Editing Protecting group (section)

==Common protecting groups==

===Alcohol protecting groups===
The classical protecting groups for alcohols are [[ester]]s, deprotected by [[nucleophile]]s; [[Organosilanols|triorganosilyl]] [[Silyl ether|ethers]], deprotected by acids and fluoride ions; and [[Acetal|(hemi)acetals]], deprotected by weak acids.  In rarer cases, a carbon [[ether]] might be used.

The most important esters with common protecting-group use are the [[Acetate ester|acetate]], [[Benzoate ester|benzoate]], and [[pivalate ester]]s, for these exhibit differential removal.  Sterically hindered esters are less susceptible to nucleophilic attack:

: Chloroacetyl > acetyl > benzoyl > pivaloyl

[[File:Tms_protecting.svg|thumb|Trimethylsilyl chloride, activated with imidazole, protects a secondary alcohol]]
Triorganosilyl sources have quite variable prices, and the most economical is [[chlorotrimethylsilane]] (TMS-Cl), a [[Müller-Rochow synthesis|Direct Process]] byproduct. The trimethylsilyl ethers are also extremely sensitive to acid hydrolysis (for example [[silica gel]] suffices as a proton donator) and are consequently rarely used nowadays as protecting groups.

Aliphatic methyl ethers cleave with difficulty and only under drastic conditions, so that these are in general only used with quinonic phenols.  However, hemiacetals and acetals are much easier to cleave.  [[File:THPmeth.png|440x440px|alt=Protection of alcohol as tetrahydropyranyl ether followed by deprotection. Both steps require acid catalysts.|center|frameless]]

==== List ====
Esters:
* [[Acetyl]] (Ac) – Removed by acid or base (see [[Acetoxy group]]).
* [[Benzoyl]] (Bz) – Removed by acid or base, more stable than Ac group.
* [[Pivaloyl]] (Piv) – Removed by acid, base or reductant agents. It is substantially more stable than other acyl protecting groups.

Silyl ethers:
* {{Anchor|TBDMS}}[[Trimethylsilyl]] (TMS)&nbsp;— [[Potassium fluoride]], [[acetic acid]] or [[potassium carbonate]] in [[methanol]]<ref>P.J. Kocieński: ''Protecting Groups'', p.&nbsp;29.</ref> 
* [[Triethylsilyl group|Triethylsilyl]]&nbsp;— 10–100× stabler than a TMS group.<ref>P.J. Kocieński: ''Protecting Groups'', p.&nbsp;31.</ref>  Cleaved with trifluoroacetic acid in water/[[tetrahydrofuran]],<ref>Tod K Jones, Robert A. Reamer, Richard Desmond, Sander G. Mills: "Chemistry of tricarbonyl hemiketals and application of Evans technology to the total synthesis of the immunosuppressant (−)-FK-506", in: ''[[J. Am. Chem. Soc.]]'', '''1990''', ''112'', pp.&nbsp;2998–3017; [[doi:10.1021/ja00164a023]].</ref> acetic acid in water/tetrahydrofuran,<ref>Dieter Seebach, Hak-Fun Chow, Richard F.W. Jackson, Marius A. Sutter, Suvit Thaisrivongs, Jürg Zimmermann: "(+)-11,11{{prime}}-Di-O-methylelaiophylidene – preparation from elaiophylin and total synthesis from (R)-3-hydroxybutyrate and (S)-malate", in: ''[[Liebigs Ann. Chem.]]'', '''1986''', pp.&nbsp;1281–1308; [[doi:10.1002/jlac.198619860714]].</ref> or [[hydrogen fluoride]] in water or pyridine<ref>David A. Evans, Stephen W. Kaldor, Todd K. Jones, Jon Clardy, Thomas J. Stout: "Total synthesis of the macrolide antibiotic cytovaricin", in: ''[[J. Am. Chem. Soc.]]'', '''1990''', ''112'', pp.&nbsp;7001–7031; [[doi:10.1021/ja00175a038]].</ref>
* {{Anchor|TOM}}''tert''-Butyldimethylsilyl (TBDMS or TBS)&nbsp;— Cleaved with acetic acid in tetrahydrofuran/water,<ref>James A. Marshall, Richard Sedrani: "A convergent, highly stereoselective synthesis of a C-11-C-21 subunit of the macbecins", in: ''[[J. Org. Chem.]]'', '''1991''', ''56'', pp.&nbsp;5496–5498; [[doi:10.1021/jo00019a004]].</ref> Pyridinium tosylate in methanol,<ref name="JACS_1990_49913">James D. White, Motoji Kawasaki: "Total synthesis of (+)-[[latrunculin]] A", in: ''[[J. Am. Chem. Soc.]]'', '''1990''', ''112'', pp.&nbsp;4991–4993; [[doi:10.1021/ja00168a071]].</ref> trifluoroacetic acid in water,<ref>Morris J. Robins, Vicente Samano, Mark D. Johnson: "Nucleic acid-related compounds. 58. Periodinane oxidation, selective primary deprotection, and remarkably stereoselective reduction of tert-butyldimethylsilyl-protected ribonucleosides. Synthesis of 9-(β-D-xylofuranosyl)adenine or 3'-deuterioadenosine from adenosine", in: ''[[J. Org. Chem.]]'', '''1990''', ''55'', pp.&nbsp;410–412; [[doi:10.1021/jo00289a004]].</ref> hydrofluoric acid in [[acetonitrile]],<ref>R. Roger F. Newton, Derek P. Reynolds, Colin F. Webb, Stanley M. Roberts: "A short and efficient total synthesis of (±) prostaglandin D<sub>2</sub> methyl ester involving a new method for the cleavage of a dimethyl-t-butylsilyl ether", in: ''[[J. Chem. Soc., Perkin Trans. 1]]'', '''1981''', pp.&nbsp;2055–2058; [[doi:10.1039/P19810002055]].</ref> pyridinium fluoride in tetrahydrofuran,<ref>Kyriacos C. Nicolaou, R. A. Daines, T. K. Chakraborty: "Total synthesis of amphoteronolide B", in: ''[[J. Am. Chem. Soc.]]'', '''1987''', ''109'', pp.&nbsp;2208–2210; [[doi:10.1021/ja00241a063]].</ref> [[tetrabutylammonium fluoride]] in THF.<ref>Leo A. Paquette, Annette M. Doherty, Christopher M. Rayner: "Total synthesis of furanocembranolides. 1. Stereocontrolled preparation of key heterocyclic building blocks and assembly of a complete seco-pseudopterane framework", in: ''[[J. Am. Chem. Soc.]]'', '''1991''', ''109'', pp.&nbsp;3910–3926; [[doi:10.1021/ja00036a045]].</ref>  Commonly protects 2'-hydroxy function in [[oligonucleotide synthesis]]. 
* Triisopropylsilyl (TIPS) ethers)&nbsp;— Similar conditions to TBS but longer reaction times.<ref>P.J. Kocieński: ''Protecting Groups'', p.&nbsp;40.</ref>
* ''tert''{{Nbh}}Butyldiphenylsilyl (TBDPS)&nbsp;— Similar conditions to TBS but even longer reaction times (100–250× slower than TBS and 5–10× slower than TIPS)

