Effects of lanthanide complexes on the facial reactivity of 2-(2′,3′,4′,6′-tetra-O-acetyl-β-D- glucopyranosyloxy)benzaldehyde in hetero-Diels-Alder reactions and a model to account for such effects

Article abstract of DOI:10.1039/a704463a

Changes in the facial reactivity of 2-(2′,3′,4′,6′-tetra-O-acetyl-β-D- glucopyranosyloxy)benzaldehyde towards (E)-1-methoxy-3-(tert-butyldimethylsiloxy)buta-1,3-diene in the presence of lanthanide(fod)₃ complexes can be correlated with the ioni

Full text of DOI:10.1039/a704463a

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Effects of lanthanide complexes on the facial reactivity of
2-(2A,3A,4A,6A-tetra-O-acetyl-b-d-glucopyranosyloxy)benzaldehyde in
hetero-Diels–Alder reactions and a model to account for such effects
Richard P. C. Cousins,a Woan Chee Ding,b Robin G. Pritchardb and Richard J. Stoodley*b
a Medicinal Science, Glaxo Wellcome Medicines Research Centre, Stevenage, Hertfordshire, UK SG1 2NY
b Department of Chemistry, UMIST, PO Box 88, Manchester, UK M60 1QD
Changes in the facial reactivity of 2-(2A,3A,4A,6A-tetra-
towards
(E)-1-methoxy-3-(tert-butyldimethylsiloxy)buta-1,3-diene
in the presence of lanthanide(fod)3 complexes can be
correlated with the ionic radius of the lanthanide metal.
into the dihydropyranones 6 and 7 in the presence of TFA.
O-acetyl-b-D-glucopyranosyloxy)benzaldehyde
Clearly, BF3·OEt2 and ZnCl2 in THF promoted attack mainly at
the si-face of the aldehyde moiety of compound 1 whereas
Eu(fod)3 in toluene induced preferential re-face addition.
Here we describe efforts that have led to improvements in the
practicality and stereoselectivity of the hetero-Diels–Alder
reaction; we also propose a model to account for the variation in
the facial reactivity of the salicylaldehyde derivative 1.
Seeking initially to increase the stabilities of the cyclo-
adducts† (compounds 8 and 10 were very prone to undergo
desilylative eliminations to give the pyranones 6 and 7), we
investigated the reaction of the aldehyde 1 with the diene 32‡
under the afore-cited cycloaddition conditions. The use of
ZnCl2 in THF and Eu(fod)3 in toluene afforded the cycloadducts
9 and 11 in ratios of 67:33 and 18:82. From the latter reaction,
it was possible to isolate the cycloadduct 11,§ mp 175–176 °C,
[a]D +53 (c 0.3, CH2Cl2), in 75% yield after crystallisation. In
accord with its structure, the cycloadduct 11 was transformed
into the dihydropyranone 7 (82% yield after crystallisation).
Expecting that a ‘matched’ chiral europium(iii) complex
would improve the diastereoselectivity, the use of (+)-Eu(hfc)3,
(2)-Eu(hfc)3, (+)-Eu(tfc)3 and (2)-Eu(tfc)3 (5 mol% of each)
as promoters was studied in toluene. Surprisingly, there was
little difference in the effects of the enantiomeric catalysts and
the selectivities were poor. Thus, the cycloadducts 9 and 11
were produced in ratios of 59:41 and 61:39 with (+)-Eu(hfc)3
and (2)-Eu(hfc)3, and in ratios of 45:55 and 47:53 with
(+)-Eu(tfc)3, and (2)-Eu(tfc)3.
Recently, we reported notable 1,5-asymmetric inductions in the
reaction of the salicylaldehyde derivative 1 with Danishefsky’s
diene 2 in the presence of Lewis acids.1 The use of BF3·OEt2
and SnCl4 (100 mol% of each) in THF led to ca. 27:3:63:7
mixtures of compounds 4–7, which were transformed by the
action of TFA into 90:10 mixtures of the dihydropyranones 6
and 7. With ZnCl2 (100 mol%) in THF and Eu(fod)3 (5 mol%)
in toluene, the cycloadducts 8 and 10 were produced in ratios of
86:14 and 25:75; the cycloadducts 8 and 10 were converted
OSiMe2R
O
R*O
O
R*O
OH
OMe
OMe
1
2 R = Me
3 R = But
4
The importance of the metal in lanthanide(fod)3 complexes in
determining the facial reactivity of the aldehyde 1 towards the
diene 3 is illustrated by the results shown in Table 1. In the first
O
O
O
R*O
OH
R*O
O
R*O
O
OMe
Table 1 Outcome of the reaction of aldehyde 1 and diene 3 in the presence
of lanthanide(fod)3 complexesa
5
6
7
Lanthanide ionic
radius/Åb
Catalyst
Ratio 9:11c
OSiMe2R
OSiMe2R
La(fod)3
Ce(fod)3
Pr(fod)3
1.06
1.03
1.01
0.99
0.95
0.94
0.91
0.89
0.88
0.86
< 5:95
< 5:95
< 5:95
< 5:95
18:82
26:74
55:45
61:39
69:31
66:34
R*O
O
R*O
O
d
OMe
OMe
Nd(fod)3
8 R = Me
9 R = But
10 R = Me
11 R = But
e
Eu(fod)3
Gd(fod)3
Dy(fod)3
Ho(fod)3
Er(fod)3
Yb(fod)3
H
O
O
LA
O
O
H
LA
13
a
Typically, the reactions were conducted using aldehyde 1 (0.1 mmol),
diene 3 (0.2 mmol) and the complex (ca. 4 mol%) in dry toluene (2 cm3).
12
b
c
1
Ref. 3. The ratio was determined by 300 MHz H NMR spectroscopic
d
OAc
analysis of the crude product and/or the derived pyranones 6/7. The
O
R* =
reaction involving Ce(fod)3 was significantly slower than the others
(requiring ca. 48 h for completion compared with ca. 5 h). The use of
different concentrations of Eu(fod)3 (ca. 10 and ca. 0.5 mol%) did not affect
the ratio of cycloadducts produced.
e
OAc
OAc OAc
Chem. Commun., 1997
2171

