Acid-labile groups

One potential approach extends the idea of chemical amplification introduced in our preceding description of dry-film resists. In 1982, Ito and co-workers (37,38) recognized that if a photosensitizer producing an acidic product is photolyzed in a polymer matrix containing acid-labile groups, the acid will serve as a spatially localized catalyst for the formation or cleavage of chemical bonds. 

Although there are other convenient procedures for the conversion of sulphides into sulphoxides and sulphones, the phase-transfer catalysed reaction using Oxone has the advantage that the oxidation can be conducted in the presence of other readily oxidized groups, such as amines, alkenes, and hydroxyl groups, and acid-labile groups, such as esters and carbamates [6, 7], Hydrolysis of very acid-labile groups, such as ketals, can result in production of the keto sulphone. 

An alternative mechanistic scheme in which TMCS first reacts with alcohols to form hydrogen chloride which then activates the phosphoroamidite in situ seems to be unlikely. It is known that TMCS reacts very slowly with alcohols unless a catalyst is present [36]. Formation of HCl would effect the removal of an acid labile group like DMTr attached to a base or tert-hutyl... 

A highly selective and mild procedure for cleavage of TBDMS ethers to the corresponding alcohols by using Oxone was developed recently. Interestingly, it has been found that ferf-butyldiphenylsilyl (TBDPS) ether and certain acid-labile groups such as tetrahydropy-ranyl (THP),, V-Boc or a carbon-carbon double bond remain unaffected under the reaction... 

The side chains of the amino acids in this approach are also protected with acid-labile groups (f-butyl esters and BOC, for example), so that they too are revealed only in the final deprotection step. 

The deprotection of 4-phenyl-1,3-dioxolanes to liberate free carbonyl compounds over Pd-C is possible without affecting acid labile groups such as 0-silyl ether and O-THP (tetrahydropyranyl) ether (eq. 13.22).47... 

This is the most widely used class of SP linkers. Historically, the SPS of peptides (see Section 2.1) was developed using building blocks protected with acid-labile groups, thus allowing a convenient simultaneous cleavage and deprotection in the final step of the synthesis. Four commercially available acid-labile linkers are depicted in Fig. 1.7 in resin- and compound-bound forms. The preferred cleavage conditions for each linker are also provided. 

Pyridinium fluorochromate is a stable solid, which can be stored for long periods." h is as reactive as PCC, but slightly less acidic (pH of a 0.01 M solution = 2.4S compared to 1.7S for PCQ, and thus substrates with acid labile groups can be oxidized without the need to add a buffer." With 1.S equiv. of oxidant in dichloromethane at room temperature, primary and secondary alcohols are oxidized to aldehydes and ketones in high yield (Table 9). Unfortunately, ( )/(Z)-isomerization has been observed during the oxidation of allylic alcohols." ... 

Bipyridinium chlorochromate (4) is a mild, air stable nonhygroscopic oxidant. It is weaker than PCC, and thus 2-4 equiv. are required to obtain good yields of carbonyl compounds. The bipyridyl system acts as an internal buffer, permitting the ready oxitktion of alcohols in sul trates with acid labile groups. Bipyridinium chlorochromate will also oxidize sulfides to sulfoxides and sulfones." ... 

Pyridinium chromate on silica ° is also a good general oxidant, even in the presence of acid labile groups. In contrast to PCC on alumina this oxidant may be stored at room temperature for one year, with no loss of activity. It is convenient to use it in the form of a column when performing small scale oxidations the substrate is allowed to stand on the column for a few hours, and tiien the carbonyl compound is obtained simply by eluting the column with a suitable solvent. 

Enynes which have the secondary or tertiary center at the propargylic position are isomerized to 2-alkenyl-methylenecyclopentane in moderate to high yield with a catalytic amount of [CpRu(CH3CN)3]PF6 in acetone or dimethylformamide (DMF) [25], This catalyst system is acidic, and an acid-labile group such as a dimethyl acetal 54 is hydrolyzed to aldehyde 55. 

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