A-Hydroxycarboxamides synthesis

The TiCU-mediated synthesis of (24) from (4) and (5) by Seebach et alP proceeds particularly well, as has been demonstrated by many examples yields of up to 98% are encountered. This variant of the a-hydroxycarboxamide synthesis proceeds via an a-adduct (28) of TiCU and presumably a species (29) with pentacoordinated Ti. 

The A-hydroxycarboxamide group is a key fragment of many siderophores so that a convenient synthesis of this group is crucial for further progress. A variety of methods have been attempted for the preparation of hydroxamic acids starting from carboxylic acids. Although some of these methods are quite efficient for the preparation of substituted hydroxamic acids, the preparation of the parent compound is still a problem and yields are often moderately unacceptable, in part due to the low solubility of the parent hydroxylamine hydrochloride in organic solvents. 

Synthesis of a-hydroxycarboxamides by add catalyzed reaction of an isocyanide with an aldehyde or ketone (see 1st edition)... 

A great variety of carbonyl compounds has been used in this reaction in order to produce the respective a-hydroxycarboxamides, but to the best of our knowledge, formaldehyde had never been reported in the literature as the carbonyl component in the synthesis of (24). We wondered whether or not formaldehyde displays any abnormal behavior in the preparation of (24), but we noticed that in dilute sulfuric acid paraformaldehyde reacted with isocyanides to form (24 R, = H R = Bu, Oct , c-Hex and 0-CIC6H4)... 

The resulting a-hydroxycarboxamides have been interestingly employed as intermediate for the synthesis of more complex scaffolds, hi fact, as in Ugi reaction (Chapter 7), the combination of these MCRs with a further transformation has gained much attention in the last years for the preparation of structurally diverse complex molecules. Many... 

Aldol derivative synthesis Kitagawa and Taguchi group have shown a rearrangement of a-alkoxycarboxamides 41 which proceeds with a high level of retention at the migrating center to give optically active /3-hydroxycarboxamides 42 (equation 22). ... 

One of the oldest reports of a synthesis of a highly substituted 3-pyrrolin-2-one involved a type e cyclization. Bashour and Lindwall treated y-oxo-P-hydroxycarboxamide 205 with HCl and obtained a product presumed to be 5-hydroxy-3-pyrrolin-2-one 206 (Scheme 46 1935JA178). Given the similarity of reactions that have been reported since then (e.g.. Scheme 42), this probably was the correct structural assignment. Moon later reported a synthesis of 4-acyl-3-pyrrolin-2-ones via thermal cyclization of y-ketocar-boxamides (1977JOC2219). 

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