Benzyl ethers:

*[[Benzyl]] (Bn)&nbsp;— Removed by [[hydrogenolysis]].<ref>P.J. Kocieński: ''Protecting Groups'', pp.&nbsp;46–49.</ref> Bn group is widely used in sugar and nucleoside chemistry.
* [[Trityl]] (triphenylmethyl, Tr)&nbsp;— Removed by acid<ref>Michel Bessodes, Dimitri Komiotis, Kostas Antonakis: "Rapid and selective detritylation of primary alcohols using formic acid", in: ''[[Tetrahedron Lett.]]'', '''1986''', ''27'', pp.&nbsp;579–580; [[doi:10.1016/S0040-4039(00)84045-9]].</ref><ref>B. Helferich: ''[[Carbonhydr. Chem. Biochem.]]'', '''1948''', ''3'', pp.&nbsp;79.</ref><ref>M.L. García, J. Pascual, L. Borràs, J.A. Andreu, E. Fos, D. Mauleón, G. Carganico, F. Arcamone: "Synthesis of new ether glycerophospholipids structurally related to modulator", in: ''[[Tetrahedron]]'', '''1991''', ''47'', pp.&nbsp;10023–10034; [[doi:10.1016/S0040-4020(01)96051-X]].</ref> and hydrogenolysis
* [[PMB ether|''p''-Methoxybenzyl ether]] (PMB)&nbsp;— Removed by acid, hydrogenolysis, or oxidation&nbsp;– commonly with [[2,3-Dichloro-5,6-dicyano-1,4-benzoquinone|DDQ]].<ref>Yuji Oikawa, Tadao Yoshioka, Osamu Yonemitsu: "Specific removal of o-methoxybenzyl protection by DDQ oxidation", in: ''[[Tetrahedron Lett.]]'', '''1982''', ''23'', pp.&nbsp;885–888; [[doi:10.1016/S0040-4039(00)86974-9]].</ref>
* ''p'',''m''{{Nbh}}Dimethoxybenzyl ether&nbsp;— Removed via oxidation with DDQ or ceric ammonium chloride<ref>See literature for ''p''{{nbh}}methoxybenzyl.</ref>

