3 Alkenes by Fragmentation, Mechanistic Views III A

REVISTA BOLIVIANA DE QUMICA
Bolivian Journal of Chemistry

Received 04 10 2015
Vol. 32, No.2, pp. 37-44, May./Jun. 2015

32(2) 37-44, May/Jun. 2015
Published 06 30 2015
Accepted 06 25 2015
Vila et Bravo
SYNTHESIS OF ALKENES BY FRAGMENTATION REACTIONS;

MECHANISTIC VIEWS; THE ORGANIC CHEMISTRY NOTEBOOK
SERIES, A DIDACTICAL APPROACH, N 5
Jos L. Vila, Jos A. Bravo*
Department of Chemistry, Laboratorio de Sntesis y Hemisntesis, Instituto de Investigaciones en Productos
Naturales IIPN, Universidad Mayor de San Andrs UMSA, P.O. Box 303, Calle Andrs Bello s/n, Ciudad
Universitaria Cota Cota, Tel. 59122792238, La Paz, Bolivia. joselu62@hotmail.com, jabravo@umsa.bo
Keywords: Organic Chemistry, Fragmentation reaction, oxidative decarboxylation, carboxylic

acids, Alkenes, Mechanisms of Reactions.
ABSTRACT
This is the fifth chapter in the series published by the same authors: The Organic Chemistry Notebook Series, a
Didactical Approach.
Here we offer the mechanistic views of the synthesis of alkenes by fragmentation reactions. The aim of this
series of studies is to help students to have a graphical view of organic synthesis reactions of diverse nature.
Fragmentation reactions can conduct to the synthesis of alkenes. This is not a common method, but useful under
determined conditions. For example, the fragmentation of monotoluene-p-sulphonates or methanesulphonates of
suitable cyclic 1,3-diols is reviewed and the corresponding mechanism proposed. The preparation of Ecyclodecenone and cyclodecadienes by fragmentation of substituted decalylboranes is also described mechanistically.
The description of the fragmentation of bicyclic compounds to afford alkenes like macrolides from acetaltosylate is
also included here. The preparation of acyclic alkenes from cyclic precursors is also mechanistically described here.
We have used a series of reactions reviewed by W. Carruthers, and we have proposed didactical and mechanistic
views for them. This latest approach is included in the synthetic methods reviewed by W. Carruthers with respect to
the Formation of carbon-carbon double bonds. Spanish title: Sntesis de alquenos por reacciones de fragmentacin; vistas
mecansticas; De la serie: El cuaderno de notas de qumica orgnica, un enfoque didctico, N5.
*Corresponding author: jabravo@umsa.bo

ANALYSIS AND MECHANISTIC PROPOSALS
Fragmentation of monotoluene-p-sulphonates or methanesulphonates
As academics we are concerned with the didactical importance of covering the needs of debutant students in organic
synthesis. This is the fifth study in: The Organic Chemistry Notebook Series, a Didactical Approach [1-4].
Fragmentation reactions can conduct to the synthesis of alkenes. This is not a common method, but useful under
determined circumstances. For example, the fragmentation of monotoluene-p-sulphonates or methanesulphonates of
suitable cyclic 1,3-diols on treatment with base is reviewed and the corresponding mechanism proposed [5,6].
Characteristically, when the bonds C-X and C(a)-C(b) are arranged in a trans anti-parallel manner, the reaction
happens very rapidly in a concerted way to provide an alkene whose stereochemistry exclusively depends on the
relative orientation of groups in the cyclic compound of start. See Figure 1.
X
(a)
O
(b) H
R
:B
X: leaving group (LG), e.g. -OSO2C6H4CH3-p,
H
(a)
(b)
R
H
-OSO2CH3
Figure 1. Fragmentation of cycle to give an alkene activated by base; reviewed by W. Carruthers [5]
An example of this reaction is the decalin structure 1 where the tosyloxy LG and its adjacent angular H are cis
whose fragmentation gives rise to (E)-cyclodecenone (Figure 2). In the other hand, in the isomer 2, where the
tosyloxy LG and the vicinal angular H are trans, the fragmentation conducts to the isomer (Z)-cyclodecenone (Figure
Downloadable from: Revista Boliviana
37
de Qumica. Volumen 32 N2. Ao 2015
http://www.bolivianchemistryjournal.org, http://www.scribd.com/bolivianjournalofchemistry

