Tuning the reactivity of O-tert-butyldimethylsilylimidazolyl aminals towards organolithium reagents

Article abstract of DOI:10.1055/s-2003-40838

O-tert-Butyldimethylsilylimidazolyl aminals are N,O-acetals that form readily from aldehydes, and although they function as aldehyde stabilizing and protecting groups under various conditions, we report here that they react with organolithium reagents similarly to the parent aldehydes. The mechanism involves the intermediate formation of a 2-imidazolyl anion as is exemplified by the isolation of 2-TBDMS-imidazole. Substitution of the imidazolyl moiety at the 2-position renders these aldehyde derivatives stable to organolithium reagents, thus allowing for the tuning of their reactivity.

Full text of DOI:10.1055/s-2003-40838

LETTER
1451
Tuning the Reactivity of O-tert-Butyldimethylsilylimidazolyl Aminals
Towards Organolithium Reagents
Reactivity of
O
-
h
tert-Butyldim
a
ethylsilyl
n
A
a
minals sis Gimisis,*a Pavel Arsenyan,a,b Dimitris Georganakis,a Leondios Leondiadisc
a
Organic Chemistry Laboratory, Department of Chemistry, University of Athens, Panepistimiopolis, 15771 Athens, Greece
Fax +30(210)7274761; E-mail: gimisis@chem.uoa.gr
b
c
Visiting Researcher, Latvian Institute for Organic Synthesis, Aizkraukles 21, Riga, 1006, Latvia
Mass Spectrometry and Dioxin Analysis Laboratory, IRRP, National Centre for Scientific Research ‘Demokritos’, 15310 Athens, Greece
Received 26 April 2003
nals react with organolithium reagents similarly to the
parent aldehydes. On the other hand, substitution at the 2-
position of the imidazole moiety renders this protecting
group stable in the presence of the above reagents.
Abstract: O-tert-Butyldimethylsilylimidazolyl aminals are N,O-
acetals that form readily from aldehydes, and although they func-
tion as aldehyde stabilizing and protecting groups under various
conditions, we report here that they react with organolithium re-
agents similarly to the parent aldehydes. The mechanism involves
the intermediate formation of a 2-imidazolyl anion as is exemplified
by the isolation of 2-TBDMS-imidazole. Substitution of the imida-
zolyl moiety at the 2-position renders these aldehyde derivatives
stable to organolithium reagents, thus allowing for the tuning of
their reactivity.
In the initial exploratory work, we utilized stable alde-
hydes 1a–c and transformed them to the corresponding
N,O-acetals 2a–c in high yields, under the previously re-
ported conditions (Scheme 1).5 In the case of aldehydes
1d,e, application of the N,O-acetal formation conditions
led to the isolation of 2d and 2e, respectively, as single
diastereomers.7 The high diastereoselectivity observed in
the formation of 2d,e could be attributed to the reversibil-
ity of the initial, N,O-hemiacetal-forming, reaction. The
reaction is governed by thermodynamic control, and only
one of the isomeric N,O-hemiacetals is subsequently
trapped by TBDMSCl, thus leading to the most stable
N,O-silylacetal.
Key words: aldehydes, N,O-acetals, protecting groups, organome-
tallic reagents, Brook rearrangements
The silylation of aldehydes1 and ketones2,3 with N-(tri-
methylsilyl)-imidazole as well as other silylated azoles2,3
has been known for more than thirty years to produce tri-
methylsilyl N,O-acetals and ketals. Nevertheless, these
chromatographically labile carbonyl derivatives have not
been used extensively as synthetic intermediates. Recent-
ly, a tert-butyldimethylsilyl aminal derivative of formal-
dehyde has been employed as a protecting group for the
amino function of purines.4 Similar O-tert-butyldimethyl-
silylimidazolyl aminals have been proposed as versatile
aldehyde protecting groups.5 The latter protecting group is
rather useful in the case of labile chiral a-alkoxy alde-
hydes such as 1d,e, which are prone to condensation and/
or epimerization. Other previously prepared 5¢-nucleosi-
dyl aldehydes have been used without further purification
in the next step, often a Wittig reaction.6
Although we were unable to generate crystals of either 2d
or 2e suitable for X-ray crystallography, molecular mod-
eling and NOE results (Scheme 1) indicate that the O-TB-
DMS group lies away from the ribofuranose ring with the
imidazolyl substituent being almost vertical to the ribo-
furanose plane. We thus propose an S configuration for
the 5¢-carbon.
