Asymmetric hetero-Diels-Alder reaction of glyoxylate esters and Danishefsky's diene catalyzed by chiral bis(oxazoline)-lanthanide complexes

Article abstract of DOI:10.1016/S0040-4039(00)00144-1

Asymmetric hetero-Diels-Alder reactions of glyoxylate esters and Danishefsky's diene catalyzed by various chiral bis(oxazoline)-lanthanide complexes afforded the corresponding aldol adducts, which upon treatment with trifluoroacetic acid, furnished the he

Full text of DOI:10.1016/S0040-4039(00)00144-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2203–2206
Asymmetric hetero-Diels–Alder reaction of glyoxylate esters
and Danishefsky’s diene catalyzed by chiral
bis(oxazoline)–lanthanide complexes
Changtao Qian ∗ and Longcheng Wang
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai, 200032, China
Received 11 November 1999; accepted 18 January 2000
Abstract
Asymmetric hetero-Diels–Alder reactions of glyoxylate esters and Danishefsky’s diene catalyzed by various
chiral bis(oxazoline)–lanthanide complexes afforded the corresponding aldol adducts, which upon treatment with
trifluoroacetic acid, furnished the hetero-Diels–Alder product in up to 77% enantiomeric excess and 73% isolated
yield. © 2000 Elsevier Science Ltd. All rights reserved.
In recent years, C2-symmetric chiral bis(oxazoline) ligand–metal complexes have received a great
deal of attention due to their successful use in various asymmetric catalytic processes,1 but there are few
reports of the use of these ligands in lanthanide catalysis.2 Here we wish to report the development of
chiral bis(oxazoline)–lanthanide complexes as a new type of asymmetric catalyst for hetero-Diels–Alder
reactions of glyoxylate esters and Danishefsky’s diene, wherein a significant effect of slow addition of
Danishefsky’s diene is observed in increasing not only the enantioselectivity, but also the chemical yield.
Ligands 2 and 3 were synthesized in two steps by coupling the corresponding acyl chloride and amino
alcohol followed by intramolecular ring closure by stirring these intermediates with aqueous methanolic
NaOH.1a Ligand 4 was prepared according to the literature method.1a Ligand 5 was synthesized from
∗
Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00144-1
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2,6-dibromopyridine with a small modification of the intramolecular condensation process1a (Scheme 1).
The chiral catalysts were prepared by the reaction of an equimolar amount of lanthanide triflate and the
ligand in the presence of MS 4 Å in 1:3 CH2Cl2:Et2O at room temperature under a nitrogen atmosphere.
Though these Ln(III) complexes were not isolated, we assume the structures of complexes derived from
3, 4 and 5 are similar to 6. However, the structure of the complex obtained from ligand 2 is different
from the above.3 The lanthanide complexes thus prepared were examined as asymmetric catalysts for the
hetero-Diels–Alder reaction (Scheme 2).
Scheme 1. (a) BuLi, Et2O, −78°C, 2 h; (b) CuCl2, O2, 40% yield; (c) BuLi, THF; (d) CO2, 25% yield; (e) SOCl2; (f)
(S)-phenylglycinol; (g) SOCl2, 74% yield; (h) NaHCO3, CH2Cl2, 95% yield; (i) NaOH, MeOH; (j) Ln(OTf)3, CH2Cl2:Et2O=1:3,
MS 4 Å, rt
Scheme 2.
Typically, cyclocondensation was effected by stirring an equiv. of the glyoxylate ester with the chiral
catalyst (10 mol%) at rt overnight, followed by slow addition of 1.1 equiv. of Danishefsky’s diene. The
resulting mixture was stirred at −78°C, and the progress of the reaction was monitored by TLC. The
reaction was quenched with aqueous saturated NaHCO3 to provide the mixture (1:1 determined by 300
MHz NMR) of the corresponding Mukaiyama aldol products 9 as well as the pyranone products 10
(Scheme 2) after standard work-up. The crude mixture, upon treatment with an excess of trifluoroacetic
acid in CH2Cl2 at rt for 1 h, furnished the cyclocondensation product 10. The level of enantioselection
associated with various hetero-Diels–Alder cycloadducts was analyzed by chiral HPLC analysis (Daicel
Chiralpack AD column). The representative results are summarized in Table 1.
Significantly, all lanthanide catalysts complete the hetero-Diels–Alder reaction within 16 h except for
entry 4 in which the lanthanide complex catalyzes diene decomposition into 4-methoxy-3-butene-2-one.
Ytterbium catalysts provide the higher enantioselectivity. After screening of a variety of bis(oxazoline)
ligands, 2,6-bis[40-(s)-isopropyloxazoli-2-yl] pyridine (3a) is proved to give the most satisfactory results.
It should be noted here that the geometry and coordination number of the ligand are both important.
The presence of MS 4 Å is found to be essential. In the absence of MS 4 Å, both the chemical yield
and enantioselectivity for pyranone formation are lowered. Furthermore, the mixed solvent of ether and

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Table 1
Asymmetric catalytic hetero-Diels–Alder reaction
dichloromethane is the best. Interestingly, higher enantioselectivity was obtained by using the sterically
less demanding methyl glyoxylate and slow addition of Danishefsky’s diene by syringe pump. It should
be pointed out that the glyoxylate ester should be stirred vigorously with the lanthanide catalyst for at
least eight hours so the substrate can be fully coordinated by the lanthanide complex.
The combination of the best conditions Ln(Yb), ligand (iPr-pybox, 3a), mixed solvent of ether and
dichloromethane and slow addition of the Daneshefsky’s diene achieved an enantioselectivity of 77%
for the hetero-Diels–Alder reaction of methyl glyoxylate, a better enantioselectivity than obtained with
cationic bis(oxazolines)–Cu,4 other lanthanide complexes5 and the (±)-BINOL–Ti-activator system,6
and is even comparable to the (R)-BINOL–Ti-activator system.7 The chiral ligand can be recovered in
80–90% isolated yield. Further investigations of this novel catalytic system are underway.
Acknowledgements
Financial support from the National Natural Sciences Foundation of China and the Chinese Academy
of Sciences is gratefully acknowledged.

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