Adamantane hydroxylation

The kinetics of product evolution in a typical reaction of adamantane hydroxylation showed an initial induction period followed by a fast, apparently zero-order phase with the maximum rate and highest efficiencies (Fig. 2). Deviation from linear behavior took place only after 90% oxygen donor and 80% of the substrate had been consumed. When Ru (TPFPP)(0)2, prepared by reaction of Ru"(TPFPP)(CO) with 3-chloroperbenzoic acid was used as the catalyst, no induction time was detected and zero-order kinetics were observed as well. The well defined and characteristic UV-vls spectra of metalloporphyrins provide an invaluable tool for the mechanistic studies. Thus, monitoring the state of the metalloporphyrin catalysts during the course of both model reactions by UV-vis spectroscopy revealed that the initial form of the catalyst remained the predominant one throughout the oxidation, i.e. in the Ru°(TPFPP)(CO) catalyzed reaction c.a. 80% of the porphyrin catalyst existed as Ru"(TPFPP)(CO) and in Ru (TPFPP)(0)2 catalyzed reaction more than 90% of... 

Figure 2. Adamantane Hydroxylation Catalyzed by Ru"(TPFPP)(CO) and Ru (TPFPP)(0)2, [adamantane] = [pyCl2NO] = 0.02 M, [catalyst] = 50 pM, CH2CI2,4(PC. TO = moles of product/moles of catalyst...

Figure 5. Eyring plot of adamantane hydroxylation catalyzed by Ru VtPFPP)(0)2...

Similar results were obtained with Ru (TPFPP)(CO) as the catalyst [5]. A kinetic scheme consistent with this observation is as follows as long as the oxidant OD is present in excess, the active Ru(III) catalyst will exist as the adduct Ru(III)-OD. The reactive oxoRu(V) would then be formed in the rate determining step, which is independent of the concentration of the oxidant (OD) (Fig. 3). The temperature dependence of adamantane hydroxylation yielded a linear Eyring plot for the observed rate constants determined over the range of 25 - 65°C with an apparent = 19 kcal/mol (Fig. 5). 

Facial selectivity of 5-substituted adamantan-2-ones (6) was initially studied by Giddings and Hudec [62], followed by intensive studies by le Noble s group [63-66]. Electron-withdrawing substituents such as phenyl (6b), fluoro (6c), hydroxyl and trifluoromethyl groups at the 5 position favored the syn addition... 

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. 

Adamantane (A) and adamantan-4-one (B) were specifically hydroxylated at the quaternary C-1 by cytochrome P450j, to produce C and D. In contrast, the eukaryotic cytochrome P450lm2 formed in addition to the C-2 compound from adamantane, and both 5-hydroxy-adamantan-l-one (D) and the 4-a fi-hydroxyadamantan-l-one (E) from adamantan-4-one (Figure 3.18b) (White et al. 1984). 

P450 is able to hydroxylate the -CHj group of the quaternary methyl group of 5,5-difluorocamphor (Figure 7.45a) to the 9-hydroxymethyl compound (Fble and Dawson 1984), and both adamantane and adamantan-4-one at the -CH quaternary carbon atom (Figure 7.45b) (White et al. 1984). 

The ruthenium-substituted sandwich-type POM WZnRu2(OH)(H20)(A W9034)2]11 (X- Zn2+ or Co2+, Figure 13.1) catalyzed the selective hydroxylation of adamantane with Oz as an oxidant[58,59] ... 

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%. ... 

A further use of the system is to mediate the reaction of adamantane with carbon monoxide and oxygen to form 1-adamantanecarboxylic acid . When long-wavelength light (>300 nm) is used, hydroperoxides efficiently generate hydroxyl radicals without the use of metal ions and would be an extremely useful source of hydroxyl radicals, particularly in the design of DNA-cleaving molecules . ... 

Raag, R. and Poulos, T. L. (1991) Crystal structures of cytochrome complexed with camphane, thiocamphor and adamantane factors controlling P450 substrate hydroxylation. Biochemistry 30, 2674-2684. 

Ru(CO)(TPFPP) (TPFPP=5,10,15,20-tetrapentafluorophenylporphyrinate) is made from the hgand and RUjCCO),. The system Ru(CO)(TPFPP)/(Cl2PyNO)/ CH2Cy65°C catalysed the hydroxylation of adamantane and of c/x-and trans-decalm, with high selectivity and complete stereoretention, and epoxidised 1-octene. Intermediacy of a TPFPP-Ru(lll) and an oxo-Ru(V) species was proposed [877]. 

RuCl(dmso)(tpa)](PF ) and RuCl(dmso)(BPG) (tpa=tris(2-pyridylmethyl) amine, BPG=A,iV-bis(2-pyridylmethyl)glycmate) no preparation was given. The X-ray crystal structure of the (tpa) complex showed sulfur co-ordination from (dmso). As [RuCl(dmso)(tpa)](PFg) and RuCl(dmso)(BPG)/MCPBA/CHCl3 they catalysed hydroxylation of adamantane [951]. 

It has been also found that PhIO as an oxidant in the presence of a catalytic amount of sulfonated manganese and iron porphyrin supported on poly(vinylpyridinium) polymers in olefin epoxidation and alkane hydroxylation is a better oxidant than Bu4NHS05 °. Oxidation of adamantane to 1-adamantanol in good yield using BU4NHSO5 and acetone in the presence of aqueous NaHCOs was also reported . ... 

Fluorination and hydroxylation are observed in reactions with substituted adamantanes 15, while the product distribution and number of products depend on the reaction conditions (with or without the HF scavenger Na2C03).21... 

Selective poly hydroxylation of adamantane is possible.87 A concerted insertion mechanism closely resembling to the mechanism of ozonation has been... 

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... 

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