Protectinggroups

Protecting Groups
Krishna P. Kaliappan
Department of Chemistry
Indian Institute of Technology-Bombay
Mumbai 400 076 INDIA
http://www.chem.iitb.ac.in/~kpk
kpk@chem.iitb.ac.in
10/26/20 CH (401) slides should not be used for commercial purposes

Protecting Groups
What are protecting groups?
Groups, which are temporarily attached to a functional group
Make these functional groups not to react under certain reaction
conditions in subsequent steps.
Cleaved after its job is done
Why do you need protecting groups?
When a molecule has more than one functional group, then there is a
likely possibility that functional groups interfering with each other
while carrying out a reaction.
When principles of selectivity can’t be applied, then protection of one

functional group is really necessary to carry out a reaction on the
other functional group.
CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 2

Protecting Groups
Why do you need protecting groups?
O O
CO2Et CH2OH
O O
O O
CO2Et CH2OH

Protecting Groups
Drawbacks
1. Two additional steps are required.
2. One for the introduction of the protecting group and the other for
removing it.
3. So, more the number or protecting groups in your synthetic

scheme, more the number of steps.
The best protecting group is “NO PROTECTING GROUP”

Protecting Groups
What is orthogonal protecting group strategy?
When more than one functional group of similar type, with very little
difference in terms of reactivity, present in the molecule, selective
protection of one can be achieved in the presence of other by taking
advantage of steric effects, stereoelectronic effects etc.,
The development of such orthogonal protecting group strategies

makes it possible to remove one set of protecting groups, in any
order, using reagents and conditions that do not affect the protecting
groups in other sets.
This orthogonal protecting group strategy is regularly utilized in the

synthesis oligosaccharides where more number of hydroxyl groups
with subtle difference in reactivity are present.

Protecting Groups
Types of Protecting Groups
Permanent: These are stable protecting groups, survives many steps

in a long synthetic route (early introduction & late removal). These
protecting groups are used for functional groups which require no
manipulation for most of the steps
Temporary: These protecting groups (as the name suggests) should be

selectively installed and removed as and when required without
affecting the permanent protecting groups.

Protecting Groups
Criteria for selecting protecting groups
Should be cheap & commercially available
Should be easily introduced under milder conditions
Should not create any additional stereocenters
Should be stable throughout the reaction, work up and purification
Should be easily removed under milder conditions
Byproducts should be easily separated from the required product

Functional Groups
Hydroxy
Functional
Groups
Carbonyl Amines

Hydroxyl Group
Primary
Phenols Secondary
Hydroxyl
DIols Tertiary

Carbonyl Group
Carboxylic acids
Carbonyl
Aldehydes Ketones

Amines
Aliphatic Primary
Amines
Aliphatic Secondary Aromatic

Protecting Groups for Alcohols
12
PG for Alcohols
Introduction of protecting groups
R O H + X PG R O PG + HX
Removal of protecting groups
R O PG + HY R O H + Y PG

PG for Alcohols
Alkyl Ethers
Silyl Ethers Alcohols Benzyl Ethers
Esters

PG for Alcohols
ROMe, ROMOM, ROMEM, ROBOM, ROTHP, ROEE
Alkyl
ethers
ROBn, ROPMB ROTr

RONAP, ROMeTr, Benzyl Esters ROAc, ROAcCl, ROBz,
Alcohols
RO-o-NO2Bn, ethers ROPiv, ROCOCF3
RO-p-NO2Bn,
Silyl
ethers
ROTMS, ROTES ROTIPS, ROTBS, ROTBDPS

Alkyl Ethers
Methyl Ether
EE Ether MOM Ether
Alkyl
Ethers
THP Ether MEM Ether
BOM Ether

Benzyl Ethers
Benzyl Ether
o-NO2Bn Ether PMB Ether
Benzyl
Ethers
OMe-Tr Ether NAP Ether
Tr Ether

Silyl Ethers
TMS Ether
TBDPS Ether TES Ether
Silyl
Ethers
TBDMS Ether TIPS Ether
IPDMS Ether

Esters
Acetate
Pivalate ester Chloroacetate
Esters
Trifluoroacetate Dichloroacetate
Trichloroacetate

Esters
Benzoate
Troc Boc
Esters
Alloc CBz
Fmoc

1,2-Diols
Acetonide
Cyclic carbonate Cycloalkylidene
1,2-Diols
Di-t-Butylsilylene Benzylidene
p-Methoxybenzylidene

