Editing Protecting group (section)

==Orthogonal protection==
[[Image:Tyrosine Protected V.4.png|thumb|right|Orthogonal protection of L-Tyrosine (Protecting groups are marked in <span style="color:blue;">'''blue'''</span>, the amino acid is shown in '''black'''). ('''1''') Fmoc-protected [[amino group]], ('''2''') benzyl ester protected [[carboxyl group]] and ('''3''') ''tert''-butyl ether protected phenolic [[hydroxyl group]] of Tyrosine.]]

'''Orthogonal protection''' is a strategy allowing the specific deprotection of one protective group in a multiply-protected structure. For example, the amino acid [[tyrosine]] could be protected as a benzyl ester on the carboxyl group, a fluorenylmethylenoxy carbamate on the amine group, and a ''tert''-butyl ether on the phenol group. The benzyl ester can be removed by hydrogenolysis, the fluorenylmethylenoxy group (Fmoc) by bases (such as piperidine), and the phenolic ''tert''-butyl ether cleaved with acids (e.g. with trifluoroacetic acid).

A common example for this application, the Fmoc peptide synthesis, in which peptides are grown in solution and on solid phase, is very important.<ref name="FMOC">{{Cite book|title = Fmoc Solid Phase Peptide Synthesis|last1 = Chan|first1 = Weng C.|publisher = [[Oxford University Press]]|year = 2004|isbn = 978-0-19-963724-9|last2 = White|first2 = Peter D.}}</ref> The protecting groups in [[solid-phase synthesis]] regarding the reaction conditions such as reaction time, temperature and reagents can be standardized so that they are carried out by a machine, while yields of well over 99% can be achieved. Otherwise, the separation of the resulting mixture of reaction products is virtually impossible (see also {{slink||Industrial applications}}).<ref>Weng C. Chan, Peter D. White: ''Fmoc Solid Phase Peptide Synthesis'', S.&nbsp;10–12.</ref>  
<gallery widths="200" heights="200" perrow="5">
File:SPPS1is.svg|Schematic diagram of a solid-state peptide synthesis with orthogonal protecting groups '''X''' and '''Y'''
File:SPPS2is.svg|Fmoc solid state peptide synthesis with orthogonal protecting groups
</gallery>

A further important example of orthogonal protecting groups occurs in [[carbohydrate]] chemistry.  As carbohydrates or [[hydroxyl group]]s exhibit very similar reactivities, a transformation that protects or deprotects a single hydroxy group must be possible for a successful synthesis.

=== Cleavage categorization ===
Many reaction conditions have been established that will cleave protecting groups. One can roughly distinguish between the following environments:<ref>Michael Schelhaas, Herbert Waldmann: "Schutzgruppenstrategien in der organischen Synthese", in: ''[[Angewandte Chemie]]'', '''1996''', ''103'', pp.&nbsp;2195–2200; [[doi:10.1002/ange.19961081805]] (in German).</ref>

* [[Acid]]-labile protecting groups
* [[Base (chem)|Base]]-labile protecting groups
* [[Fluoride]]-labile protecting groups
* [[Enzyme]]-labile protecting groups
* [[Reduction (chem)|Reduction]]-labile protecting groups
* [[Oxidation]]-labile protecting groups
* Protecting groups cleaved by heavy metal salts or their complexes.
* [[Photochemistry|Photo]]labile protecting groups
* Double-layered protecting groups

Various groups are cleaved in acid or base conditions, but the others are more unusual.

Fluoride ions form very strong bonds to [[silicon]]; thus silicon protecting groups are almost invariably removed by fluoride ions.  Each type of counterion, i.e. cleavage reagent, can also selectively cleave different silicon protecting groups depending on [[steric hindrance]]. The advantage of fluoride-labile protecting groups is that no other protecting group is attacked by the cleavage conditions.

[[Lipase]]s and other enzymes cleave ethers at [[biological pH]] (5-9) and [[Body temperature|temperatures]] (30–40&nbsp;°C).  Because enzymes have very high substrate specificity, the method is quite rare, but extremely attractive.

Catalytic [[hydrogenation]] removes a wide variety of [[benzyl group]]s: ethers, esters, urethanes, carbonates, etc.

Only a few protecting groups can be detached oxidatively: the methoxybenzyl ethers, which oxidize to a [[quinomethide]].  They can be removed with [[ceric ammonium nitrate]] (CAN) or [[dichlorodicyanobenzoquinone]] (DDQ).
[[File:PMB_deprotection.svg|center|frameless|440x440px]]
[[File:PMB_deprotection_mechanismn.svg|center|frameless|440x440px]]
[[allyl group|Allyl compounds]] will [[Isomerization|isomerize]] to a vinyl group in the presence of [[noble metal]]s.  The residual [[enol ether]] (from a protected alcohol) or [[enamine]] (resp. amine) hydrolyzes in light acid.

Photolabile protecting groups bear a [[chromophore]], which is activated through radiation with an appropriate wavelength and so can be removed.<ref>V.N. Rajasekharan Pillai: "Photoremovable Protecting Groups in Organic Synthesis", in: ''[[Synthesis (journal)|Synthesis]]'', '''1980''', pp.&nbsp;1–26.</ref>  For examples the ''o''-nitrobenzylgroup ought be listed here.
[[File:Photodeprotection_is.svg|center|alt=Mechanism of photodeprotection of an o-nitrobenzyl ether and formation of an alcohol|frameless|440x440px]]
The rare double-layer protecting group is a protected protecting group, which exemplify high stability.