A homoenolate generated by tellurium/lithium exchange reaction was employed in a straightforward enantioselective synthesis of (+)-endo-brevicomin in 70% yield and 84.4% e.e.Um homoenolato gerado pela reação de troca telúrio/lítio foi aplicado na síntese enantioseletiva do (+)-endo-brevicomin com 70% de rendimento isolado e 84,4% de e.e.FAPESPCNPqCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

COMASSETO, João V.

DOS SANTOS, Alcindo A.

FERRARINI, Renan S.

PRINCIVAL, Jefferson L.

A homoenolate generated by tellurium/lithium exchange reaction was employed in a straightforward enantioselective synthesis of (+)-endo-brevicomin in 70% yield and 84.4% e.e.Um homoenolato gerado pela reação de troca telúrio/lítio foi aplicado na síntese enantioseletiva do (+)-endo-brevicomin com 70% de rendimento isolado e 84,4% de e.e

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A concise enantioselective synthesis of (+)-endo-brevicomin accomplished by a tellurium/metal exchange reaction

Universidade de São Paulo

Journal of the Brazilian Chemical Society

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Com
m
unication
J. Braz. Chem. Soc., Vol. 19, No. 5, 811-812, 2008.
Printed in Brazil - ©2008  Sociedade Brasileira de Química
0103 - 5053  $6.00+0.00
*e-mail: alcindo@dq.ufscar.br
A Concise Enantioselective Synthesis of (+)-endo-Brevicomin Accomplished 
by a Tellurium/Metal Exchange Reaction
Renan S. Ferrarini,a Jefferson L. Princival,a João V. Comassetoa and Alcindo A. Dos Santos*,b
aInstituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, CP 26077, 
05599-970 São Paulo-SP, Brazil
bDepartamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos-SP, Brazil
Um homoenolato gerado pela reação de troca telúrio/lítio foi aplicado na síntese enantioseletiva 
do (+)-endo-brevicomin com 70% de rendimento isolado e 84,4% de e.e.
 A homoenolate generated by tellurium/lithium exchange reaction was employed in a 
straightforward enantioselective synthesis of (+)-endo-brevicomin in 70% yield and 84.4% e.e.
Keywords: tellurium/lithium exchange, homoenolate, epoxide opening
Introduction
Organometallics are among the most commonly 
used reagents in both organic and inorganic chemistry. 
Because of their importance for preparative purposes 
many organometallics are commercially available. Among 
them, organolithiums are probably the most popular and 
versatile, because they can act as bases and nucleophiles 
as well as precursors of many other organometallics by 
transmetallation. Commonly, organolithium reagents 
are prepared by direct lithiation via acid / base reaction, 
reduction of halides with elemental lithium,1 by tin/
lithium exchange or by reductive cleavage of sulphides.2
Complementary to these methodologies, is the tellurium/ 
lithium exchange reaction.3 Previously we demonstrated 
the synthetic application and efficacy of the tellurium/ 
lithium exchange reaction to generate functionalized 
organolithium reagents4 as well as to prepare other 
classes of organometallics, including organomagnesium,5
organocoper,5-7 and organocerium7 reactive reagents. 
Herein, we report the enantioselective synthesis of the 
pine beetle pheromone (+)-endo-brevicomin8 (1) and its 
racemic mixture using a telluride as the key precursor of a 
functionalized organometallic reagent.
Results and Discussion
The racemic synthesis of (+/-)-(exo/endo)-brevicomin 
was performed by the sequence presented in Scheme 1. 
Epoxy-ether 2, was prepared in 55 % overall isolated 
yield as follows: Vinyl magnesium bromide was reacted 
with propanal, followed by epoxidation with m-CPBA 
and finally, the crude epoxy-alcohol was treated with ethyl 
vinyl ether in the presence of pyridinium p-toluenesulfonate 
(PPTS) in dichloromethane. With 2 in hand, telluride 37 was 
treated with one equivalent of n-butyl-lithium promoting 
the instantaneous tellurium/lithium exchange reaction. It 
is worth to mention that the tellurium/lithium exchange 
reaction can be easily verified by TLC analysis, since the 
consumption of 3 is accompanied by formation of the 
non polar di-butyltelluride. The resulting organolithium 
was converted into the higher order cyanocuprate in the 
usual way, and then reacted with 2.5,6,9 The hydroxy-ketal 
originated from this reaction was directly treated with 
hydrochloric acid or p-TSA resulting in the racemic mixture 
of (+/-)-(endo/exo)-brevicomin (1) in 70% isolated yield.
The enantioselective synthesis of (+)-endo-brevicomin 
was carried out using the enantioenriched epoxide 
(2R,3S)-2 which was prepared from 1-penten-3-ol by 
kinetic resolution epoxidation according to the procedure 
reported by Sharpless at al10 and applied latter by Mori8
for the same substrate (Scheme 2).
The enantiomeric purity of 2 could not be directly 
measured by chiral capillary gas chromatography. 
A Concise Enantioselective Synthesis of (+)-endo-Brevicomin J. Braz. Chem. Soc.812
However, the reaction of 2 with the higher order 
cyanocuprate, prepared from telluride 3, as described 
before, yielded the enantioenriched endo-brevicomin 
which was subjected to chiral capillary gas chromatography 
revealing an optical purity of 84.4% e.e. This value 
was confirmed by polarimetric analysis ([A]
D
20 +69.3° 
(c = 1.0, diethyl ether), comparing with literature data.8
In this way we can conclude that (2R,3S)-2 was obtained 
with the same optical purity, i.e. 84.4% e.e., on the kinetic 
Sharpless epoxidation since no racemisation has been 
observed by Mori at al.8 for this substrate under the same 
experimental conditions employed by us.
Conclusion
In conclusion, (+)-endo-brevicomin was synthesized in 
one step and 70% isolated yield starting from the known 
enantioenriched epoxy-ether 27 by using a tellurium/ 
metal exchange reaction. Currently, some functionalized 
organotellurides are being used in our laboratory in the 
synthesis of some other bioactive compounds, including 
pheromones.
Acknowledgments
The authors thank FAPESP, CNPq and CAPES for 
support.
References
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Received: April 17, 2008
Web Release Date: June 2, 2008
FAPESP helped in meeting the publication costs of this article.
Scheme 2. Kinetic resolution epoxidation of 1-penten-3-ol (+69.3º, 
c= 1.0, diethyl ether, 84.4% e.e.).
Scheme 1. Racemic synthetic route of (exo/endo)-brevicomin.


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A concise enantioselective synthesis of (+)-endo-brevicomin accomplished by a tellurium/metal exchange reaction

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