New glyco-oxazolidin-2-ones as chiral auxiliaries in boron-mediated asymmetric aldol reactions

Article abstract of DOI:10.1016/S0957-4166(99)00503-0

Two new chiral glyco-oxazolidin-2-one auxiliaries based on D-glucose are described. Some N-acyl derivatives were synthesized and used in dialkylboron-mediated asymmetric aldol reactions. All reactions delivered as the major diastereomer those predicted by the Zimmerman-Traxler model and were separated by column chromatography and mostly isolated in moderate to good yields. Copyright (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(99)00503-0

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 371–374
New glyco-oxazolidin-2-ones as chiral auxiliaries in boron-
mediated asymmetric aldol reactions
Michael Stöver, Arne Lützen and Peter Köll ∗
University of Oldenburg, Department of Chemistry, Carl-von-Ossietzky-Str. 9-11, D-26111 Oldenburg, Germany
Received 29 October 1999; accepted 11 November 1999
Abstract
Two new chiral glyco-oxazolidin-2-one auxiliaries based on D-glucose are described. Some N-acyl derivatives
were synthesized and used in dialkylboron-mediated asymmetric aldol reactions. All reactions delivered as the ma-
jor diastereomer those predicted by the Zimmerman–Traxler model and were separated by column chromatography
and mostly isolated in moderate to good yields. © 2000 Elsevier Science Ltd. All rights reserved.
Chiral oxazolidin-2-ones as introduced and developed by Evans and co-workers1 have become
versatile auxiliaries for various reactions in modern stereoselective synthesis. Based on a very sim-
ple approach to glyco-oxazolidin-2-ones, that was discovered in our laboratory in cooperation with
Hungarian colleagues,2 we recently reported on the D-xylose derived glyco-oxazolidin-2-ones 3,5-O-
isopropylidene- and 3,5-O-benzylidene-α-D-xylofurano[1,2-d]oxazolidin-20-one for the same purposes.
Their practical value in the resolution of racemic carboxylic and sulfonic acids, in diastereoselective
α-alkylations, α-acylations, α-halogenations and aldol reactions has been demonstrated.3
The success of these acetal protected reagents in stereoselective synthesis encouraged us to look
for other glyco-oxazolidin-2-ones as chiral auxiliaries. We decided to explore the applicability of the
two new compounds 3,5,6-tri-O-methyl-1-deoxy-α-D-glucofurano[1,2-d]-10,30-oxazolidin-20-one 4 and
3,5,6-tri-O-pivaloyl-1-deoxy-α-D-glucofurano[1,2-d]-10,30-oxazolidin-20-one 7. Both are prepared from
very inexpensive D-glucose. The use of methyl ether protecting groups in 4 and pivaloyl protecting groups
in 7 were chosen to obtain auxiliaries that are more stable towards acidic conditions in order to employ
them in reactions the previous auxiliaries could not be used for. Another interesting aspect is the different
steric demand of these protecting groups. Because of their importance in the asymmetric construction of
carbon–carbon bonds we decided to examine the performance of these new auxiliaries in some aldol
additions.
The first step in the synthesis of auxiliary 4 was the permethylation of 1,2-O-isopropylidene-α-D-
glucofuranose 1 (Scheme 1).4 After 1,2-deprotection of obtained compound 2 the resulting derivative 3
was converted into the target compound 4.2
∗
Corresponding author. E-mail: koell@uni-oldenburg.de
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00503-0
tetasy 3138

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M. Stöver et al. / Tetrahedron: Asymmetry 11 (2000) 371–374
Scheme 1. Synthesis of 3,5,6-tri-O-methyl-1-α-D-glucofurano[1,2-d]-10,30-oxazolidin-20-one 4. Reagents: (i) MeI, NaOH,
DMF, 3.5 h, rt; (ii) acetic acid 50%, 100°C, 5 h; (iii) KOCN, NaH2PO4, H2O, 2 h, 60°C
The synthesis of the pivaloyl protected auxiliary 7 was started by addition of potassium cyanate to
D-glucose (Scheme 2).2 The resulting oxazolidin-2-one 6 was smoothly converted into target compound
7 by addition of pivaloylchloride and pyridine in dichloromethane.5
Scheme 2. Synthesis of 3,5,6-tri-O-pivaloyl-1-deoxy-α-D-glucofurano[1,2-d]-10,30-oxazolidin-20-one 7. Reagents: (i) KOCN,
NaH2PO4, H2O, 2 h, 60°C; (ii) 1.2 equiv. pivaloychloride, pyridine, CH2Cl2, rt, 3 d
A number of different N-acyl substrates of both auxiliaries were easily prepared in good yields by
accommodating Kunieda’s technique using N,N-dimethyl-aminopyridine as catalyst6 in order to study
the steric influence of the substituents in the α-position of the N-acyl moiety on the diastereoselectivity
(Scheme 3, Table 1).
Scheme 3. N-Acylation procedure. Reagents: (i) 1.2 equiv. Et3N, 0.2 equiv. DMAP, CH2Cl2, rt, 1 h
Table 1
N-Acylation products of auxiliaries 4 and 7
The formation of the boron enolates using dibutylboryltrifluoromethanesulfonate (n-Bu2BOTf) and
diisopropylethylamine (DPEA) and the subsequent aldol condensation was carried out by adapting a
method by Evans et al. (Scheme 4, Table 2).7 For the reaction of the methyl ether protected N-acyl
derivatives, dichloromethane was used as solvent, whereas diethyl ether was the solvent of choice for the
1
reaction of the pivaloyl protected N-acyl precursors. The diastereomeric ratios were determined by H
NMR spectroscopy. In most cases it was possible to separate the major diastereomer by simple column
chromatography in yields varying from 23 to 70%.
The high selectivities can be explained by applying the widely accepted Zimmerman–Traxler peri-
cyclic chair-like transition state model.8 A non-chelated transition state is assumed to be responsible for

