A generally applicable method for the synthesis of protected α‐oxygenated carbonyl compounds is reported. It is based on the single‐electron‐transfer oxidation of easily generated enolates to the corresponding α‐carbonyl radicals. Coupling with the stable free radical TEMPO provides α‐(piperidinyloxy) ketones, esters, amides, acids or nitriles in moderate‐to‐excellent yields. Enolate aggregates influence the outcome of the oxygenation reactions significantly. Competitive reactions have been analyzed and conditions for their minimization are presented. Chemoselective reduction of the products led to either N–O bond cleavage to α‐hydroxy carbonyl compounds or reduction of the carbonyl functionality tomonoprotected 1,2‐diols or O‐protected amino alcohols.

A unified strategy for the total synthesis of the methyl esters of all phytoprostane (PhytoP) classes bearing two ring-oxygen atoms based on an orthogonally protected common precursor is described. Racemic 16-F-, 16-E-PhytoP and their C-16 epimers, which also occur as racemates in Nature, were successfully obtained. The first total synthesis of very sensitive 16-D-PhytoP succeeded, however, it quickly isomerized to more stable, but so far also unknown Δ-16-D-PhytoP, which may serve as a more reliable biomarker for D-type PhytoP. The dioxygenated cyclopentane ring carrying the ω-chain with the oxygen functionality in the 16-position was approached by a radical oxidative cyclization mediated by ferrocenium hexafluorophosphate and TEMPO. The α-chain was introduced by a new copper-catalyzed alkyl-alkyl coupling of a 6-heptenyl Grignard reagent with a functionalized cyclopentylmethyl triflate.

An efficient method for the synthesis of monoprotected syn‐ or cis‐1,2‐diol derivatives by reduction of easily accessible α‐(2,2,6,6‐tetramethylpiperidinyloxy) ketones is reported. The α‐(tetramethylpiperidinyloxy) group as the stereodirecting group induces in unhindered acyclic or cyclic ketones complete syn‐ or cis‐diastereoselectivity, respectively, with L‐Selectride. For more hindered derivatives, where L‐Selectride becomes unreactive, LiAlH4 proved effective, essentially showing the same high selectivity. The diastereoselectivity of the reduction can be rationalized for acyclic ketones by the Felkin–Anh model, whereas for cyclic substrates, attack from the face opposite to the tetramethylpiperidinyloxy group predictably prevails with high selectivity regardless of the substitution pattern. The liberation of free diols was achieved by reductive N–O bond cleavage of the alkoxyamine unit.