Syntheses of optically active trifluoronorcoronamic acids.

Article abstract of DOI:10.1021/ol0059955

Syntheses of optically active trifluoronorcoronamic acid 6 and its diastereomer 9 are described. Highly stereospecific and diastereoselective S(N)2 cyclization of gamma-cyanohydrins 3a and 3b gave cyclopropyl nitriles 4a and 4b. Hydrolysis of the cyano gr

Full text of DOI:10.1021/ol0059955

ORGANIC
LETTERS
2000
Vol. 2, No. 16
2423-2425
Syntheses of Optically Active
Trifluoronorcoronamic Acids
Toshimasa Katagiri, Minoru Irie, and Kenji Uneyama*
Department of Applied Chemistry, Faculty of Engineering, Okayama UniVersity,
Okayama 700-8530, Japan
uneyamak@cc.okayama-u.ac.jp
Received April 28, 2000
ABSTRACT
Syntheses of optically active trifluoronorcoronamic acid 6 and its diastereomer 9 are described. Highly stereospecific and diastereoselective
SN2 cyclization of γ-cyanohydrins 3a and 3b gave cyclopropyl nitriles 4a and 4b. Hydrolysis of the cyano group and deprotection of the amino
group of 4a provide trifluoronorcoronamic acid 6. Hofmann rearrangement of the amide which was generated by hydrolysis of the cyano
group and oxidative cleavage of the aryl ring of 4b to provide trifluoro-allo-norcoronamic acid 9.
The cyclopropyl amino acids, 1-aminocyclopropane-1-car-
boxylic acid, and its derivatives have been of interest to
scientists for their roles and reactions in vivo,1 which include
roles as intermediates in the biosynthesis of the fruit ripening
hormone ethylene,2 as components of bacterial phytotoxins,3
and as intermediates in the biosynthesis of cyclic amino acid
azetidine-2-carboxylic acid.4 Norcoronamic acid 1 is such a
naturally occurring cyclopropyl amino acid which was
isolated after hydrolysis of bacterial toxin norcoronatine from
Pseudomonas syringae.5
of peptides containing the amino acid, controlling interactions
with enzymes and receptors.1a Fluorination of the compound
could result in a further change of properties, via electronic
effects and by modifying chemical stability.6 Although there
are many published examples of the synthesis of cyclopropyl
amino acids, there have been few reports on the fluorinated
analogues of cyclopropyl amino acids.7 To date there has
been no report on the fluorinated analogue of norcoronamic
acid, 2-trifluoromethyl-1-aminocyclopropane-1-carboxylic
acid.
Herein, we wish to report stereoselective syntheses of
trifluorinated norcoronamic acid 6 and its diastereomer 9,
2-trifluoromethyl-1-aminocyclopropane-1-carboxylic acid,
(6) (a) Fluorine-containing Amino Acids Synthesis and Properties;
Kukhar’, V. P., Soloshonok, V. A., Eds.; John Wiley & Sons: New York,
1995. (b) Welch, J. T.; Eswarakrishnan, S. Fluorine in Bioorganic
Chemistry; John Wiley & Sons: New York, 1991. (c) Chemistry of Organic
Fluorine Compounds II; Hudlicky, M., Pavlath, A. E., Eds.; American
Chemical Society: Washington, DC, 1995.
The conformationally constrained nature of the cyclopropyl
amino acids is of interest and may affect the conformation
(7) Sloan, M. S.; Kirk, K. L. Tetrahedron Lett. 1997, 38, 1677.
(1) (a) Stammer, C. H. Tetrahedron 1990, 46, 2231. (b) Burgess, K.;
Ho, K.-K.; Moye-Sherman, D. Synlett 1994, 575 and references therein.
(2) Burroughs, L. F. Nature 1957, 179, 360. Baldwin, J. E.; Adlington,
R. M.; Lajoie, G. A.; Rawlings, B. J. J. Chem. Soc., Chem. Commun. 1985,
1496.
(3) Mitchell, R. E. Phytochemistry 1985, 24, 1485.
(4) Leete, E.; Louters, L. L.; Rao, H. S. P. Phytochemistry 1986, 25,
2753.
(8) The compound having S configuration of 75% ee is commercially
available: (a) Furuhashi, K. Chirality in Industry; Collins, A. N., Sheldrake,
G. N., Crosby, J., Eds.; John Wiley & Sons: New York, 1992; p 167.
Optically pure 2,3-epoxy-1,1,1-trifluoropropane and its synthon are also
available in laboratory scales: (b) Bussche-Hunnefeld, C. von der; Cescato,
C.; Seebach, D. Chem, Ber. 1992, 125, 2795. (c) Ramachandran, P. V.;
Gong, B.; Brown, H. C. J. Org. Chem. 1995, 60, 41. (d) Shimizu, M.;
Sugiyama, K.; Fujisawa, T. Bull. Chem. Soc. Jpn. 1996, 69, 2655. (e)
Katagiri, T.; Obara, F. Jpn. Kokai Tokkyo Koho 1994, Jp06-247953. (f)
Vanhessche, K. P. M.; Sharpless, K. B. Chem. Eur. J. 1997, 3, 517.
(5) Ichihara, A.; Shiraishi, K.; Sato, H.; Sakamura, S.; Nishiyama, K.;
Sakai, R.; Furusaki, A.; Matsumoto, T. J. Am. Chem. Soc. 1977, 99, 636.
10.1021/ol0059955 CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/13/2000

