Ajoy K Banerjee1*, Betzabeth Briceño1, Alexis Maldonado1, Liadis Bedoya1, Elvia V Cabrera2 and Dioni Arrieche3
1Chemistry Center, Venezuelan Institute of Scientific Research (IVIC), Caracas, Venezuela
2Faculty of Chemical Engineering, Central University of Ecuador, Quito, Ecuador
3Department of Chemistry, Technical University Federico Santa María, Valparaíso, Chile
Submission: December 13, 2020;Published: January 04, 2021
*Corresponding author: Ajoy K Banerjee, Centro de Química, IVIC, Apartado- 21827, Caracas-1020A, Venezuela
How to cite this article: Ajoy K B, Betzabeth B, Alexis M, Liadis B, Elvia V C, et al. Lead Tetraacetate in Organic Synthesis. Organic & Medicinal Chem
IJ. 2021; 10(3): 555788. DOI: 10.19080/OMCIJ.2021.10.555788
Lead tetraacetate (LTA),a versatile oxidizing agent for different functional groups, has been widely used for oxidative decarboxylation of carboxylic acid, cleavage of 1,2-diol, formation of the cyclic ether, acetoxylation, methylation, dehydrogenation etc. The present micro review describes the utility of LTA in 1,2-glycol-cleavage and decarboxylation of carboxylic acid.
Keywords: Lead tetraacetate (LTA); Oxidative decarboxylation; Glycol cleavage; Bromination
The commercially available LTA is hygroscopic and turns brown due to the formation of lead oxide. Therefore, LTA should be stored in absence of moisture, kept tightly sealed and stored under 10oC in the dark and in the presence of about 5% glacial
acetic acid. LTA is very toxic and may be absorbed through the skin. Due to the high toxicity the reagent should be handled with care in chemical fume hood. It is soluble in hot acetic acid, benzene, cyclohexane, chloroform, and carbon tetrachloride.
LTA is one of the most frequently used reagents for the cleavage of glycols and for the preparation’s carbonyl compounds. The reactions are performed either in aprotic solvents (benzene, nitrobenzene,1,2-dichloroethane) or in protic solvents such as acetic acid . The role of LTA in glycol cleavage is highly dependent on the structure and stereochemistry of the substrate. The cleavage of diols proceeds via a cyclic intermediate . as shown in Scheme 1. The cleavage of cis diol occurs more easily than the trans-diol which does not permit the easy formation of
the cyclic intermediate. Some examples are given in Scheme 2.
The diol 1 on treatment  with LTA in benzene affords
aldehyde 2 but the diols 3 and 4 with LTA suffer4 cleavage and
yield ketone 5. 1,2-Glycol cleavage  by LTA has been widely
applied for the oxidation of carbohydrates and sugars . The
diol 6 on oxidation with LTA in acetic acid yields the aldehyde 7.
The reactivity of individual glycol units in sugar molecules is often
different and thus the LTA reaction is helpful tool for structural
determination and for degradation studies in carbohydrate
chemistry . It has been observed that trans-1,2-diols which
are cleaved slowly with LTA in acetic acid are readily cleaved if
pyridine is used as reaction solvent .
The cyclopropene ester 9, prepared from the bromo derivative
of cis-1,2-hydrocatechol 8, on treatment with LTA produces  the
cyclopropane aldehyde 10 which is a potential intermediate for
the cis-pyrethroid class of insecticides. The trans-diol 12, obtained
from D-mannitol 11, with LTA affords ketone  13 in unspecified
yield. Reduction of 13 with sodium borohydride produces the
alcohol 14 which is utilized for the synthesis of mixed-acid
phospholipids polyunsaturated fatty acid as shown in Scheme 3.
Decarboxylation of carboxylic acid
Oxidative decarboxylation of carboxylic acids by LTA has
been frequently used in the synthesis of terpenoid compounds.
Oxidative decarboxylation by LTA depends on the conditions of
reaction, core agents and structure of acids and hence a variety of
products such as acetate esters, alkanes, alkenes, and alkyl halides
can be obtained . The reactions are performed  in nonpolar
solvents (benzene, carbon tetrachloride) or polar solvents (acetic
acid, pyridine, HMPA). Decarboxylation of primary and secondary
carboxylic acids usually affords acetate esters as major products.
