Hydroxy aldehydes lactones

The lactone concept is not restricted to the simple model biaryl synthesis presented here. It has been successfully expanded to a broad series of structurally diverse biaryl substrates (e.g., lactones with additional stereocenters and functional groups, configurationally stable lactones, seven-membered lactones, and again configurationally unstable biaryl hydroxy aldehydes ), to different activation modes in the ring-opening step (e.g., use of metallated nucleophiles, carbonyl activation by Lewis acids, (Ti -complexation, etc.), and for various strategies of stereoselection (e.g., external vs. internal asymmetric induction). ... 

The /S-bromodihydropyran (652) on halogen-metal exchange with f-butyllithium affords a useful organometallic (653) that can function as the equivalent of a 5-hydroxy aldehyde enolate (Scheme 151) (79TL67). The vinyllithium species adds to ketones and aldehydes at -110 °C in good yield and also reacts in a conjugate mode with a,/S-unsaturated carbonyl compounds in the presence of copper(I) ions. On hydrolysis and oxidation, the dihydropyran component (654) can be transformed into a substituted 5-lactone (655). 

In addition, Cushman and co-workers121 reported the synthesis of a 1-hydroxyethylene dipeptide with a Pro moiety at the C-terminus using the reaction between an a-amino aldehyde and a lithium cyclopentanone enolate. Matternich and Liidi 22 described the synthesis of a y-(aminoalkyl)-a-hydroxy-y-lactone starting from the addition of an a-amino aldehyde to a pyruvate enolate. 

The construction of the C2-C3 bond of the 1-hydroxyethylene moiety by the addition of a two-carbon fragment to aminoalkyl epoxides, amino ketones, p-amino-a-hydroxy aldehydes, or 4-amino-3-oxo phosphonates was also studied. As summarized in Scheme 14, Evans et al.[28] added a malonate to an aminoalkyl epoxide and the product spontaneously cyclized, leading to a lactone.— Then, the second side chain was incorporated into the a-carbon of the lactone, providing a mixture of C2 epimers. The final compound was obtained by hydrolysis and decarboxylation. The lack of diastereoselectivity of this method is offset by the small number of steps and the accessibility to all eight possible stereoisomers. Biihlmayer et al.[30] also used a similar method, but they transformed the epoxide into the apparently more reactive iodide. Then, the iodide compound was treated with an enolate. 

Dimethoxyoxetanes.1 In the presence of ZnCl2, this ketal reacts with 0-hydroxy aldehydes to give 2,2-dimethoxyoxetanes, which can be converted into 4-hydroxy-3-methyl-8-lactones and 5,6-dihydro-2-pyrones. In one case, an optically active lactone was obtained in 80% ee from an optically active y-hydroxy aldehyde. 

The cyclic acetal is a protected form of the hydroxy-aldehyde and oxidation under acidic conditions (Cr03 in H2S04) gives a good yield of the spirocyclic lactone. In the whole process from allyl silane to lactone, the allyl silane is behaving as a d3 synthon or homoenolate. 

The hydroxy aldehyde 108 was converted into lactone 109 (a 1 1 diastereomeric mixture) by a samarium-mediated cyclization reaction (Scheme 23) <1997TL8245>. 

These enol carbamates are stable to acid, but undergo methanolysis in the presence of methanesulfonic acid and Hg(OAc)2 to form y-lactol methyl ethers, with retention of configuration at C, and C4. These products can be oxidized (8, 97) to -y-lactones. The overall process thus provides a route to protected -y-hydroxy aldehydes. 

Ketenylidenetriphenylphosphorane, (QH,),P- C=C=0 (1), 10, 450-451 11, 281 Macrocyclic lactones. The ylides 3, fomed by reaction of acetals (2) of long-chain hydroxy aldehydes with 1, can be conver ed into the ylides 4, which undergo an... 

The oxidation of primary alcohols to the corresponding carboxylic acid or ester generally requires fairly powerful oxidants, and in most cases the issue of selectivity is dealt with by protection of other oxidiz-able functionality within the molecule. One important area in which this need not be the case is the oxidation of symmetrical and unsymmetrical diols to the corresponding lactone. The general scheme is presented in Scheme S, and relies on an initial chemoselective oxidation to the hydroxy aldehyde, which is in equilibrium with the lactol. This lactol is then oxidized to the lactone. In some cases it is possible to halt the reaction at the lactol stage, but usually the lactone is the product. Most of this section will be concerned with this type of selective oxidation. 

The reduction of lactones with DIBAL provides lactols. Lactols are latent hydroxy aldehydes. 

In a study by Wicha directed to the synthesis of prostaglandins from the Corey lactone, the use of BFs-EtaO to catalyze the addition of the lithium sulfone anion (470) to aldehydes was demonstrated (equation 109). The use of Lewis acid catalysis results in significantly improved yields for the addition component of the Julia coupling. In this example, the addition of either the lithium or the magnesium sulfone anion proceeded in low yield. With the addition of BF3-Et20, the p-hydroxy sulfone can either be isolated, or directly converted to an alkene in one pot. This sequence was originally developed to deal with the specific problem of a-hydroxy aldehydes, and the difficulty of sulfone anion addition to these adducts. Other problems with addition of the sulfone adduct may be amenable to this solution as well. 

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