from an optically active epoxide. Our approach is based on
a cyclization of optically active 4-hydroxy-5,5,5-trifluoronor-
valine cyanide derivatives 3, which were derived from the
reaction between optically active 2,3-epoxy-1,1,1-trifluoro-
propane 28 with substituted acetonitriles.9 The key cyclization
step to cyclopropane 4 involved an SN2 reaction (inversion
of configuration at the electrophilic center) with high
diastereoselectivity and created the amino acid R-carbon as
a new stereogenic center.10 Thus, the configuration of the
epoxide controls the stereochemistry of the final product in
our strategy.
the optically pure trifluoronorcoronamic acid 6 in 67% yield
(Scheme 1).11
Scheme 1
Preparation of the cyanohydrin 3a as a diastereomeric
mixture was conducted in a manner similar to that described
in our previous reports.9 The yield of 3a was 73%, while
the diastereomeric excess of 3a was ca. 30% de. The
diastereomeric mixture of cyanohydrin 3a was then cyclized
to cyclopropyl cyanide 4a without further purification. In
the course of this intramolecular nucleophilic substitution,
one of the chiral centers was epimerized via a planar cyano-
stabilized carbanion. Then, highly diastereoselective cycliza-
tion occurred to yield cyclopropyl cyanide 4a, controlled by
the steric effect exerted by the trifluoromethyl group attached
to the chiral carbon. The yield of 4a was 82%, and the
diastereomeric excess of 4a was found to be >99%.
Recrystallization of 4a gave optically pure 4a in 70% yield.8
Oxidative degradation of the pyrrole ring of 4a gave amino
nitrile 5 (71%); then hydrolysis of the cyano group afforded
Configuration of cyclopropylcyanide 4a was confirmed
by X-ray crystallographic analysis; the ORTEP diagram of
4a is shown in Figure 1.12
(9) Katagiri, T.; Akizuki, M.; Kuriyama, T.; Shinke, S.; Uneyama, K.
Chem. Lett. 1997, 549.
(10) Katagiri, T.; Irie, M.; Uneyama, K. Tetrahedron: Asymmetry 1999,
10, 2583.
(11) Spectroscopic data for trifluoronorcoronamic acid hydrochloride
monohydrate (6): white powder, mp 200 °C (dec); [R]20 +13.6 (c 1.2,
D
H2O); IR (KBr) 3448, 3040, 1618 cm-1; 1H NMR (D2O) δ 1.58 (ddq, J )
10, 8, 1, 1H), 1.90 (dd, J ) 8, 7, 1H), 2.17-2.38 (ddq, J ) 10, 7, 7, 1H);
19F NMR (CDCl3, C6F6 internal standard) δ 106.9 (d, J ) 7). Anal. Calcd
for C5H9ClF3NO3: C, 26.86; H, 4.06; N, 6.26. Found: C, 27.08; H, 4.32;
N, 6.47.
(12) Crystal data for cyclopropyl cyanide 4a: C11H11F3N2; Mr ) 228.22;
orthorhombic; P212121; a ) 8.1846(6), b ) 19.407(2), and c ) 7.0250(6)
Å, V ) 1115.8400 Å3, Z ) 4, Dx ) 1.358 g/cm3; µ ) 1.17 cm-1 for Mo
KR radiation (λ ) 0.7107 Å). The structure was solved by a direct method
(SIR 92) and refined by a full-matrix least-squares method. Final R was
0.078 and Rw was 0.107 for 916 reflections with I0 > 3.00σ(I0). Reflection/
parameter ratio was 5.87. Goodness of fit indicator was 3.70. Max shift/
error in final cycle was 0.06.
(13) Spectroscopic data for N-Boc-trifluoro-allo-norcoronamic acid (9):
white solid, mp 158-159 °C; [R]20D -25.5 (c 3.2, CDCl3); IR (KBr) 3370,
1700 cm-1; 1H NMR (CDCl3) δ 1.45 (s, 9H), 1.81 (m, 1H), 2.00 (m, 1H),
2.52 (m, 1H), 5.15 (br, 1H); 19F NMR (CDCl3, C6F6 internal standard) δ
100.5 (d, J ) 6); EI-MS (rel int) 169 (17, M+ - Boc), 59 (33), 57 (100),
41 (27). Anal. Calcd for C10H14F3NO4: C, 44.61; H, 5.24; N, 5.20. Found:
C, 44.69; H, 5.05; N, 5.58.
(14) Present diastereomeric configurations of the cyclopropanes 4a and
4b are consistent with our previous X-ray crystallographic results of the
derivative from 1-phenyl-1-cyano-2-trifluoromethylcyclopropane having
(1S,2S) configuration, see ref 10.
(15) Crystal data for cyclopropyl cyanide 4b: C13H12F3NO2; Mr
)
271.24; orthorhombic; P212121; a ) 12.9184(5), b ) 14.0537(5), and c )
7.0743(2) Å, V ) 1284.35(8) Å3, Z ) 4, Dx ) 1.403 g/cm3; µ ) 1.23 cm-1
for Mo KR radiation (λ ) 0.7107 Å). The structure was solved by a direct
method (SIR 92) and refined by a full-matrix least-squares method. Final
R was 0.065 and Rw was 0.084 for 1343 reflections with I0 > 3.00σ(I0).
Reflection/parameter ratio was 7.30. Goodness of fit indicator was 3.12.
Max shift/error in final cycle was 0.09.
(16) Johnson, R. A.; Sharpless, K. B. Catalytic Asymmetric Synthesis;
Ojima, A., Ed.; Wiley-VCH: New York, 1993; p 103. Jacobsen, E. N.
Catalytic Asymmetric Synthesis; Ojima, A., Ed.; Wiley-VCH: New York,
1993; p 159.
Figure 1. X-ray structure of 4a.
A similar preparation of the diastereomeric mixture of
cyanohydrins 3b followed by cyclization gave cyclopropyl
cyanide 4b in 67% yield and 90% diastereomeric excess.
Recrystallization of 4b gave enantiomerically pure cyclo-
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Org. Lett., Vol. 2, No. 16, 2000