Acetals:
* [[Dimethoxytrityl]]{{Anchor|DMT}}, [bis-(4-methoxyphenyl)phenylmethyl] (DMT)&nbsp;— Removed by weak acid. DMT group is widely used for protection of 5'-hydroxy group in nucleosides, particularly in [[Oligonucleotide synthesis#Phosphoramidite building blocks|oligonucleotide synthesis]].
* Methoxytrityl [(4-methoxyphenyl)diphenylmethyl] (MMT) – Removed by acid and hydrogenolysis.
* [[Benzyloxymethyl group|Benzyloxymethyl]]&nbsp;— Comparable stability to MOM, MEM und SEM,<ref>P.J. Kocieński: ''Protecting Groups'', p.&nbsp;77.</ref> but also admits reductive removal: sodium in liquid ammonia,<ref>H. Nagaoka, W. Rutsch, G. Schmidt, H. Ito, M.R. Johnson, Y. Kishi: "Total synthesis of rifamycins. 1. Stereocontrolled synthesis of the aliphatic building block", in: ''[[J. Am. Chem. Soc.]]'', '''1980''', ''102'', pp.&nbsp;7962–7965; [[doi:10.1021/ja00547a037]].</ref><ref>W. Clark Still, Dominick Mobilio: "Synthesis of asperdiol", in: ''[[J. Org. Chem.]]'', '''1983''', ''48'', pp.&nbsp;4785–4786; [[doi:10.1021/jo00172a070]].</ref> catalytic hydrogenation (palladium hydroxide on activated carbon), or Raney nickel in ethanol<ref>Masahiro Hirama, Mitsuko Uei: "A chiral total synthesis of compactin", in: ''[[J. Am. Chem. Soc.]]'', '''1982''', ''104'', pp.&nbsp;4251–4253; [[doi:10.1021/ja00379a037]].</ref><ref>W. Clark Still, Shizuaki Murata, Gilbert Revial, Kazuo Yoshihara: "Synthesis of the cytotoxic germacranolide eucannabinolide", in: ''[[J. Am. Chem. Soc.]]'', '''1983''', ''105'', pp.&nbsp;625–627; [[doi:10.1021/ja00341a055]].</ref>
* Ethoxyethyl ethers (EE) – Cleavage more trivial than simple ethers e.g. 1N [[hydrochloric acid]]<ref>{{cite journal |last=Kamaya |first=Yasushi |author2=T Higuchi |year=2006 |title=Metabolism of 3,4-dimethoxycinnamyl alcohol and derivatives by Coriolus versicolor |journal=FEMS Microbiology Letters |volume=24 |issue=2–3 |pages=225–229 |doi=10.1111/j.1574-6968.1984.tb01309.x |doi-access=free}}</ref>
* [[2-Methoxyethoxymethyl chloride|Methoxyethoxymethyl ether]] (MEM)&nbsp;— Removed by hydrobromic acid in tetrahydrofuran<ref>Serge David, Annie Thieffry, Alain Veyrières: "A mild procedure for the regiospecific benzylation and allylation of polyhydroxy-compounds via their stannylene derivatives in non-polar solvents", in: ''[[J. Chem. Soc., Perkin Trans. 1]]'', '''1981''', pp.&nbsp;1796–1801; [[doi:10.1039/P19810001796]].</ref> or [[zinc bromide]] in dichloromethane<ref>Kaoru Fuji, Shigetoshi Nakano, Eiichi Fujita: "An Improved Method for Methoxymethylation of Alcohols under Mild Acidic Conditions", in: ''[[Synthesis (journal)|Synthesis]]'', '''1975''', pp.&nbsp;276–277.</ref>
* [[Methoxymethyl ether]] (MOM)&nbsp;— Removed by 6&nbsp;M hydrochloric acid in tetrahydrofuran/water<ref>Paul A. Wender, Carlos R. D. Correia: "Intramolecular photoinduced diene-diene cyaloadditions: a selective method for the synthesis of complex eight-membered rings and polyquinanes", in: ''[[J. Am. Chem. Soc.]]'', '''1987''', ''109'', pp.&nbsp;2523–2525; [[doi:10.1021/ja00242a053]].</ref>
* [[Tetrahydropyranyl]] (THP)&nbsp;— Removed by acetic acid in tetrahydrofuran/water,<ref>Karel F. Bernady, M. Brawner Floyd, John F. Poletto, Martin J. Weiss: "Prostaglandins and congeners. 20. Synthesis of prostaglandins via conjugate addition of lithium trans-1-alkenyltrialkylalanate reagents. A novel reagent for conjugate 1,4-additions", in: ''[[J. Org. Chem.]]'', '''1979''', ''44'', pp.&nbsp;1438–1447; [[doi:10.1021/jo01323a017]].</ref> ''p''{{nbh}}toluenesulfonic acid in methanol<ref>Elias J. Corey, Haruki Niwa, Jochen Knolle: "Total synthesis of (S)-12-hydroxy-5,8,14-cis,-10-trans-eicosatetraenoic acid (Samuelsson's HETE)", in: ''[[J. Am. Chem. Soc.]]'', '''1978''', ''100'', pp.&nbsp;1942–1943; [[doi:10.1021/ja00474a058]].</ref>
* [[Methylthiomethyl ether]]&nbsp;— Removed by acid{{Citation needed|date=February 2024}} or [[HSAB theory|soft]] metal oxidants: base-buffered [[Mercury(II) chloride|mercuric chloride]] in wet acetonitrile<ref>Elias J. Corey, Mark G. Bock: "Protection of primary hydroxyl groups as methylthiomethyl ethers", in: ''[[Tetrahedron Lett.]]'', '''1975''', ''16'', pp.&nbsp;3269–3270; [[doi:10.1016/S0040-4039(00)91422-9]].</ref> or [[silver nitrate]] in wet tetrahydrofuran<ref>Elias J. Corey, Duy H. Hua, Bai Chuan Pan, Steven P. Seitz: "Total synthesis of aplasmomycin", in: ''[[J. Am. Chem. Soc.]]'', '''1982''', ''104'', pp.&nbsp;6818–6820; [[doi:10.1021/ja00388a074]].</ref>
* Tris(isopropyl)silyloxymethyl (TOM)&nbsp;— Commonly protects 2'-hydroxy function in [[oligonucleotide synthesis]].
* [[(Trimethylsilyl)ethoxymethyl group|β{{nbh}}(Trimethylsilyl)ethoxymethyl]]&nbsp;— More labile than MEM and MOM to acid hydrolysis: 0.1&nbsp;M hydrochloric acid in methanol,<ref>Robert C. Gadwood, Renee M. Lett, Jane E. Wissinger: "Total synthesis of (±)-poitediol and (±)4-epipoitediol", in: ''[[J. Am. Chem. Soc.]]'', '''1984''', ''106'', pp.&nbsp;3869–3870; [[doi:10.1021/ja00325a032]].</ref> concentrated hydrofluoric acid in acetonitrile,<ref name="JACS_1990_49913"/> boron trifluoride etherate in dichloromethane,<ref>Steven D. Burke, Gregory J. Pacofsky: "The ester enolate claisen rearrangement. Total synthesis of (±)-ethisolide", in: ''[[Tetrahedron Lett.]]'', '''1986''', ''27'', pp.&nbsp;445–448; [[doi:10.1016/S0040-4039(00)85501-X]].</ref> or [[tetrabutylammonium fluoride]] in HMPT ([[Hexamethyl phosphoric acid triamide]]) or in tetrahydrofuran<ref>Toshiyuki Kan, Masaru Hashimoto, Mitsutoshi Yanagiya, Haruhisa Shirahama: "Effective deprotection of 2-(trimethylsilylethoxy)methylated alcohols (SEM ethers). Synthesis of thyrsiferyl-23 acetate", in: ''[[Tetrahedron Lett.]]'', '''1988''', ''29'', pp.&nbsp;5417–5418; [[doi:10.1016/S0040-4039(00)82883-X]].</ref><ref>Joseph P. Marino, Scott L. Dax: "An efficient desilylation method for the generation of o-quinone methides: application to the synthesis of (+)- and (−)-hexahydrocannabinol", in: ''[[J. Org. Chem.]]'', '''1984''', ''49'', pp.&nbsp;3671–3672; [[doi:10.1021/jo00193a051]].</ref>
Other ethers:
* ''p''-Methoxyphenyl ether (PMP) – Removed by oxidation.{{Citation needed|date=February 2024}}
* [[Butyl group#Tert-butyl as Protecting group|Tert-butyl ethers]] (tBu) – Removed with anhydrous trifluoroacetic acid, [[hydrogen bromide]] in acetic acid, or 4&nbsp;N hydrochloric acid<ref>P.J. Kocieński: ''Protecting Groups'', pp.&nbsp;59–60.</ref>
* [[Allyl group|Allyl]]&nbsp;— Removed with potassium ''tert''{{nbh}}butoxide<ref>P.J. Kocieński: ''Protecting Groups'', p.&nbsp;62.</ref> [[DABCO]] in methanol, palladium on activated carbon, or diverse platinum complexes – conjoined with acid workup.<ref>R.E. Ireland, D.W. Norbeck: "Convergent synthesis of polyether ionophore antibiotics: the synthesis of the monensin bis(tetrahydrofuran) via the Claisen rearrangement of an ester enolate with a β-leaving group", in: ''[[J. Am. Chem. Soc.]]'', '''1985''', ''107'', pp.&nbsp;3279–3285; [[doi:10.1021/ja00297a038]].</ref>
* Methyl ethers – Cleavage is by TMSI in dichloromethane or acetonitrile or chloroform. An alternative method to cleave methyl ethers is BBr<sub>3</sub> in DCM
* [[Tetrahydrofuran]] (THF){{Clarification needed|reason=Where does the ether attach?|date=February 2024}} – Removed by acid.