The N,O-acetal function in 2d was stable under the condi-
tions used for cleaving the 2-amide protection (NH4OH,
MeOH, Scheme 1). It could readily be converted back to
the aldehyde 1d by short treatment (60 min) with NH4F in
methanol, at 60 ºC, under which conditions the secondary
3¢-O-TBDMS group was stable.
N
As previously reported,5 the N,O-acetals 2a–e proved sta-
ble in the presence of MeMgCl with only traces of the cor-
responding aldehyde observed under prolonged reaction
(results not shown). On the other hand, reaction of 2a–e
with LDA in THF at –78 °C followed by quenching at
0 °C with aq NaHCO3, led to the isolation of the parent
aldehyde in high yield (entries 1, 6, 9, 12, 15, Table 1).
O
O
OHC
N
1d, X = H
1e, X = OTBDMS
NH
NHCOiPr
N
TBDMSO
X
Figure 1
We were interested in purifying and storing such labile
aldehydes as stable derivatives, which could successively
react in situ with organolithium reagents. We wish to re-
port here that O-tert-butyldimethylsilylimidazolyl ami-
The less reactive aromatic aldehydes could also be isolat-
ed in high yield after treatment of 2a,b with 1 equivalent
of t-BuLi, at –78 °C for 10 min followed by warming to
0 °C and quenching with aq NaHCO3 (entries 1, 6). Appli-
Synlett 2003, No. 10, Print: 05 08 2003.
Art Id.1437-2096,E;2003,0,10,1451,1454,ftx,en;G09303ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

1452
T. Gimisis et al.
LETTER
Table 1 Reactions of N,O-Acetals 2a–e
Entry
SM
2a
2a
2a
2a
2a
2b
2b
2b
2c
R
R¢
Conditionsa
Product
1a
Yield%
90/89b
89
1
2
Ph
–
b or c
Ph
Me
n-Bu
Ph
e
3a8
3
Ph
e
3b9
3c10
3d11
1b
90
4
Ph
e
65
5
Ph
t-Bu
–
e
84
6
4-(MeO)C6H4
4-(MeO)C6H4
4-(MeO)C6H4
t-Bu
b or c
88/85b
92
7
Me
t-Bu
–
e
e
b
e
e
3e8
8
3f12
1c
80
9
85
10
11
2c
t-Bu
t-Bu
Ph
3g13
3d
80
2c
t-Bu
77
12
13
14
2d
2d
2d
–
t-Bu
–
b or d
e
f
1d
3hc
4d
78/88b
55
85
O
GiBu
TBDMSO
X
X = H
X = OTBDMS
15
2e
t-Bu
b or d
1e
82/90b
a Conditions are described in Scheme 1.
b Yields for the two possible routes, respectively.
c Isolated as a chromatographically separable mixture of diastereomers (ca. 1:1).
cation of 2 equivalents of an organolithium reagent, such Based on the results described above, we propose that the
as MeLi, n-BuLi, t-BuLi or PhLi to 2a–c under the same mechanism (Scheme 2) involves an initial proton abstrac-
conditions led to the corresponding alcohols 3a–g which tion of the 2-H proton of imidazole, as it is known that
were isolated in high yields (Scheme 1, Table 1). Finally, strong bases such as LDA or organolithium reagents can
2d reacted smoothly with 3 equivalents of t-BuLi at –78 readily effect this proton abstraction.15 This is indeed a
°C providing a 1:1 diastereomeric mixture of the corre- standard functionalization route for substituted imida-
sponding t-Bu adducts 3h (entry 13).14 The lack of dia- zoles. The resulting anion can induce an oxygen-to-car-
stereoselectivity in this step indicates that the chirality of bon 1,4-silyl-migration reaction of the TBDMS group,
the 5¢-carbon of the N,O-acetal is most probably lost thereby regenerating the aldehyde and a 2-TBDMS-imi-
before the nucleophilic addition step, as suggested by the dazolyl anion.
experimental evidence (vide infra).
