Protecting groups photochemical removal

This approach offers unique opportunities for the generation of multi-functionalized cyclic 2-azadiene systems. A wide variation of the substitution pattern at the positions N-1 and C-6 can be determined by an appropriate choice of the aldehyde and amine. Various substituents can easily be introduced at the C-3 position via addition/elimination reactions on the sensitive imidoyl chloride moiety [24]. Upon reaction with bi-functional reagent, an adequately AT-protected 2(lH)-pyrazinone was elaborated into C-nucleoside analogues (Scheme 8). The desired skeleton and functionalities were obtained by oxidation-cyclization reaction followed by photochemical removal of the protective o-nitrobenzyl group [25]. 

Silyl protecting groups are the gold standard for the protection of alcohols.234 Novel photochemically removable protection groups for alcohols have been developed by Brook et a/.23S and Pirrung et al,236 For instance, cyclo-pentanol can be reacted with tris(trimethylsilyl)chlorosilane 53 in the presence of a mild base to yield the protected silyl ether 54. The protection group can be removed conveniently upon UV irradiation or by the use of Bu4NF (Scheme 12). 

Nitrophenyl)ethylene glycol was used to protect simple aldehydes and ketones, as well as some steroids. Acetals were prepared under acid catalysis, leading, in the case of chiral carbonyl compounds to diaste-reoisomers. The photochemical removal of the protecting group was in several instances complicated by the instability of some carbonyl derivatives to irradiation at 350 nm otherwise, yields were in the range of 83-90% (see Scheme 19). 

The half-deprotected product was obtained in 65% yield. Of course, such a yield is insufficient from a synthetic point of view, the photovariant of the redox reaction is not simple instrumentally, and the duration of the reaction (5 h) is too long. Nevertheless, this approach is promising, and deserves attention and development. Thus, the photochemical method proved to be successful in the removal of protecting groups based on covalently linked donor-acceptor systems (Lee and Falvey 2000). 

Banerjee, A. Falvey, D. E. Protecting groups that can be removed through photochemical electron transfer mechanistic and product studies on photosensitized release of carboxyl-ates from phenacyl esters. J. Org. Chem. 1997, 62, 6245-6251. 

Furuta, T., Hirayama, Y. and Iwamura, M. (2001) Anthraquinone-2-ylmethoxy-carbonyl (Aqmoc) a new photochemically removable protecting group for alcohols. Organic Letters, 3, 1809-1812. 

Pirrung, M.C. and Lee, Y.R. (1993) Photochemically-removable silyl protecting groups. Journal of Organic Chemistry, 58, 6961—6963. 

A new and efficient route to endo-hirsutene has been described which uses, as the key step, the oxetane (11) from the intramolecular photocycloaddition of (12) (Rawal et ai), and 3-deoxy-D-arabino-2-heptulopyranosonic acids can be synthesised photochemically from Barton esters such as (13) (Barton and Liu). Interest in the development of photochemically removable protecting groups continues, and the irradiation of the 4-hydroxyphenacyl-protected system (14) is reported to release ATP with a quantum yield of 0.37 (Givens and Park). Benzoylbenzoate esters of primary and secondary alcohols undergo cleavage in the presence of electron donor molecules and it is proposed that such esters could be effective photolabile protecting groups for alcohols and that thiols can be similarly protected (Jones et al.). 

The Bhcmoc group was developed as a photochemically removable protective group for caged compounds. Among the series tested this one showed the highest photochemical efficiency in its release of an alcohol. ... 

For a reviews covering the photolytic removal of protective groups, see V. N. R. Pillai, Synthesis, 1 (1980) C. G. Bochet, /. Chem. Soc., Perkin Trans. 1, 125 (2002) P. Pellic-cioli Anna and J. Wirz, Photochemical Photobiological Sciences Official Journal of the European Photochemistry Association and the European Society for Photohiology, 1, 441 (2002). 

Thymidine and 2 -deoxycytidine phosphoramidite monomers have been prepared using 3 -[2-(2-nitrophenyl)propyloxycarbonyl] protecting groups, which are removed photochemically, to allow for 5 3 DNA synthesis by photolitho-... 

The dimethyl phosphite esters (431) undergo a photochemically catalysed Arbuzov i.somerization to the phosphonates (432 n = 1-3). The silyl protecting groups may be removed with Ph P/CBr and the resultant (w-bromoalkyl)phosphonic esters made to react with an activated heterocyclic base, the example of adenine being illustrated... 

The irradiation of CBr4 in MeOH has been reported as an effieient photochemical means of removing protecting groups (Chen et ai. Chapter 3). Examples are the release of (13b) from (13a) in 89% yield, and (14b) from (14a) in 86% yield. 

Dimethoxybenzoin (DMB) carbonates (39) were found to be photochemically removable alcohol protecting groups. DMB carbonates can be installedby the carbamate product (38) of DMB-OH (37) and iV,iV -carbonyldiimidazole activated by methylation (eqs 32 and 33). ... 

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