Wittig synthesis lactols

Orito also developed a variation of this synthesis, based on the Wittig reaction of the phosphonium salt from isobutylbromide with a series of lactols. After alcohol-to-acid oxidation, a mixture of MNA isomers is obtained, then isomerized with nitrous acid [61,62]. 

The two major carotenoids in Shepherdia canadensis were lycopene (16) and methyl apo-6 -lycopenoate (21). The latter was synthesised from apo-8 -lycopenal (22) by the appropriate Wittig condensation. The synthesis of methyl-bixin (24) with the natural cis double bond derived from the lactol (23) is outlined in Scheme 1. ... 

On the other hand, attempted synthesis of 3-cp/-australine (10) from 144 has failed (Scheme 14). The lactol 144 was subjected to a Wittig reaction to produce the alkene 158, which was triflated followed by azidolysis to give the alkene 159. Ozonolysis of 159 followed by oletination of the resulting aldehyde 160 with the allylic borane reagent produced the diene 161 in 50% overall yield from the alkene 159. Heating of 161 in chloroform produced the two cyclized products 162 and 163 in equal amounts. Subjection of 163 to different conditions has failed to produce the ketone 164 required for the synthesis of 10, where decomposition had taken place. 

The synthesis of the C1-C7 fragment, which corresponds to the lactone, starts with the homoallylic alcohol 2 which was prepared from 1. The existing stereocenter and the conjugate addition method of Evans [21] allow the control of the C5 stereocenter. The homoallylic alcohol 2 was oxidatively cleaved and homologated to the trans enoate 3 by a Wittig olefination. Treatment of 3 with benzaldehyde and a catalytic amount of KHMDS provided acetal 4. The internal Michael addition of the hemiacetal intermediate proceeds with complete stereoselectivity [22]. After deprotection and oxidation, the corresponding aldehyde was treated with Amberlyst-15 and then with camphor sulfonic acid (CSA), to yield pyrane 5 as a mixture of (3- and a-anomers (1.8/1). This compound was converted to the thiophenyl acetal 6 (4 steps) as this compound can be hydrolyzed later under mild conditions (Hg +) with subsequent oxidation of the lactol to the desired lactone. Compound 6 represents the C1-C7 fragment of discodermolide (Scheme 1). 

Completion of the synthesis was readily achieved. Diastereoselective reduction of the ketone was accomplished with (S)-BINOL/LiAlH4. Then, removal of the tether by acidic hydrolysis, which also effected silyl ether deprotection, afforded dihydroxy lactol 223 allowing introduction of the final side chain using a Wittig reaction (Scheme 10-71). 

The remainder of the synthesis parallels that of L-daunosamine lactol formation (73% yield), Wittig reaction (56% yield), and acid hydrolysis (46% HF-methanol, 33% yield). 

In the synthesis of D-ristosamine (388), all that is required is inversion of the 5-methyl group of lactone 393. This is readily accomplished by opening the lactone ring with potassium superoxide, acidification to pH 4, and a Mitsunobu reaction. Once again, reduction of the lactone to lactol (71% yield) followed by Wittig reaction and acid hydrolysis (HCl, methanol) affords the desired sugar 388, isolated as the diacetate in 23% yield [124]. 

For the total synthesis of halichondrin B, Kishi and Duan [11] have developed the preparation of heptoside fragment 21 from t-mannonic y-lactone 19. In this strategy, the Wittig reaction was performed on an anomeric lactol with methoxymethylenetriphenylphosphorane. Osmylation and acetylation yielded the protected i-glycero-i-manno-heptose derivative in 58% overall yield after four steps (Scheme 2.6). 

The most recent formal synthesis of (—)-swainsonine (378) to invoke the C-l/C-2 bond-forming approach, byjung and coworkers, used D-erythro-nolactone protected as the bis(benzyl) ether 431 as the chiral educt (Scheme 60). " Although reduction with diisobutylaluminum hydride and Wittig reaction of the resulting lactol with benzylidenetriphenylphosphorane gave a mixture of cis- and fra s-alkenes, isomerization with thiophenol and AIBN produced the fraws-alkene (+)-432 exclusively. Swem oxidation... 

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