Thioamides, reduction aldehydes

Thioamides were converted to aldehydes by cautious desulfurization with Raney nickel [1137, 1138] or by treatment with iron and acetic acid [172]. More intensive desulfurization with Raney nickel [1139], electroreduction [172], and reduction with lithium aluminum hydride [1138], with sodium borohydride [1140] or with sodium cyanoborohydride [1140] gave amines in good to excellent yields. 

Peptide aldehydes can be synthesized via hydrolysis of thiazolidine precursors with mercury or copper salts (Scheme 10). 56 The Phe-thiazolidine derivative 27 was prepared from reduction of dihydrothiazole ring in 26, which was formed from a (5-hydroxy thioamide cyclization of 25 using the Mitsunobu reaction. N-Terminal Boc and Z groups on thiazolidine pseudopeptides such as Boc-Ala-Phe-thiazolidine and Z-Phe-Tyr-thiazolidine are stable to hydrolysis that affords Boc-Ala-Phe-H and Z-Phe-Tyr-H. 56 ... 

A few 6- and 8-cyanopurines have been prepared and undergo characteristic nitrile addition reactions rather readily. Thus, alkaline hydrolysis produces carboxamides, then carboxylic acids, alcoholysis leads to imidates, ammonolysis to amidines, hydrazinolysis to amidhydrazines, hydroxylamine to amidoximes, and hydrogen sulfide to thioamides. Acid hydrolysis tends to give the decarboxylated acid derivative. Reduction either by sodium-ethanol or, preferably, by catalytic hydrogenation affords aminoalkylpurines and addition of Grignard reagents produces, in the first place, acylpurines. As with aldehydes, most of the compounds examined have been relatively non-polar derivatives. Table 28 lists some reactions and relevant literature. 

Although amides are the least reactive of the common acid derivatives under most circumstances, they are involved in several reductive syntheses of aldehydes. As described below the conversion can be accomplished by one-electron reducing agents (though relatively powerful ones), and there are specific types of amide which can be caused to decompose to aldehydes. Moreover, amides are precursors of imi-doyl chlorides, Vilsmeier complexes and thioamides, which can also be reduced to aldehydes as discussed in later sections. 

Ireland utilized a sulfide ring contraction process for the ring-forming step of his synthesis of 47 (see Scheme 1.16) The diethyl acetal of 5-hydroxyhexanal (73) was converted to the trichloroethyl carbonate and the acetal hydrolized to produce aldehyde 74 in 86% yield. Addition of the zinc enolate of N,N-dimethylethanethioamide (75) to 74 then afforded an intennediate hydroxy thioamide which was subjected to acylation and reductive carbonate cleavage to yield 76 (53%). Acylation with chloroacetyl chloride was followed by ring closure to give the macrocycle 77 (24%). 

Imines are reduced by triethylsilane to their amines when the proper Ir orNi catalysts areemployed. Non-metal-mediated reductions of C=N groups by EtsSiH are also possible. Among these, the trifluorosulfonic acid promoted reductive amidation of aliphatic and aromatic aldehydes with EtsSiH is an excellent way to mono (V-alkylate aliphatic and aromatic amides, thioamides, carbamates, and ureas (eq 26). It is also worth noting that trifluorosulfonic acid/EtsSiH reduces acyl- and tosylhydrazones to hydrazines and 2-aminopyrimidines to 2-amino-dihydro-or 2-aminotetrahydropyrimidines (eq 27). ... 

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