=== 1,2-Diols ===
The 1,2{{nbh}}diols ([[glycol]]s) present for protecting-group chemistry a special class of alcohols.  One can exploit the adjacency of two hydroxy groups, e.g. in [[sugars]], in that one protects both hydroxy groups codependently as an [[acetal]]. Common in this situation are the [[Benzyl group|benzylidene]], [[Isopropyl group|isopropylidene]] and [[Cyclohexyl group|cyclohexylidene]] or [[Cyclopentyl group|cyclopentylidene]] acetals.
[[File:Acetals_is.svg|alt=Applied acetal|center|400x400px]]
An exceptional case appears with the benzylideneprotecting group,which also admits reductive cleavage.  This proceeds either through catalytic hydrogenation or with the hydride donor [[Diisobutylaluminium hydride|diisobutyl aluminum hydride]] (DIBAL). The cleavage with DIBAL deprotects one alcohol group, for the benzyl moiety stays as a benzyl ether on the second, sterically hindered hydroxy group.<ref>András Lipták, János Imre, János Harangi, Pál Nánási, András Neszmélyi: "Chemo-, stereo- and regioselective hydrogenolysis of carbohydrate benzylidene acetals. Synthesis of benzyl ethers of benzyl α-D-, methyl β-D-mannopyranosides and benzyl α-D-rhamnopyranoside by ring cleavage of benzylidene derivatives with the LiAlH<sub>4</sub>-AlCl<sub>3</sub> reagent", in: ''[[Tetrahedron]]'', '''1982''', ''38'', pp.&nbsp;3721–3727; [[doi:10.1016/0040-4020(82)80083-5]].</ref><ref>James A. Marshall, Joseph D. Trometer, Bruce E. Blough, Thomas D. Crute: "Stereochemistry of SN2' additions to acyclic vinyloxiranes", in ''J. Org. Chem.'', '''1988''', ''53'', pp.&nbsp;4274–4282 [[doi:10.1021/jo00253a020]].</ref>
[[File:DIBAL_cleavage_of_benzylidenacetales_is.svg|alt=Cleaving a benzylidene acetal with DIBAL|center|400x400px]]

===Amine protecting groups===
[[File:Tert-Butoxycarbonyl protected Glycine Structural Formulae V.1.png|thumb|250px|BOC [[glycine]]. The ''tert''-butyloxycarbonyl group is marked <span style="color:blue;">'''blue'''</span>.]]Amines have a special importance in [[peptide synthesis]], but are a quite potent [[nucleophile]] and also relatively strong [[Base (chem)|bases]].  These characteristics imply that new protecting groups for amines are always under development.<ref>P.J. Kocieński: ''Protecting Groups'', p.&nbsp;186.</ref>

[[Amine group]]s are primarily protected through [[acylation]], typically as a [[carbamate]].  When a carbamate deprotects, it evolves [[carbon dioxide]].  The commonest-used carbamates are the ''tert''-butoxycarbonyl, benzoxycarbonyl, fluorenylmethylenoxycarbonyl, and allyloxycarbonyl compounds.

Other, more exotic amine protectors are the [[phthalimide]]s, which admit reductive cleavage,<ref>John O. Osby, Michael G. Martin, Bruce Ganem: ''An Exceptionally Mild Deprotection of Phthalimides'', in: ''[[Tetrahedron Lett.]]'', '''1984''', ''25'', pp.&nbsp;2093–2096; [[doi:10.1016/S0040-4039(01)81169-2]].</ref> and the trifluoroacetamides, which hydrolyze easily in base.  [[Indole]]s, [[pyrrole]]s und [[imidazole]]s&nbsp;— verily any aza-heterocycle&nbsp;— admit protection as ''N''{{nbh}}sulfonylamides,which are far too stable with aliphatic amines.<ref>P.J. Kocieński: ''Protecting Groups'', pp.&nbsp;220–227.</ref>  ''N''{{nbh}}benzylated amines can be removed through [[catalytic hydrogenation]] or Birch reduction, but have a decided drawback relative to the carbamates or amides: they retain a basic nitrogen.

