Masked aldehyde

In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation and is then reductively removed after alkylation. The reagent in Entry 6 is prepared by dilithiation of allyl hydrosulfide using n-bulyl lithium. After nucleophilic addition and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry 7 uses the epoxidation of a vinyl silane to form a 7-hydroxy aldehyde masked as a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl groups containing aldehydes masked as acetals. 

Piperidines bearing a masked aldehyde function in the e-position are easily transformed into quinolizidine compounds through intramolecular reductive amination after deprotection (acetal precursors) or oxidative cleavage (tv e-diols). Some examples are given below. 

An enantioselective synthesis of (—)-lupinine 6 was based on a similar reductive amination process. In this case, (k)-phcnylglycinol was used to obtain a chiral nonracemic oxazololactam which was cyclized after reduction of N-C and O-C bonds and subsequent hydrolysis of the masked aldehyde <2004T5433>. 

Six-membered cyclic guanidine 197 was transformed into the corresponding bicyclic guanidine hemiaminal after deprotection of the Cbz and contemporary cyclization on the masked aldehyde function (Equation 4). This product, 198, was then employed in a Biginelli reaction to form a precursor of alkaloid batzelladine F <1999JOC1512>. 

Intramolecular Allylboration. In one rare but impressive example involving a masked aldehyde, a domino hydroformylation/allylboration/hydroformyla-tion reaction cascade has been designed to generate bicyclic annulated... 

Trioxolanes are key intermediates in the ozonolysis of alkenes (Section 4.16.8.2). This reaction is of considerable importance in synthetic chemistry where ozonide intermediates are often reduced (to aldehydes or alcohols) or oxidized (to carboxylic acids) in situ. Advantage has been taken of the stability of certain derivatives to investigate selective chemical reactions. An example of selective reduction is shown in Scheme 47 <91TL6454> with other uses of the 1,2,4-trioxolane ring as a masked aldehyde or ester referred to in Section 4.16.5.2.1. 

Enolates can also function as masked aldehydes or ketones and a new synthesis of 2-substituted pyrimidine-5-carboxylic esters 652 used a doubly masked dialdehyde 651, where one aldehyde was protected as an acetal and the other was used in the form of its sodium enolate <2002S720>. 

In the sea, the brown algae give unusual diterpenes, tlK red seaweeds polyhalogenated mono- and higher terpenes and C,5 acetogenins, and the green seaweeds cyclopeptides and masked-aldehyde sesquiterpenes (Table 9.1). Freshwater algae are fewer and, as for as it is known, unproductive. 

A new synthesis of dibenzo[a,g]quinolizinium derivatives also makes use of an aldehyde cyclization (Scheme 80) (75JAP(K)7596599). In one example, a benzyl bromide bearing an acetal-masked aldehyde group in the ortho position (126) was allowed to react with the anion (127) generated by the action of phenyllithium on a Reissert compound. The condensation product was heated with alkali to cleave the benzoyl and cyano groups to yield the isoquinoline (128), then the acetal was cleaved and the resulting aldehyde cyclized to (129), presumably under acid conditions. 

Martin has described the synthesis of hexahelicene-2-carbaldehyde by irradiation of a polymer supported 1,2-diarylethylene containing a masked aldehyde function 26 suspended in benzene for 4 h. After prolonged hydrolysis (60 h) the product was obtained in low yield (5 %). 

The oxonium ion intermediate of the type 34 normally collapses by the attack of a nucleophile OH or OAc to yield a masked aldehyde or hemi-acetal-acetate group. However, in this particular case the approach of... 

A limited number of studies concerning DoM reactions of masked aldehydes and ketones have been described [790R(26)1] this is particularly true of pi-deficient heterocycles. 

The oxazoles and their derivatives have played a variety of fascinating roles in the preparation of new molecular systems. Much of this chemistry stems from their ability to serve as diene components (azabutadiene equivalents) in reactions with a variety of dienophilic agents, to undergo nuclear metallation, to activate attached aryl or alkyl groups to deprotonation (thus functioning as masked aldehydes, ketones or carboxylic acid groups), and to serve as useful electrophiles on conversion to AT-alkylated salts. 

An intramolecular [3 + 2] nitrone cycloaddition reaction has been employed in the chiral assembly of L-acosamine and L-daunosamine (81JA3956). Heating the masked aldehyde (503) with the oxalate salt of (-)-(S)-7V-hydroxy-a-methylbenzenemethanamine generated a nitrone which underwent intramolecular cycloaddition to give an 82 18 mixture of diastereomers (504) and (505). The N—O bond of the major isomer was cleaved with zinc... 

Being restricted to DHAP as the nucleophile, aldol additions will only generate ketoses and derivatives from which aldose isomers may be obtained by biocatalytic ketol isomerization (cf. Sect. 7.1) [306]. For a more direct entry to aldoses the inversion strategy may be followed (Scheme 19) [290] which utilizes monoprotected dialdehydes. After aldolization and stereoselective chemical or enzymatic ketone reduction, the remaining masked aldehyde function is deprotected to provide the free aldose. Further examples of the directed, stereodivergent synthesis of sugars and related compounds such as aza- or thiosugars are collected in Sect. 7. 

Solid-phase schemes have also been used for the synthesis of the K2K and di-K2K dendrons.1 L2X These dendrons can be further modified with electrophiles and nucleophiles. N-Terminal Ser, which can be readily converted into an aldehyde at neutral pH in an aqueous condition, has been used by Spetzler and Tam[89l as a convenient masked aldehyde precursor. The solid-phase synthesis of aldehyde K2K dendrons by Fmoc chemistry is illustrated in Scheme 7. 

Cys(StBu) was coupled to the side chain. After removal of the Fmoc protecting group, the peptide was cleaved from the resin with TFA to give the linear peptide 76. The Ser moiety attached to the first Lys served as a masked aldehyde, which was oxidized to aldehyde 77 by sodium periodate. The cyclic peptide 78 was formed by utilizing the intramolecular oxime formation from the reaction between the Lys-side-chain-tethered O-alkylhydroxylamine and the aldehyde. 

The diol (43) obtained from dihydroxylation of acrolein benzene-1,2-dimethanol acetal (entry 11) is a masked glyceraldebyde and has the potential to be a very useful synthon. Although the enantiomeric purity of the crude diol formed in this reaction is 84% ee, one recrystallization from ethyl acetate improves it to 97% ee in 55% recovery yield. The masked glyceraldehyde 43 is converted via the tosylate 44 to the masked glycidaldehyde 45 in an overall yield of 85%. Both these masked aldehydes are superior to the free aldehydes in terms of handling ease, stability, and safety. The aldehydes can be released from the acetal under the mild conditions of catalytic hydrogenolysis [45]. 

Depending upon the pH compound 166 exhibits a ring-chain tautom-erism, and ring-closed form could be used as a masked aldehyde precursor (07PNA10780,08JOC734, 08USA2008/0138292). 

The sequence 32—>33—>34—>35 (Scheme 8) also illustrates in-between DoM but, in addition, the important conversion of amides into more useful FG and a method to override the normal Friedel-Crafts reactivity by use of a carbo-desilyla-tion reaction (37) [31]. Amide DMG which have been tested in developing methods for conversion to corresponding acid derivatives and masked aldehyde DMG and the parent carboxylic acid are useful to consider (36). 

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