This is a novel type of a retro-[1,4]-Brook16,17 (or West18)
rearrangement, one of the less favored [1,n]-O- to C-silyl
migrations related to the original [1,2]-C to O- Brook re-
H
arrangement.19 It is reminiscent of the 1,4-O-to-C silyl mi-
TBDMSO
f
N
H
gration reported by Keay and coworkers in furan
systems.17a–17c,17f To our knowledge, this is the first in-
stance of a retro-[1,4]-Brook rearrangement involving an
imidazolyl system. More interestingly, it appears to be the
first reported Brook-type rearrangement which involves
N
N
O
H
N
(for 2d)
2a–e
N
H
R
O
N
NH
NH2
e
TBDMSO
N
H
H
b, c, or d
a
4d
TBDMSO
HO
R
R'
RCHO
N
1a–e
3a–h
NLi
RLi
Li
Si
N
Scheme 1 Synthesis and reactions of N,O-acetals 2a–e and NOE
contacts in 4d. R and R¢ groups are given in Table 1. Conditions:
(a) TBDMSCl (1.5 equiv), imidazole (5 equiv), DMF, r.t. overnight
(b) LDA, THF, –78 °C (c) R¢Li (1.0 equiv), THF, –78 °C (d) NH4F,
MeOH, 60 °C, 1 h (e) R¢Li (2.0 equiv), THF, –78 °C (f) NH4OH in
methanol.
N
1a–e
+
2a–e
Si
R
O
B
A
Scheme 2 Proposed reaction mechanism.
Synlett 2003, No. 10, 1451–1454 © Thieme Stuttgart · New York

LETTER
Reactivity of O-tert-Butyldimethylsilylimidazolyl Aminals
1453
dissociation of the O-Si from the C-Si moieties through indication of the validity of the proposed mechanism. Fur-
C-N bond cleavage. The increased stability of the result- thermore, they provide a synthetic tool that allows for the
ing N-imidazolyl anion B relative to the initial 2-C-imida- tuning of the reactivity of aldehyde N,O-acetals, depend-
zolyl anion A (Scheme 2), as well as the liberation of the ing on whether nucleophilic addition by organolithium
aldehyde through C-N bond cleavage, are most likely the reagents is desired or not.
driving forces for this reaction.
In conclusion, we have shown that the reactivity of O-silyl
We were interested in providing further evidence in sup- imidazolyl aminals towards organolithium reagents can
port of this intriguing reaction mechanism. The prediction be tuned by the choice of the imidazole used. 2-Substitut-
put forth by the proposed mechanism was that it could be ed imidazolyl aminals are stable, as is exemplified by the
possible to isolate a 2-silyl-substituted imidazole from the 2-methyl analogs (6b,c) whereas 2-unsubstituted imida-
reaction mixture as a side product. Such 2-silyl imidazoles zolyl aminals react readily with organolithium reagents
have been reported to be unstable species,20 although a with the same ease as the parent aldehydes. The experi-
2-tert-butyldiphenyl-silylimidazole is known.21 Short col- mental evidence supports the involvement of a novel type
umn chromatography of the crude reaction mixture from of a retro-[1,4]-Brook rearrangement. We believe that this
a scale-up reaction of 2b (entry 8, Table 1) on deactivated duality of function will render these aldehyde derivatives
silica did indeed lead to the isolation of a non-polar com- useful to synthetic organic chemists.24 Application of this
pound that was attributed to 2-tert-butylsilylimidazole new methodology to nucleoside and amino acid deriva-
1
based on its H and 13C NMR data.22 In order to corro- tives is currently in progress.
borate its structure we proceeded to an independent
synthesis of 5 (Scheme 3) starting from N-trimethyl-
Acknowledgment
silylimidazole that yielded the same unstable compound
1
in 82% yield as judged by its H NMR and 13C NMR
We thank Prof. A. Yiotakis for support and helpful discussions.
Support of this research by NATO (fellowship no. DOO 850 to
P.A.), the Greek G.S.R.T. and the University of Athens (Program
70/4/5725) is gratefully acknowledged.
spectra.22
i. LDA, THF
N
N
–78 °C, 30 min
LDA, THF
2b
3b
+
References
TBDMS
N
ii. TBDMSCl, THF
–78 to 0 °C, 1 h
82 %
N
H
–78 °C, 1 h
SiMe3
(1) Ogawa, T.; Matsui, M. Agr. Biol. Chem. 1970, 34, 969.
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5
Scheme 3 Independent synthesis of 5.
(3) Andrews, P. A.; Bachur, N. R.; Musser, S. M.; Wright, J.;
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Tetrahedron Lett. 1996, 37, 7833.