Received 04 10 2015
Vol. 32, No.2, pp. 37-44, May./Jun. 2015

32(2) 37-44, May/Jun. 2015
Accepted 06 25 2015
Vila et Bravo
3). In both cases (1 and 2, Figure 2 and 3, respectively) the relative orientation of the hydrogen atoms (H-9 and H10, and H-9 and H-8) in the decalin structure is retained in the alkene [5]. Compounds 1 and 2 under treatment with
base experiment an easy breaking of the trans antiparallel bonds [5] in contrast with the less immediate and less
selective breaking of the anti parallel arrangement of bonds as in compound 3. The treatment of 3 with base gives a
mixture of products containing only a very small amount of (E)-cyclodecenone. This reaction has been used to
prepare a variety of Z- and E-cyclodecenone and cyclononenone derivatives, notably in the course of the synthesis of
caryophyllene [5,6].
H
1
2
10 (b)
OH
(a)
OTos
H
H
(b)
(a)
O
OTos
10
t-C 4H9O- K+
10
7
6
7
5
1'
3
3
10
t-C 4H9OH
H
: trans antiparallel breaking bonds
Tos: H3C
SO2
++ K OSO2C6H4CH3-p
Figure 2. Synthesis of (E)-cyclodecenone by fragmentation of decalin structure, reviewed by W. Carruthers [5]; mechanistic
views proposals
OTos
H
9
10 (b)
3
4
(a)
OH
2
3 (b) TosO
8
7
t-C 4H9O- K+
10
5
(a)
5
6
2'
H
O
9
8
3
4
10
t-C 4H9OH
10
: trans antiparallel breaking bonds Tos:
1
4
H
(b)
10
5
(a)
O
H
8
6
7
OTos
3
: cis parallel breaking bonds
++ K OSO2C6H4CH3-p
Figure 3. Synthesis of (z)-cyclodecenone by fragmentation of decalin structure, reviewed by W. Carruthers [5]; mechanistic
views proposals
38

Received 04 10 2015
Vol. 32, No.2, pp. 37-44, May./Jun. 2015

32(2) 37-44, May/Jun. 2015
Accepted 06 25 2015
Vila et Bravo
This reaction was used in an extended way to produce cyclodecadienes [5,7,8]. The appropriately substituted
decalylboranes (readily available from the appropriate alkenes obtained by hydroboration) served to this purpose
[5,7,8]. See Figure 4.
1
2
OSO2CH3
CH3 H
10
CH3
B2H6
10
CH3
H2 B-
H2 B
OSO2CH3 The infraplanar attack of BH3 gives