==== Selection ====
Carbamates:
* [[Carbamate]] group – Removed by acid and mild heating.
* [[Carboxybenzyl|Carbobenzyloxy]] (Cbz) group&nbsp;— Removed by [[hydrogenolysis]]: [[hydrogen]] and [[palladium]] on [[activated carbon]],<ref>P.J. Kocieński: ''Protecting Groups'', p.&nbsp;195.</ref> or lithium or sodium in liquid ammonia.<ref>Robert M. Williams, Peter J. Sinclair, Dongguan Zhai, Daimo Chen: "Practical asymmetric syntheses of α-amino acids through carbon-carbon bond constructions on electrophilic glycine templates", in: ''[[J. Am. Chem. Soc.]]'', '''1988''', ''110'', p.&nbsp;1547–1557; [[doi:10.1021/ja00213a031]].</ref>
* [[Methoxybenzyl|''p''-Methoxybenzyloxycarbonyl]] (Moz or MeOZ) group – Removed by [[hydrogenolysis]], more labile than Cbz
* [[Tert-butyloxycarbonyl protecting group|''tert''-Butyloxycarbonyl]] (Boc) group&nbsp;— Removed by concentrated strong acid (such as HCl<ref>Glenn L. Stahl, Roderich Walter, Clarck W. Smith: "General procedure for the synthesis of mono-N-acylated 1,6-diaminohexanes", in: ''[[J. Org. Chem.]]'', '''1978''', ''43'', pp.&nbsp;2285–2286; [[doi:10.1021/jo00405a045]].</ref> or CF<sub>3</sub>COOH<ref>Naomi Sakai, Yasufumi Ohfune: "Total synthesis of galantin I. Acid-catalyzed cyclization of galantinic acid", in: ''[[J. Am. Chem. Soc.]]'', '''1992''', ''114'', pp.&nbsp;998–1010; [[doi:10.1021/ja00029a031]].</ref>), or by heating to >80&nbsp;°C.  Common in [[solid phase peptide synthesis]].  
* 9-Fluorenylmethyloxycarbonyl ([[Fmoc]]) group&nbsp;— Removed by base, such as 20–50&nbsp;% [[piperidine]] in [[dimethylformamide]] (DMF)<ref>Weng C. Chan, Peter D. White: ''Fmoc Solid Phase Peptide Synthesis'', pp.&nbsp;27–30.</ref> or [[N-Methyl-2-pyrrolidone|''N''-Methyl-2-pyrrolidone]],<ref>Gregg B. Fields: [http://www.renyi.hu/~stipsicz/skin/PepsynthProt/Ch_2.pdf ''Methods for Removing the Fmoc Group.''] (PDF; 663&nbsp;kB) In: Michael W. Pennington, Ben M. Dunn (eds.): ''Peptide Synthesis Protocols''  volume 35, 1995, ISBN 978-0-89603-273-6, pp.&nbsp;17–27.</ref> or 50% [[morpholine]] in DMF for sensitive [[Glycoproteins|glycopeptides]].<ref>B. Liebe, H. Kunz: ''Festphasensynthese eines tumorassoziierten Sialyl-Tn-Antigen-Glycopeptids mit einer Partialsequenz aus dem "Tandem Repeat" des MUC-1-Mucins'' In: ''Angew. Chem.'' volume 109, 1997, pp.&nbsp;629–631 (in German).</ref><ref>ChemPep Inc.: [http://www.chempep.com/ChemPep-Fmoc-Solid-Phase-Peptide-Synthesis.htm ''Fmoc Solid Phase Peptide Synthesis.''] retrieved 16 November 2013.</ref>  Common in [[solid phase peptide synthesis]]
* [[Allyloxycarbonyl group|Allyloxycarbamate]] group&nbsp;— Removed with complexes of metals like palladium(0) or [[nickel]](0).<ref>P.J. Kocieński: ''Protecting Groups'', pp.&nbsp;199–201.</ref>  
Other amides:
* [[Acetyl]] ({{vanchor|Ac}}), [[Benzoyl]] ({{vanchor|Bz}}) groups&nbsp;&mdash; common in [[Oligonucleotide synthesis#Phosphoramidite building blocks|oligonucleotide synthesis]] for protection of N<sup>4</sup> in [[cytosine]] and N<sup>6</sup> in [[adenine]].  Removed by base, often aqueous or gaseous [[ammonia]] or [[methylamine]].  Too stable to readily remove from aliphatic amides.
* [[2,2,2-Trichloroethoxycarbonyl chloride|Troc]] (trichloroethyl chloroformate ) group – Removed by Zn insertion in the presence of acetic acid
* [[Tosyl]] (Ts) group – Removed by concentrated acid (HBr, H<sub>2</sub>SO<sub>4</sub>) & strong reducing agents ([[sodium]] in liquid [[ammonia]] or [[sodium naphthalenide]])
* Other sulfonamide ([[Nosyl]] & [[Nps group|Nps]]) groups&nbsp;— Removed by [[Samarium(II) iodide|samarium iodide]], [[thiophenol]] or other soft thiol nucleophiles, or [[tributyltin hydride]]<ref>{{cite journal |last=Moussa |first=Ziad |author2=D. Romo |year=2006 |title=Mild deprotection of primary N-(p-toluenesufonyl) amides with SmI<Sub>2</sub> following trifluoroacetylation |journal=[[Synlett]] |volume=2006 |issue=19 |pages=3294–3298 |doi=10.1055/s-2006-951530}}</ref>
Benzylamines:
* [[Benzyl]] (Bn) group – Removed by [[hydrogenolysis]]
* [[p-Methoxybenzyl|''p''-Methoxybenzyl]] (PMB) – Removed by [[hydrogenolysis]], more labile than benzyl
* [[3,4-Dimethoxybenzyl]] (DMPM) – Removed by [[hydrogenolysis]], more labile than ''p''-methoxybenzyl
* [[p-methoxyphenyl|''p''-Methoxyphenyl]] (PMP) group – Removed by [[ammonium cerium(IV) nitrate]] (CAN)

===Carbonyl protecting groups===
The most common protecting groups for carbonyls are acetals and typically cyclic acetals with diols.  The runners-up used are also cyclic acetals with 1,2{{nbh}}hydroxythiols or dithioglycols&nbsp;– the so-called ''O'',''S''– or ''S'',''S''-acetals.[[File:Ethylenglycol_is.svg|thumb|Ethylene glycol]]
[[File:1,3-Propanediol.svg|thumb|1,3{{nbh}}Propadiol]]
Overall, trans-acetalation plays a lesser role in forming protective acetals; they are formed as a rule from glycols through dehydration.  Normally a simple glycol like [[ethylene glycol]] or [[1,3-propadiol]] is used for acetalation.Modern variants also use glycols, but with the hydroxyl hydrogens replaced with a trimethylsilyl group.<ref>T. Tsunoda, M. Suzuki, R. Noyori: "A facile procedure for acetalization under aprotic conditions", in: ''[[Tetrahedron Lett.]]'', '''1980''', ''21'', pp.&nbsp;1357–1358; [[doi:10.1016/S0040-4039(00)74575-8]].</ref><ref>Juji Yoshimura, Shigeomi Horito, Hiroriobu Hashimoto: "Facile Synthesis of 2,3,4,6-Tetra-O-benzyl-D-glucopyranosylidene Acetals Using Trimethylsilyl Trifluoromethanesulfonate Catalyst", in: ''[[Chem. Lett.]]'', '''1981''', ''10'', pp.&nbsp;375–376; [[doi:10.1246/cl.1981.375]].</ref>

Acetals can be removed in acidic aqueous conditions.  For those ends, the mineral acids are appropriate acids.  [[Acetone]] is a common cosolvent, used to promote dissolution.  For a non-acidic cleavage technique, a [[palladium(II) chloride]] acetonitrile complex in acetone<ref>Bruce H. Lipshutz, Daniel Pollart, Joseph Monforte, Hiyoshizo Kotsuki: "Pd(II)-catalyzed acetal/ketal hydrolysis/exchange reactions", in: ''[[Tetrahedron Lett.]]'', '''1985''', ''26'', pp.&nbsp;705–708; [[doi:10.1016/S0040-4039(00)89114-5]].</ref> or [[iron(III) chloride]] on [[silica gel]] can be performed with workup in chloroform.<ref>Kwan Soo Kim, Yang Heon Song, Bong Ho Lee, Chi Sun Hahn: "Efficient and selective cleavage of acetals and ketals using ferric chloride adsorbed on silica gel", in: ''[[J. Org. Chem.]]'', '''1986''', ''51'', pp.&nbsp;404–407; [[doi:10.1021/jo00353a027]].</ref>

Cyclic acetals are very much more stable against acid hydrolysis than acyclic acetals.  Consequently acyclic acetals are used practically only when a very mild cleavage is required or when two different protected carbonyl groups must be differentiated in their liberation.<ref>P.J. Kocieński: ''Protecting Groups'', S.&nbsp;167–170.</ref>

Besides the ''O'',''O''-acetals, the ''S'',''O''- and ''S'',''S''-acetals also have an application, albeit scant, as carbonyl protecting groups too. [[Thiol]]s, which one begins with to form these acetals, have a very unpleasant stench and are poisonous, which severely limit their applications. [[Thioacetal]]s and the mixed ''S'',''O''-acetals are, unlike the pure ''O'',''O''-acetals, very much stabler against acid hydrolysis.  This enables the selective cleavage of the latter in the presence of [[sulfur]]-protected carbonyl groups.

