Dihydroxyl radicals

Reaction Scheme 7.2 summarizes the reaction mechanism for 1-butene (l-C4Hg) as an example of alkenes. The hydroxyalkyl radicals formed by the pathways (a) and (b) is a kind of alkyl radicals mentioned in the previous Sect. (7.2.2), and exclusively forms hydroxyperoxy radicals by the reaction with O2 in the atmosphere. From the hydroxyperoxy radicals, oxyradicals (hydroxybutoxy radicals) and NO2 (pathways (d), (k)), and partially hydroxybutyl nitrate (pathways (e), (1)) are produced by the reaction with NO as in the case of alkylperoxy radicals described in the previous paragraph. The yields of hydroxylalkyl nitrates are 2-6 % for C4-C6 alkenes (O Brien et al. 1998), which is about half of those for alkyl nitrates from the alkoxy radicals. Hydroxy alkoxy radicals formed in pathways (d) and (k) are known to follow the three reaction pathways, unimolecular decomposition ((g), (n)), H-atom abstraction by O2 ((h), (o)), and dihydroxyl radical formation by isomerization (p), corresponding to reactions (7.25), (7.24) and... 

The hydroxyalkoxy radicals formed in pathway (k) can take place isomerization by intramolecular shift of H-atom via a six-membered ring as in the case of the alkoxy radical in the previous paragraph. Dihydroxyl aldehyde is then formed in pathways (q), (r), (s) though dihydroxyl radicals which has two OH groups in a molecule. The formation of dihydroxyl aldehyde has been confirmed in the laboratory experiment, and the yield of dihydroxyl aldehyde (3,4-dihydroxyl butanal) is 0.04 for 1-butene but it is as high as 0.6 for 1-octene (Kwok et al. 1996b). Under the low NOx concentrations, a part of hydroxyperoxy radicals react with HO2, and is known to produce hydroxyhydroperoxy butane (pathways (f), (m)) (Hatakeyama et al. 1995 Tuazon et al. 1998). 

The uncatalysed p-coumaric acid oxidation led to the formation of intermediates (not shown here) almost similar to those of the catalysed reaction, without formation of dihydroxylated aromatic compounds, such as 3,4- dihydroxybenzaldehyde. This result shows that the catalyst may promote the hydroxylation of aromatic ring by enhancing the formation of hydroxyl radicals in the reaction mixture. 

Cyclohexenones 34 also undergo a highly diastereoselective dihydroxylation to give cii-diols 39 (Scheme 11).22 These diol amides are converted to hydroxylactones 40 by an acid-catalyzed process involving retro aldol-realdolization prior to transacylation. The enantiomers of hydroxylactones 40 are obtained from iodolactones 35 by iodide exchange with 2,2,6,6-tetramethylpiperidin-l-yloxy free radical (TEMPO) followed by reductive cleavage of the TEMPO derivative with Zn in ElOAc. The enantiomeric purity of the hydroxylactones prepared by either route is 95-98% ee. 

Asymmetric cyclopropanation, 57, 1 Asymmetric dihydroxylation, 66 2 Asymmetric epoxidation, 48, 1 61, 2 Asymmetric reduction, 71, 1 Asymmetric Strecker reaction, 70, 1 Atom transfer preparation of radicals, 48, 2... 

The first example of the use of a polymer-bound cinchona alkaloid in the AD was described in 1990 by Sharpless [48,49], The polymer was readily obtained by radical co-polymerization of 9-(p-chlorobenzoyl)quinidine acrylate with acrylonitrile. First applications in dihydroxylations of frans-stilbene using NMO as co-oxidant yielded products with enantioselectivities in the range of 85 -93 % ee. It is interesting that a repetitive use of the polymer was possible without great loss of reactivity, indicating that the metal was retained in the polymeric array. 

Anti-tumor compound (205)-irinotecan (1) was prepared in 13 steps with an overall yield of 1.15 % for the longest linear synthesis. The short and selective preparation of aryl iodide 11 features two key steps - ortho metalation and Sharpless asymmetric dihydroxylation. In only one step 11 is transformed into the target molecule 1 by application of a radical domino annulation with isonitrile 15. This method gives access to the broad family of campthotecin derivatives because of the quite impressive generality of the substrates that can be employed. 

More recently, Petri et a/.[136] have copolymerized the chiral ligand (QHN)2-PHAL (Scheme 9.3) directly with ethylglycol dimethacrylate using AIBN as radical initiator. This material revealed high activities (68-80 % yield) and enantioselectivities (ee > 98 %) for asymmetric dihydroxylation of frans-stilbene using K3Fe(CN)6 as secondary oxidant. However, the authors noted that the catalytic material still contained unbound bis-alkaloid. 

