Lactols Lactone

The 9 — 15 fragment was prepared by a similar route. Once again Sharpless kinetic resolution method was applied, but in the opposite sense, i.e., at 29% conversion a mixture of the racemic olefin educt with the virtually pure epoxide stereoisomer was obtained. On acid-catalysed epoxide opening and lactonization the stereocentre C-12 was inverted, and the pure dihydroxy lactone was isolated. This was methylated, protected as the acetonide, reduced to the lactol, protected by Wittig olefination and silylation, and finally ozonolysed to give the desired aldehyde. 

The slow oxidation of primary alcohols, particularly MeOH, is utilized for the oxidation of allylic or secondary alcohols with allyl methyl carbonate without forming carbonates of the alcohols to be oxidized. Allyl methyl carbonate (564) forms 7r-allylpalladium methoxide, then exchange of the methoxide with a secondary or allylic alcohol 563 present in the reaction medium takes place to form the 7r-allylpalladium alkoxide 565, which undergoes elimination of j3-hydrogen to give the ketone or aldehyde 566. The lactol 567 was oxidized selectively with diallyl carbonate to the lactone 568 without attacking the secondary alcohol in the synthesis of echinosporin[360]. 

Conjugate addition of methyl magnesium iodide in the presence of cuprous chloride to the enone (91) leads to the la-methyl product mesterolone (92) Although this is the thermodynamically unfavored axially disposed product, no possibility for isomerization exists in this case, since the ketone is once removed from this center. In an interesting synthesis of an oxa steroid, the enone (91) is first oxidized with lead tetraacetate the carbon at the 2 position is lost, affording the acid aldehyde. Reduction of this intermediate, also shown in the lactol form, with sodium borohydride affords the steroid lactone oxandrolone... 

In addition to its other properties, interest in the potential use of the vasodilative properties of prostaglandin El, alprostadil ( ), has led to several conceptually different syntheses.For this purpose, the classic Corey process has to be modified by reversing the order of addition of the side chains to allow for convenient removal of the unwanted double bond in the upper side chain. For example, Corey lactone is protected with dihydropyran (acid catalysis), reduced to the lactol with diisobutyaluminum hydride, and then subjected to the usual Wittig reaction to give intermediate This is... 

With the co side chain at C-12 in place, we are now in a position to address the elaboration of the side chain appended to C-8 and the completion of the syntheses. Treatment of lactone 19 with di-isobutylaluminum hydride (Dibal-H) accomplishes partial reduction of the C-6 lactone carbonyl and provides lactol 4. Wittig condensation8 of 4 with nonstabilized phosphorous ylide 5 proceeds smoothly and stereoselectively to give intermediate 20, the bistetra-hydropyranyl ether of ( )-1, in a yield of -80% from 18. The convergent coupling of compounds 4 and 5 is attended by the completely selective formation of the desired cis C5-C6 olefin. 

Cleavage of the imidazolidine moiety by acidic hydrolysis led to chiral lactols 17, which can be further oxidized to lactones 19 or reduced to diols 1848. 

Lactams 618 <5-Lactols 627 Lactones 617 reactions of 636 synthesis of 632, 737, 815 a,fl-unsaturated - see a,/J-Unsaturated lactones... 

The adduct cyclized to a lactol mixture that was oxidized by TPAP-NMMO to give the corresponding lactones in an 8 1 ratio (86% yield). Hydrolysis in the presence of H202 gave the P-D lactone and recovered chiral auxiliary. 

MISCELLANEOUS BENZOHETEROCYCLES Partial reduction of lactone 166 (using for example diisobutylaluminum hydride in the cold) affords lactol 167. Condensation with nitromethane leads to the corresponding alkylated tetrahydrobenzopyran 170. The sequence probably starts by aldol reaction of the hydroxylactone form of the lactol (168) with nitrome thane to give the vinyl nitro intermediate 169 ... 

As demonstrated by Hoffmann and coworkers, hydroformylation can also be combined with an allylboration and a second hydroformylation, which allows the formation of carbocycles and also heterocycles [213]. A good regioselectivity in favor of the linear aldehyde was obtained by use of the biphephos ligand [214]. Reaction of the allylboronate 6/2-76 having an B-configuration with CO/H2 in the presence of catalytic amounts of Rh(CO)2(acac) and biphephos led to the lactol 6/2-80 via 6/2-77-79 (Scheme 6/2.17). In a separate operation, 6/2-80 was oxidized to give the lactone 6/2-81 using tetrabutyl ammonium perruthenate/N-methylmorpholine N-oxide. 

A novel lactone and lactol synthesis was achieved by Cossy and coworkers [268], usinga CM followedby ahydrogenationandaringclosure. Ina typical procedure, aso-lution of acrylic acid or acrolein and an allylic or homoallyhc alcohol is stirred at room temperature under 1 atm of H2 in the presence of the ruthenium catalyst 6/3-16a and Pt02. Under these conditions, the homoallylic alcohols 6/3-101 (n= 1) and acrylic acid 6/3-102 led to the lactones 6/3-103 and the reduced alcohol 6/3-104 with acrolein, the corresponding lactols were obtained, together with 6/3-104 (Scheme 6/3.30). 

A recent paper 26) also reported that the photo [2 + 2] reaction between the olefin (63) and the ester (56) would yield the desired photoadduct (64), which was then reduced by LiAlH4 to afford the diol (65). The diol (65), upon oxidation, gave the a-methylene-S-lactone (67) via the intermediate lactol (66) (Table 3)26). 

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