Adamantane tertiary hydroxylation

As in the case of the epoxidation reaction with HOF/MeCN, this tertiary hydroxylation method can be used for the introduction of the l o isotope. For example, when adamantane, is treated with the oxidizing... 

This dry ozonation procedure is a general method for hydrox-ylation of tertiary carbon atoms in saturated compounds (Table 1). The substitution reaction occurs with predominant retention of configuration. Thus cis-decalin gives the cis-l-decalol, whereas cis- and frans-l,4-dimethylcyclohexane afford cis- and trans-1,4-dimethylcyclohexanol, respectively. The amount of epimeric alcohol formed in these ozonation reactions is usually less than 1%. The tertiary alcohols may be further oxidized to diols by repeating the ozonation however, the yields in these reactions are poorer. For instance, 1-adamantanol is oxidized to 1,3-adamantane-diol in 43% yield. Secondary alcohols are converted to the corresponding ketone. This method has been employed for the hydroxylation of tertiary positions in saturated acetates and bromides. 

The tra x-[Ru (0)2(por)] complexes are active stoichiometric oxidants of alkenes and alkylaro-matics under ambient conditions. Unlike cationic macrocyclic dioxoruthenium I) complexes that give substantial C=C bond cleavage products, the oxidation of alkenes by [Ru (0)2(por)] affords epoxides in good yields.Stereoretentive epoxidation of trans- and cw-stilbenes by [Ru (0)2(L)1 (L = TPP and sterically bulky porphyrins) has been observed, whereas the reaction between [Ru (0)2(OEP)] and cix-stilbene gives a mixture of cis- and trani-stilbene oxides. Adamantane and methylcyclohexane are hydroxylated at the tertiary C—H positions. Using [Ru (0)2(i)4-por)], enantioselective epoxidation of alkenes can be achieved with ee up to 77%. In the oxidation of aromatic hydrocarbons such as ethylbenzenes, 2-ethylnaphthalene, indane, and tetrahydronaphthalene by [Ru (0)2(Z>4-por )], enantioselective hydroxylation of benzylic C—H bonds occurs resulting in enantioenriched alcohols with ee up to 76%. ... 

The hydroxylation occurs preferentially at tertiary position (adamantane C-l C-2 = 25-48 1) unless steric hindrances exist. Some configuration inversion ( 10% in cis-decaline hydroxylation at C-9) and bromination in the presence of BrCCl3 have been observed. The double bond scrambling... 

The other alkanes were found to be much less reactive. Cyclohexane gave a cyclohexanol-one mixture, and adamantane was preferentially hydroxylated at the tertiary positions cis-decalin gave a mixture of cis- and frnns-9-decanol (together with 1- and 2-decalones), suggesting the transient formation of radical carbon intermediates, which were also revealed by trapping experiments with CC14. 

Hydroxylation of alkanes preferentially occurs at the more nucleophilic tertiary C—H positions, but some of these systems using 2-mercaptoethanoF or metallic iron powder d hydroxylate adamantane with preference for the secondary position. However, none of these systems hydroxylates cis-decalin with retention of configuration at the hydroxylated atom. ... 

Hydroxylation of tertiary carbon atoms on silica gel. Israeli chemists have devised an experimental method for hydroxylation of saturated hydrocarbons at tertiary positions by ozone adsorbed on silica gel in this way concentrations of ozone of 4.5% by weight at -78 can be attained. First the hydrocarbon is impregnated on the silica gel and then ozone is passed through at -78° until the silica gel is saturated. After the silica gel has warmed to 20, the product is eluted. Tertiary alcohols can be obtained in this way in high yield with almost complete retention of configuration. The secondary alcohol adamantane-2-ol was oxidized to the ketone by this method. 

Adamantane and cis-decalm were hydroxylated with high selectivity, complete stereo-retention, extraordinarily high rates (up to 800 turnovers min ), and high efficiency with up to 15,000 turnovers. Similar conversions were obtained when Ru(VI)(TPFPP)(0)2 and Ru(VI)(TPFPBr8P)(0)2 were used as catalysts. Oxygenation of less reactive substrates such as benzene and cyclohexane proceeded with lower but still significant turnover numbers (100-3,000). Tertiary vs secondary selectivity in adamantane oxidation was above 210. No rearrangement products were detected in cw-decalin hydroxylation. 

The catalytic system consisting of PhIO and various iron porphyrins hydroxylates unactivated alkanes under ambient conditions [83,88]. The substrates studied were cyclohexane, cycloheptane, adamantane, cis-decahydronaphthalene and norcarane, and the catalysts - Fe(TPP)Cl, Fe(TTP)Cl, Fe(TNP)Cl and Fe(TMP)Cl. Monohydroxylated products predominated in all cases, with maximum yields of 30-39 % based on PhIO. High selectivity for tertiary centers (adamantane), retention of configuration at carbon (cis-decaline), and a large kinetic isotope effect (12.9) have ben observed. The free radical trap bromotrichloromethane changes the product distribution, pointing to a radical mechanism. The mechanism (Scheme 4) is essentially the same as that proposed previously for alkane oxidation by cytochrome P-450 [89]. 

In the case of the hydroxylation of inactivated alkanes, the yields and distributions of products are sensitive to the peripheral substitution pattern of the porphyrin. Table 4 lists the results from the oxidation of adamantane with iodosylbenzene and three iron porphyrins Fe (TPP)Cl, Fe (TTP)Cl (TTP tetrakis(o-tolyl)porphyrin), and Fe (TMP)Cl [44]. Apparently, there is a high degree of selectivity for tertiary centers over secondary centers. In addition, with increasing substitution of the porphyrin peripheral groups, the relative reactivity of tertiary and secondary hydrogens decreased from 48 1 to 11 1. Details of the steric effect of the porphyrin peripheral groups to the selectivity will be discussed later. 

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