propyl cyanide 4b in 33% yield. Hydrolysis of the cyano
group gave amide 7 (79%); then Hofmann rearrangement
followed by oxidative degradation of aromatic ring of amine
8 gave Boc-protected trifluoro-allo-norcoronamic acid 9 in
30% yield (two steps) (Scheme 2).13
Scheme 2
Figure 2. X-ray structure of 4b.
chiral epoxidation,16 the optically active epoxide has become
a reliable class of chiral building blocks. Our present strategy
would therefore be a highly reliable method for stereocon-
trolled preparation of cyclopropyl amino acids. Studies on
the scope of the present strategies for the preparation of other
cyclopropyl amino acids are now in progress.
Acknowledgment. We thank SC-NMR Laboratory of
Configuration of the cyclopropyl nitrile compound 4b was
also confirmed by X-ray crystallographic analysis; the
ORTEP diagram of compound 4b is shown in Figure 2.14,15
The present strategies for the preparation of cyclopropyl
amino acids are characterized by utilization of the chiral
center from epoxide, which controls the stereochemistry of
the amino acid R-carbon in the course of the cyclization.
The R-carbon of the amino acid was epimerized upon
becoming a cyano-stabilized carbanion and did not therefore
influence the stereochemistry of the final cyclopropane at
all. Also, the cyano group is convenient for the preparation
of amino acids, because it can be converted both to an amino
group via Hofmann-type rearrangement and to a carboxyl
group via simple hydrolysis. Because of recent advances in
1
Okayama University for 19F and H NMR analyses and the
Venture Business Laboratory of Graduate School of Okaya-
ma University for X-ray crystallographic analysis. This work
was partly support by Monbusho (Grant-in-Aid for Scientific
Research on Priority Areas, No. 706 (Dynamic Control of
Stereochemistry) and No. 12650854) and by The Shorai
Foundation for Science and Technology.
Supporting Information Available: Full experimental
details and characterization data for compounds 3a, 4a, 4b,
5, 6, 7, and 9 and CIF files for 4a and 4b. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL0059955
Org. Lett., Vol. 2, No. 16, 2000
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