A hr dm 3. Recently, the electrochemical incineration of p-benzoquinone in acetate buffer has been reported by Houk et al. [54]. The cell was similar to that above cited for 4-chlorophenol oxidation (see Sec. III.B), with a Ti or Pt anode coated with a film of the oxides of Ti, Ru, Sn, and Sb. These anodes are stable but somewhat less efficient than an Fe(III)-doped Pb02 film coated on Ti employed in a previous work [55], The COD of 50 mL of 100 ppm / -benzoquinone decreased from an initial value of 190 to 2 ppm during 64 hr of electrolysis at 1 A. The major intermediate products identified were hydroquinone and aliphatic acids including maleic, succinic, malonic, and acetic acids. The suggested reaction sequence is given in Fig. 13, where succinic acid is obtained from a cathodic reduction of maleic acid, which is formed from the breakdown of the dihydroxylated derivative generated by an attack of adsorbed hydroxyl radicals onto p-benzoquinone. Further mineralization of succinic acid occurs via its consecutive oxidation to malonic and acetic acids. 

The synthesis of L-daunosamine began with the condensation of trans-crotonaldehyde (56) with dibenzylhydrazine (Scheme 17). Sharpless asymmetric dihydroxylation of the resulting ( )-a, (3-unsaturated hydrazone 57 afforded the syn-diol 58 (70% yield, 89% ee by HPLC), and silylation with chlorodimethyl-vinylsilane then provided the radical cyclization precursor 59 in 98% yield. In the key step, exposure to thiyl radicals generated from PhSH and AIBN led to radical cyclization of dibenzylhydrazone 59. The unstable cyclic intermediate was then directly treated with fluoride to afford vinyl adduct 60 in 77% yield (dr 91 9, H NMR). In control experiments with corresponding monosilyl derivatives, the (3-O-silyl... 

The strategy is impressively simple the phthalazine derivative 15 can readily be prepared from quinine in one step. Being a divinyl derivative, it can be submitted as a cross-linking unit in the radical polymerization of methyl methacrylate (MMA) or 2-hydroxy methacrylate (HEMA). Thereby, an immobilized (DHQ-PHAL) derivative 16 is obtained, which is suited for the asymmetric dihydroxylation of frantr-stilbene (>99 % ee) and ( )-cinnamic acid methyl ester (>99 % ee. Table 1). The insoluble catalyst can be recovered by simple filtration, and its repeated... 

Flavones show antioxidant activity in different models. They neutralize free radicals, complex iron ions, and can prevent lipid oxidation (Pietta, 2000). This antioxidant activity is related to the phenolic hydroxyls present on the flavone nucleus, and the presence of ortho-dihydroxyl grouping (catechol groups) is known to be particularly effective for antioxidant activity. Conjugations with sugars always decrease the antioxidant activity, but can have positive effects on the solubility of the flavonoids in aqueous systems. 

Asymmetric dihydroxylation of trifluoromethylalkenes is also useful for construction of enantio-enriched trifluoromethylated diols usable for trifluoromethylated amino acids with chiral hydroxyl group. Thus, Sharpless AD reaction of 16 provides diol 17 with excellent enantioselectivity. Regioselective and stereospecific replacement of the sulfonate moiety in 18 with azide ion enables the introduction of nitrogen functionality. A series of well-known chemical transformation of 19 leads to 4,4,4-trifluorothreonine 20 (see Scheme 9.6) [16]. Dehydroxylative-hydrogenation of 21 by radical reaction via thiocarbonate and subsequent chemical transformation synthesize enantio-enriched (S)-2-amino-4,4,4-trifluoro-butanoic acid 22 [16]. Both enantiomers of 20 and 22 were prepared in a similar manner from (2R,3S)-diol of 17. 

Density fimctional theory (DFT) calculations show that this mechanistic hypothesis is energetically reasonable. The generation of the HO-Fe =0 oxidant from the [(TPA)Fe -OOH(OH2)] intermediate was found to have a thermodynamic cost of only 5 kcal/mol and a kinetic barrier of 20 kcal / mol (Fig. 18.5) [52]. Furthermore, the HO-Fe =0 oxidant could carry out either epoxidation or cis-dihydroxylation of the olefin, depending on which oxygen atom of the oxidant initiated attack of the substrate [53]. Thus, epoxidation occurs by 0x0 attack on the olefin, forming the first C-O bond and an intermediate carbon-based radical, which then reboimds to form the second C-O bond. On the other hand, czs-dihydroxylation is initiated by hydroxo attack to form the first C-O bond and an intermediate carbon-based radical, followed by reboimd with the 0x0 group to form the second C-O bond. 

Oppolzer and coworkers [147, 454] have developed a class of reagents based on the enantiomeric bomane-2,10-sultam skeleton 1.133. These chiral auxiliaries are easily prepared from the enantiomeric 10-camphosulfonic adds [455]. Saturated or a,P-unsaturated TV-acylsultams 1.134, occasionally prepared from Af-silyl precursors [396], have been used very frequently. Asymmetric alkylations, animations and aldol reactions of enolates or enoxysilane derivatives of 1.134 (R = R CH2) [147, 404, 407, 456-460] are highly selective. The a,(3-unsaturated TV-acylsultams 1.134 (R = R R"C=CH) suffer highly stereoselective organocuprate 1,4-additions [147, 173], cyclopropanations [461], [4+2] and [3+2] cydoadditions [73,276,454,462], OSO4 promoted dihydroxylations [454,463] and radical addi-... 

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