Alkylethers
NaH, MeI, THF
OR
Ag2O, MeI NaH, CH3OCH2Cl, THF
OR OR
CH2N2 (Phenols) DIEPA, CH3OCH2Cl, THF

ROMe Alcohols ROMOM
BBr3, DCM HCl, THF
OR OR
HCl, ROH AcCl, EtOH
OR
TMSCl/NaI
Difficult to cleave except for phenols

Alkylethers
Benzyloxymethyl ether (BOM)

NaH, CH3OCH2CH2OCH2Cl, THF
OR
DIPEA, PhCH2OCH2Cl, DCM
DIPEA, CH3OCH2CH2OCH2Cl, THF
ROBOM Alcohols ROMEM

H2, Pd-C, EtOH ZnBr2
OR OR
Li, Liq. NH3 TiCl4

Alkylethers
, PPTS, DCM
O O , PTSA, DCM
ROTHP Alcohols ROEE
PPTS, EtOH PPTS, EtOH
OR OR
Amberlyst H-15, MeOH Amberlyst H-15, MeOH
Creates one more chiral center

Benzylethers
NaH, BnBr, THF
OR
KH, BnCl, THF NaH, PMBCl, THF
OR OR
NH NH
Cl3C OBn , CSA Cl3C OPMB , CSA

ROBn Alcohols ROPMB
H2, Pd-C, EtOH H2, Pd-C, EtOH

OR OR
Li, Liq. NH3 Li, Liq. NH3
OR OR
BBr3, DCM DDQ, MeOH

OR
Benzyl ethers are stable
CAN, MeOH

PMB ethers
NaH, THF
RO
ROH OMe
Cl
MeO
PMP
OH OPMB DDQ O O
R DCM, MS
R
CAN DIBAL-H
OR
DDQ
PMBO OH
OH OH
R
R

Benzyl Ethers
Selective for primary alcohols
Highly sensitive to acid

2-Naphthylmethyl ether (NAP)
Cl
NaH, , THF
Ph3CCl, Et3N, THF
RONAP Alcohols ROTr

H2, Pd-C, EtOH Mild Acid R1
OR
Li, Liq. NH3
NAP ethers could be cleaved R2 Tr

selectively in the presence of Bn
ethers
R3
Nitrobenzyl ethers
o-Nitrobenzyl ethers p-Nitrobenzyl ethers
Cl Cl
NaH, , THF NaH, , THF
NO2 O2N
RO-oNb Alcohols RO-pNb
Photolysis @ 320nm H2/Pd-C

OR
DDQ
OR
Electrochemical
o-Nitrobenzyl ethers are cleaved conditions
under photochemical conditions

Protection of Phenols
Most of the protecting groups used for alcohols are applicable for
phenols.
Common phenolic protecting groups are:
OMe OtBu O OBn
Methylether t-Butylether Allylether Benzylether
R1 O O
R2
Si R
O R3 O R O O O OR
Silylethers Phenyl Phenyl

esters carbonates Acetals

Methyl Ethers
Protection
NaOH, Me2SO4
OH OR OMe
K2CO3, MeI
OR
CH2N2
Deprotection
BBr3, DCM
OMe OR OH
EtSNa, DMF
OR
TMSI
OR
HCl, MeOH

TMS and TES Ethers
TMS Ether TES Ether
Easy to introduce Easy to introduce
Used for transient protection More stable than TMS
Very labile to acid and water Selectively cleavable
TMSCl, Py, DMAP TESCl, Py, DMAP

OR OR
TMSCl, Im, DMAP, DCM TESCl, Im, DMAP, DCM
OR OR
TMSOTf, DIPEA, DCM TESOTf, DIPEA, DCM
ROTMS Alcohols ROTES
AcOH/H2O, 15 h
dil. Acid OR
F- source

TIPS and TBS Ethers
TIPS Ether TBS Ether
Easy to introduce Selective protection of 1o alcohols
More stable than TMS/TES Stable to base and mild acid
TBSOTf is a good reagent for 2o

alcohols
TIPSCl, Py, DMAP
TBDMSCl, Py, DMAP
OR OR
TIPSCl, Im, DMAP, DCM TBDMSCl, Im, DMAP, DCM
OR OR
TIPSOTf, DIPEA, DCM TBDMSOTf, DIPEA, DCM
Alcohols ROTBS
ROTIPS
AcOH/H2O, 15 h Fluorides like
OR TBAF, KF, HF.Py, CsF
F- source

