Asymmetric Synthesis of Eucomol via Enantioselective Oxidation of Enol Phosphate

Article abstract of DOI:10.1080/10426507.2014.980411

Stereoselective synthesis of a few derivatives of the homoisoflavanone class of natural products is described.

Full text of DOI:10.1080/10426507.2014.980411

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Phosphorus, Sulfur, and Silicon and the
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Asymmetric Synthesis of Eucomol via
Enantioselective Oxidation of Enol
Phosphate
Ewa Krawczyka, Grażyna Mielniczaka, Marek Koprowskia & Krzysztof
Owsianika
a Department of Heteroorganic Chemistry, Center of Molecular and
Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza,
Łódź, Poland
Accepted author version posted online: 06 Dec 2014.
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To cite this article: Ewa Krawczyk, Grażyna Mielniczak, Marek Koprowski & Krzysztof Owsianik (2015)
Asymmetric Synthesis of Eucomol via Enantioselective Oxidation of Enol Phosphate, Phosphorus,
Sulfur, and Silicon and the Related Elements, 190:5-6, 691-693, DOI: 10.1080/10426507.2014.980411
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Phosphorus, Sulfur, and Silicon, 190:691–693, 2015
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2014.980411
ASYMMETRIC SYNTHESIS OF EUCOMOL VIA
ENANTIOSELECTIVE OXIDATION OF ENOL PHOSPHATE
Ewa Krawczyk, Graz˙yna Mielniczak, Marek Koprowski,
and Krzysztof Owsianik
Department of Heteroorganic Chemistry, Center of Molecular and
Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza, Ło´dz´, Poland
GRAPHICAL ABSTRACT
Abstract Stereoselective synthesis of a few derivatives of the homoisoflavanone class of
natural products is described.
Keywords Eucomol; eucomin; enol phosphate; enantioselective oxidation
INTRODUCTION
Natural products, homoisoflavones or homoisoflavanones, were discovered by Bohler
and Tamm – the chemist from University in Basel, who isolated two members of this class:
(-)-(S)- eucomol and eucomin from the bulbs of Eucomis bicolor BAK (Liliaceae).1
The only one enantioselective synthesis of 5,7-O-dimethyleucomol 1, was real-
ized by Davis2 and co-workers in 1990, using own chiral reagent, (-)-[(8,8-dimethoxy-
camphoryl)sulfonyl] oxaziridine, for asymmetric α-hydroxylation of the lithium enolate of
5,7-dimethoxy-3-(4-methoxybenzyl)chroman-4-one.
As a part of our interest in the application of organophosphorus derivatives in the
synthesis of functionalized, enantiomerically enriched, cyclic compounds, we have elabo-
rated upon a methodology based on another type of enol derivative – readily available enol
phosphates – for the synthesis of α-hydroxy carbonyl compounds.3 Herein, we present our
studies on the asymmetric synthesis of the title compound, namely 5,7-O-dimethyleucomol
1.
Received 27 August 2014; accepted 20 October 2014.
Address correspondence to Graz˙yna Mielniczak, Department of Heteroorganic Chemistry, Center of Molec-
ular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363, Ło´dz´, Poland. E-mail:
migrena@cbmm.lodz.pl
691

692
E. KRAWCZYK ET AL
RESULTS AND DISCUSSION
Our approach to the synthesis of the enantiomeric 5,7-O-dimethyleucomol 1 was
based on the asymmetric oxidation of the corresponding enol phosphate 2, using organic
catalyst – chiral oxidant dioxirane, generated in situ from fructose derivative 3, and also
chiral Sharpless’ reagent.4 This enol phosphate 2 was prepared by the standard procedure,
from the dihydroeucomin 4 (derived from 5,7-O-dimethyleucomin 5 by hydrogenation)
and diethylphosphorochloridate (Scheme 1).
Scheme 1
Several methods of the synthesis of the key compound – 5,7-O-dimethyleucomin 5
and its analogs have been described in literature.5 We decided to explore the procedure,
reported for the synthesis of its analogs by Basavaiah6 and co-workers. This procedure
involved the conversion of adduct 6 into acid 7 via two step transformation. Ring closure in
7 with trifluoroacetic anhydride gave the final product – 5,7-O-dimethyleucomin 5. Next,
hydrogenation of 5 and subsequent phosphorylation reaction afforded the desired enol
phosphate 2 (Scheme 1).
The asymmetric epoxidation of enol phosphate 2 using the chiral dioxirane generated
from Oxone (2KHSO5•KHSO4•K2SO4) and fructose ketone 3 was carried out under
catalytic conditions and afforded a new epoxide 8 with high enantiomeric excess, albeit
in low yield (15%) (Scheme 2). The structure of the epoxide 8 was characterized by mass
spectrometry and NMR spectroscopy. The characteristic chemical shift of the 2-H epoxide
proton in 8 (δH = 5.14 ppm) corresponds to the literature reports.7,8
Thus, we used another approach to the synthesis of enantiomeric eucomols. This
oxidation reaction of enol phosphate 2 was performed according to described Sharpless’
procedure,4 elaborated for catalytic asymmetric dihydroxylation reactions of tetrasubsti-
tuted cyclic enol derivatives (Scheme 3).
The desired 5,7-O-dimethyleucomol 1 was obtained in good yield but with low
enantiomeric excess of 18%.
Further investigation of the influence of substituents at phosphorus and the choice of
the asymmetric oxidation conditions continues.

ASYMMETRIC SYNTHESIS OF EUCOMOL
693
Scheme 2
Scheme 3
FUNDING
The authors are grateful for financial support of The National Science Centre, project
No UMO-2011/01/B/ST5/06664.
REFERENCES
1. Bohler, P.; Tamm, Ch. Tetrahedron Lett. 1967, 3479.
2. Davis F. A.; Chen B-Ch. Tetrahedron Lett. 1990, 31, 6823.
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2599. (b) Koprowski, M.; Łuczak, J.; Krawczyk, E. Tetrahedron 2006, 62, 12363. (c) Krawczyk,
E.; Mielniczak, G.; Owsianik, K.; Łuczak, J. Tetrahedron: Asymm. 2012, 23, 1480.
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1993, 115, 8463.
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Synth. Commun. 2005, 35, 563. (e) Poisson, T.; Gembus. V.; Dalla, V.; Oudeyer, S.; Levacher,
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4.58 ppm) of the isomeric epoxide 5,7-O-dimethyl-3-(4-methoxybenzylidene)-3,α-oxido-4-one
is cited in the literature. Tetrahedron 1970, 26, 2787.