The formation of ''S'',''S''-acetals normally follows analogously to the ''O'',''O''-acetals with acid catalysis from a dithiol and the carbonyl compound. Because of the greater stability of thioacetals, the equilibrium lies on the side of the acetal.  In contradistinction to the ''O'',''O''{{nbh}}acetal case, it is not needed to remove water from the reaction mixture in order to shift the equilibrium.<ref>P.J. Kocieński: ''Protecting Groups'', pp.&nbsp;176.</ref>

''S'',''O''-Acetals are hydrolyzed a factor of 10,000 times faster than the corresponding ''S'',''S''-acetals. Their formation follows analogously from the thioalcohol. Also their cleavage proceeds under similar conditions and predominantly through mercury(II) compounds in wet acetonitrile.<ref>P.J. Kocieński: ''Protecting Groups'', pp.&nbsp;178–180.</ref>

For aldehydes, a temporary protection of the carbonyl group the presence of ketones as [[hemiaminal]] ions is shown below. Here it is applied, that aldehydes are very much more activated carbonyls than ketones and that many addition reactions are reversible.<ref>Samuel J. Danishefsky, Nathan B. Mantlo, Dennis S. Yamashita, Gayle. Schulte: "Concise route to the calichemicin-esperamicin series: the crystal structure of an aglycone prototype", in: ''[[J. Am. Chem. Soc.]]'', '''1988''', ''110'', pp.&nbsp;6890–6891; [[doi:10.1021/ja00228a051]].</ref><ref>John N. Haseltine, Maria Paz Cabal, Nathan B. Mantlo, Nobuharu Iwasawa, Dennis S. Yamashita, Robert S. Coleman, Samuel J. Danishefsky, Gayle K. Schulte: "Total synthesis of calicheamicinone: new arrangements for actuation of the reductive cycloaromatization of aglycon congeners", in: ''[[J. Am. Chem. Soc.]]'', '''1991''', ''113'', pp.&nbsp;3850–3866; [[doi:10.1021/ja00010a030]].</ref>
[[File:Danishefsky_endiine.svg|alt=Temporary protection of an aldehyde|center|500x500px]]

==== Types of protectants ====
* [[Acetal]]s and [[Ketal]]s – Removed by acid. Normally, the cleavage of acyclic acetals is easier than of cyclic acetals.
* [[Acylal]]s – Removed by [[Lewis acid]]s.
* [[Dithiane]]s – Removed by metal salts or oxidizing agents.

===Carboxylic acid protecting groups===
The most important protecting groups for [[carboxylic acid]]s are the esters of various alcohols.  Occasionally, esters are protected as ortho-esters or [[oxazoline]]s.<ref>P.J. Kocieński: ''Protecting Groups'', pp.&nbsp;119.</ref>

Many groups can suffice for the alcoholic component, and the specific cleaving conditions are contrariwise generally quite similar: each ester can be hydrolyzed in a basic water-alcohol solution. Instead, most ester protecting groups vary in how mildly they can be formed from the original acid.