TBDPS ethers
TBDPS Ether
Stable to base and acid
Selective for primary alcohols
TMS/TES/TIPS can be selectively removed in the presence of TBS/TBDPS
TBS can be selectively removed in the presence of TBDPS by acid

TBDPSCl, Py, DMAP
OR
TBDPSCl, Im, DMAP, DCM
OR
TBDPSOTf, DIPEA, DCM
Alcohols ROTBDPS
Fluorides like
TBAF, KF, HF.Py, CsF
Esters
O R1
R OH R
O
Formation: Activated acid, base, DMAP, solvent
Activated acid: Acid Chlorides, Anhydrides, Activating agents
Acid chloride: SOCl2, Oxalylchloride, PCl5
Activating agents: CDI, DCC, HOBT, NHS, PySSPy, Mukaiyama’s reagent

Acetates
O R1
R OH R
O
Properties: Stable to acid and mild base

Not compatible with strong nucleophiles
such as organometallic reagents
Formation: Ac2O, pyridine

Acetyl chloride, pyridine
Cleavage: K2CO3, MeOH, reflux KCN, EtOH, reflux

NH3, MeOH LiOH, THF, H2
Enzyme hydrolysis (Lipase)

Pivaloates
O C
R OH R
O
Properties: Selective for primary alcohols

Removed with mild bases
Formation: t-Butylacetyl chloride, Py

t-Butylacetic anhydride, Base
Cleavage: K2CO3, MeOH

LAH, Et2O

Chloroacetates
O
R OH R Cl
O
Properties: Removed with Zn dust or thiourea
Formation: Chloroacetyl chloride, Base
Cleavage: Zn dust
Thiourea

Trifluoroacetates
F
F
O
R OH R F
O
Properties: Removed with base
Formation: Trifluoroacetyl chloride, Base

Trifluoroacetic anhydride, Base

Benzoates
O
R OH R
O
Properties: More stable than acetates wrt hydrolysis
Formation: Benzoyl chloride, Base

Benzoyl cyanide, Base
Benzoic anhydride, Base

KCN, MeOH

Protecting Groups for Diols
40
1,2-Diols
R2 R3
OH Aldehyde or O O
R1
R Ketone, H+
OH R R1
Isopropylidenes (acetonides)
HO OH Acid O O
R1 R2 Acetone or
R1 R2
OMe OMe
or
OMe
Cleavage Mild aqueous acid
1,2-acetonide formation is usually favored over 1,3-acetonides

1,2-Diols
Cycloalkylidene ketals
n
HO OH Acid O O
R1 R2
or R1 R2
O O
Cyclopentylidenes are slightly easier to cleave than acetonides

Cyclohexylidenes are slightly harder to cleave than acetonides

1,2-Diols
Benzylidene acetals
Ph
HO OH
Acid O O
R1 R2 CH(OMe)2 CHO
R1 R2
or
Cleavage: Acid hydrolysis or hydrogenolysis
1,3-Benzylidene formation is usually favored over 1,2-Benzylidene
Benzylidenes are usually hydrogenolyed slower than benzyl ethers or

olefins

1,2 & 1,3-Diols
Benzylidene acetals & Acetonides
Ph
OH
PhCHO O
O
CH2OH ZnCl2
PhCHO
OH
CH2OH ZnCl2 O Ph
O
OH
Acetone TrO
TrO
O
PPTS, CuSO4 O OH
OH OH

1,2-Diols
p-Methoxybenzylidene acetals
Ph
HO OH
Acid O O
R1 R2 CH(OMe)2 CHO
R1 R2
or
OMe OMe
Cleavage: Acid hydrolysis or hydrogenolysis or DDQ or CAN
Hydrolyzed about 10 times faster than regular benzylidenes

Other Reactions
Ph
TiCl4 HO OBn
O O
NaCNBH3
MeO2C CO2Me
MeO2C CO2Me
O Br
O NBS
Ph O Ph O
O OMe O OMe
HO CH3CN HO
OH OH
PMP
OH OPMB DDQ PMBO OH
O O DIBAL-H
R DCM, MS R
R

1,2-Diols
Cyclic Carbonates
O
HO OH Im2CO O O
R1 R2
R1 R2
Formation: Im2CO or phosgene or triphosgene
Cleavage: Removed with bases

