Olefinic aldehydes, reduction

Because the olefin geometry in compound 9 will most certainly have a bearing on the stereochemical outcome of the hydroboration step, a reliable process for the construction of the trans trisubsti-tuted olefin in 9 must be identified. A priori, the powerful and predictable Wittig reaction28 could be used to construct E u, [3-unsaturated ester 10 from aldehyde 11. Reduction of the ethoxycarbonyl grouping in 10, followed by benzylation of the resulting primary alcohol, would then complete the synthesis of 9. Aldehyde 11 is a known substance that can be prepared from 2-furylacetonitrile (12). 

RuCl2(PPh3)3 has been shown to catalyze the reduction of several aldehydes, but does not have widespread scope. This catalyst is not chemoselective and, in the presence of alkenes, would favor olefin reduction over that of the aldehyde. Noyori and coworkers showed that chemoselectivity is easily introduced by the addition of ethylene-diamine as a ligand (Scheme 15.6) [29, 30]. This system requires the presence of co-catalytic KOH/i-PrOH as an activator. 

Another stereoselective synthesis (Scheme 11) is based on sugar aldehyde 35 and intermediate 36 subsequent 1,2-O-isopropylidine deprotection, N,0-debenzylation/olefin reduction/reductive cyclization in a single pot, and O-acetylation result in the formation of bicyclic aza sugar 37 (09TA1217). 

The synthesis of the 1,6-linked ester was straightforward as outlined in Scheme 6. We were able to convert alcohol 23 to aldehyde 24 using Swern oxidation conditions. Wittig reaction was followed by olefin reduction and saponification to bring the sequence as far as 26. Esterification of 26 with olefin alcohol la, mediated by DCC, then afforded the target ester 27 in good overall yield (13). 

The proposed reaction mechanism (see Scheme 4) is similar to that which is well established for olefin reduction, with the insertion of a meial-hydride bond into the carbonyl group coordinated to (he metal center. A mechanism in which reduction occurs by a simple nucIcopliiUc attack of the hydrogen atom of the transition metal hydride (which behaves like Blit or AlHa ) into the carbonyl group of the aldehyde, cannot be ignored ... 

The hydroxycarbenes can easily explain the tormation of aldehydes by reductive elimination from the metal and of alcohols by further hydrogenation. Olefins would be the result of the cleavage of the carbcnoid with the formation... 

Nevertheless, it must be pointed out that the formation of such transient species has never been spectroscopically observed. Native CDs are effective inverse phase-transfer catalysts for the deoxygenation of allylic alcohols, epoxydation,or oxidation " of olefins, reduction of a,/ -unsaturated acids,a-keto ester,conjugated dienes,or aryl alkyl ketones.Interestingly, chemically modified CDs like the partially 0-methylated CDs show a better catalytic activity than native CDs in numerous reactions such as the Wacker oxidation,hydrogenation of aldehydes,Suzuki cross-coupling reaction, hydroformylation, " or hydrocarboxylation of olefins. Methylated /3-CDs were also used successfully to perform substrate-selective reactions in a two-phase system. 

A number of derivatives of compound A were prepared that included acetates, ethers, olefin reduction products, aldehyde and ketone reduction products, aromatic decarbonylated derivatives, and derivatives where the aldehyde was converted to a methyl ester [122]. 

From singlet state it has been found that the following reactions often compete with the 1,3-rearrangements cis-trans isomerization, decarbonyl ation, aldehyde formation, ketene formation, olefin reduction, Norrish t q)e-II cleavage with cydobutanol formation, [2-J-2] cycloaddition, and inter tem crossing with concomitant 1,2-acyl shift. From the triplet state a similar series of reactions have been reported including 1,3-acyl shift. 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

The key intermediate 25 was prepared efficiently from aldehyde 23, obtained by reduction of nitrile 22 with Dibal-H. Treatment of 23 with the lithium salt of frans-diethyl cinnamylphosphonate furnishes compound 24 in 75 % yield and with a 20 1 ratio of E Z olefin stereoisomers. The stage is now set for the final and crucial operations to complete the molecular skeletons of endiandric acids A and B. 

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