Another prediction set forth by the proposed mechanism
was that blocking of the proton abstraction from the 2-po-
sition of imidazole would stabilize these N,O-acetals and
render them stable in the presence of basic organometallic
reagents. Such a stabilization is of synthetic interest as it
would provide the means for tuning the reactivity of N,O-
acetals based on the need of either protection or reaction.
(5) Quan, L. G.; Cha, J. K. Synlett 2001, 1925.
(6) (a) Saha, A. K.; Schairer, W.; Waychunas, C.; Prasad, C. V.
C.; Sardaro, M.; Upso, D. A.; Kruse, L. I. Tetrahedron Lett.
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G. Biorg. Med. Chem. 1999, 7, 2473. (d) Gunji, H.; Vasella,
A. Helv. Chim. Acta 2000, 83, 1331.
N
TBDMSCl,
R'Li
2-methylimidazole
CH3
N
1b,c
(7) 2d: Yield: 55%, white solid, mp (MeOH/H2O): 264–265 °C.
Rf (CH2Cl2/MeOH, 9:1): 0.34. 1H NMR (300 MHz, CDCl3)
d 0.07, 0.08, 0.12, 0.16 (s, 3 H each), 0.82 (s, 18 H), 1.33,
1.36 (d, 3 H each), 1.72–1.80 (m, 1 H), 2.02–2.10 (m, 1 H),
2.95 (hpt, 1 H), 4.13 (d, 1 H, J = 1.4 Hz, H-4¢), 4.53 (d, 1 H,
J = 4.9 Hz, H-3¢), 5.74 (d, 1 H, J = 1.5 Hz, H-5¢), 5.85 (dd,
1 H, J = 11.0 Hz, 4.4 Hz, H-1¢), 7.14 (s, 2 H), 7.60 (s, 1 H),
DMF, r.t., 12 h
R
OTBDMS
6b, R = 4-(MeO)C6H4, 92 %
6c, R = tBu, 84 %
Scheme 4 Synthesis of 2-methyl analogs 6b,c.
7.71 (s, 1 H), 11.78 (br s, 1 H), 12.15 ppm (br s, 1 H). 13
C
We therefore proceeded to the synthesis of the 2-methyl-
imidazolyl analogs (6b and 6c) of compounds 2b and 2c,
respectively, which were obtained in high yield under the
standard conditions (Scheme 4).23 Application of 2 equiv-
alents of any of the previously applied organolithium re-
agents at –78 °C to 6b or 6c caused no reaction after 1 h
at –78 °C, whereas only traces of aldehyde were detected
after warming up to 0 °C with the more reactive t-BuLi
reagent. The results from this last experiment are a further
NMR (125 MHz, CDCl3) d –5.2, –4.8, –4.4, –4.1, 18.3, 18.6,
19.1, 19.6, 25.9, 36.7, 38.7, 70.6, 81.6, 85.6, 89.8, 115.9,
123.0, 128.8, 139.3, 139.5, 148.3, 148.7, 156.1, 180.1 ppm.
IR (KBr): 2922, 1708, 1680, 1610, 1548, 840 cm–1. MS
(ESI): 632.4 [M + H]+, 222.5 [B + H]+. Anal. Calcd for
C29H49N7O5Si2: C, 55.12; H, 7.82; N, 15.52; Found: C,
55.30; H, 7.81; N, 15.55.
2e: Yield 50%, white solid, Rf (CH2Cl2/MeOH, 9:1): 0.38.
1H NMR (300 MHz, CDCl3) d –0.38, –0.28, 0.07, 0.09, 0.16,
0.18 (s, 3 H each) 0.74, 0.89, 0.91 (s, 9 H each) 1.32 (s, 3 H)
Synlett 2003, No. 10, 1451–1454 © Thieme Stuttgart · New York

1454
T. Gimisis et al.
LETTER
1.36 (s, 3 H) 2.92–3.00 (hpt, 1 H) 4.18 (d, 1 H, H-4¢) 4.32 (d,
1 H, H-3¢) 4.73 (s,1 H, H-2¢) 5.46 (d, 2 H, H-5¢) 5.70 (s, 1 H,
H-1¢) 7.18 (d, 2 H) 7.58 (s, 1 H) 7.73 (s, 1 H) 11.48 (br s, 1
H) 12.25 ppm (br s, 1 H). MS (ESI): 762.6 [M + H]+, 222.5
[B + H]+. Anal. Calcd for C35H63N7O6Si3: C, 55.15; H, 8.33;
N, 12.86; Found: C, 55.00; H, 8.30; N, 12.90.
