and Jung reported the synthesis of δ-lactones from cyclohexenones via δ-hydroxy
acid [37] (Scheme 1). The protocol involves dihydroxylation of enone 15 with
osmium tetroxide, oxidative cleavage of diol with lead tetraacetate, and reduction
of the resulting secoaldehyde-acid 16 with sodium borohydride followed by acid
treatment to afford the desired lactone 18.
The same transformation has also been accomplished in one pot by Chavdarian
and Heathcock [38] (Scheme 2). Ozonolysis of cyclohexenone 19 in methanol at
À60
C, followed by the addition of excess sodium borohydride at 0
C, afforded
δ-lactone 21 in 45 % yield. The generality of this method was demonstrated using
different cyclohexenones to obtain the corresponding δ-lactones.
Coke and Richon have constructed the δ-lactone framework of
n-hexadecalactone, the proposed pheromone isolated from Vespa orientalis,
through lactonization of a hydroxy acid intermediate [39] (Scheme 3). The optically
pure amino alcohol 22 obtained by resolution was converted to the optically active
epoxide 23 by quaternization, followed by Hofmann elimination. Addition of the
dianion of propiolic acid to epoxide 23, and subsequent reduction of the resulting
acetylenic hydroxy acid with hydrogen and palladium, provided the saturated
hydroxy acid 25, which spontaneously cyclized to afford δ-lactone 12. In a similar
way, the enantiomer of amino alcohol 22 was also transformed into the antipode of
lactone 12. Furthermore, using this method, any terminal epoxide can easily be
converted to the corresponding saturated δ-lactone in two steps.
Another approach to the synthesis of δ-lactones from δ-hydroxy masked acids
has been demonstrated by Khan and Paterson [40] (Scheme 4). ZnBr 2 -catalyzed
phenylthioalkylation of ketene bis(trimethylsilyl)acetals 26 with appropriate
α-chlorosulphides 27 afforded the corresponding alkylated product 28, which on
hydrolysis underwent lactonization to provide the δ-lactone 29.
A general approach for the synthesis of δ-lactones from δ-hydroxy esters and
amides has been described by Yamaguchi et al. [41]. The strategy involves addition
of lithium enolates generated from the esters or amides to oxetanes 30 to afford the
corresponding δ-hydroxyesters or δ-hydroxyamides 31 (Scheme 5). Hydrolysis of
these intermediates and subsequent lactonization was achieved under either acidic
or basic conditions to furnish δ-lactone 32.
In another report on the synthesis of insect pheromone 12 by Gerth and Giese,
lactonization of a δ-hydroxy ester has been used to build the δ-lactone skeleton [42]
(Scheme 6). The radical generated from iodide 33 was treated with ethyl acrylate to
afford ester 34, which upon saponification and lactonization furnished lactone 36.
Ester 34 was also converted into the lactonic pheromone of the oriental hornet 12
through a series of transformations. Cleavage of the acetonide group of ester 34,
monotosylation, and protection of the secondary alcohol yielded tosylate 37.
Homologation of tosylate 37 followed by a one-pot deprotection and lactonization
furnished pheromone 12.
100
K. Palanichamy and K.P. Kaliappan
acid [37] (Scheme 1). The protocol involves dihydroxylation of enone 15 with
osmium tetroxide, oxidative cleavage of diol with lead tetraacetate, and reduction
of the resulting secoaldehyde-acid 16 with sodium borohydride followed by acid
treatment to afford the desired lactone 18.
The same transformation has also been accomplished in one pot by Chavdarian
and Heathcock [38] (Scheme 2). Ozonolysis of cyclohexenone 19 in methanol at
À60
C, followed by the addition of excess sodium borohydride at 0
C, afforded
δ-lactone 21 in 45 % yield. The generality of this method was demonstrated using
different cyclohexenones to obtain the corresponding δ-lactones.
Coke and Richon have constructed the δ-lactone framework of
n-hexadecalactone, the proposed pheromone isolated from Vespa orientalis,
through lactonization of a hydroxy acid intermediate [39] (Scheme 3). The optically
pure amino alcohol 22 obtained by resolution was converted to the optically active
epoxide 23 by quaternization, followed by Hofmann elimination. Addition of the
dianion of propiolic acid to epoxide 23, and subsequent reduction of the resulting
acetylenic hydroxy acid with hydrogen and palladium, provided the saturated
hydroxy acid 25, which spontaneously cyclized to afford δ-lactone 12. In a similar
way, the enantiomer of amino alcohol 22 was also transformed into the antipode of
lactone 12. Furthermore, using this method, any terminal epoxide can easily be
converted to the corresponding saturated δ-lactone in two steps.
Another approach to the synthesis of δ-lactones from δ-hydroxy masked acids
has been demonstrated by Khan and Paterson [40] (Scheme 4). ZnBr 2 -catalyzed
phenylthioalkylation of ketene bis(trimethylsilyl)acetals 26 with appropriate
α-chlorosulphides 27 afforded the corresponding alkylated product 28, which on
hydrolysis underwent lactonization to provide the δ-lactone 29.
A general approach for the synthesis of δ-lactones from δ-hydroxy esters and
amides has been described by Yamaguchi et al. [41]. The strategy involves addition
of lithium enolates generated from the esters or amides to oxetanes 30 to afford the
corresponding δ-hydroxyesters or δ-hydroxyamides 31 (Scheme 5). Hydrolysis of
these intermediates and subsequent lactonization was achieved under either acidic
or basic conditions to furnish δ-lactone 32.
In another report on the synthesis of insect pheromone 12 by Gerth and Giese,
lactonization of a δ-hydroxy ester has been used to build the δ-lactone skeleton [42]
(Scheme 6). The radical generated from iodide 33 was treated with ethyl acrylate to
afford ester 34, which upon saponification and lactonization furnished lactone 36.
Ester 34 was also converted into the lactonic pheromone of the oriental hornet 12
through a series of transformations. Cleavage of the acetonide group of ester 34,
monotosylation, and protection of the secondary alcohol yielded tosylate 37.
Homologation of tosylate 37 followed by a one-pot deprotection and lactonization
furnished pheromone 12.
100
K. Palanichamy and K.P. Kaliappan