no coincidence with the results in the
bibliography [5,7,8]
H
H
H3B
3
CH3
OSO2CH3
CH3
CH3
OSO2CH3
7
CH3
CH3
H3B
H
B-H2
CH3
OSO2CH3
10
5
2
CH3
10
OSO2CH3
9
10
5
2
OH-
H
2
4
OH-
9
7
6
BH2
CH3
H
10
10
OSO2CH3
OSO2CH3
10
CH3
9
8
2
4
4'
7
6
Figure 4. Extended fragmentation reaction for the preparation of cyclodecadienes. Reviewed by W. Carruthers [5]; mechanistic
views
Some important remarks regarding Figures 2-4 include the fact that structures signaled as 1, 2 and 4 are
designed according to the framework molecular models employed and shown in photographs. These models forced
the current conformers named as 1, 2 and 4.
Another application of fragmentation can be observed in the bridged-bicyclic compound 5 to obtain compound 6
[5,9,10]. This synthesis produces the correct relative orientation of the substituents in both rings, the all as reviewed
by W. carruthers [5]; see Figure 5; the corresponding mechanistic analysis is shown in Figure 6.
H
O
*
OMes
OCOC6H5
t-C 4H9O- K+
OCOC6H5
THF, 25oC
Mes = CH3SO2
Bazzenene
Figure 5. Fragmentation of the bridged-bicyclic compound 5 to obtain compound 6. Reviewed by W. Carruthers [5]
Figure 6 reveals, thanks to the application of molecular models, that the stereochemistry at the chiral centre (*)
in compound 6, defined as for the benzoate substituent in Figure 5, is erroneous [5]. The molecular model on the
down photograph in Figure 6 clearly exhibits the stereochemistry for the benzoate substituent of 6 as . In this
scheme the intermediate 5 is submitted to a free rotation around the inter-rings bond resulting in a
stereochemistry for the benzoate substituent at the chiral centre (*) contrarily to what is signalled in the reference
reviewed by W. Carruthers [5].
39

Received 04 10 2015
Vol. 32, No.2, pp. 37-44, May./Jun. 2015

32(2) 37-44, May/Jun. 2015
Accepted 06 25 2015
Vila et Bravo
H t-C 4H9O
Ph
O
O
O
OMes K+
OCOC6H5
CO
O
OCOC6H5
Mes = CH3SO2
5
5'
* : chiral centre
t-C 4H9OH
+ KOSO CH
2
3
5'
5
hand represents the cyclohexenone moiety
free rotation
O
*
free rotation
around the bond
connecting both rings
OCOC6H5
(rotate 120)
OCOC6H5
OCOC6H5
*
5'
5'
5
hand represents the cyclohexenone moiety
Figure 6. Fragmentation of the bridged-bicyclic compound 5 to obtain compound 6. Mechanistic view and analysis
In another application we find the example of the double fragmentation of the acetaltosylate 7 triggered by loss
of carbon dioxide from the carboxylate anion to obtain the macrolide 8 [5,11]. All these reactions so far described
are based on a sole principle: the breaking bonds are trans antiparallel. In 7, the bond C10-C5 is antiperiplanar (trans
antiparallel) to the equatorial tosylate and so are to the equatorial electron pair sp3 axes of the acetal function (9). In
the acetal function (9), the O9-C8 bond is also antiperiplanar to the carboxylate (Figure 7). See the mechanism in
Figure 8.
O
H
TosO
10
O9
10
CH3
HN
CH3
;
1
O9
+ CO2
Tos
6
10
4
3
8
7
O
H
O
7
CH3
H
O-
9
5
10
: antiperiplanar
COO8 7
: antiperiplanar
Figure 7. Fragmentation of the acetal function 7 into macrolide. Reviewed by W. Carruthers [5].
The fact of the antiperiplanar disposition of bonds in decalin-type cyclic compounds permit to predict in a
feasible way the breaking of these bonds, (if disposed in such a way), and therefore to predict a prospective alkene.
Since the molecular models coincide with the alkenes stereochemistry of Figure 8 (structure 8), then, it has been
demonstrated that the present approach to the synthesis of alkenes by fragmentation of cyclic structures of the
decalin-type, is a trustable synthetic method in the prediction of stereochemistry of prospective alkenes.
40