If a mixture of acetate and olefin is formed, it is recommended to
perform the reaction in presence of potassium acetate . The
cyclohexane carboxylic acid 15 if heated under reflux with LTA in
benzene furnishes a mixture of acetate 16 and the olefin 17 but
only the acetate 16 is produced in high yield when heated with
potassium acetate in acetic acid (Scheme 4).
The monocarboxylic acid on oxidation with LTA in presence of
copper (II) salts gives mainly alkenes (Scheme 5). The free radical
mechanism is generally accepted . Rosefuran 19 has been
obtained in crude form (70%) by the oxidative decarboxylation
of 3-methyl-2-furoic acid 18 with LTA in boiling benzene in the
presence of copper acetate . Bisdecarboxylation  of
compounds containing carboxyl groups on adjacent carbons can
be achieved with LTA in the presence of oxygen and pyridine.
Thus, the dicarboxylic acid  20 on decarboxylation affords
the tetrahydrobenzene 21. Similarly, the acid  22 if subjected
to bisdecarboxylation can yield compound 23 (Scheme 6). The
compounds containing germinal carboxyl groups (malonic acid
derivatives) 24 are decarboxylated with LTA to give gem diacetate
which can easily be hydrolyzed to ketone  25.
The LTA decarboxylation of tertiary carboxylic acids gives a
mixture of alkenes and acetate esters. O-methylpodocarpic acid
26 on heating with LTA yields a mixture of olefins  27, 28,
29 and acetates 30 and 31. In addition a lactone 32 is obtained
(Scheme 7). Banerjee and collaborators  have observed that
the decarboxylation of the acid 34, prepared from the cyclic ether
33, with LTA, pyridine and DMF  affords a mixture of olefins 35
(scheme 8). The transformation of 35 into the ketone 36 is affected
in two steps: (a) demethoxylation  with sodium iodide, boron
tribromide, 15-crown ether-5, (b) oxidation  with Jones
Reagent. Bromination of 36 followed by dehydrobromination
and aromatization respectively yield tetraol 37 in 60% Yield. The
tetraol 37 is a potential intermediate  for the synthesis of
diterpenoid quinones cryptotanshinone and tanshinone IIA.
Masamune and collaborators  have also studied the
decarboxylation of tertiary carboxylic acid with LTA in relation
of the studies on the synthesis of the terpene glutinosone. The
lactone 39, prepared from the ketoester 38, on alkaline hydrolysis
and acetylation respectively is converted to the acid 40 (Scheme
9). The acid 40 on being heated with LTA and DMF undergoes
decarboxylation and produces a mixture of olefins 41. Treatment
of 41 with methanolic potassium hydroxide (5%) followed by the
addition of triphenyl methyl fluoborite afford glutinosone 42.
Oxidative decarboxylation reaction has proved usefull in the
synthesis  of sesquiterpene furoventalene 46 as depicted in
the scheme 10. m-Anisic ester 43 is converted into the ester 44
in three steps (reductive alkylation, metalation, and alkylation).
Acidic hydrolysis and cyclization of the ester 44 yield dihydro
benzofuran 45. Alkaline hydrolysis and oxidative decarboxylation
with LTA lead the formation of furoventalene 46. Banerjee and
collaborators  have utilized oxidative decarboxylation for
the synthesis of sesquiterpene (±) frullanalide the details are
described in scheme 11.
The ketone acid 48, prepared from the cyclic ether 47, on
heating with LTA and copper (II) acetate undergoes oxidative
decarboxylation yielding enone 49. Alkylation of 49 with ethyl
bromoacetate produces ketoester 50 which on reduction with
sodium borohydride in methanol followed by stirring with
hydrochloric acid afford the lactone 51. As the lactone 51, has
already converted  into (±) frullanalide 52 the present
synthesis of 51 constitutes a formal total synthesis  of
Another interesting use of oxidative decarboxylation 
with LTA is shown in scheme 12. The acid 53 on decarboxylation
with LTA gives a mixture of olefins 54. Epoxidation followed
by hydrolysis with Lewis acid produces aldehyde 55 which on
methylation and oxidation respectively afford Callitrisic acid 56.
The above-mentioned examples exhibit the importance of LTA in
the synthesis of terpenoid compounds.
LTA has also been utilized for acetoxylation [27,28] of ketones
in enol form, nuclear methylation , oxidation  of phenols.
Alkyl sulfides , alkyl hydroperoxides  and organometallic
compounds are also oxidized33 by LTA. Several cyclic ethers have
been synthesized by LTA oxidation .