M. Stöver et al. / Tetrahedron: Asymmetry 11 (2000) 371–374
373
Scheme 4. Boron-mediated aldol reaction. Reagents: (i) 1.2 equiv. iPr2NEt, 1.15 equiv. n-Bu2BOTf, 0°C, 30 min; (ii) 1.1 equiv.
R00CHO, −78°C, 20 min; (iii) 0°C, 1 h; (iv) pH 7 – phosphate buffer:methanol (2:3); (v) methanol:H2O2 (2:1)
Table 2
Results of boron-mediated aldol reactions
aDetermined by 500 MHz 1H NMR spectroscopy using 1 D Win NMR software from Bruker.
bAfter column chromatography.
cThe major product could not be isolated in pure form.
the formation of the observed S1 and A2 major products. The four possible configurations are shown in
Scheme 5.
Scheme 5. The four possible diastereomers
In the case of the non-arylic N-acyl derivatives this can be explained by the formation of a Z-enolate
which is attacked from its less hindered re-face. However, the phenylacetyl derivatives 10 and 13 give rise
to the E-enolate which is attacked from the si-face, resulting in the expected A2 product. Not surprisingly,
the observed selectivities are usually higher for the auxiliary 7 with its sterically more demanding pivaloyl
protecting groups.

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M. Stöver et al. / Tetrahedron: Asymmetry 11 (2000) 371–374
The absolute configurations were determined by the cleavage of some of the β-hydroxy acids from
the auxiliaries using lithium hydroperoxide9 and subsequent comparison of the specific rotations with
literature values. It should be noted that the auxiliaries could always be recovered in high yields.
1
The structures of all isolated compounds were confirmed by H and 13C NMR spectroscopy, MS
measurements, and microanalyses. According to these studies, 4 and 7 can be used as efficient chiral
auxiliaries in stereoselective boron-mediated aldol reactions. Further investigations are in progress.
References
1. Evans, D. A.; Takaks, J. M.; McGee, L. R.; Ennis, M. D.; Mathre, D. J.; Bartroli, J. Pure Appl. Chem. 1981, 53, 1109–1127.
2. (a) Kovács, J.; Pintér, I.; Lendering, U.; Köll, P. Carbohydr. Res. 1991, 210, 155–166; (b) Kovács, J.; Pintér, I.; Töth, G.;
Györgydeák, Z.; Köll, P. Carbohydr. Res. 1993, 239, 95–106; (c) Kovács, J.; Pintér, I.; Abeln, D.; Kopf, J.; Köll, P. Carbohydr.
Res. 1994, 257, 97–106; (d) Kovács, J.; Pintér, I.; Köll, P. Carbohydr. Res. 1995, 272, 255–262.
3. (a) Köll, P.; Lützen, A. Tetrahedron: Asymmetry 1995, 6, 43–46; (b) Köll, P.; Lützen, A. Tetrahedron: Asymmetry 1996, 7,
637–640; (c) Lützen, A.; Köll, P. Tetrahedron: Asymmetry 1997, 8, 29–32; (d) Lützen, A.; Köll, P. Tetrahedron: Asymmetry
1997, 8, 1193–1206.
4. Ciucanu, I.; Kerek, F. Carbohydr. Res. 1984, 131, 209–217.
5. Kunz, H.; Harreus, A. Liebigs Ann. Chem. 1982, 41–48.
6. Ishizuka, T.; Kunieda, T. Tetrahedron Lett. 1987, 28, 4185–4188.
7. (a) Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem. Soc. 1981, 103, 2127–2129; (b) Evans, D. A.; Nelson, J. V.; Vogel, E.;
Taber, T. R. J. Am. Chem. Soc. 1981, 103, 3099–3111.
8. Zimmerman, H. E.; Traxler, M. D. J. Am. Chem. Soc. 1957, 79, 1920–1922.
9. Evans, D. A.; Britton, T.; Ellman, J. A. Tetrahedron Lett. 1987, 28, 6141–6144.