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octacoordination (and, as a consequence, are able to form
chelated complexes).4
The results reported herein are of both mechanistic and
synthetic note. Although the catalytic activity of lanthanide
complexes in hetero-Diels–Alder reactions has been exten-
sively investigated since Danishefsky’s foundation studies,5 the
finding that the nature of the cation can have a significant
impact upon the facial reactivity of a chiral aldehyde is novel.**
The possibility that this effect is linked to the ionic radius of the
lanthanide cation and its ability to form a monodentate versus a
bidentate complex warrants further study. From a synthetic
context, the technology permits the efficient assembly of
compounds 7 and 11 in multi-gram quantities; earlier, only the
dihydropyranone 6 was accessible in high yield.1
O(13′)
O(6′)
O(11)
O(5′)
O(4′)
O(2)
We thank the CVCP for an ORS award (to W. C. D.) and a
referee for drawing our attention to ref. 8.
O(3′)
O(2′)
O(7)
O(9′)
Footnotes and References
O(7′)
* E-mail: richard.stoodley@umist.ac.uk
† Our interest in such cycloadducts stems from the expectation that their
dihydropyran rings can be elaborated into glycopyranose-like structures;
such products, which may be regarded as ‘scaffolded’ disaccharides,
represent a novel and potentially interesting class of compounds.
‡ The diene 3 was prepared by a modification of the literature route (see ref.
2) in which (E)-4-methoxybut-3-en-2-one was treated with tert-butyldime-
thylsilyl triflate and triethylamine (see ref. 6).
Fig. 1 Molecular structure of compound 1
four examples, essentially complete ( > 95:5) re-face selectiv-
ity of the aldehyde 1 was observed. In the remaining examples,
there was (in the main) a gradual increase in si-face selectivity
as the ionic radius of the lanthanide metal decreased. Sig-
nificantly, from a synthetic standpoint, it was possible to isolate
the cycloadduct 11 in 90% yield after crystallisation from the
reaction of the salicylaldehyde 1 (11 mmol) and the diene 3 in
the presence of Pr(fod)3.
In the hope that its solid-state structure would reveal
‘preorganisation’ that might shed light on the stereoinductions,
compound 1 was subjected to an X-ray crystallographic
analysis. The molecular structure,¶ shown in Fig. 1 with its
atomic labelling, indicates that the re-face of the aldehyde
moiety is shielded by the 2A-O-acetyl group of the sugar.∑
Evidence that the solid-state conformation of compound 1
was maintained in solution (C6D6) was adduced from an NOED
spectroscopic study. Thus, irradiation of the anomeric hydrogen
atom (1A-H) caused an 8% enhancement of the aryl 3-hydrogen
atom (3-H); similarly, irradiation of 3-H enhanced 1A-H by
6%.
§ New compounds displayed analytical and spectral properties that
supported their assigned structures.
¶ Crystal data for 1: C21H24O11, M = 452.4, monoclinic, space group P21
(no. 4), a = 12.625(6), b = 6.929(5), c = 13.262(4) Å, b = 97.89(3)°,
U = 1149(11) Å3, Z = 2, Dc = 1.307 g cm23, F(000) = 476, m(Mo-
