1.2- Diols alkene oxidation

Diol epoxides, a very special and highly reactive subclass of alkene oxides encountered in the metabolism of polycyclic aromatic hydrocarbons. 

The overall reaction catalyzed by epoxide hydrolases is the addition of a H20 molecule to an epoxide. Alkene oxides, thus, yield diols (Fig. 10.5), whereas arene oxides yield dihydrodiols (cf. Fig. 10.8). In earlier studies, it had been postulated that epoxide hydrolases act by enhancing the nucleo-philicity of a H20 molecule and directing it to attack an epoxide, as pictured in Fig. 10.5, a [59] [60], Further evidence such as the lack of incorporation of 180 from H2180 into the substrate, the isolation of an ester intermediate, and the effects of group-selective reagents and carefully designed inhibitors led to a more-elaborate model [59][61 - 67]. As pictured in Fig. 10.5,b, nucleophilic attack of the substrate is mediated by a carboxylate group in the catalytic site to form an ester intermediate. In a second step, an activated H20... 

Osmium-catalyzed oxidation is one of the most useful routes to dihydroxylation of alkenes to give the corresponding diols. This oxidation proceeds in the presence... 

The treatment of an alkene by 5yn-hydroxylation, followed by periodic acid (HIO4) cleavage, is an alternative to the ozonolysis, followed by reductive work-up. 5yn-diols are oxidized to aldehydes and ketones by periodic acid (HIO4). This oxidation reaction divides the reactant into two pieces, thus it is called an oxidative cleavage. 

Dihydroxylation, the addition of two hydroxy groups across a C = C bond, converts fluorinated alkenes into different products depending on the presence or absence of a fluorine atom at the hydroxylated carbon. Partially fluorinated alkenes with vicinal hydrogen atoms attached to the C = C bond can be hydroxylated to vicinal diols. When the reaction is performed with a sufficiently strong oxidizing agent, the initially formed diols are oxidized to vicinal diketones as the end products. 

Since H202 is easier to handle than 02, we will focus on the use of the former. Many metals can be used for this transformation [50]. Among them, iron compounds are of interest as mimics of naturally occurring non-heme catalysts such as methane monooxygenase (MMO) [51a] or the non-heme anti-tumor drug bleomycin [51b]. Epoxidation catalysts should meet several requirements in order to be suitable for this transformation [50]. Most importantly they must activate the oxidant without formation of radicals as this would lead to Fenton-type chemistry and catalyst decomposition. Instead, heterolytic cleavage of the 0—0 bond is desired. In some cases, alkene oxidation furnishes not only epoxides but also diols. The latter transformation will be the topic of the following section. 

As a metabolic pathway, alkene oxidation is not common. When an alkene is oxidized, an epoxide forms. The epoxide normally reacts with water and opens to a 1,2-diol. The alkene in carbamazepine (8.20) is oxidized to a small degree to form the corresponding epoxide (8.21) (Scheme 8.7). 

A detailed investigation showed that PhB(OH)2 does not interfere with the chiral ligand, leaving the enantioselective step of alkene oxidation intact. Its main role-apart from protecting the diol products against potential over-oxidation - is to remove the diol via an electrophilic cleavage, which is in contrast to the conventional hydrolytic cleavage of the AD protocols.126... 

Alkenes give diols after oxidation by cold, dilute KMnO solution, n bonds are broken but a bonds are not affected by this oxidation. 

Monoesterification of HO(CH OHAlkenes react with diols under oxidative carbonylation conditions catalyzed by PdCl, and CuCl, to give hydroxy esters (equation I). Internal alkenes show similar reactivity. 

In close analogy with the osmylation reaction, kinetic data are consistent with a mechanism involving initial reagent-substrate interaction to form a charge-transfer complex with subsequent breakdown via oxametallacyclobutane 1 to the metastable cyclic manganate(V) 2. This diester is believed to lead to the desired diol as well as to other alkene oxidation products. 

Diols are oxidatively cleaved by reaction with periodic acid (HIO4) to yield carbonyl compounds, a reaction similar to the KMnO cleavage of aJkenes just discussed. The sequence of (1) alkene hydroxylation with OsO< j followed by (2) diol cleavage with HIO4 is often an excellent alternative to direct alkene cleavage with ozone or potassium permanganate. 

Alkenylalkyldimethoxyboronates have been shown to rearrange with inversion of geometry, leading to substituted alkenes (equation 57), ° and alkenyltrialkylboronates react with epoxides to yield 1,4-diols after oxidation (Scheme 48). ° ... 

Diols are oxidatively cleaved to ketones and/or aldehydes by periodic acid (HIO4). Ozonolysis oxidatively cleaves alkenes to ketones and/or aldehydes when worked up under reducing conditions and to ketones and/or carboxylic acids when worked up under oxidizing conditions. Acidic solutions and hot basic solutions of potassium permanganate also oxidatively cleave alkenes to ketones and/or carboxylic acids. 

The oxidation reactions of either permanganate or osmium tetroxide with an alkene lead to a vicinal diol. The functional group exchange for this process is that shown. In other words, a diol is obtained by dihydro lation of an alkene. Oxidative cleavage reactions such as ozonolysis eventually lead to an aldehyde, ketone, or carboxylic acid, depending on the substituents attached to the unit... 

An additional contribution to the field ofbiomimetic non-heme iron complexes for alkene oxidation was recently reported by Klein Gebbink and coworkers [109]. They found that iron(II) complexes formed with the neutral ligand propyl 3,3-bis(l-methylimidazol-l-yl)propionate (20) were active as catalysts for the oxidation of various simple alkenes. When complex 21 was employed as the catalyst for the oxidation of cyclooctene in the presence of 10 equivalents of hydrogen peroxide, a mixture of epoxide and diol in a ratio of 2.5 1 was obtained. However, the conversion was rather poor (39%). 

Cleavage is believed to occur via a cyclic intermediate similar to the one formed with osminm tetroxide (Section 8.16A) and intermediate formation of a 1,2-diol. Alkenes with monosnbstitnted carbon atoms are oxidatively cleaved to salts of carboxylic acids. 

The reaction of terminal allyl alcohols proceeds in a 5-endo fashion to give five-membered ring compounds regioselectively and stereoselectively. Subsequent oxidation affords 2,3-5 y -l,3-diols preferentially, regardless of the nature of the catalyst (eq 1). The stereoselectivity increases with increased bulkiness of the al-lylic substituent and the nature of the alkene substituent (see below). 5-Exo type cyclization occurs with homoallyl alcohols to form five-membered heterocycles and 1,3-diols after oxidation. Two chiral centers are produced in this reaction. The 2,3-relationship (anti) is controlled by the allylic substituent, while the 3,4-relationship is determined by the stereochemistry of the alkene the hydrosilation occurs by cis addition of Si-H to the alkene (eq 2). ... 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

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