==== Protecting groups ====
* [[Methyl]] [[esters]]&nbsp;— Also removed by acid{{Citation needed|date=February 2024}} or [[pig liver esterase]].<ref>Peter Mohr, Nada Waespe-Šarčević, Christoph Tamm, Krystyna Gawronska, Jacek K. Gawronski: "A Study of Stereoselective Hydrolysis of Symmetrical Diesters with Pig Liver Esterase", in: ''[[Helv. Chim. Acta]]'', '''1983''', ''66'', pp.&nbsp;2501–2511; [[doi:10.1002/hlca.19830660815]].</ref><ref>Théophile Tschamber, Nada Waespe-Šarčević, Christoph Tamm: "Stereocontrolled Synthesis of an Epimer of the C(19)-to-C(27) Segment of Rifamycin S", in: ''[[Helv. Chim. Acta]]'', '''1986''', ''69'', pp.&nbsp;621–625; [[doi:10.1002/hlca.19860690311]].</ref>  Can be formed from diazomethane in [[diethyl ether]],<ref>Yves Rubin, Carolyn B. Knobler, Francois Diederich: "Precursors to the cyclo[n]carbons: from 3,4-dialkynyl-3-cyclobutene-1,2-diones and 3,4-dialkynyl-3-cyclobutene-1,2-diols to cyclobutenodehydroannulenes and higher oxides of carbon", in: ''[[J. Am. Chem. Soc.]]'', '''1990''', ''112'', pp.&nbsp;1607–1617; [[doi:10.1021/ja00160a047]].</ref><ref>Sunggak Kim, Yong Gil Kim, Deog-il Kim: "A novel method for selective dioxolanation of ketones in the presence of aldehydes", in: ''[[Tetrahedron Lett.]]'', '''1992''', ''33'', pp.&nbsp;2565–2566; [[doi:10.1016/S0040-4039(00)92243-3]].</ref><ref>G. Bauduin, D. Bondon, Y. Pietrasanta, B. Pucci: "Reactions de transcetalisation – II: Influence des facteurs steriques et electroniques sur les energies de cetalisation", in: ''[[Tetrahedron]]'', '''1978''', ''34'', pp.&nbsp;3269–3274; [[doi:10.1016/0040-4020(78)80243-9]].</ref> [[caesium carbonate]] and methyl iodide in ''N'',''N''{{nbh}}dimethylformamide,<ref>John E. McMurry, Stephen J. Isser: "Total synthesis of longifolene", in: ''[[J. Am. Chem. Soc.]]'', '''1972''', ''94'', pp.&nbsp;7132–7137; [[doi:10.1021/ja00775a044]].</ref> or methanol and catalytic trimethylsilyl chloride<ref>M.P. Bosch, M. Pilar Bosch, Francisco Camps, Jose Coll, Angel Guerrero, Toshio Tatsuoka, Jerrold Meinwald: "A stereoselective total synthesis of (±)-muzigadial", in: ''[[J. Org. Chem.]]'', '''1986''', ''51'', pp.&nbsp;773–784; [[doi:10.1021/jo00356a002]].</ref>
* [[Benzyl]] esters&nbsp;— Also removed by hydrogenolysis.<ref>F. Zymalkokowski: ''Katalytische Hydrierung'', Ferdinand Enke Verlag, Stuttgart 1965, pp.&nbsp;127–133.</ref>
* [[Benzhydryl compounds|Benzhydryl]] esters&nbsp;— Same as benzyl, but easier to cleave<ref>P.J. Kocieński: ''Protecting Groups'', pp.&nbsp;136.</ref>
* [[tert-Butyl|''tert''-Butyl]] esters – Also removed by acid<ref>Ulrich Schmidt, Thomas Beuttler, Albrecht Lieberknecht, Helmut Griesser: "Aminosäuren und peptide – XXXXII. Synthese von Chlamydocin + epi-Chlamydocin", in: ''[[Tetrahedron Lett.]]'', '''1983''', ''24'', pp.&nbsp;3573–3576; [[doi:10.1016/S0040-4039(00)88171-X]] (in German).</ref><ref>Elias J. Corey, Plato A. Magriotis: "Total synthesis and absolute configuration of 7,20-diisocyanoadociane", in: ''[[J. Am. Chem. Soc.]]'', '''1987''', ''109'', pp.&nbsp;287–289; [[doi:10.1021/ja00235a052]].</ref> and some reductants.  Can be formed from [[carboalkoxylation]]: isobutene in dioxane and catalytic sulfuric acid<ref>Elias J. Corey, Kyriacos C. Nicolaou, Takeshi Toru: "Total synthesis of (±)-vermiculine", in: ''[[J. Am. Chem. Soc.]]'', '''1975''', ''97'', pp.&nbsp;2287–2288; [[doi:10.1021/ja00841a058]].</ref><ref>Tainejiro Hiyama, Akihiro Kanakura, Hajime Yamamoto, Hitosi Nozaki: "General Route to α,β-unsaturated Aldehydes of Homoterpenoid and terpenoid Structure. Sythesis of JH-II and β-Sinensal", in: ''[[Tetrahedron Lett.]]'', '''1978''', ''19'', pp.&nbsp;3051–3054; [[doi:10.1016/S0040-4039(01)94936-6]].</ref><ref>F. Huet, A. Lechevallier, M. Pellet, J.M. Conia: "Wet Silica Gel; A Convenient Reagent for Deacetalization", in: ''[[Synthesis (journal)|Synthesis]]'', '''1978''', pp.&nbsp;63–64.</ref>
* 2,6{{Nbh}}Dialkylphenols (e.g. [[2,6-Xylenol|2,6-dimethylphenol]], [[Propofol|2,6-diisopropylphenol]], [[2,6-di-tert-butylphenol|2,6-di-''tert''-butylphenol]])&nbsp;— Also removed in [[1,8-Diazabicycloundec-7-ene|DBU]]-catalyzed high-pressure methanolysis at room temperature.<ref>{{cite journal | author = Romanski | title = High-pressure transesterification of sterically hindered esters | journal = [[Tetrahedron Lett.]] | volume = 53 | issue = 39 | pages = 5287–5289 |date=Sep 2012 | doi = 10.1016/j.tetlet.2012.07.094 |first = J.|last2 = Nowak|first2 = P.|last3 = Kosinski|first3 = K.|last4 = Jurczak|first4 = J.|doi-access = free }}</ref>
* Allyl esters&nbsp;— As with allyl ethers, also removed by diverse platinum complexes&nbsp;– connected with acid workup<ref>P.J. Kocieński: ''Protecting Groups'', pp.&nbsp;139–142.</ref>
* [[Silyl]] esters – Also removed by base and [[organometallic]] reagents.
* [[Orthoesters]] – Converted to standard ester by mild aqueous acid
* [[Oxazoline]] – Removed by strong hot acid (pH < 1, T > 100&nbsp;°C) or alkali (pH > 12, T > 100&nbsp;°C), but not e.g. [[Lithium aluminium hydride|LiAlH<sub>4</sub>]], [[organolithium reagent]]s or [[Grignard reagent|Grignard (organomagnesium) reagents]]

=== Alkene ===
Alkenes rarely need protection or are protected. They are as a rule only involved in undesired side reactions with [[Electrophile|electrophilic]] attack, [[isomerization]] or catalytic hydration. For alkenes two protecting groups are basically known:

* Temporary halogenation with bromine to a ''trans''{{nbh}}1,2{{nbh}}dibromoalkane: the regeneration of the alkene then follows with preservation of conformation via elemental [[zinc]]<ref>Ahmed M. Tafesh, Jens Weiguny: "A Review of the Selective Catalytic Reduction of Aromatic Nitro Compounds into Aromatic Amines, Isocyanates, Carbamates, and Ureas Using CO", in: ''[[Chem. Rev.]]'', '''1996''', ''96'', pp.&nbsp;2035–2052; [[doi:10.1021/cr950083f]].</ref><ref>Evan L. Allred, Boyd R. Beck, Kent J. Voorhees: "Formation of carbon-carbon double bonds by the reaction of vicinal dihalides with sodium in ammonia", in: ''[[J. Org. Chem.]]'', '''1974''', ''39'', pp.&nbsp;1426–1427; [[doi:10.1021/jo00926a024]].</ref><ref>Timothy S. Butcher, Feng Zhou, Michael R. Detty: "Debrominations of vic-Dibromides with Diorganotellurides. 1. Stereoselectivity, Relative Rates, and Mechanistic Implications", in: ''[[J. Org. Chem.]]'', '''1998''', ''63'', pp.&nbsp;169–176; [[doi:10.1021/jo9713363]].</ref><ref>C. J. Li, David N. Harpp: "Bis(triphenylstanyl)telluride a mild and selective reagent for telluration and debromination", in: ''[[Tetrahedron Lett.]]'', '''1990''', ''31'', pp.&nbsp;6291–6293; [[doi:10.1016/S0040-4039(00)97045-X]].</ref><ref>Corrado Malanga, Serena Mannucci, Luciano Lardicci: "Carbon-halogen bond activation by nickel catalyst: Synthesis of alkenes, from 1,2-dihalides", in: ''[[Tetrahedron]]'', '''1998''', ''54'', pp.&nbsp;1021–1028; [[doi:10.1016/S0040-4020(97)10203-4]].</ref> or with [[titanocene dichloride]].<ref>Byung Woo Yoo, Seo Hee Kim, Jun Ho Kim: "A Mild, Efficient, and Selective Debromination of vic-Dibromides to Alkenes with Cp<sub>2</sub>TiCl<sub>2</sub>/Ga System", in: ''[[Bull. Korean Chem. Soc.]]'', '''2010''', ''31'', pp.&nbsp;2757–2758; [[doi:10.5012/bkcs.2010.31.10.2757]].</ref>
* Protection through a [[Diels-Alder reaction]]: the transformation of an alkene with a diene leads to a cyclic alkene, which is nevertheless similarly endangered by electrophilic attack as the original alkene. The cleavage of a protecting diene proceeds thermically, for the Diels-Alder reaction is a reversible (equilibrium) reaction.<ref>Antonius J. H. Klunder, Jie Zhu, Binne Zwanenburg: "The Concept of Transient Chirality in the Stereoselective Synthesis of Functionalized Cycloalkenes Applying the Retro-Diels-Alder Methodology", in: ''[[Chem. Rev.]]'', '''1999''', ''99'', pp.&nbsp;1163–1190; [[doi:10.1021/cr9803840]].</ref><ref>Hideyuki Tanaka, Takashi Kamikubo, Naoyuki Yoshida, Hideki Sakagami, Takahiko Taniguchi, Kunio Ogasawara: "Enantio- and Diastereocontrolled Synthesis of (−)-Iridolactone and (+)-Pedicularis-lactone", in: ''[[Org. Lett.]]'', '''2001''', ''3'', pp.&nbsp;679–681; [[doi:10.1021/ol0070029]].</ref><ref>Martin Banwell, David Hockless, Bevyn Jarrott, Brian Kelly, Andrew Knill, Robert Longmore, Gregory Simpson: "Chemoenzymatic approaches to the decahydro-as-indacene cores associated with the spinosyn class of insecticide", in: ''[[J. Chem. Soc., Perkin Trans. 1]]'', '''2000''', pp.&nbsp;3555–3558; [[doi:10.1039/b006759h]].</ref>

