Novel, efficient and regiospecific alkylation/arylation/heteroarylation of unsymmetrical azo compounds

Article abstract of DOI:10.1055/s-2006-926331

Excellent regioselectivity is observed in the addition of diverse organometallic nucleophiles to unsymmetrical azo compounds. Primary/secondary/ tertiary alkyl, aryl and heteroaryl substituents were introduced this way in high yields. Georg Thieme Verlag

Full text of DOI:10.1055/s-2006-926331

PAPER
843
Novel, Efficient and Regiospecific Alkylation/Arylation/Heteroarylation of
Unsymmetrical Azo Compounds
A
lkylation/Arylati
l
on/Het
groarylation
a
of
U
nsymmetrical
T
Az
o
Compoun
š
ds ubrik,a Rannar Sillard,b Uno Mäeorg*a
a
Institute of Organic and Bioorganic Chemistry, University of Tartu, Jakobi 2, 51014 Tartu, Estonia
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171-77 Stockholm, Sweden
Fax +372(7)375245; E-mail: uno.maeorg@ut.ee
b
Received 6 September 2005
metrical azoimides.6 Knochel generated diarylamines by
amination of substituted aryl azo tosylates with arylmag-
nesium, followed by subsequent one-pot allylation, reduc-
tion and hydrolysis.7 Regioselectivity of such addition is
presumably thermodynamically controlled by the differ-
ence in the electronegativities of the both nitrogen-at-
tached functional groups.
Abstract: Excellent regioselectivity is observed in the addition of
diverse organometallic nucleophiles to unsymmetrical azo com-
pounds. Primary/secondary/tertiary alkyl, aryl and heteroaryl sub-
stituents were introduced this way in high yields.
Key words: azo compounds, hydrazines, regioselectivity, neigh-
boring group effects, protecting groups
However, due to the reasons mentioned above, our main
interest is to preserve hydrazine skeleton intact. It is well
known that alkyl azo compounds are labile and tend to re-
group to corresponding hydrazones, thus making no use
for practical synthesis. Unlike them, azo compounds con-
taining aryl and acyl/alkoxycarbonyl groups are suffi-
ciently stable and readily available.4d
Many hydrazines with general formula R1R2NNR3R4 (R1–
R4 = alkyl, acyl or aryl substituent) exhibit incredible bio-
logical activity and are used in the treatment of various
diseases. A few vivid examples can refer to tuberculosis,
Parkinson disorder and hypertension. Chemical structure
of atazanavir, which represent an example of extremely
useful peptidomimetics, also includes genuine hydrazine
skeleton.1
1-Alkoxycarbonyl-2-arylhydrazines were synthesized by
two methods: highly selective catalytic arylation of alkoxy-
carbonylhydrazines with triarylbismuth diacetates4d or
acylation of monoarylhydrazines (yields 80–90%). Fur-
ther oxidation in very mild conditions furnishes azo com-
pounds in high yields (90–100%) as it is demonstrated in
Scheme 1.8 However, only Troc and PhCO groups could
be introduced into DNPNHNH2 (DNP = 2,4-dinitro-
phenyl) by direct acylation (yields: 43 and 84%, respec-
tively). Attempts to use Ac, Boc or Cbz were unsuccessful
due to side reactions. Also, it was not possible to oxidize
either TrocNHNHDNP or PhCONHNHDNP, despite the
plenty of reagents we have tested [MnO2, Br2/Py, NaBO3,
PyN-oxide, MCPBA, CF3CO3H, H2O2·(NH2)2CO].
