Lactones aldol-type reactions

A similar method has been described by Badia and co-workers who used chiral amides derived from pseudoephe-drine.139 Moreover, a zirconium-mediated Claisen-aldol tandem reaction of an a,cr-dialkylated ester with several aldehydes has been reported (Scheme 39).140 After the initial Claisen condensation, zirconium enolate intermediate 92 reacts with various types of aldehydes through aldol-type reaction and subsequent lactonization, providing the corresponding pyran-2,4-diones. 

Aldol-type reaction of zinc esters. This titanium reagent promotes condensation of (ethoxycarbonylalkyl)iodozinc compounds (13, 220) with aldehydes or ketones to provide hydroxy esters and/or lactones. The active reagent may be (ethoxycarbonyl)alkyltriisopropoxytitanium. 

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). 

Lithium tri-sec-butylborohydride, 21 B-3-Pinanyl-9-borabicyclo[3.3.1]-nonane, 249 Sodium borohydride, 21 (3-Hydroxy esters and lactones By aldol-type reactions (R)-( + )-f-Butyl p-tolylsulfinylace-tate, 59 Cadmium, 60... 

Highly stereoselective aldol reactions of lithium ester enolates (LiCR1 R2CC>2R3) with (/0-2-(/ -tolylsulfiny I (cyclohexanone have been attributed to intermediacy of tricoordinate lithium species which involve the enolate and the sulfinyl and carbonyl oxygens of the substrates.43 The O-metallated /<-hydroxyalkanoatcs formed by aldol-type reaction of carbonyl compounds with enolates derived from esters of alkanoic acids undergo spontaneous intramolecular cyclization to /1-lactones if phenyl rather than alkyl esters are used the reaction has also been found to occur with other activated derivatives of carboxylic acids.44... 

The mechanistic proposal for the formation of these p-laclonc products is related to that for the formation of y-lactones (Scheme 17). Initial formation of the conjugate enamine Ila is followed by a proton transfer from oxygen to carbon thereby forming the enolate V. In an aldol-type reaction this enolate attacks the electrophilic ketone providing zwitte-rions VI. The subsequent cyclization to the lac tone 18 then liberates the NHC catalyst. 

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]. 

The mechanism of this remarkable reaction (Scheme 42) may involve an aldol type condensation between two molecules of the appropriate quinone to yield an intermediate (232) which undergoes ring opening to the ketene (233). Intramolecular interception of the ketene (233) would produce lactone (234), a tautomer of bovilactone-4,4 (230). The biosynthesis of bovilactone-4,4 from boviquinone-4 may follow similar lines. 

Alkyl halides are less investigated in this protocol. a-Halo ethers, thioethers, and lactones can be used in this protocol. a-Halocarbonyl compounds react abnormally with allyl- and acetonyltins to give oxiranes via the attack at the carbonyl followed by the cyclization (Scheme 34).p°]-P3] -pjjg reaction appears to be a variation of a simple Lewis-acid-catalyzed aldol-type condensation. On the other hand, if a catalyst without phosphine ligand is used, 1,4-diketone is formed (Scheme 35). 

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