Ka) = 1.00 cm21, crystal size 0.40 3 0.15 3 0.15 mm. A total of 1947
reflections were measured, 1658 unique (Rint = 0.084) after an empirical
absorption correction (max., min. transmission = 1.00, 0.84), on a Rigaku
AFC6S diffractometer using w–2q scans (l = 0.71069 Å) at 20 °C. The
structure was solved by direct methods and refined by full-matrix least-
squares based on F2, with all non-hydrogen atoms anisotropic and hydrogen
atoms constrained in calculated positions. The final cycle converged to
R = 0.054 and wR2 = 0.138 based on 679 observed reflections [I > 2s(I)]
and 293 variables (R
= = 0.210 for all data). CCDC
0.190, wR2
182/579.
∑ A related shielding effect was noted in the X-ray structure of 5-(2A,3A,4A,6A-
tetra-O-acetyl-b-d-glucopyranosyloxy)-1,4-naphthoquinone and invoked
to account for the high facial reactivity of the dienophile in Diels–Alder
reactions (see ref. 7).
** The enantioselectivities of Diels–Alder reactions catalysed by com-
plexes of lanthanide(OTf)3 and (R)-binaphthol can be influenced by added
achiral ligands and by the lanthanide metal (see ref. 8).
From the afore-cited findings, we propose that compound 1
can be activated by Lewis acids in two ways. The formation of
a monodentate complex of type 12, in which the Lewis acid is
coordinated to the aldehyde carbonyl O-atom syn to the
aldehyde H-atom, is postulated to be the basis of the si-face
reactivity; this pattern is predominant in aldol reactions induced
1 R. P. C. Cousins, A. D. M. Curtis, W. C. Ding and R. J. Stoodley,
Tetrahedron Lett., 1995, 36, 8689.
2 R. E. Ireland, P. A. Aristoff and C. F. Hoyng, J. Org. Chem., 1979, 44,
4318.
3 F. A. Cotton, G. Wilkinson and P. L. Gaus, Basic Inorganic Chemistry,
3rd edn., Wiley, New York, 1995, p. 267 and 616.
4 S. Cotton, Lanthanides and Actinides, MacMillan, London, 1991,
p. 58.
.
by BF3 OEt2 and SnCl4 and in hetero-Diels–Alder reactions
promoted by ZnCl2 and the ‘late’ lanthanides. The generation of
a chelated complex, e.g. of type 13 in which the Lewis acid is
coordinated to the aldehyde carbonyl O-atom and the glycosidic
O-atom, provides a possible explanation for the re-face
selectivity; this behaviour is a feature of cycloaddition reactions
initiated by the ‘early’ lanthanides. Presumably, because of the
‘lanthanide contraction’ (in which the radii of lanthanide cations
decrease with increasing atomic number),3 the ‘late’ lanthanides
favour heptacoordination (and, therefore, the formation of
monodentate complexes) whereas the ‘early’ lanthanides prefer
5 G. A. Molander, Chem. Rev., 1992, 92, 29.
6 H. Emde, D. Domsch, H. Feger, U. Frick, A. Go¨tz, H. H. Hergott,
K. Hofmann, W. Kober, K. Kra¨geloh, T. Oesterle, W. Steppan, W. West
and G. Simchen, Synthesis, 1982, 1.
7 B. Beagley, A. D. M. Curtis, R. G. Pritchard and R. J. Stoodley, J. Chem.
Soc., Perkin Trans. 1, 1992, 1981.
8 S. Kobayashi and H. Ishitani, J. Am. Chem. Soc., 1994, 116, 4083.
Received in Liverpool, UK, 24th June 1997; 7/04463A
2172
Chem. Commun., 1997