Oxidative deprotection mechanism

The conversion of 2 and 15 into the corresponding a,p-unsaturated aldehydes 17 has been judged to rely on one or both of the two competing mechanisms depicted in Scheme 5.4. The detection, on some substrates [27, 37], of the transient allylic alcohol 16 clearly suggests that an early PMB group removal followed by a subsequent oxidation in situ of 16 under single electron transfer (SET) conditions [39] may take place (Scheme 5.4A). The latter transformation is supposed to occur via formation of the stabilized cation intermediate 18, overall obtained by H and e abstractions from 16 by DDQ. Similarly, when no allylic alcohol intermediate, even at low temperature, could be detected, a direct oxidative deprotection mechanism has been postulated, involving formation of the hemiacetal intermediate 20 via cation 19 (Scheme 5.4B). 

A good example of the useful participation of a protecting group in a chemical transformation is shown in the following scheme. Suggest a mechanism for the conversion of 2-bromo-4-methoxyphenyl ether 2.1 to the bicyclic derivative 2.2 as well as a mechanism for the oxidative deprotection of 2.2 to 23 using ceriu-m(lV) ammonium nitrate. 

A radical anion can lose an anionic leaving group to give a neutral free radical, and in the reverse direction, a neutral free radical can combine with an anionic nucleophile to give a new radical anion. A radical cation can also combine with a nucleophile. Such steps occur in the SrnI mechanism (Chapter 2), in dissolving metal reductions, and in oxidative deprotections. These two-electron reactions have obvious counterparts in carbocation chemistry. 

One of the most Irequently observed pathways for the oxidation of alcohols involves the formation of a covalent/co-ordinate bond between oxygen atom and the oxidizing agent with the loss of hydroxyl hydrogen atom. For, structural reasons, this mechanism is obviously forbidden for ethers. As a consequence, oxidative deprotection/ oxidation of ethers is much less frequently encountered and is of minor synthetic importance in classical organic chemistry. It is fairly obvious from the percentage yields of the biotransformed product(Table II) of the all the substrates chosen, that this above procedure is synthetically viable. 

The reaction mechanism (Scheme 6.25) involves formation of a cationic 7t-allylpalladium complex by the oxidative addition of the substrate onto the catalyst. In case of a dimethylallyloxycarbonyl protecting group this step is disfavoured compared to Alloc and therefore the removal of dimethylallyl groups is slower or requires more catalyst. Accordingly, in homogeneous CH3CN/H2O solutions deprotection of (allyl)phenylacetate proceeded instantaneously with 2 mol % [Pd(OAc)2]/TPPTS while it took 85 min to remove the dimethylallyl group (cinnamyl is an intermediate case with 20 min required for complete deprotection). The reactivity differences are... 

The corresponding methyl-derivative (342, R = Me) leads to a furan under these conditions but deprotection by mercuric oxide and boron trifluoride produces an E/Z mixture of diketones corresponding to (343). Replacing one of the phenyl substituents in (342, R = H) with methyl leads instead to the (E)-ketone (344). Various mechanisms are possible for these reactions, but an attractive one involves methylation on sulphur and ring expansion to (345), followed by trapping by water and ring opening272 ... 

Chloramine T (Af-chloro-/ -toluenesulfonamide. sodium salt) is a cheap oxidant that has been used occasionally for the deprotection of dithianes.157 In the example depicted in Scheme 2.72. a dithiane is cleaved in the presence of an a, p-unsaturated 0,0-acetaL158 A likely mechanism for the reaction involves the formation of an intermediate sulfilimine. Several heavy metal oxidants have also been exploited for cleaving 5,5-acetals including lead(IV), thallium(lll) [Scheme... 

In the early 1970s, Barton et al. published the results of their woik on the oxidation of acetals and ethers by hy de transfer. o They observed that substituted benzyl ethers and benzyloxy carbonates, on brief exposure to trityl tetrafluoroborate in dichloromethane at 0 C followed by aqueous work-up, afforded go( yields of the parent alcohols together with the corresponding bennldehydes. Undw the same conditions, the tetrahydropyranyl ether of cholesterol was also efficiently deprotected. A mechanism was proposed which involved an initial hydrogen abstraction, followed by quenching of the resulting stabilized cation by water (Scheme 6). 

Figure 2.5 Solid Phase DNA Synthesis. 5 -dimethoxytrityl (DMT)-deprotection of resin bound 3 -terminal deoxynucLeoside residue is effected with trichloroacetic acid (TCA) (mechanism shown) Thereafter the first coupling reaction is enabled by phosphoamidite activation with tetrazole (mechanism shown) followed by oxidation of the newly formed diester linkage to a phosphodiester link. The process of 5 -DMTr deprotection, phosphoramidite coupling and then diester oxidation, continues for as many times as required (n-times), prior to global deprotection and resin removal under basic conditions.

In the presence of a nickel(II) catalyst, suUamates can be used as nitrogen sources for the intramolecular vicinal diamination of alkenes 141 (Scheme 16.37). While the mechanism of this oxidative transformation is not fully understood, the reaction bears the advantage that cyclic sulfamates 142 undergo selective deprotection under conventional conditions. Hence, this diamination protocol represents an attractive approach to free aminomethyl pyrrolidines (100). 

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