Protecting Groups for Carbonyls
48
PG’s for Aldehydes/Ketones
O O O O O O O O
R1 R2 R1 R2 R1 R2 R1 R2
Dimethyl 1,3-Dioxolane 1,3-Dioxane 2,2-Dimethyl

acetal 1,3-dioxane
S S S S O S
S S
R1 R2 R1 R2 R1 R2
R1 R2
S,S-Dimethyl 1,3-Dithiolane 1,3-Dithiane 1,3-Oxathiolane
thioacetal
Order of Reactivity
Aldehydes > acyclic ketones = cyclohexanones > cyclopentanones >
α,β-unsaturated ketones = α,α-substituted ketones > aromatic ketones
Dimethyl acetals/ketals
O
O O
R1 R2 R1 R2
Formation Cleavage
1. MeOH, Dry HCl 1. Acetone, PTSA
2. Sc(OTf)3, CH(OMe)3 2. TFA, CHCl3, H2O
MeO OMe
3. , PTSA
4. TMSOMe, TMSOTf, DCM

Dimethyl acetals/ketals
O
O
Acetone
O
D-Glucose
ZnCl2
HO O
O
MeO OMe
OH OH , DME O OH
HO O
OH O
SnCl2
OH OH OH O
TiCl4 OMe
O O O
MeOH, Et3N OMe

1,3-Dioxolones/1,3-Dioxanes
O
O O O O O O
R1 R2 R1 R2 R1 R2 R1 R2
Formation Cleavage
n
HO OH , Toluene, PTSA 1. Acetone, PPTS, H2O, Heat
n 2. 1M HCl, THF
TMSO OTMS , TMSOTf, DCM
3. Me2BBr, DCM, -78 oC
-78 oC

O O
O O
O O
HO OH OH OH
PTSA, Toluene PTSA, Toluene
O O
O
HO OH
O PTSA, Toluene O
Double bond increases the electron density at the carbonyl

carbon of the Ɑ,ℬ-unsaturated ketones
HO OH
O
O PTSA, Toluene
O

TMSO OTMS
O
O TMSOTf, DCM
-78 oC O
This procedure developed by Noyori, at lower temperature, the

double bond doesn’t migrate.
O H O O HO
O
HO OH
PTSA, Toluene
CH3 CH3
Steric hindrance could be used to selectively protect one of the

carbonyl groups

1,3-Dithiolones/1,3-Dithianes
HS SH
S
O BF3.OEt2, DCM
-20 oC S
Since thioacetals are quite stable towards hydrolysis, no need to

remove water from the reaction mixture.
Double bond migration is also not observed as this reaction is

done at a lower temperature
S S
TFA S
MeO S O
O
OHC
MeO O O
Selective removal of acetal is possible in the presence of

thioacetal

1,3-Dithiolones/1,3-Dithianes
Ra-Ni, H2
HgCl2, CaCO3 S
EtOH
O Acetone S
Cleavage of dithianes and dithiolanes:
Hg(ClO)4, MeOH, CHCl3, 25 oC

NBS, acetone, 0 oC
I2, DMSO
CAN, aq. CH3CN
m-CPBA, Ac2O
DDQ, aq. CH3CN

1,3-Dithioxolones/1,3-Dithianes
1,3-dioxolanes and 1,3-dioxanes can be readily converted into

1,3-dithiolanes and 1,3-dithianes
O O SH SH S S
BF3.Et2O

1,3-Dithioxolones/1,3-Dithianes
Fluoride cleavable ketal
O O
LiBF4
O O O
O
O
Me3Si
Base cleavable ketal
HO SO2Ph SO2Ph
O OH O
DBU, DCM
O O
R1 R2 pTSA R1 R2
R1 R2

PGs for Carboxylic Acids
O O O O
R O R O Ph
R OMe R O
tButyl Ester Phenyl Ester
Methyl Ester Allyl Ester
O O R O O NO2
R
Bn Si
R O R O R R O CCl3 R O
Benzyl Ester Silyl Ester Halo Ester o-Nitrobenzyl Ester
OR TMS
OR O O O N
R OR TMS R O
R O R O
Orthoester TMS ethyl
Ester SEM Ester 1,3-Oxzoline

PGs for Carboxylic Acids
1. Alkyl esters:
Formation: Fischer esterification (RCOOH + R’OH + H+)

Acid chloride + ROH, pyridine
t-Butyl esters: Isobutylene & acid
Methyl esters: Diazomethane
Cleavage: LiOH, THF, H2O

