Aldehydes, acetal formation from reduction

A protected version of the aldehyde 174 comes from acetal formation and reduction of the remaining C02H group. Acid catalysed hydrolysis of the acetal gives the lactone 177 that is protected as 178. Hydrolysis and oxidation give 179 ready for the Wittig reaction. 

Other syntheses of the tetracyclic intermediates 434 and 436 that merit mention, and thus constitute additional formal syntheses of (-1-)-quebrachamine, have been contributed by Fuji et aL and by Asaoka and Takei. Fuji s approach (279) starts with the chiral lactone 446, which is readily available from 2-ethyl-5-valerolactone. Partial reduction to the aldehyde stage, followed by acetal formation, gave 447, which on condensation and reduction (lithium aluminum hydride) gave a mixture of C-3 epimers 434, the late intermediate in the (+)-quebrachamine synthesis (Scheme 41). 

The C-17 to C-22 subunit of ionomycin (937) is synthesized by regioselective fragmentation of an appropriately substituted tetrahydrofuran (935), which is readily accessible from (R)-malic acid (Scheme 137) [205]. Alkylation of the dianion of diethyl (7 )-malate (897) with methyl iodide provides anti-929 in 69% yield with 10 1 stereoselectivity. Reduction of the esters, acetal formation, oxidation of the primary alcohol of 930 to an aldehyde, and Wittig olefination furnishes a,j -unsaturated ester 931. 

The rationalization of the formation of this unexpected product is shown in Figure 10.32. Removal of the acetate group from the Cl position under the basic conditions provided hemiacetal 98a, which is in equilibrium with aldehyde alcohol 98b. Reduction of 98a yields the expected triol 94a. However, there is a possibility of the attack of the oxy-anion from the C-5 position at the C3 center with the elimination of benzyl alcohol. The resulting oxetane 99 is then opened by the primary alkoxylate (formed after reduction of the carbonyl group), providing finally the anhydrosugar... 

This silyl hydrazone formation-oxidation sequence was originally developed as a practical alternative to the synthesis and oxidation of unsubstituted hydrazones by Myers and Furrow [31]. The formation of hydrazones directly from hydrazine and ketones is invariably complicated by azine formation. In contrast, silyl hydrazones can be formed cleanly from /V,/V -bis(7< rt-butyldimethylsilyl)hydrazine and aldehydes and ketones with nearly complete exclusion of azine formation. The resulting silylhydrazones undergo many of the reactions of conventional hydrazones (Wolff-Kishner reduction, oxidation to diazo intermediate, formation of geminal and vinyl iodides) with equal or greater efficiency. It is also noteworthy that application of hydrazine in this setting may also have led to cleavage of the acetate substituents. 

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

Abstract Aldehydes obtained from olefins under hydroformylation conditions can be converted to more complex reaction products in one-pot reaction sequences. These involve heterofunctionalization of aldehydes to form acetals, aminals, imines and enamines, including reduction products of the latter in an overall hydroaminomethylation. Furthermore, numerous conversions of oxo aldehydes with additional C.C-bond formation are conceivable such as aldol reactions, allylations, carbonyl olefinations, ene reactions and electrophilic aromatic substitutions, including Fischer indole syntheses. 

Aldehyde 82 was extremely reactive and was best isolated as the hydrate 84a. Indeed, recrystallization of the aldehyde 82 from ethanol gave 3-(l-ethoxy-l-hydroxymethyl)fervenulin 84b, while reaction with ethylene glycol gave the cyclic acetal 76a. The reactivity of the aldehyde 82 was exploited by easy Schiff base formation upon reaction with /i-aminobenzoylglutamic acid, a process that was followed by reduction to give the fervenulin-based folic acid analogue 85 <1996JHC949>. 

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