Dimenthoxyphosphorylimino-3,3,3-trifluoropropionate as a novel chiral building block in asymmetric synthesis of fluorinated α-amino acids derivatives

Article abstract of DOI:10.1080/10426507.2010.522634

A convenient method for the preparation of dimenthoxyphosphoryliminotrifluoropropionate, bearing the stereodirecting dimenthoxy-phosphoryl group at the nitrogen atom, was developed. The synthetic potential of this novel chiral building block for diastereo

Full text of DOI:10.1080/10426507.2010.522634

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Phosphorus, Sulfur, and Silicon and the
Related Elements
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Dimenthoxyphosphorylimino-3,3,3-
trifluoropropionate as a Novel Chiral
Building Block in Asymmetric Synthesis
of Fluorinated α-Amino Acids Derivatives
Yuliya V. Rassukana a , Yaroslav Y. Khomutnyk a , Anatoly D. Synytsya
a & Petro P. Onys’ko a
a Institute of Organic Chemistry, NAS of Ukraine, Kyiv, Ukraine
Version of record first published: 25 Apr 2011.
To cite this article: Yuliya V. Rassukana, Yaroslav Y. Khomutnyk, Anatoly D. Synytsya & Petro P.
Onys’ko (2011): Dimenthoxyphosphorylimino-3,3,3-trifluoropropionate as a Novel Chiral Building Block
in Asymmetric Synthesis of Fluorinated α-Amino Acids Derivatives, Phosphorus, Sulfur, and Silicon and
the Related Elements, 186:4, 718-720
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Phosphorus, Sulfur, and Silicon, 186:718–720, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.522634
DIMENTHOXYPHOSPHORYLIMINO-3,3,3-
TRIFLUOROPROPIONATE AS A NOVEL CHIRAL BUILDING
BLOCK IN ASYMMETRIC SYNTHESIS OF FLUORINATED
α-AMINO ACIDS DERIVATIVES
Yuliya V. Rassukana, Yaroslav Y. Khomutnyk,
Anatoly D. Synytsya, and Petro P. Onys’ko
Institute of Organic Chemistry, NAS of Ukraine, Kyiv, Ukraine
Abstract A convenient method for the preparation of dimenthoxyphosphoryliminotrifluoro-
propionate, bearing the stereodirecting dimenthoxy-phosphoryl group at the nitrogen atom,
was developed. The synthetic potential of this novel chiral building block for diastereoselective
synthesis of trifluoromethyl containing amino acid derivatives was demonstrated.
Keywords Amidophosphates; amino acids; asymmetric synthesis; chiral auxiliary; trifluo-
ropyruvate imines
INTRODUCTION
The occurrence of α-amino acids in biological systems underlies the importance of
new methods for their synthesis in enantiomerically pure forms. Fluorine is a unique tool
for modifying bioactivity. Consequently, there is a growing interest in the synthesis of chiral
fluorine containing building blocks.
RESULTS AND DISCUSSIONS
We have developed a convenient method for the preparation of trifluoroiminopy-
ruvate 4 bearing the stereodirecting dimenthoxy-phosphoryl group at the nitrogen atom
(Scheme 1).
Dimenthyl phosphite 1 was obtained with the use of commercially available (L)-
menthol according to the described procedure1 and was transformed into amidophosphate
2 by the Atherton–Todd reaction, yield 85%, [α]D = −91.6◦. The reaction of amidophos-
phate 2 with methyl trifluoropyruvate and subsequent dehydration of intermediate addition
product 3 afforded the target imine 4 bearing a stereodirecting and at the same time acti-
vating dimenthoxyphosphoryl group at the nitrogen atom.
Received 26 July 2010; accepted 7 September 2010.
Address correspondence to Petro P. Onys’ko, Institute of Organic Chemistry, NAS of Ukraine, 5 Murmans’ka
St., 02660 Kyiv, Ukraine. E-mail: onysko@rambler.ru
718

DIMENTHOXYPHOSPHORYLIMINO-3,3,3-TRIFLUOROPROPIONATE
719
Scheme 1 Preparation of trifluoroiminopyruvate 4, bearing chiral auxiliary at the nitrogen atom.
The synthetic potential of imine 4 is demonstrated in Scheme 2. In particular, the
high reactivity of the compound allows its easy functionalization even with weak C-, O-,
S-, and P-centered nucleophiles to afford various chiral trifluoroalanine derivatives bearing
the hydrogen (5), an alkoxy group (6), a heterocyclic moiety (7), or a phosphinoyl residue
(8) at the α-atom.
It should be noted that in spite of moderate de in the reactions studied, they can
be used for preparative asymmetric synthesis; crystalline compounds 5–8 can be easily
O
de, %
19F NMR)
Y,
%
MeO
[H]
CF3
(
H
HN
[H]
>95
NaBH4
15
25
–78°C, THF
P
O
O
O
NaBH(OAc)
99
95
3
5
O
O
BH
34
4
HP(O)RR
Indole
MeOH
R=Ph, OEt, OiPr.
H
O
P
N
R
R
O
MeO
CF3
O
MeOOC
MeOOC
HN
CF3
CF3
O
HN
P
HN
P
O
P
O
7
O
O
O
O
O
O
8
6
Scheme 2 Diastereoselective functionalization of trifluoroiminopyruvate 4.

720
Y. V. RASSUKANA ET AL.
enriched by simple recrystallization. Thus, after only one crystallization from petroleum
ether, protected trifluoroalanine 5 was obtained with de exceeding 99%.
REFERENCE
1. Kolodiazhnyi, O. I.; Grishkun, E. V.; Sheiko, S.; Demchuk, O.; Thoennessen, H.; Jones, P. G.;
Schmutzler, R. Tetrahedron: Asymmetry 1998, 9, 1645–1649.