Deoxygenation reactions mechanisms

The low reactivity of alkyl and/or phenyl substituted organosilanes in reduction processes can be ameliorated in the presence of a catalytic amount of alkanethiols. The reaction mechanism is reported in Scheme 5 and shows that alkyl radicals abstract hydrogen from thiols and the resulting thiyl radical abstracts hydrogen from the silane. This procedure, which was coined polarity-reversal catalysis, has been applied to dehalogenation, deoxygenation, and desulfurization reactions.For example, 1-bromoadamantane is quantitatively reduced with 2 equiv of triethylsilane in the presence of a catalytic amount of ferf-dodecanethiol. 

The deoxygenation of nitroxides by (TMS)3SiH is shown in Reaction (4.43) [79]. Indeed, the reaction of this silane with TEMPO, in the presence of thermal or photochemical radical initiators, afforded the corresponding amine in quantitative yield, together with the siloxane (TMS)2Si(H)OSiMc3. The apparently unexpected detection of the siloxane can be accounted for by the reaction mechanism shown in Scheme 4.4. 

In detailed reaction mechanism, two pathways are proposed, as shown in eq. 7.3. Path a is the formation of an alkoxy thiocarbonyl radical [I], together with Bu3SnSCH3, while path b is the formation of an adduct radical [II] onto methyl xanthate (1) by Bu3Sn Based on the study with 119Sn-NMR, it was found that the deoxygenation reaction proceeds via path b [4, 5]. Other examples are shown in Tables 7.1 and 7.2. 

Deoxygenation of phosphine oxides can be achieved by the sequence outlined in Scheme 10. Although the reaction mechanism was not established, it seems not unreasonable to suggest that the phosphorane (108) is an intermediate. Details of further applications of the triphenylphosphine-carbon tetrachloride system to... 

Equation (24) has been chosen as an example of the radical deoxygenation of secondary alcohols via thiono esters [58], whereas Eq. (25) represents an example of deamination of primary amines via isocyanides [7, 54]. The reaction mechanism of these reductions is similar to that described for tin hydride, i.e. attack of silyl radical on the C=S or N=C moieties to form a radical intermediate which undergoes -scission to form alkyl radicals. Hydrogen abstraction from the hydride gives the product and the (TMS)3Si radical, thus completing the cycle of this chain reaction. 

Acetazolamide and chlorthalidone have also been shown to photosensitize the reduction of nitro blue tetrazolium in phosphate-buffered saline solution. The reaction is more efficient under deoxygenated conditions and in the presence of superoxide dismutase. These results indicate that direct electron transfer occurs from either the excited state of 7 or 8 to the substrate, especially oxygen. No doubt, superoxide ion could be involved as an intermediate when oxygen is present. On the basis of these results, a photochemical reaction mechanism of acetazolamide and nitro blue tetrazolium is postulated as shown in Figure 63.9. 

It was found that 1,2,4-triazine 4-oxides 55 are active enough to react with cyanamide under basic conditions according to the deoxygenative mechanism to form 5-cyanamino-l,2,4-triazines 73 (00TZV1128). This reaction seems to be facilitated by the easy aromatization of cr -adducts by the Elcb elimination of water. 

Unexpectedly, neither direct complexation nor the deoxygenated complexes 95 or 96136,137 were observed in the reaction of diphenylthiirene oxide (18a) with iron nonacarbonyl. Instead, the red organosulfur-iron complex 97138 was isolated12, which required the cleavage of three carbon-sulfur bonds in the thiirene oxide system (see equation 33). The mechanism of the formation of 97 from 18a is as yet a matter of speculation. 

Meinwald and coworkers71 studied the chemistry of naphtho[l, 8-bc]thiete and its S-oxides. The reaction of the sulphone 2 with LAH (equation 29) is of particular and direct relevance to this section since it is different from the reductions that have been discussed thus far, because the major reaction pathway is now cleavage of an S—C bond, rather than a deoxygenation of the sulphur atom. The major product (equation 29) was isolated in 65% yield two minor products accounted for a further 15% yield. One of the minor products is 1-methylthionaphthalene and this was most probably produced by an initial reduction of the strained 1,8-naphthosulphone, 2, to the thiete, which was then cleaved to the thiol and subsequently methylated. Meinwald also showed71 that the thiete was subject to cleavage by LAH as well as that both molecules were susceptible to attack and cleavage by other nucleophiles, notably methyllithium. These reactions are in fact very useful in attempts to assess a probable mechanism for the reduction of sulphones by LAH and this will be discussed at the end of this section. 

The structure of the reagent, the mechanism of epoxide opening, deoxygenations, dimerizations and intermolecular additions will be discussed first before covering the preparatively much more important cyclization reactions [36]. 

Scheme 3.18 Potential mechanism for the samarium-mediated deoxygenation reaction...

Attempts to establish the structure of the initial adduct by NMR-spectroscopy failed because of the low solubility of 27. This makes it impossible to draw a clear conclusion as to whether the ammonia adds to C-6 (as occurs in the case of the A-methylpyrimidinium salts) or at C-2. Since NMR spectroscopy of a solution of 4,6-diphenylpyrimidine in potassium amide/liquid ammonia strongly supports the formation of an anionic C-2 adduct (75UP1], it is justified to assume that also in the deamination of 27 by liquid ammonia, a C-2 adduct 28 is involved (Scheme III. 16). It is evident that the major part of the deamination (73%) does not involve a ringopening reaction the main deamination reaction occurs by an Sn2 attack of ammonia on the A-amino group in 27. A similar mechanism has also been postulated in the deoxygenation of pyrimidine A-oxides, when they are heated with liquid ammonia (Scheme III.16) [77UP2]. 

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