Chemoselective hydroxylation

The methodology was extended to show chemoselective hydroxylation (imide over ester) and a-hy-droxylation of extended enolates. It also provided support for a stepwise mechanism (see Section 2.3.2.1.2.iii) involving a counterion dependent equilibrium. 

Unactivated alkanes can be oxidized with the RuCl3/NaI04 system [85-91]. Tertiary C-H bonds undergo chemoselective hydroxylation to afford the corresponding tertiary alcohols (Eq. 3.53) [85]. 

Larsen AT, May EM, Auclair K (2011) Predictable stereoselective and chemoselective hydroxylations and epoxidations with P450 3A4. J Am Chem Soc 133 7853-7858... 

The reaction is regioselective, producing / ara-phenols from monosubstituted benzene derivatives. Furthermore, alkylarenes with reactive side-chain sp C-H bonds could be chemoselectively hydroxylated without significant formation of side-chain oxygenated products. Kinetic and mechanistic models of the oxidation of phenol with HP, catalysed by a new macrocyclic cobalt(II) complex, have been proposed. The catalytic system displayed high catalytic activity and the catalytic character of a metalloenzyme, although it did not attain the catalytic efficiency of enzymes. 

AC2O, BF3 Et20, THE, 0°. These conditions give good chemoselectivity for the most nucleophilic hydroxyl group. Alcohols are acetylated in the presence of phenols. 

Huonnations with DAST proceed with high chemoselectivity In general, under very mild reaction conditions usually required for the replacement of hydroxyl groups, other functional groups, including phenolic hydroxyl groups [112], remain intact This provides a method for selective conversion of hydroxy esters [95 97] (Table 6), hydroxy ketones [120, 121], hydroxy lactones [722, 123], hydroxy lactams [124] and hydroxy nitriles [725] into fluoro esters, fluoro ketones, fluoro lactones, fluoro lactams, and fluoro nitnles, respectively (equations 60-63)... 

Scheme 4 outlines the synthesis of key intermediate 7 in its correct absolute stereochemical form from readily available (S)-(-)-malic acid (15). Simultaneous protection of the contiguous carboxyl and secondary hydroxyl groups in the form of an acetonide proceeds smoothly with 2,2 -dimethoxypropane and para-toluene-sulfonic acid and provides intermediate 26 as a crystalline solid in 75-85 % yield. Chemoselective reduction of the terminal carboxyl group in 26 with borane-tetrahydrofuran complex (B H3 THF) affords a primary hydroxyl group that attacks the proximal carbonyl group, upon acidification, to give a hydroxybutyrolactone. Treat-... 

Scheme 24) [38]. Chemoselective enolization of the less substituted enone moiety under hydrogenation conditions accompanied by subsequent aldol reaction provided the corresponding hydroxyl-enones, such as 87-89, which could be converted to various building blocks for polypropionate synthesis. p-Me2N styryl vinyl enone also was employed successfully as an enolate precursor, as demonstrated by the formation of hydroxy enone 90. 

Elaboration of triol 88b to bryostatin 7 requires chemoselective hydrolysis of the Cl methyl ester in the presence of the C7 and C20 acetates, macrolide formation, installation of the C13 and C21 methyl enoates, and, finally, global deprotection. The sequencing of these transformations is critical, as attempts to introduce the C21 methyl enoate to form the fully functionalized C-ring pyran in advance of macrolide formation resulted in lactonization onto the C23 hydroxyl. In the event, trimethyltin hydroxide promoted hydrolysis [73] of the Cl carboxylate of triol 88b, and subsequent trie thy lsilylation of the C3 and C26 hydroxyls each occurs in a selective fashion, thus providing the seco-acid 89. Yamaguchi macrolacto-nization [39] proceeds uneventfully to provide the macrolide 67 in 66 % yield (Scheme 5.14). 

Several other examples have been reported in which thioglycosides were used as glycosyl acceptors. Thus, thioglycosides containing free hydroxyls can be coupled chemoselectively with glycosyl bromides and chlorides in the presence of silver triflate or tin(II) chloride-silver perchlorate as the promoter system [12,53,56,162,218-221]. 

While a variety of techniques are available for the monoprotection of symmetrical diols, there are few methods that allow for the chemoselective functionalization of the more hindered hydroxyl in an unsymmetrical 1,3-diol.5 The acid-catalyzed reaction of an unsymmetrically substituted cyclic formal with acetyl chloride described here invariably proceeds via preferential rupture of the less congested C(2)-0 bond to give a product having an acetate at the less congested site... 

A double mediatory system consisting of modified TEMPO and halide ion or metal ion was also exploited for the oxidation of alcohols [53-55]. A number of carbohydrates have been chemoselectively oxidized at the primary hydroxyl group to uronic acids [56]. 

A more subtle example of identical functional groups with different steric enviroment is found in the intermediate H which Corey [8] uses in the synthesis of fumagillin (13). The two identical secondary hydroxyl groups in the cyclohexane derivative H can be differentiated by using a bulky reagent since the axially disposed hydroxyl group is less accesible than the one which is equatorially disposed and can be chemoselectively methylated (12) in the presence of sodium rert-amylate (Scheme 12.2). 

The less hindered peripheric secondary hydroxyl group of the key intermediate 28 was chemoselectively tosylated (29), submitted to an internal Wharton-Grob fragmentation (30). After attack on the carbonyl group (3i) with methyllithium and activation of the secondary alcohol as the corresponding tosylate, the resulting... 

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