Chemospecific Preparation of Both Enantiomers of α-Terpinyl Trifluoroacetate

Article abstract of DOI:10.1081/SCC-120027295

(R)- and (S)-α-Terpinyl trifluoroacetate can easily be prepared in 56-64% yield and high ee by the reaction of (R)- and (S)-limonene with trifluoroacetic acid in cyclohexane. The products were fully characterized by ¹H and ¹³C NMR, I

Full text of DOI:10.1081/SCC-120027295

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Chemospecific Preparation of Both Enantiomers of
α‐Terpinyl Trifluoroacetate
Marcio C. S. de Mattos a , Ricardo B. Coelho a & Antonio M. Sanseverino a
a Instituto de Química, Departamento de Química Orgânica, Universidade Federal do Rio
de Janeiro, Caixa Postal 68545, 21945‐970, Rio de Janeiro, Brazil
Available online: 16 Aug 2006
To cite this article: Marcio C. S. de Mattos, Ricardo B. Coelho & Antonio M. Sanseverino (2004): Chemospecific
Preparation of Both Enantiomers of α‐Terpinyl Trifluoroacetate, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 34:3, 541-545
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 3, pp. 541–545, 2004
Chemospecific Preparation of Both
Enantiomers of a-Terpinyl
Trifluoroacetate
*
Marcio C. S. de Mattos, Ricardo B. Coelho,
and Antonio M. Sanseverino
´ ´ ˆ
Instituto de Quımica, Departamento de Quımica Organica, Universidade
Federal do Rio de Janeiro, Rio de Janeiro, Brazil
ABSTRACT
(R)- and (S)-a-Terpinyl trifluoroacetate can easily be prepared in 56–
64% yield and high ee by the reaction of (R)- and (S)-limonene with
trifluoroacetic acid in cyclohexane. The products were fully characterized
by 1H and 13C NMR, IR and MS and theirs Chiral-HRGC analysis
showed there is no loss of optical activity during the reaction.
Key Words: Limonene; p-Menthenes; Terpinyl trifluoroacetate.
*
´
Correspondence: Marcio C. S. de Mattos, Instituto de Quımica, Departamento de
´
ˆ
Quımica Organica, Universidade Federal do Rio de Janeiro, Caixa Postal 68545,
21945-970, Rio de Janeiro, Brazil; Fax: þ55-21-25627133; E-mail: mmattos@iq.
ufrj.br.
541
DOI: 10.1081/SCC-120027295
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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542
de Mattos, Coelho, and Sanseverino
INTRODUCTION
Electrophilic additions to limonene may suffer from issues of selectivity
(1). Sometimes additions occur to both double bonds of a same molecule (e.g.
bromination, acid-catalyzed hydration) or mixture of addition products to the
disubstituted and trisubstituted double bonds are obtained (e.g. epoxidation,
carbenoid addition).[1] Recently, we communicated that the surface-mediated
hydrohalogenation of both enantiomers of limonene produced the a-terpinyl
halides chemo- and regiospecifically.[2,3] The enantiomeric excess of the
products were determined by Chiral-High Resolution Gas Chromatography
(Chiral-HRGC).
In 1976, Roberts published a kinetic study on the reaction of limonene
with trifluoroacetic acid and the product (a-terpinyl trifluoroacetate) was
characterized by 1H NMR only.[4] As part of our continuing interest in
chemospecific functionalization of limonene,[1–3,5] we have revisited this
reaction using both enantiomers of limonene and communicate our results
here.
RESULTS
The reaction of (R)-limonene (10 mmol) with trifluoroacetic acid
(10 mmol) in cyclohexane was performed at room temperature in an open
flask for 1 h. After work up, (R)-a-terpinyl trifluoroacetate was obtained in
64% yield and .99% optical purity. The same reaction performed with
(S)-limonene led to (S)-a-terpinyl trifluoroacetate in 56% yield (Sch. 1).
Chiral-HRGC of (R)-a-terpinyl trifluoroacetate showed ee . 99%
[similar to the ee of the starting (R)-limonene], indicating that there is no
loss of optical activity in this reaction. On the other hand, Chiral-HRGC of
(S)-a-terpinyl trifluoroacetate showed the presence of small amount of the
(R)-enantiomer, attributed to the fact that our (S)-limonene used was not
Scheme 1.

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a-Terpinyl Trifluoroacetate
543
Table 1. Chiral-HRGC and polarimetric analysis of both enantiomers of limonene
and a-terpinyl trifluoroacetate.
Compound
tR (min)a
ee (%)b
[a]2D8
22.2
.99
þ118.7 (neat)
21.6
159.8
157.9
.86
.99
.87
2103.4 (neat)
þ44.5 (8.2%, cyclohexane)
240.3 (8.2%, cyclohexane)
aSee Experimental for chiral-HRGC conditions of analysis.
bDetermined by integration of the areas of the peaks in Chiral-HRGC.
enantiomerically pure (ee . 86%). In fact, the stereoselectivity in both
reactions are similar, as the products should have the same ee of the substrates.
Table 1 summarizes the Chiral-HRGC and polarimetric analysis of substrates
and products.
These results are important because in a protic media the enantiopurity
of limonene can be totally or partially destroyed by protonation of the
disubstituted double bond followed by 1,2-hydrogen shift from the
stereogenic center.[6] Another possibility is the loss of optical activity by
protonation-deprotonation of the trisubstituted double bond of limonene or
product.