As a consequence, a remarkable number of strategies have
been developed in order to systematize the synthesis of
multi-substituted hydrazines, making it robust and suit-
able for industry.2 Basic approach employs a set of rele-
vant protecting groups and stepwise introduction of
substituents. Each step is in fact an NH substitution reac-
tion: alkylation, acylation or arylation. Alkylation is nor-
mally performed under phase-transfer catalysis or
Mitsunobu conditions; both alkylation and acylation de-
pend strongly on the pKa of the substrate.3 The introduc-
tion of aryl substituent is more complicated, requiring
organobismuth reagents or palladium catalysis.4
Contrary to NH substitution as a way to derivatize a hy-
drazine precursor, another approach would use direct ad-
dition reaction to the N=N bond. Actually, azo
compounds with two alkoxycarbonyl groups are known as
versatile electrophiles (DEAD, DBAD). The correspond-
ing electrophilic aminations are widely used in the prepa-
ration of hydrazines, which in turn are employed as the
source of derivatized amines and amino acids via the
cleavage of N–N bond.5
Ar1NHNH2
MnO2 or
Br2/Py
Ar1NHNHCOR1
Ar1N=NCOR1
Ac)
Cl
Bi(O
CH2Cl2
Ar
, –60 °C
R1CONHNH2
Ar1 = Ph, o-Tol; R1CO = Boc, Ac, Z
Cu, CH
Scheme 1 Synthesis of unsymmetrical aryl azo compounds
The reaction, as outlined in Scheme 2, was never reported
before. The process can be easily monitored by TLC. Re-
gardless of the fact that the reaction closely resembles ti-
tration (extremely fast, ca. 15–20 min at –80 °C), the
addition is still regiospecific, as it was confirmed by the
1H NMR analysis of the crude mixtures. Namely,
R1CONH proton is clearly distinguishable from ArNH,
which should appear if the addition happens to be nonse-
lective. Also, the reaction of BuLi with BocN=NPh yield-
Surprisingly, there are only two reports regarding nucleo-
philic addition to unsymmetrically substituted azo com-
pounds. Evans used chiral Cu complexes in
enantioselective amination of enol silanes with unsym-
SYNTHESIS 2006, No. 5, pp 0843–0846
x
x
.
x
x
.2
0
0
6
Advanced online publication: 07.02.2006
DOI: 10.1055/s-2006-926331; Art ID: Z16605SS
© Georg Thieme Verlag Stuttgart · New York

844
O. Tšubrik et al.
PAPER
ed BocNHNPh(Bu), a compound which was described Arylzinc was too slow to react and aryllithium might
previously.4d 1H, 13C NMR data and HRMS spectra were sometime pose a problem, e.g. as in the case of the forma-
identical in both cases (see experimental).
tion of 2-thienyllithium, where BuLi attacked 50% of ar-
omatic H instead of performing the halogen–metal
exchange. A solution of citric acid in THF was found to
be the best option to quench the reaction at low tempera-
tures.
O
R1C
O
R1C
Alkyl-Li
(Mg, Zn)
Ar2MgCl
(Ar2Li)
Ar2
Ar1
R2
Ar1N=NCOR1
N
N
N
N
Ar1
H
H
The reasonable explanation of the unusual selectivity of
the addition is still not known. At the first sight, it seems
that the reaction is ruled mostly by the difference in elec-
tronegativities of R1CONH and NHAr, but it is difficult to
imagine that the process is thermodynamically controlled
and there is a fast equilibrium between two possible an-
ions RCON––NRAr and RCONHN––Ar at –80 °C. There-
fore, a possibility of kinetic control via steric hindrance
was checked using AcN=NPh as starting material. De-
spite low steric hindrance on AcNH in comparison to
bulky BocNH, the latter compound still gave very selec-
tive addition of alkylzinc compounds. Finally, steric hin-
drance on aryl substituent was increased using ortho-tolyl
substituent [see examples with BocN=N(o-Tol)] where no
difference from BocN=NPh was detected.
Scheme 2 Regioselective alkylation/arylation
The results of the derivatization are shown in Table 1. Or-
ganolithium and organomagnesium compounds gave ex-
tremely fast alkylation. The yield and the purity increase
with lowering of the temperature. However, according to
NMR studies, the formation of side products is not due to
the nonselectivity of addition. The only case where we
have observed nonspecific addition, was actually the reac-
tion between i-PrMgCl and BocN=NPh, probably due to
the extreme reactivity of such organomagnesium reagents
1
(PhNH proton was clearly visible in the H NMR of the
product). Organozinc compounds, which are easily pre-
pared from organolithiums just before use, were found to
be versatile alkylating reagents. The reaction time is still
the same 15 minutes, but side products are not detected.
BuLi and ArMgHal were added directly to azo com-
pounds, since the reverse version – addition of azo com-
pounds to BuLi resulted in the incomplete reaction and
formation of side products. However, in the case of orga-
nozinc reagents the reverse addition sequence is more
convenient from the practical point of view and was ac-
complished with no problems.
Metal–halogen exchange reactions were used to generate
heteroarylmagnesium derivatives in situ.9 For arylation,
organomagnesium reagents seem to be most convenient.