Received 04 10 2015
Vol. 32, No.2, pp. 37-44, May./Jun. 2015

32(2) 37-44, May/Jun. 2015
Accepted 06 25 2015
Vila et Bravo
O
2
10
4
3
TosO
O9
10
CH3
HN
CH3
+ CO2
Figure 8. Fragmentation of the acetal function 7 into macrolide 8. Mechanistic views
Fragmentation is also applied in the generation of acyclic alkenes using cyclic compounds as precursors. The
definition of the geometry of alkene can be derived from the stereochemistry in the cyclic precursor [5]. Exempli
gratia, the ketone 12 which is intermediate in the synthesis of the juvenile hormone was made stereospecifically
through the application of two fragmentation steps [5,12], see Figure 9. The intermediate compounds 10 and 11,
possess such a geometry that allow the readily fragmentation at each step [5,12].
OH
OH
NaH, THF
TosO
H
OH
OTos
H
several
steps
O
O
HO
10
NaH, THF
11
H
12
Figure 9. Two successive fragmentation steps in the synthesis of acyclic alkenes from cyclic compounds. Reviewed by W.
Carruthers [5].
41

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Vol. 32, No.2, pp. 37-44, May./Jun. 2015

32(2) 37-44, May/Jun. 2015
Accepted 06 25 2015
Vila et Bravo
The mechanistic views of this synthesis are shown in Figure 10.

H-Na+
OH
H
Et
TosO
TosO
H
OH
OH
Me
H
OH
Et
O
Me
+ H2 + TosONa
OH
OH
Li+-AlH4
H
O
H
H
-
H
Al H
Li+
H
H
Li
Al OH
Al
OH
Li+
H
Al OH
Li
++ Li OH
OH
OH
-Al
H
OH
OH
-Al
OH
Al
++ Li OH
OH
Li
H
Al OH
Li+
HO
OH
OH
+
+LiOH
H
H
OH
-Al
O
+
H
H
Li+
OH
HO
H
Al
Li+-OH
H+
+LiOH
H2O
H
H
Al
OH
H
H
Al
+LiOH
OH
H
H
HO
H
OH
+
Al
H2O
H
H
HO
H
OH
OH
+
Li
H2O
O
Li+
OH
OH
Li+
OH
O
+
Li
H
Al OH
HO
Figure 10. Two successive fragmentation steps in the synthesis of acyclic alkenes from cyclic compounds. Mechanistic views.
42

Received 04 10 2015
Accepted 06 25 2015
Vila et Bravo
OH
H
Al
HO
H
OH
HO
O H
-
HO
H
HO
Al
HO
+-
+ Li OH
OH
HO
-Al
O
Li+
HO
Li
HO
OH
H
H
Li
HO
Al OH
Al
OH
HO
O-
OTos =
O
O-
HO
O
HO
HO
OH
Ph
H O
H+,Catalytic amount
Li+
OH
HO
OH
-Al
HO
OH
H O
HO
+LiOH
+Al
+ Li OH
OH
OH
H2O
H
+LiOH
OH
OH
HO
Li
OH
H2O
O
H
Vol. 32, No.2, pp. 37-44, May./Jun. 2015

32(2) 37-44, May/Jun. 2015
Ph
H+
O
O S Ph
Ph
H O
HO
H
O+H2
S O
-H2O, H+
OTos
H O
HO
HO
H
11
OTos
H
H
O
H
H-Na+
O
H
O
H
12
11
NaOTos + H2
Figure 10(Cont.). Two successive fragmentation steps in the synthesis of acyclic alkenes from cyclic compounds. Mechanistic
views.
ACKNOWLEDGEMENTS
The authors express their gratitude to Prof. Eduardo Palenque from the Department of Physics, Universidad Mayor
de San Andrs, for his bibliographic support.
REFERENCES
1.
2.
3.
4.
Bravo, J. 2005, Bol. J. of Chem., 23, 1. (http://www.bolivianchemistryjournal.org, 2005).