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de Mattos, Coelho, and Sanseverino
EXPERIMENTAL
General
(R)-limonene (Dierberger) and (S)-limonene (Aldrich) were distilled prior
to use [b.p. 176–1788C, lit. 1788C][7] and other chemicals were used as
received. 1H NMR and 13C NMR were acquired on a Bruker DRX-300
(300 MHz and 75 MHz, respectively) spectrometer in CDCl3 solutions with
TMS as internal standard. IR spectra were recorded on a Perkin–Elmer 1600
FT-IR spectrometer (KBr film). MS were obtained on a Hewlett–Packard
HP5896-A HRGC-MS using electron impact (70 eV). Polarimetric analysis
were done on a Jasco DIP 370 polarimeter. Chiral-HRGC analysis by FID
were performed on a Varian 3400 CX chromatograph with a Cyclodex-B
(J. & W. Scientific) with 30 m (length), 0.25 mm (i.d.) and 0.25 mm (film
thickness) capillary silica column and He (50 cm/s) as carrier gas (split 1/20).
Conditions of analysis: injector temperature: 2408C, detector temperature:
2408C, column temperature: 508C.
(R)-a-Terpinyl trifluoroacetate. To a stirred solution of (R)-limonene
(1.36 g, 10 mmol) in cyclohexane (10 mL), CF3CO2H (0.80 g, 10 mmol) was
slowly added at room temperature. After 1 h, the solution was washed with
water (5 mL), 5% NaHCO3 (5 mL), water (5 mL) and then dried (Na2SO4).
The solvent was removed under reduced pressure (2 Torr) and low heating
(,508C) to produce pure (R)-a-terpinyl trifluoroacetate (1.60 g, 64%).a 1
H
NMR: d 1.15–1.45 (m, 2H), 1.54 (s, 3H), 1.55 (s, 3H), 1.65 (s, 3H), 1.73–2.07
(m, 5H), 5.37 (broad s, 1H) ppm. RMN 13C: d 22.7, 23.0, 23.3, 23.7, 26.2,
30.6, 42.6, 91.9, 114.5 (q, JC–F 285.4 Hz), 119.7, 134.1, 156.2 (q, JC–F
40.8 Hz) ppm. IR: n 2931, 1778, 1447, 1372, 1219, 1170, 1123, 861,
778 cm21. MS: m/z (%) 137 (Mþ-CF3CO2, 13), 136 (49), 121 (100), 93 (75).
Polarimetric and Chiral-HRGC analysis are shown in Table 1.
(S)-a-Terpinyl trifluoroacetate. Same as above, (S)-limonene used
instead of (R)-enantiomer, obtained 1.40 g (56%). Polarimetric and Chiral-
HRGC analysis are shown in Table 1.
aThe purity of a-terpinyl trifluoroacetate (.99%) was checked by comparison of its
analytical data with the previously reported (4) as well as by co-injection in HRGC
with two chromatographic columns of different polarities (CARBOWAX and RTX-5)
that showed only one peak.

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a-Terpinyl Trifluoroacetate
ACKNOWLEDGMENT
AMS thanks CNPq for a fellowship.
545
REFERENCES
´
1. de Mattos, M.C.S.; Kover, W.B. Metodologias especıficas para a
funcionalizac¸a˜o da ligac¸a˜o dupla 8,9 do Limoneno. Quim. Nova 1991,
14 (2), 91–97.
2. de Mattos, M.C.S.; Sanseverino, A.M. A convenient and simplified
preparation of both enantiomers of a-terpinyl chloride. Synth. Commun.
2000, 30 (11), 1975–1983.
3. Sanseverino, A.M.; de Mattos, M.C.S.; Kover, W.B. Surface-mediated
chemospecific hydrobromination of limonene: stereoselective transforma-
tion of the enantiomers of limonene into a-terpinyl bromide. J. Chem. Res.
(S) 2000, 2000 (7), 346–347.
4. Roberts, R.M.G. Kinetics and mechanism of addition of acids to olefins.
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polarmedia. J. Chem. Soc. Perkin Trans. 2 1976, 12, 1374–1379.
5. de Mattos, M.C.S.; de Souza, S.P.L.; Elias, S.M. Transition metal salts
mediated radical addition of ethyl acetoacetate to limonene. Heterocycl.
Commun. 2001, 7 (3), 249–252.
6. Bates, R.B.; Caldwell, E.S.; Klein, H.P. Equilibration of p-menthadienes in
acids and bases. J. Org. Chem. 1969, 34 (9), 2615–2617.
7. Weast, R.C. Handbook of Chemistry and Physics, 65th Ed., CRC Press:
Boca Raton, 1985; C–361.
Received in the USA August 14, 2003

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