Table 1 Addition of Nucleophiles to Ar1N=NCOR1
In conclusion, the described procedure is an efficient way
to introduce alkyl or aryl substituents into protected azo
compound. The reaction has a number of substantial ad-
vantages: high yields and high selectivity, the introduction
of secondary and tertiary alkyl substituent is not far differ-
ent from primary. The addition is fast and sensitivity to
steric hindrance is diminished. Organozinc reagents seem
to be more suitable for alkylation in comparison to organ-
olithium, while organomagnesium is the reagent of choice
for arylation.
Substrate
Nucleophile
3-PyMgCl
i-PrZnCl
3-ThienylMgCl
BuLi
Product
1a
Yield (%)
81
BocN=NPh
BocN=NPh
BocN=NPh
BocN=NPh
BocN=NPh
BocN=NPh
BocN=NPh
BocN=NPh
ZN=NPh
1b
1c
92
91
1d
1d
1e
82a
BuZnCl
ca. 100
81
p-TolMgBr
p-TolMgBr
t-BuZnCl
BuLi
NMR spectroscopy was performed on a Bruker AC 200P spectrom-
eter, operating at 200 MHz (1H NMR) and 50 MHz (13C NMR).
TMS was used as internal standard. Melting points were deter-
mined on a Gallenkamp melting point apparatus. High-resolution
mass spectrometry was carried out on a Ettan ESI-ToF electrospray
time-of-flight instrument.
1e
ca. 100a
97
1f
2a
70
ZN=NPh
BuZnCl
2a
85
Oxidation of Hydrazines with MnO2; (1-tert-Butoxycarbon-
yl)phenyldiazene; Typical Procedure
ZN=NPh
i-PrMgCl
BuZnCl
2b
3a
77
BocNHNHPh (1.52 g, 7.5 mmol) was dissolved in CH2Cl2 (10 mL).
Activated MnO2 (3.26 g, 5 equiv) was added and the reaction was
monitored by TLC (1:4 EtOAc–hexane). After the starting material
had been consumed (15–20 min), the suspension was filtered and
the filtrate evaporated, furnishing 1.35 g of BocN=NPh as dark or-
ange oil (90%).
AcN=NPh
AcN=NPh
AcN=NPh
BocN=N(o-Tol)
BocN=N(o-Tol)
96
i-PrMgCl
t-BuZnCl
BuZnCl
3b
3c
88
54
4a
91
1H NMR (CDCl3): d = 1.67 [s, 9 H, C(CH3)3], 7.5–7.6 (m, 3 H,
C6H5), 7.8–7.9 (m, 2 H, C6H5).
p-TolMgCl
4b
93
13C NMR (CDCl3): d = 28.0 ([C(CH3)3], 123.5, 129.2, 133.3, 151.8
(C6H5), 161.3 (C=O).
a Reaction was conducted at –100 °C.
Synthesis 2006, No. 5, 843–846 © Thieme Stuttgart · New York

PAPER
Alkylation/Arylation/Heteroarylation of Unsymmetrical Azo Compounds
845
Addition of Nucleophiles to Azo Compounds; tert-Butyl 1-Iso-
propyl-2-phenylhydrazine-1-carboxylate (1b); Typical Proce-
dure
1f
White crystals; mp 123–124 °C.
1H NMR (CDCl3): d = 1.17 [s, 9 H, (CH3)3CN], 1.42 [s, 9 H,
C(CH3)3], 6.42 (br s, 1 H, NH), 7.1–7.3 (m, 5 H, C6H5).
13C NMR (CDCl3): d = 26.8 [(CH3)3CN], 28.4 [C(CH3)3], 58.9
[(CH3)3CN], 79.8 [C(CH3)3], 124.9, 125.9, 128.2, 148.1 (C6H5),
155.7 (C=O).
HRMS (ESI): m/z calcd for C15H25N2O2 [MH]+: 265.1916; found:
265.1956.
An oven-dried flask was charged with a melt of ZnCl2 (100 mg, 0.74
mmol, 1.3 equiv) under argon, then evacuated and backfilled with
argon. At 0 °C, THF (2 mL) was added to dissolve the solid, fol-
lowed by a 1.6 M solution of i-PrMgCl in THF (0.46 mL, 0.74
mmol). The reaction mixture was stirred for 0.5 h and then cooled
down to –80 °C. A solution of BocN=NPh (117 mg, 0.567 mmol)
in THF (2 mL) was added dropwise and the obtained mixture stirred
for 20 min. TLC (1:4 EtOAc–hexane) confirmed that the starting
material had been consumed. The reaction was quenched by adding
a solution of citric acid (240 mg, 2 equiv) in THF (3 mL). The mix-
ture was stirred, then partitioned between H2O (5 mL) and CH2Cl2
(30 mL). The aqueous phase was extracted with CH2Cl2 (3 × 10
mL) and the combined organic phases were dried (MgSO4) and
evaporated, to give the crude product as a white solid. Purification
by chromatography (1:4 EtOAc–hexane) furnished 136 mg (92%)
of 1b pure by TLC; white crystals (hexane–CHCl3); mp 97–99 °C.
