Lactols diols, synthesis

The completion of the synthesis of key intermediate 2 requires only a straightforward sequence of functional group manipulations. In the presence of acetone, cupric sulfate, and camphorsulfonic acid (CSA), the lactol and secondary hydroxyl groups in 10 are simultaneously protected as an acetonide (see intermediate 9). The overall yield of 9 is 55 % from 13. Cleavage of the benzyl ether in 9 with lithium metal in liquid ammonia furnishes a diol (98% yield) which is subsequently converted to selenide 20 according to Grie-co s procedure22 (see Scheme 6a). Oxidation of the selenium atom... 

Selective protection of the primary alcohol gave 138 (P=TBDMS), which was then esterified with ( )-3-hexenoic acid to produce the key intermediate 139 for cyclization. Ireland ester-enolate Claisen rearrangement and hydrolysis produced a protected hydroxyacid, which, after reduction of the acid and deprotection of the alcohol, yielded meso diol 128 more quickly and efficiently than in the previous synthesis. The meso diol was then converted to the racemate of the lactol pheromone 130 as previously described. 

With a good route to the key meso diol 128 in hand, the authors turned their attention to desymmetrization, using the known asymmetric hydrolysis of meso diacetates by Lipase AK (Scheme 23). The meso diol 128 was first converted to diacetate 140, and then hydrolyzed with Lipase AK to cleave selectively one of the two acetates, producing chiral hydroxyester 141. Oxidation, cleavage of the acetate, and lactonization yielded the (3S,4.R) lactone 129. The corresponding lactol (3S,4 )-130 was found to be the enantiomer of the compound produced in the HLADH synthesis. 

Diols were converted to lactols by TPAP/NMO/PMS/CHjCN [352] or TPAP/NMO/ PMS/CH Clj-CHjCN [353] oxidation of a keto hemi-ketal by TPAP/NMO/PMS/ CH Cl in an avermectin synthesis yielded a lactol, via an intermediate retro-aldol [354], The 1,4-diols in Fig. 2.19 (R=C3H, Ph) produced lactones with TPAP/ NMO/PMS/CHjClj as did the 1,5-diol HO(CH3) C(OH)C5H, [46]. 

The synergy between nitroalkanes and aqneons medium has been the key idea for the one-pot synthesis of 8-nitroalkanols (38) as shown in Figure 2.8, hydroxytetrahy-drofurans (lactols) (39), 1,4-diketones (40), and 1,4-diols (41). 

One year later, Kitazume et al. also described the synthesis of 6-deoxy-6,6,6-trifluoro-D-mannose and D-allose using intermediate (45,55)-76 (Scheme 5.10). Thus, oxidation of 76 with potassium permanganate in the presence of catalytic 18-crown-6 provided the diol 84 as the only isomer in 42% yield. Protection of diol moiety in 84 as its acetonide followed by DlBAL-H reduction afforded the lactol 85, which was subjected to the t-BuOK promoted isomerization to give the desired fluoro sugar 86 in 35% yield. The precursor 87 of fluoro sugar 89 was obtained by reduction... 

An enantioselective synthesis of ( —)-(2i ,3i ,6S,8i )-epi-nonactic acid (124) is shown in Scheme 89. The reduction of (122) with diethylmethoxyborane/sodium borohydride yields a iyn-diol (not isolated), which cyclizes spontaneously to the lactol (123). Pyridinium -toluenesulfonate-catalyzed dehydration, desulfurization with Raney nickel, Rh/Al203-catalyzed hydrogenation, and hydrolysis of the ester group affords (124) <94JOC3898>. 

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