[[File:Alkene_protecting_groups_is.svg|alt=Schemata of alkene protecting groups|center|400x400px]]

===Phosphate protecting groups===
* 2-cyanoethyl{{Anchor|CNEt}} – removed by mild base. The group is widely used in [[Oligonucleotide synthesis#Phosphoramidite building blocks|oligonucleotide synthesis]].
* [[Methyl]] (Me){{Anchor|Me}} – removed by strong nucleophiles ''e.c''. thiophenole/TEA.

===Terminal alkyne protecting groups===
For alkynes there are in any case two types of protecting groups. For terminal alkynes it is sometimes important to mask the acidic hydrogen atom. This normally proceeds from deprotonation (via a strong base like [[methylmagnesium bromide]] or [[butyllithium]] in tetrahydrofuran/[[dimethylsulfoxide]]) and subsequently reaction with chlorotrimethylsilane to a terminally TMS-protected alkyne.<ref>{{Cite book |last1=Clayden |first1=Jonathan |url=https://archive.org/details/organicchemistry00clay_0/page/1291 |title=Organic Chemistry |last2=Greeves |first2=Nick |last3=Warren |first3=Stuart |last4=Wothers |first4=Peter |publisher=[[Oxford University Press]] |year=2000 |isbn=978-0-19-850346-0 |pages=[https://archive.org/details/organicchemistry00clay_0/page/1291 1291] |url-access=registration}}</ref> Cleavage follows hydrolytically&nbsp;– with potassium carbonate in methanol&nbsp;– or with fluoride ions like for example with [[tetrabutylammonium fluoride]].<ref>Wenzel E. Davidsohn, Malcolm C. Henry: "Organometallic Acetylenes of the Main Groups III–V", in: ''[[Chem. Rev.]]'', '''1967''', ''67'', pp.&nbsp;73–106; [[doi:10.1021/cr60245a003]].</ref>
[[File:Alkin_tms_is.svg|center|500x500px|Alkyne TMS protection]]
In order to protect the triple bond itself, sometimes a transition metal-alkyne complex with [[dicobalt octacarbonyl]] is used. The release of the cobalt then follows from oxidation.<ref>Barry J. Teobald: "The Nicholas reaction: the use of dicobalt hexacarbonyl-stabilised propargylic cations in synthesis", in: ''[[Tetrahedron]]'', '''2002''', ''58'', pp.&nbsp;4133–4170; [[doi:10.1016/S0040-4020(02)00315-0]].</ref><ref>Kenneth M. Nicholas, R. Pettit: "An alkyne protection group", in: ''[[Tetrahedron Lett.]]'', '''1971''', ''37'', pp.&nbsp;3475–3478; [[doi:10.1016/S0040-4039(01)97209-0]].</ref><ref>Richard E. Connor, Kenneth M. Nicholas: "Isolation, characterization, and stability of α-[(ethynyl)dicobalt hexacarbonyl] carbonium ions", in: ''[[J. Organomet. Chem.]]'', '''1977''', ''125'', C45–C48; [[doi:10.1016/S0022-328X(00)89454-1]].</ref><ref>Rosa F. Lockwood, Kenneth M. Nicholas: "Transition metal-stabilized carbenium ions as synthetic intermediates. I. α-[(alkynyl)dicobalt hexacarbonyl] carbenium ions as propargylating agents", in: ''[[Tetrahedron Lett.]]'', '''1977''', pp.&nbsp;4163–4166; [[doi:10.1016/S0040-4039(01)83455-9]].</ref><ref>K.M. Nicholas, R. Pettit: "On the stability of α-(alkynyl)dicobalt hexacarbonyl carbonium ions", in: ''[[J. Organomet. Chem.]]'', '''1972''', ''44'', C21–C24; [[doi:10.1016/0022-328X(72)80037-8]].</ref>
===Other===
<ul>
<li>

[[Photolabile Protecting Groups|Photolabile protecting groups]]

As a [[proof of concept]] orthogonal deprotection is demonstrated in a [[photochemical]] [[transesterification]] by [[trimethylsilyldiazomethane]] utilizing the [[kinetic isotope effect]]:<ref>{{Cite journal |last1=Blanc |first1=Aurélien |last2=Bochet |first2=Christian G. |date=2007 |title=Isotope Effects in Photochemistry: Application to Chromatic Orthogonality |url=http://doc.rero.ch/record/8583/files/bochet_iep.pdf |journal=[[Org. Lett.]] |volume=9 |issue=14 |pages=2649–2651 |doi=10.1021/ol070820h |pmid=17555322}}</ref>  [[Image:OrthogonalprotectionApplicationInPhotochemistry.png|upright=1.35|center|frameless|Orthogonal protection Application in Photochemistry]]  Due to this effect the [[quantum yield]] for deprotection of the right-side ester group is reduced and it stays intact. Significantly by placing the deuterium atoms next to the left-side ester group or by changing the wavelength to 254&nbsp;nm the other monoarene is obtained.

</li>
</ul>