Hydroperoxide nucleophilic reductions

The reaction between alkyl hydroperoxides and enones has also been carried out using the same catalyst 28c and showing a similar behavior (Scheme 3.31). While the reaction usually leads to the formation of an epoxide as final product, under the optimized conditions and, in particular, by the correct election of the alkyl hydroperoxide nucleophile, the reaction can be directed to the formation of the p-peroxy-substituted ketone product in excellent yields and enantioselectivities. Reduction of these adducts allowed the preparation of the corresponding p-hydroxy ketone, therefore showing that the methodology is suitable for carrying out the formal enantioselective conjugate addition of OH to enones. 

The nucleophiles that are used for synthetic purposes include water, alcohols, carboxylate ions, hydroperoxides, amines, and nitriles. After the addition step is complete, the mercury is usually reductively removed by sodium borohydride, the net result being the addition of hydrogen and the nucleophile to the alkene. The regio-selectivity is excellent and is in the same sense as is observed for proton-initiated additions.17... 

Binding of 4-hydroxybenzoate (S) in the phenolate form facilitates flavin reduction by NADPH. After NADP+ release, the flavin hydroquinone reacts with molecular oxygen to yield the flavin C4a-hydroperoxide oxygenation species. Protonation of the distal oxygen of the peroxflavin facilitates the electrophilic attack on the nucleophilic carbon center of the substrate phenolate. After monooxygenation, the resulting hydroxyflavin is... 

In 1982, Evans reported that the alkylation of oxazolidinone imides appeared to be superior to either oxazolines or prolinol amides from a practical standpoint, since they are significantly easier to cleave [83]. As shown in Scheme 3.17, enolate formation is at least 99% stereoselective for the Z(0)-enolate, which is chelated to the oxazolidinone carbonyl oxygen as shown. From this intermediate, approach of the electrophile is favored from the Si face to give the monoalkylated acyl oxazolidinone as shown. Table 3.6 lists several examples of this process. As can be seen from the last entry in the table, alkylation with unactivated alkyl halides is less efficient, and this low nucleophilicity is the primary weakness of this method. Following alkylation, the chiral auxiliary may be removed by lithium hydroxide or hydroperoxide hydrolysis [84], lithium benzyloxide transesterification, or LAH reduction [85]. Evans has used this methology in several total syntheses. One of the earliest was the Prelog-Djerassi lactone [86] and one of the more recent is ionomycin [87] (Figure 3.8). 

Based in part on an analysis of the reactivity of Ru and Mn oxidation catalysts, it seems that Mn=0 centers are electron deficient and subject to nucleophilic attack by reductants. In the electrophilic Mn=0 models, the O—O bond-forming step involves nucleophilic attack by H2O/ OH on a Mn=0 species. In the proposal by Pecoraro and co-workers,the So Si transition involves PCET path A, but the transitions of S2 —> S3 —> S4 involve path B, as shown in Figure 27. This leads to the formation of Ca-bound OH and Mn=0 species. Nucleophilic attack of the OH on the Mn=0 forms a terminal hydroperoxide, which then displaces CN on a second terminal Mn and is oxidized to O2. 

Figure 27 Proposed mechanism of water oxidation by Pecoraro and co-workers. Light-driven steps are indicated by solid arrows and spontaneous steps by dashed arrows. Reduction of Yz by mechanism B in Figure 23 in Si S2 S3 forms a terminal Mn=0 species. Nucleophilic attack on the Mn=0 by a Ca-bound hydroxide forms hydroperoxide, which subsequently displaces CP and is oxidized on another Mn center.

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