 H, s), 1.13 (3 H, s),
1.20 (3 H, s), 1.24 (3 H, s), 1.32 (3 H, s), 1.36 (3 H, s), 1.44
(3 H, s), 1.27–1.51 (6 H, m), 1.68 (1 H, d, J = 12.8 Hz), 2.34
(1 H, d, J = 12.8 Hz), 2.36 (3 H, s), 3.79 (1 H, d, J = 8.4 Hz),
3.89 (1 H, d, J = 8.4 Hz), 7.16 (2 H, d, J = 8.2 Hz), 7.60 (2
H, d, J = 8.2 Hz). 13C NMR (100 MHz, CDCl3): δ = 15.3,
18.6, 18.9, 19.6, 25.0, 26.3, 28.0, 31.4, 31.5, 38.0, 47.4, 50.0,
58.3, 70.5, 81.0, 126.3, 127.0, 130.6, 137.2, 175.8. ESI-
HRMS: m/z calcd for C24H39N2O [M + H]+: 371.3062;
found: 371.3053.
(7) For the copper-mediated diamination of alkenes in similar
manner to the oxyamination, see: Sequeira, F. C.;
Turnpenny, B. W.; Chemler, S. R. Angew. Chem. Int. Ed.
2010, 49, 6365.
(8) Pickard, P. L.; Tolbert, T. L. J. Org. Chem. 1961, 26, 4886.
(9) The copper-catalyzed/-mediated aminooxygenation with
sulfonamide and TEMPO generally needed high
temperature (110–130 °C), see ref. 6.
(10) Zhang and Zhu reported copper-catalyzed aerobic reactions
of N-allyl amidines that afforded formylimidazoles via
aminooxygenation of the alkene, see: Wang, H.; Wang, Y.;
Liang, D.; Liu, L.; Zhang, J.; Zhu, Q. Angew. Chem. Int. Ed.
2011, 50, 5678.
(11) (a) Rauws, T. R. M.; Maes, B. U. W. Chem. Soc. Rev. 2012,
41, 2463. (b) Caron, S.; Wei, L.; Douville, J.; Ghosh, A.
J. Org. Chem. 2010, 75, 945; and references cited therein.
(12) The reactions might be initiated by aminocupration of
putative copper iminyl species onto alkene followed by
conversion of the resulting organocopper species into the C–
O bond with TEMPO. For a review on synthetic applications
of TEMPO, see: Vogler, T.; Studer, A. Synthesis 2008, 1979.
(13) Recent literature precedents have shown that Cu(II) species
and TEMPO make a Cu(III)–TEMPO complex that works as
an ionic electrophile, see: (a) Wang, Y.-F.; Toh, K. K.; Lee,
(17) General Procedure for the Synthesis of 1-[(1,2-Diphenyl-
4,5-dihydro-1H-imidazol-4-yl)methoxy]-2,2,6,6-
tetramethylpiperidine (5a)
To a 25 mL Schlenk tube was added amidine 4a (136.7 mg,
0.58 mmol), Cu(OAc)2 (113.0 mg, 0.62 mmol), and TEMPO
(135.5 mg, 0.87 mmol) in DMF (6.0 mL). The reaction was
then heated at 80 °C for 24 h. The reaction was quenched
with ammonium buffer solution (pH 9) at r.t. It was then
extracted three times with EtOAc. The organic phase was
then washed with H2O and brine and dried over MgSO4. The
solvent was removed in vacuo, affording crude residue,
which was purified by flash column chromatography
(hexane–EtOAc = 80:20, gradually 20% EtOAc increment
every time after 50 mL eluent, until 100% EtOAc was
reached) to provide 5a (126.8 mg, 0.33 mmol) in 56% yield
(94% purity).
Synlett 2012, 23, 1657–1661
© Georg Thieme Verlag Stuttgart · New York

LETTER
Analytical Data
Aminooxygenation of Alkenylimines and Alkenylamidines
1661
J = 7.1, 7.4 Hz), 7.15 (2 H, dd, J = 7.6, 7.8 Hz), 7.25–7.29 (2
H, m), 7.35 (1 H, dd, J = 7.1, 7.4 Hz), 7.51 (2 H, d, J = 7.4
Hz). 13C NMR (100 MHz, CDCl3): δ = 17.0, 19.9, 20.1, 33.1,
33.3, 39.6, 56.7, 60.0, 63.5, 78.6, 122.6, 123.1, 128.1, 128.2,
128.6, 128.7, 129.8, 131.3, 143.1. ESI-HRMS: m/z calcd for
C25H34N3O [M + H]+: 392.2702; found: 392.2701.
Yellow oil. IR (NaCl): 2932, 1614, 1595, 1574, 1495, 1470,
1385, 1360, 1300, 1283, 1134, 1051, 1028 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 0.97 (3 H, s), 1.08 (3 H, s), 1.17 (3
H, s), 1.24 (3 H, s), 1.42–1.49 (6 H, m), 3.95–3.98 (2 H, m),
4.05–4.08 (1 H, m), 4.22 (1 H, dd, J = 9.4, 9.9 Hz), 4.33–
4.43 (1 H, m), 6.79 (2 H, d, J = 8.1 Hz), 6.96 (1 H, dd,
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 1657–1661

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