2a
White crystals; mp 67–69 °C.
1H NMR (CDCl3): d = 0.91 (t, J = 7.2 Hz, 3 H, CH3CH2CH2CH2),
1.31 (m, 2 H, CH3CH2CH2CH2), 1.56 (m, 2 H, CH3CH2CH2CH2),
3.41 (m, 2 H, CH3CH2CH2CH2), 5.13/5.11 (s, 2 H, CH2OCO), 6.6–
6.9 (m, 3 H, NH + C6H5), 7.1–7.4 (m, 8 H, C6H5).
13C NMR (CDCl3): d = 13.9 (CH3CH2CH2CH2), 20.2
(CH3CH2CH2CH2),
(CH3CH2CH2CH2), 67.3 (CH2OCO), 113.1, 119.4, 128.2, 128.5,
129.1, 136.2, 149.2 (C6H5), 155.8 (C=O).
HRMS (ESI): m/z calcd for C18H22ClN2O2 [MCl]–: 33.1370; found:
333.1410.
28.4
(CH3CH2CH2CH2),
52.5
In general the chemical shifts of conformers in the 1H NMR spectra
are given in decreasing order of intensity and separated by slashes.
1H NMR (CDCl3): d = 1.14 [d, J = 3.8 Hz, 6 H, (CH3)2CH], 1.50/
1.39 [s, 9 H, C(CH3)3], 4.15 [m, 1 H, (CH3)2CH], 6.13 (s, 1 H, NH),
6.75–6.85 (m, 3 H, C6H5), 7.15–7.3 (m, 2 H, C6H5).
13C NMR (CDCl3): d = 18.2 [(CH3)2CH], 28.3 [C(CH3)3], 50.6
[(CH3)2CH], 80.4 [C(CH3)3], 113.5, 119.2, 129.2, 148.7 (C6H5),
155.9 (C=O).
HRMS (ESI): m/z calcd for C14H23N2O2 [MH]+: 251.1760; found:
251.1791.
2b
Yellow oil.
1H NMR (CDCl3): d = 1.13 [t, J = 5.4 Hz, 6 H, (CH3)2CH], 4.13 [m,
1 H, (CH3)2CH], 5.16/5.10 (m, 2 H, CH2OCO), 6.47/6.53 (s, 1 H,
NH), 6.7–6.9 (m, 3 H, C6H5), 7.1–7.4 (m, 7 H, C6H5).
13C NMR (CDCl3): d = 18.1 [(CH3)2CH], 50.9 [(CH3)2CH], 67.3
(CH2OCO), 113.8, 119.7, 128.2, 128.5, 130.0, 136.2, 148.4 (C6H5),
156.8 (C=O).
Structures of all compounds prepared (Table 1) were confirmed
with the help of spectral and analytical data. Analytical samples
were obtained by crystallization from hexane–CHCl3.
HRMS (ESI): m/z calcd for C17H20ClN2O2 [MCl]–: 319.1213;
found: 319.1233.
1a
Yellow oil.
1H NMR (CDCl3): d = 1.41/1.31 [s, 9 H, C(CH3)3], 7.05–7.45 (m, 7
H, NH + C6H5 + Hpyridyl), 7.71, 8.18, 8.42 (br s, 3 Hpyridyl).
3a
Yellowish crystals; mp 93.5–95 °C.
13C NMR (CDCl3): d = 28.2 [C(CH3)3], 81.6 [C(CH3)3], 120.4,
123.4, 124.0, 124.9, 129.4, 140.2, 142.7, 143.0, 145.3 (C6H5 + py-
ridyl CH, C), 155.3 (C=O).
HRMS (ESI): m/z calcd for C16H20N3O2 [MH]+: 286.1556; found:
286.1601.
