Reduction lactone ring opening

Reductive y-lactone ring opening, with concomitant desilylation at the tertiary position by LiAlH4, gave triol 17 in 80% yield. Finally, acetonide formation followed by oxidation with tetra-n-propylammonium perruthenate/A-methylmorpholine / /-oxide oxidation, led to the target aldehyde 19 in 80% overall yield. 

White et al. developed a stereospecific synthesis of Z-olefins, including isotretinoin [84]. Thus, isotretinoin was obtained by a Reformatsky reaction of p-cyclocitral with the C5 bromoester, followed by DIBAL-H lactone reduction, lactol ring opening, selective olefin bond formation with ethyl 4-diethoxyphosphoryl-3-methyl-2-butenoate and further saponification, Fig. (46). 

NaBH4 reduction of compound 11.25 104) afforded the rearranged lactone 13.2, which was formed by lactone ring opening of the initially formed 3-deoxy-6 3,7(3-dihydro-8-epilactarorufin A, followed by ring closure onto the 8a-hydroxy group. 

Table 9.4 Domino lactone ring-opening/reduction.

Epoxides provide another useful a -synthon. Nucleophilic ring opening with dianions of carboxylic acids (P.L. Creger, 1972) leads to y-hydroxy carboxylic acids or y-lactones. Addition of imidoester anions to epoxides yields y-hydroxyaldehyde derivatives after reduction (H.W. Adickes, 1969). 

Again reductive opening of the lactone ring can be achieved at the chloro lactone or a,j5-unsaturated keto lactone stages. ... 

Addition of lithiated heterocycles to aldonolactones yields carbon-linked nucleosides (56). Thus, the reaction of 2,3 5,6-di-O-isopropylidene-L-gu-lono-1,4-lactone (9b) or 2,3-O-isopropylidene-D-ribono-l,4-lactone (16a) with various lithiated heterocycles gave gulofuranosyl derivatives 53a-g or ribofuranosyl derivatives 54b,c. Gulonolactols 53a-g and ribonolactols 54b,c were acetylated with acetic anhydride in pyridine to yield their acetyl derivatives. The stereochemistry of compounds 53a-g and 54b,c was discussed in terms of the Cotton effect of circular-dichroism curves of the ring-opened alcohols formed upon reduction by sodium borohydride. The configuration at C-l of 53g was proved by means of X-ray analysis (57,58). 

When dienones such as 55 are subjected to the epoxidation conditions the electron-poorer C=C double bond is selectively epoxidized. The other C=C bond can be functionalized further, for example, it can be dihydroxylated, as shown in the synthesis of the lactone 56 (Scheme 10.11) [82]. Stannyl epoxides such as 57 (Scheme 10.11, see also Table 10.8, R1 = n-Bu3Sn) can be coupled with several electrophiles [72], reduction of chalcone epoxide 58 and ring opening with alkyl aluminum compounds provides access to, e.g., the diol 59 and to phenylpropionic acids (for example 60). Tertiary epoxy alcohols such as 61 can be obtained with excellent diastereoselectivity by addition of Grignard reagents to epoxy ketones [88, 89]. 

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