PROTECTING GROUPS IN ORGANIC SYNTHESIS

1 PROTECTING GROUPS IN ORGANIC SYNTHESIS1 Challenges in ORGANIC :56 PMProtecting GROUPS : A Necessary Evil3 Note,however, :56 PMProtecting GROUPS in ORGANIC SynthesisWhat is a PROTECTING group?Aprotectinggroup(PG)isamolecularfr ameworkthatisintroducedontoaspecificfunc tionalgroup(FG) :56 PMQualities of a Good PROTECTING Group in ORGANIC Synthesis5 Agoodprotectinggroupshouldbesuchthat:(a) Itshouldbereadily,butselectivelyintroduc edtothedesiredfunctionalgroupinapoly-fun ctionalmolecule.(b)Itshouldbestable/resi stanttothereagentsemployedinsubsequentre actionstepsinwhichthegroupbeingmasked(pr otected)isdesiredtoremaindeactivated(pro tected).

2 (c) :56 PMProtecting GROUPS in ORGANIC :56 PMProtecting GROUPS for :(a)Silylether PROTECTING GROUPS (b) Acetalprotecting groupsThese protections replace the acidic proton on an alcohol with an unreactive ether GROUPS for AlcoholsFormation81:56 PMProtecting GROUPS for AlcoholsExampleTert-Butyldimethylsilyl ethers (TBDMS)91:56 PMProtecting GROUPS for Alcohols(SilylProtecting GROUPS )CleavageFluoride sources:Tetrabutylammonium fluoride, Bu4N+F-(TBAF)Pyridine-HFHydrofluoric acid (HF)Ammonium fluoride NH4+F-101:56 PMProtecting GROUPS for Alcohols(SilylProtecting GROUPS )Synthetic Applications of Silyl PROTECTING Groups111:56 GROUPS for Alcohols(SilylProtecting GROUPS )Synthetic Applications of Silyl PROTECTING :56 PMProtecting GROUPS for Alcohols(Benzyl ether PROTECTING GROUPS )FormationCleavage151.

3 56 PMRarelyarealkylethersusedasprotectinggr oupsforalcohols, GROUPS for Alcohols(Cyclic AcetalProtecting GROUPS )FormationCleavageAcetonide PROTECTING GROUPS for 1,2-DiolsROHOHR+OOORRC onditions(a) Acid catalysed hydrolysis H+, H2O(b) AcOH / H2O161:56 PMProtecting GROUPS for Alcohols(Perspectives on their Synthetic Applications)Synthetic Applications of Ether PROTECTING Groups171:56 PMProtecting GROUPS for Alcohols(Perspectives on their Synthetic Applications)Synthetic Applications of Cyclic Acetal PROTECTING Groups181:56 PMProtecting GROUPS for Aldehydesand Ketones(Acetaland KetalProtecting GROUPS )FormationCleavageAcetalProtecting GroupAcid catalysed hydrolysis (dilute HCl or AcOH / H2O or TFA/ H2O or p-TsOH in acetone) can be :56 PMProtecting GROUPS for Aldehydes& Ketones(Acetaland KetalProtecting GROUPS )SyntheticApplicationsoftheAcetalP rotectingGroup20 Becauseofresonancestabilization,thecarbo nylofthea.

4 56 PMProtecting GROUPS for Carboxylic Acids (Esters)FormationCleavageMethylEstersRCO 2 HRCOCH3O+CH3 OHLiOHH2O221 Thecommonesterprotectinggroupsforcarboxy licacidsaremethyl, :56 PMProtecting GROUPS for Carboxylic Acids (Esters)Ethyl and benzyl esters are prepared based on the following rationale:22 Best approach:1:56 PMProtecting GROUPS for Carboxylic Acids (Esters)Mechanism of DCC coupling231:56 PMProtecting GROUPS for Carboxylic Acids (Esters)FormationCleavageEthylEsters241: 56 PMProtecting GROUPS for Carboxylic Acids (Esters)FormationCleavageByhydrogenolysi s:Averymildmethodformostfunctionalgroups exceptwithalkenes, +PhCH3H2Pd / C251:56 PMProtecting GROUPS for Amino GROUPS (CarbamateProtecting GROUPS )FormationTert-ButyloxycarbonylPro tectingGroup(BOC)261:56 PMExampleProtecting GROUPS for Amino GROUPS (CarbamateProtecting GROUPS )CleavageTert-ButyloxycarbonylProt ectingGroup(BOC)271:56 PMProtecting GROUPS for Amino GROUPS (CarbamateProtecting GROUPS )FormationCleavageBenzyloxycarbony lProtectingGroup(CBZ)281.

5 56 PMProtecting GROUPS for Carboxylic Acids(Ester PROTECTING GROUPS ) :56 PM