Oxaziridines, reduction

Oxaziridines are powerful oxidizing agents. Free halogen is formed from hydrobromic acid (B-67MI50800). Reduction by iodide in acidic media generally yields a carbonyl compound, an amine and two equivalents of iodine from an oxaziridine (1). With 2-alkyl-, 2-acyl and with N-unsubstituted oxaziridines the reaction proceeds practically quantitatively and has been used in characterization. Owing to fast competing reactions, iodide reduction of 2-aryloxaziridines does not proceed quantitatively but may serve as a hint to their presence. 

Action of catalytic amounts of vanadium compounds on oxaziridine (52) yields caprolactam almost quantitatively. Reductive opening of the oxaziridine ring and /3-scission yield radical (118), which recyclizes with elimination of the metal ion to form the lactam (63) (77JPR274). 

The next phase of the synthesis was construction of the C-ring. An aldol addition was used to introduce a 3-butenyl group at C(8) and the product was trapped as a carbonate ester. The Davis oxaziridine was then used to introduce an oxygen at C(2). After reduction of the C(3) oxygen, a cyclic carbonate was formed, and C(2) was converted... 

The hydroxyl group in alcohol 122 is then oxidized. Deprotonation of this ketone with KHMDS (1 eq.), followed by the addition of Davis oxaziridine (see Chapter 4 for a-hydroxylation of ketones)28 (2 eq.) allows the stereo-controlled introduction of the C-10 oxygen from the less hindered enolate face, providing only the (i )-hydroxyketone 123. Subsequent reduction of 123 with excess LAH provides the tetra-ol 124. Treatment of this compound with imidazole and TBSC1 followed by PPTS and 2-methoxypropene provides in one operation the acetonide 125 with 91% yield (Scheme 7-37). 

The reduction of oxaziridines, anthranils, and benzoxazines was discussed in Part I. 

A further stage of reduction is reached when an oxaziridine (32) opens in the presence of phenyl isocyanate. This can be accomplished [Eq. (34)] in a sealed tube at 85° in benzene to give a 94% yield of a... 

The metal-catalyzed oxidation of imines using molecular oxygen as the final oxidant and aldehydes as co-reductants has been studied223. Various transition metal complexes have been tested as catalysts and it is found that cobalt complexes can catalyze the selective oxidation of imines to oxaziridines in good yield (ca 80%) (Scheme 4). 

Fig. 71 Radical reactions triggered by reductive ring opening of oxaziridines...

Direct conversion of diol 395 to cytisine 31a was accomplished by a one-pot procedure. Oxidative cleavage to give the dicarboxylic acid, followed by treatment with aqueous ammonia and catalytic reduction provided racemic cytisine 31a in good yield <20000L4205>. Photolysis in benzene at 254 nm of the nitrone 396 afforded smooth rearrangement to 17-oxosparteine 195 likely through the intermediacy of an oxaziridine derivative (Scheme 80) <2002OL2577>. 

Oxaziridines are very easily reducible compounds, and their polarographic wave [273, 274] begins at the dissolution wave of the mercury. In the reduction there is formed a gem-amino alcohol that at low pH loses water with the formation of a Schiff base and at higher pH loses an amine to a carbonyl compound. The Schiff base or the carbonyl compound may be further reducible. 

The reduction of amides [176] to alcohols proceeds through a g m-amino alcohol, which loses either ammonia (or amine), forming an aldehyde, or water, forming an inline the aldehyde is then reduced to the alcohol, whereas the imine forms an amine on reduction. The intermediate gem-amino alcohol, is also formed in the reduction of oxaziridines (Chapter 18) [177], and a similar gem-diamine during the reduction of amidines to amines [68]. 

The formation and the oxidative properties of an oxaziridinium salt have been reported. With methyl fluorosulphonate the oxaziridine (30) led to the oxaziridinium salt (36) which was stable as a crystalline product at room temperature, but unstable in solution, giving (37), also obtained from (38) with methyl fluorosulphonate. NaBHt reduction of (36) led to (35). Peroxidic reactivity of (36) was shown by oxygen transfer from (36) to the imine (38) with formation of the nitrone (39) (Scheme 5). 

The key step in the asymmetric synthesis of brazilin (167a), a tetracyclic homoisoflavanoid which possesses antibacterial and antiinflammatory activities, was prepared by the enantioselective a-hydroxylation of the sodium enolate of chromanone (165) in 92% ee with chloro oxaziridine (+)-(74) <93JOCl75l>. The a-hydroxy ketone (166) was converted into (167b) in 64% overall yield from (166), by reduction of the carbonyl and acid-catalyzed cyclization (Scheme 31). 

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