1H NMR (CDCl3): d = 0.95 (t, J = 9.6 Hz, 3 H, CH3CH2CH2CH2),
1.34 (m, 2 H, CH3CH2CH2CH2), 1.96 (m, 2 H, CH3CH2CH2CH2),
1.97/1.91 (s, 3 H, CH3CO), 3.35 (t, J = 7.6 Hz, 2 H,
CH3CH2CH2CH2), 6.7–6.9 (m, 3 H, C6H5), 7.1–7.3 (m, 2 H, C6H5),
7.73/8.54 (s, 1 H, NH).
13C NMR (CDCl3): d = 13.87/13.92 (CH3CH2CH2CH2), 19.2/20/8
1c
(CH3CO)
20.23/20.21
(CH3CH2CH2CH2),
28.0/28.8
Grey crystals; mp 69–71 °C.
(CH3CH2CH2CH2), 54.8/52.1 (CH3CH2CH2CH2), 114.0/113.0,
1H NMR (CDCl3): d = 1.44 [s, 9 H, C(CH3)3], 6.8–7.2 (m, 9 H, NH
+ C6H5 + 3 Hthienyl).
120.6/119/1, 129.4/129.0, 149.2/148.8 (C6H5), 169.6/176.5 (C=O).
HRMS (ESI): m/z calcd for C12H18ClN2O [MCl]–: 241.1108; found:
13C NMR (CDCl3): d = 28.2 [C(CH3)3], 81.5 [C(CH3)3], 114.4,
120.8, 121.9, 122.1, 125.4, 128.8, 147.9, 149.2 (C6H5 + thienyl CH,
C), 154.8 (C=O).
HRMS (ESI): m/z calcd for C15H19N2O2S [MH]+: 291.1167; found:
291.1154.
241.1156.
3b
Yellow crystals; mp 100–102 °C.
1H NMR (CDCl3): d = 1.02/1.29/1.17 [d, J = 6.4 Hz, 6 H,
(CH3)2CH], 2.01/2.11 (s, 3 H, CH3CO), 4.17 [m 1 H, (CH3)2CH],
6.8–7.0 (m, 3 H, C6H5), 7.2–7.35 (m, 2 H, C6H5), 7.43 (br s, 1 H,
NH).
1e
White crystals; mp 110–112 °C.
13C NMR (CDCl3): d = 19.1/15.6/18.3 [CH3)2CH], 20.2/20.8
(CH3CO), 52.9/50.6 [(CH3)2CH], 115.3/114.0, 121.1/119.7, 129.5/
129.3, 149.1/147.9 (C6H5), 177.1/170.1 (C=O).
HRMS (ESI): m/z calcd for C11H16ClN2O [MCl]–: 227.0951; found:
227.1029.
1H NMR (CDCl3): d = 1.47/1.32 [s, 9 H, C(CH3)3], 2.31 (s, 3 H,
ArCH3), 6.85 (br s, 1 H, NH), 6.8–7.4 (m, 9 H, C6H5 + Harom).
13C NMR (CDCl3): d = 20.8 (ArCH3), 28.3 [C(CH3)3], 81.2
[C(CH3)3], 117.7, 121.0, 121.7, 129.0, 129.7, 133.2, 143.7, 146.9
(C6H5 + aryl CH, C), 155.7 (C=O).
HRMS (ESI): m/z calcd for C18H23N2O2 [MH]+: 299.1760; found:
299.1727.
Synthesis 2006, No. 5, 843–846 © Thieme Stuttgart · New York

846
3c
O. Tšubrik et al.
PAPER
References
Yellow crystals; mp 111–113 °C.
1H NMR (CDCl3): d = 1.15 [s, 9 H, C(CH3)3], 2.14 (s, 3 H, CH3CO),
7.1–7.3 (m, 5 H, C6H5), 9.22 (s, 1 H, NH).
13C NMR (CDCl3): d = 20.1 (CH3CO), 26.8 [C(CH3)3], 59.2
[C(CH3)3], 125.7, 126.7, 128.4, 147.4 (C6H5), 176.6/179.4 (C=O).
HRMS (ESI): m/z calcd for C15H25N2O2 [MH]+: 265.1916; found:
(1) Vilme, M.; Edwards, D.; McPherson-Baker, S. Drug
Forecast 2005, 30, 27.
(2) For a review, see: Ragnarsson, U. Chem. Soc. Rev. 2001, 30,
205; and references cited therein.
(3) (a) Mäeorg, U.; Grehn, L.; Ragnarsson, U. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 2626. (b) Tšubrik, O.; Mäeorg, U.
