Synthesis continued protected aldehyde

Briefly we review the chemical improvements which we achieved in the oxoalkylphosphonates field which represent the key compounds. Phosphonic aldehydes are obtained in adapting the Arbuzov procedure to 6 or V haloketals (4). A modification of the phospho-nylation conditions (t°, stoichiometry) followed by removal of the protecting group in dilute acid and then continuous extraction allows synthesis of suitably branched compounds on a large scale (5). 

Dihydrooxazoles continue to occupy an important place in organic synthesis and medicinal chemistry as they have found use as versatile synthetic intermediates, protecting groups/pro-drugs for carboxylic acids, and chiral auxiliaries in asymmetric synthesis. There are several protocols in the literature for the transformations of functional groups such as acids, esters, nitriles, hydroxyl amides, aldehydes, and alkenes to 2-oxazolines. Newer additions to these methods feature greater ease of synthesis and milder conditions. 

A facile synthetic route to a-santalol (105) from the previously known aldehyde (106) has been reported by Corey et a/. in which a stereospecific modified Wittig reaction [(i) ethylidenetriphenylphosphorane, (ii) n-butyl-lithium, and (iii) paraformaldehyde] yielded the desired cis-isomer. Erman and co-workers, in a continuation of their synthetic work on the santalols, have reported the preparation of -santalol (107) from 3-methylnorcamphor. The route also provided a sample of the tmns-isomer which had previously been considered to be the natural isomer. The use of a borate ester as a protecting group for a hydroxy-function facilitated the synthesis of dihydro- -santalol (108) as outlined in Scheme 3. (These borate esters are stable to anhydrous acid or base but are readily hydrolysed in aqueous media.)... 

Organotetracarbonylferrates, [RFe(CO)4], continue to find use in organic synthesis. A new synthesis of a-diketones consists of the reaction of aldehydes with alkyl halides and [Fe(CO)s]. The aldehyde, protected as the ethylenedithioacetal, is treated with butyl-lithium and [Fe(CO)s] to generate the acyltetracarbonylferrate (25) which then reacts with the alkyl halide to give the a-diketone in an overall yield of around 60%. [RFe(CO)4] reacts with Michael-type acceptors to give the expected product in about 90% yield [equation (10)]. ... 

The formation of a dithioacetal as an intermediate in organic synthesis is not new to most chemists. However, in recent years there has been a continuing improvement in the methods of preparation as well as the subsequent reactions. The early use of the dithioacetal group as a means to reduce carbonyl functions with Raney nickel has been expanded to extensive use as a protecting group, methylene blocking group and as an intermediate in the preparation of complex hydrocarbons, olefins, aldehydes and ketones. 

The synthesis of calcimycin continued with oxidation of 50, reaction of the aldehyde with 24 to give 51 as a mixture of Cio-diastereomers. Treatment of this mixture with 10-camphorsulfonic acid gave 52. Presumably only the desired Cio diastereomer cyclized to the spiroacetal. The synthesis was completed by reductive cleavage of the N-N bond (pyrrole nitrogen protecting group) and hydrolysis of the trifluoroacetamide and methyl ester. 

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