(17) For earlier 1,4-O-to-Csp2 silyl migrations, see: (a) Bures, E.
J.; Keay, B. A. Tetrahedron Lett. 1987, 28, 5965. (b)Bures,
E. J.; Keay, B. A. Tetrahedron Lett. 1988, 29, 1247.
(c) Spinazzé, P. G.; Keay, B. A. Tetrahedron Lett. 1989, 30,
1765. (d) Braun, M.; Mahler, H. Angew. Chem., Int. Ed.
Engl. 1989, 28, 896. (e) Kim, K. D.; Magriotis, P. A.
Tetrahedron Lett. 1990, 31, 6137. (f) Beese, G.; Keay, B. A.
Synlett 1991, 33. (g) Wang, K. K.; Liu, C.; Gu, Y. G.;
Burnett, F. N. J. Org. Chem. 1991, 56, 1914.
(18) West, R.; Lowe, R.; Stewart, H. F.; Wright, A. J. Am. Chem.
Soc. 1971, 93, 282.
(19) Brook, A. G. J. Am. Chem. Soc. 1958, 80, 1886.
(20) (a) Pinkerton, F. H.; Thames, S. F. J. Heterocycl. Chem.
1972, 9, 67. (b) Jutzi, P.; Sakrib, W. Chem. Ber. 1973, 106,
2815.
(8) Kamal, A.; Sandbhor, M.; Ramana, K. V. Tetrahedron:
Asymmetry 2002, 13, 815.
(9) Arvidsson, P. I.; Davidsson, O.; Hilmersson, G.
Tetrahedron: Asymmetry 1999, 10, 527.
(10) Chen, D.-W.; Ochiai, M. J. Org. Chem. 1999, 64, 6804.
(11) (a) Pini, D.; Rosini, C.; Bertucci, C.; Salvadori, P. Gazz.
Chim. Ital. 1986, 116, 603. (b) Screttas, C. G.; Steele, B. R.
J. Org. Chem. 1989, 54, 1013.
(12) Eichin, K. H.; Beckhaus, H. P.; Hellmann, S.; Fritz, H.;
Peters, E. M. Chem. Ber. 1983, 116, 1787.
(21) Mathews, D. P.; McCarthy, J. R.; Barbuch, R. J. J.
Heterocycl. Chem. 1988, 25, 1845.
(13) (a) Olah, G. A.; Wu, A.; Faroog, O.; Prakash, G. K. J. Org.
Chem. 1990, 55, 1792. (b) Roberts, D. D.; Hall, E. W. J.
Org. Chem. 1988, 53, 2573.
(22) 5: Yield 82%, 1H NMR (200 MHz, CDCl3): d 0.07 (s, 6 H),
1.25 (s, 9 H), 5.0 (br s, NH), 6.98 ppm (s, 2 H). 13C NMR
(53.2 MHz, CDCl3): d 1.0 (CH3), 25.9 (C), 30.3 (CH3), 125.5
(CH), 135.7 ppm (C).
(14) 3h¢: Yield 27%, white foam, Rf (CHCl3/MeOH, 9:1): 0.53.
1H NMR (500 MHz, CDCl3) d 0.11 (s, 6 H), 0.93 (s, 9 H),
1.26 (s, 9 H), 1.29 (s, 3 H), 1.31 (s, 3 H), 2.18 (dd, 1 H, J =
13.2 Hz, 5.5 Hz), 2.71 (hpt, 1 H), 2.72–2.78 (m, 1 H), 3.37
(s, 1 H, H-5¢), 4.23 (s, 1 H, H-4¢), 4.54 (d, 1 H, J = 5.9 Hz,
H-3¢), 5.33 (br s, 1 H, OH), 6.18 (dd, 1 H, J = 9.1 Hz, 5.5 Hz,
H-1¢), 7.73 (s, 1 H), 8.70 (br s, 1 H), 12.05 ppm (br s, 1 H).
13C NMR (125 MHz, CDCl3) d –4.2, –4.1, 18.4. 19.1, 19.4,
26.2, 27.0, 35.7, 36.8, 41.1, 77.0, 80.3, 88.0, 88.5, 123.4,
138.9, 147.2, 147.7, 155.5, 178.8 ppm. MS (ESI): 508.5 [M
+ H]+, 222.5 [B + H]+. Anal. Calcd for C24H41N5O5Si: C,
56.78; H, 8.14; N, 13.79; Found: C, 56.68; H, 8.18; N, 13.83.