Org. Lett. 2001, 3, 2297. (c)Brosse, N.;Jamart-Gregoire, B.
Tetrahedron Lett. 2002, 43, 249. (d) Brosse, N.; Pinto, M.-
F.; Jamart-Grégoire, B. J. Org. Chem. 2000, 65, 4370.
(e) Ragnarsson, U.; Grehn, L.; Koppel, J.; Loog, O.; Tšubrik,
O.; Bredikhin, A.; Mäeorg, U.; Koppel, I. J. Org. Chem.
2005, 70, 5916. (f) Bredikhin, A.; Tšubrik, O.; Sillard, R.;
Mäeorg, U. Synlett 2005, 1939.
(4) (a) Mauger, C.; Mignani, G. Adv. Synth. Catal. 2005, 347,
773. (b) Tšubrik, O.; Mäeorg, U.; Sillard, R.; Ragnarsson, U.
Tetrahedron 2004, 60, 8363. (c) Loog O, ; Mäeorg U,
Synlett 2004, 2537. (d) Tšubrik, O.; Mäeorg, U.;
Ragnarsson, U. Tetrahedron Lett. 2002, 43, 6213.
(e) Wolter, M.; Klapars, A.; Buchwald, S. L. Org. Lett. 2001,
3, 3803. (f) Arterburn, J. B.; Rao, K. V.; Ramdas, R.; Dible,
B. R. Org. Lett. 2001, 3, 1351.
(5) (a) List, B. J. Am. Chem. Soc. 2002, 124, 5656.
(b) Velardo-Ortiz, R.; Guijarro, A.; Rieke, R. D.
Tetrahedron Lett. 1998, 39, 9157. (c) Bombek, S.; Požgan,
F.; Kočevar, M.; Polanc, S. J. Org. Chem. 2004, 69, 2224.
(d) Leblanc, Y.; Boudreault, N. J. Org. Chem. 1995, 60,
4268.
(6) Evans, D. A.; Johnson, D. S. Org. Lett. 1999, 1, 595.
(7) Sapountzis, I.; Knochel, P. Angew. Chem. Int. Ed. 2004, 43,
897.
265.1956.
4a
Yellowish crystals; mp 73.5–74.5 °C.
1H NMR (CDCl3): d = 0.92 (s, 3 H, CH3CH2CH2CH2), 1.3–1.7
[overlapped signals, 13 H, C(CH3)3 + CH3CH2CH2CH2), 2.34
(ArCH3), 3.14 (m, 2 H, CH3CH2CH2CH2), 6.24 (s, 1 H, NH), 6.9–
7.1 (m, 4 Harom).
13C NMR (CDCl3): d = 14.0 (CH3CH2CH2CH2), 18.5
(CH3CH2CH2CH2), 20.3 (CH3CO), 28.4 [C(CH3)3], 29.6
(CH3CH2CH2CH2), 55.8 (CH3CH2CH2CH2), 80.1 [C(CH3)3], 119.8,
124.2, 126.0, 131.1, 132.8, 149.3 (C6H5), 155.2 (C=O).
HRMS (ESI): m/z calcd for C16H26N2NaO2 [MNa]+: 301.1892;
found: 301.1876.
4b
White crystals; mp 115–116 °C.
1H NMR (CDCl3): d = 1.44 [s, 9 H, C(CH3)3], 2.22/2.19 (s, 6 H,
2 × ArCH3), 2.34 (ArCH3), 6.56 (d, 2 Harom), 6.9–7.4 (m, 7 H, NH +
Harom).
13C NMR (CDCl3): d = 18.2, 20.3 (ArCH3), 28.3 [C(CH3)3], 80.7
[C(CH3)3], 114.1, 126.4, 127.0, 129.0, 129.5, 131.1, 135.4, 144.2,
145.7 (arom CH, C), 155.0 (C=O).
(8) Starr, J. T.; Rai, G. S.; Dang, H.; McNelis, B. J. Synth.
Commun. 1997, 27, 3197.
HRMS (ESI): m/z calcd for C19H24ClN2O2 [MH]+: 347.1549; found:
347.1526.
(9) Trecourt, F.; Breton, G.; Bonnet, V.; Mongin, F.; Marsais,
F.; Queginer, G. Tetrahedron 2000, 56, 1349.
Acknowledgment
This work was financially supported by the Estonian Science Foun-
dation (No. 5255).
Synthesis 2006, No. 5, 843–846 © Thieme Stuttgart · New York