Bravo, J.A., Mollinedo, P., Pearrieta, J.M., Vila, J.L. 2013, Bol. J. of Chem., 30, 24-41
(http://www.bolivianchemistryjournal.org, 2013)
Bravo, J.A., Vila, J.L. 2014, Bol. J. of Chem., 31, 61 (http://www.bolivianchemistryjournal.org, 2014)
Bravo, J.A., Vila, J.L. 2015, Bol. J. of Chem., 32, 15 (http://www.bolivianchemistryjournal.org, 2015)
43

Received 04 10 2015
Accepted 06 25 2015
Vila et Bravo
Vol. 32, No.2, pp. 37-44, May./Jun. 2015

32(2) 37-44, May/Jun. 2015
Carruthers, W. Some Modern Methods of Organic Synthesis, Cambridge University Press, 3rd ed., 1987, Worcester, U.K., pp.
156-159.
6. Corey, E.J., Mitra, R.B., Uda, U. 1964, J. Am. Chem. Soc., 86, 485.
7. Marshal, J.A. 1969, Rec. Chem. Prog., 30, 3.
8. Marshal, J.A. 1971, Synthesis, 229.
9. Kodama, M., Takahashi, T., Kurihara, T., Ito, S. 1980, Tetrahedrom Lett., 21, 2811.
10. Still, W.C., Tsai, M.Y., 1980, J. Am. Chem. Soc., 102, 3725.
11. Sternbach, D., Shibuya, M., Jaisli, F., Bonetti, M., Eschenmoser, A. 1979, Angew. Chem. Internat. edn.,, 18, 634.
12. Zurflh, R., Wall, E.N., Siddall, J.B., Edwards, J.A. 1968, J. Am. Chem. Soc., 90, 6224.
5.
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REVISTA BOLIVIANA DE QUMICA

Bolivian Journal of Chemistry

Vol. 32, No.2, pp. 37-44, May./Jun. 2015

SYNTHESIS OF ALKENES BY FRAGMENTATION REACTIONS;

Keywords: Organic Chemistry, Fragmentation reaction, oxidative decarboxylation, carboxylic

*Corresponding author: jabravo@umsa.bo

X: leaving group (LG), e.g. -OSO2C6H4CH3-p,

de Qumica. Volumen 32 N2. Ao 2015

REVISTA BOLIVIANA DE QUMICA

Vol. 32, No.2, pp. 37-44, May./Jun. 2015

: trans antiparallel breaking bonds Tos:

de Qumica. Volumen 32 N2. Ao 2015

REVISTA BOLIVIANA DE QUMICA

Vol. 32, No.2, pp. 37-44, May./Jun. 2015

OSO2CH3 The infraplanar attack of BH3 gives

de Qumica. Volumen 32 N2. Ao 2015

REVISTA BOLIVIANA DE QUMICA

Vol. 32, No.2, pp. 37-44, May./Jun. 2015

de Qumica. Volumen 32 N2. Ao 2015

REVISTA BOLIVIANA DE QUMICA

Vol. 32, No.2, pp. 37-44, May./Jun. 2015

: trans antiparallel breaking bonds

Figure 8. Fragmentation of the acetal function 7 into macrolide 8. Mechanistic views

Downloadable from: Revista Boliviana

de Qumica. Volumen 32 N2. Ao 2015

REVISTA BOLIVIANA DE QUMICA

Vol. 32, No.2, pp. 37-44, May./Jun. 2015

The mechanistic views of this synthesis are shown in Figure 10.

: trans antiparallel breaking bonds

Downloadable from: Revista Boliviana

de Qumica. Volumen 32 N2. Ao 2015

REVISTA BOLIVIANA DE QUMICA

Vol. 32, No.2, pp. 37-44, May./Jun. 2015

Bravo, J. 2005, Bol. J. of Chem., 23, 1. (http://www.bolivianchemistryjournal.org, 2005).

Downloadable from: Revista Boliviana

de Qumica. Volumen 32 N2. Ao 2015

REVISTA BOLIVIANA DE QUMICA

Vol. 32, No.2, pp. 37-44, May./Jun. 2015

Downloadable from: Revista Boliviana

de Qumica. Volumen 32 N2. Ao 2015

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