3h¢¢: Yield 28%, white foam, Rf (CHCl3/MeOH, 9:1): 0.57.
1H NMR (500 MHz, CDCl3) d 0.13 (s, 6 H), 0.93 (s, 9 H),
1.04 (s, 9 H), 1.26 (s, 3 H), 1.29 (s, 3 H), 2.25 (dd, 1 H, J =
13.2 Hz, 5.8 Hz), 2.70 (hpt, 1 H), 2.81–2.88 (m, 1 H), 3.57
(s, 1 H, H-5¢), 4.29 (s, 1 H, H-4¢), 4.76 (d, 1 H, J = 4.7 Hz,
H-3¢), 5.49 (br s, 1 H, OH), 6.18 (dd, H, J = 9.5 Hz, 5.9 Hz,
(23) 6b: Yield 92%, oil. Rf (CHCl3/MeOH, 98:2): 0.36. 1H NMR
(200 MHz, CDCl3): d –0.13, 0.05 [s, 3 H each, Si(CH3)2],
0.86 [s, 9 H, SiC(CH3)3], 2.24 (s, 3 H, CH3), 3.72 (s, 3 H,
OCH3), 6.45 (s, 1 H, CHO), 6.79 (d, 1 H, J = 8.7 Hz, Ar-H),
6.81 (s, 1 H, Imid-H), 6.87 (s, 1 H, Imid-H), 7.09 ppm (d, 2
H, J = 8.7 Hz, Ar-H). 13C NMR (53.2 MHz, CDCl3): d –5.0
(2 × CH3), 18.2 (C), 25.8 (3 × CH3), 36.6 (CH3), 55.5 (CH3),
80.6 (CH), 113.9 (C), 117.8 (C), 126.9 (2 × CH), 127.3 (2 ×
CH), 132.8 (C), 159.8 (C), 162.7 ppm (C). Anal. Calcd for
C18H28N2O2Si: C, 65.02; H, 8.49; N, 8.42; Found: C, 65.22;
H, 8.46; N, 8.45.
6c: Yield 84%, oil. 1H NMR (200 MHz, CDCl3): d –0.04,
0.03 [s, 3 H each, Si(CH3)2], 0.81 [s, 9 H, SiC(CH3)3], 0.86
[s, 9 H, C(CH3)3], 2.31 (s, 3 H, CH3), 5.06 (s, 1 H, CHO),
6.80 (s, 1 H, Imid-H), 6.90 ppm (s, 1 H, Imid-H). 13C NMR
(53.2 MHz, CDCl3): d –3.4, –2.8 (each CH3), 18.2 (C), 25.4
(3 × CH3), 25.7 (3 × CH3), 31.7 (C), 36.8 (CH3), 86.4 (CH),
117.2 (CH), 121.2 (CH), 162.9 ppm (C).
H-1¢), 7.77 (s, 1 H), 8.62 (br s, 1 H), 12.07 (br s, 1 H). 13
C
NMR (125 MHz, CDCl3) d –4.3, –3.6, 18.2, 19.0, 19.3, 26.1,
27.0, 34.2, 36.8, 42.1, 73.2, 80.7, 86.3, 91.4, 123.3, 139.2,
147.2, 147.7, 155.6, 178.7 ppm. MS (ESI): 508.5 [M + H]+,
222.5 [B + H]+.
(24) Typical Procedure: To a solution of the protected aldehyde
2a–e (0.5 mmol) in dry THF (20 mL/mmol) was added the
organolithium reagent (2 equiv, Table 1), drop-wise, at –78
°C. After stirring for 10 min at –78 °C the temperature was
let to slowly increase to 0 °C. The reaction mixture was
quenched with sat aq NaHCO3 at 0 °C, diluted with ethyl
acetate, the phases were separated and the organic phase was
washed with water, dried over sodium sulfate, and
concentrated under reduced pressure. The resulting crude
3a–h was purified by silica gel chromatography. Yields are
reported in Table 1.
(15) Iddon, B.; Ngochindo, R. I. Heterocycles 1994, 38, 2487.
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Synlett 2003, No. 10, 1451–1454 © Thieme Stuttgart · New York