Aldol-type reactions lactone synthesis

Asymmetric synthesis in aldol-type reaction involving magnesium ester or lactone enolates has also been reported. Enolate of (—)-menthyl or (-l-)-bornyl acetate reacts with substituted benzophenones or a-naphtophenones to yield, upon hydrolysis of the resulting esters, optically active /3-hydroxyacids. Although these results are interpreted in terms of a steric factor. Prelog s rules are not applicable to these reactions (equation 88). 

In the synthesis of aspyrone (994), an antibiotic isolated from the culture broth of Aspergillus species, lactaldehyde 990 supplies the asymmetric centers of the epoxide in the side chain (Scheme 134). The molecule is assembled convergently by addition of the lithium enolate of D-rhamnose-derived a-phenylseleno- -lactone 991 to aldehyde 990. After an initial aldol-type reaction, the intermediate alkoxide displaces tosylate to provide epoxide 992 with >99.8% stereoselectivity. Peroxide-induced elimination of phenylselenide furnishes TBS-protected aspyrone 993 in 61% overall yield from 990. 

Synthesis of Butyrolactones.—A chiral synthesis of five- and six-manbered lactones has been reported which involves an initial aldol-type reaction of (/J)-t-butyl (p-tolylsulphinyl)acetate to give the intermediate (136), which is converted into the butyrolactone (138) (in 80% enantiomeric excess) via the nitrile (137), as shown in Scheme 84. ... 

In synthesis of isotetronic acid derivatives, aldol-type reactions of 1,2-dicarbonyl substrates including oxalyl chloride and pyruvates are used as powerful mefhodologies. For instance, Langer et al. reported systematic investigations on such reaction of oxalyl chloride 21 wifh l,3-bis(trimethylsilyloxy)-l,3-butadienes 22 or 24 as masked dianion equivalenfs (Scheme 10) [21]. By using a catalytic amoxmt of MesSiOTf, y-lactone formation smoothly occurred to yield the lactones (E)-23 or (Z)-25, respectively. This methodology is also effective for the synthesis of medium-sized bicyclic y-bufenolides such as 25c [22]. 

An acid-catalyzed lactonization of 8-hydroxy esters has been used in the diastereoselective synthesis of cA-4,5-substituted 8-lactones by Saigo et al. [48] (Scheme 11). The ring-opening aldol-type reaction of 2-methoxy-2-(trimethylsiloxy)cyclobutanecarboxylic ester 58 with aldehydes 59 in the presence of Lewis acid afforded the corresponding adducts 60 and 61. Subsequent treatment of these products with a catalytic amount of p-TsOH gave cis- and (rans-4,5-substituted lactones in favor of the c/r-isomer 62. 

Compounds such as (R)-(-i-)-r-butyl(p-tolylsulfinyl) acetate (94) have proved to be powerful chiral synthons in asymmetric aldol-type condensation reactions [64]. Applications have included the asymmetric synthesis of p-hydroxy acids and esters [65] and naturally occurring five- and six-membered lactones [66]. 

An intramolecular diastereoselective Refor-matsky-type aldol approach was demonstrated by Taylor et al. [47] with an Sm(II)-mediated cy-clization of the chiral bromoacetate 60, resulting in lactone 61, also an intermediate in the synthesis of Schinzer s building block 7. The alcohol oxidation state at C5 in 61 avoided retro-reaction and at the same time was used for induction, with the absolute stereochemistry originating from enzymatic resolution (Scheme II). Direct re.solution of racemic C3 alcohol was also tried with an esterase adapted by directed evolution [48]. In other, somewhat more lengthy routes to CI-C6 building blocks, Shibasaki et al. used a catalytic asymmetric aldol reaction with heterobimetallic asymmetric catalysts [49], and Kalesse et al. used a Sharpless asymmetric epoxidation [50]. 

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