Enzyme hydrolysis
t-Butyl esters are cleaved with aq. acid
Bu2SnO, PhH, reflux

Alkyl Esters
DCC
BnOH OBn
OH
DCC O
O
Mitsunobu Reaction
EtOH, Ph3P OEt

OH
DEAD, Et2O O
O
H2SO4, Cat O
CO2H
OR O
1, MsCl, Py
2. tBuOH, Et3N
Aryl Esters
Due to steric hindrance, BHT and BHA do not react with
organometallic reagents
MeO OH MeO OH
BHT BHA
O O nBuLi nBu O
BHT, nBuLi
nBu Cl nBu OBHT nBu OBHT

Silyl Esters & Oxazolines
Bulky silyl esters do not react with organometallic
reagents; fluorides are required to hydrolyse
OH iPr3SiCl OSiiPr3
O Im, THF O
Oxazolines are stable to organometallic reagents,

reducing agents like LAH etc.,
OH H2N OH O
O Toluene, N
Heat

PGs for Amines
Introduction of protecting groups
Unlike alcohols, it is difficult to protect amines through alkylation
Protection R1
R NH2 R NH + R N + Quarternary
through R1 R1
alkylation
Primary and secondary amines are prone to oxidation
NH bonds undergo metallation on treatment with organometallic

reagents
Because of the presence of the lone pair of electrons, Nitrogen

could be protonated/alkylated.

PGs for Amines
Best ways to protect amines
It should be protected in such a way that further alkylation doesn’t

take place
To make the lone pairs less reactive, it is better to attach a carbonyl

group
H
N R1
R NH2 R
O
H
N O
R NH2 R R1
O
Amides could be cleaved by acids
Carbamates could be cleaved by a variety of reagents, depending

on the nature of the carbamates
PGs for Amines
O O O O
R R R R
N Me N CF3 N OMe N O
H H H H
Methyl tButylcarbamate
Methyl amide Trifluoromethyl
amide carbamate (Boc)
O SiMe3 O
O
R R
N O CCl3 R N O
H N O H
Trichloroethyl H
Trimethylsilylethyl Allyl carbamate
carbamate (Troc) (Alloc)
carbamate (Teoc)
O Ph
R O
N O
H R
Benzylcarbamate N O
H
(CBz) 9-Fluroenylmethyl
carbamate (Fmoc)
Amides
O
R
N R1
H
Amides
Basicity of nitrogen is reduced; so electrophilic attack on the

nitrogen is reduced
Amides are stable to hydrogenation, oxidation, nucleophiles &
organometallic (except organolithium) reagents
O
R
R1COCl, Py N R1
R NH2 H
Amides
H+, H2O

Carbamates
O
R
N OR1
H
Alkyl
carbamates
Carbamates are like amides and so can’t act as a nucleophile
Carbmates are stable to oxidation and aqueous bases though it may

react with reducing agents
O O
R
Cl OR1 N OR1
R NH2 H
Carbamates
K2CO3, MeOH

Benzyl carbamates (Cbz or Z)
O
O
Cl OBn R H2/Pd-C
R NH2 N OBn R NH2
Base H ROH
Formation: BnOCOCl, Na2CO3, H2O

(BnOCO)2O, dioxane, H2O
Cleavage: H2/ Pd-C

H2/ Pd-C, NH3
Pd-C, HCOONH4
BBr3, DCM
KOH, MeOH

tButyloxycarbonyl (Boc)
O
O
Cl O R HCl
R NH2 N O R NH2
OR H ROH
(Boc)2O
Base
Formation: (Boc)2O, NaOH, H2O, 25 oC

(Boc)2O, TEA, MeOH/ DMF
BocN3, DMSO
Cleavage: 3M HCl, EtOAc

TFA, PhSH, DCM
AcCl, MeOH
CAN, CH3CN

9-Fluroenylmethyloxy carbonyl (Fmoc)
O
O N
Cl O H
R NH2 R R NH2
N O
Base H
Formation: Fmoc-Cl, NaHCO3, aq. Dioxane

Fmoc-OC6F5, NaHCO3, acetone
Cleavage: Amine bases

Piperidine, morpholine, diisopropylethyl amine
TBAF, DMF

Allyloxycarbonyl (Alloc)
O
O
Pd(0)
Cl O R R NH2
R NH2 N O Et3SiH
Base H
Formation: CH2=CHCH2OCOCl, py
(CH2=CHCH2OCO)2O, DCM
Cleavage: Pd(Ph3P)4, TBTH, AcOH

Pd(Ph3P)4, Dimedone, THF

Trichloroethyloxycarbonyl (Troc)
O CCl3
O CCl3
Cl O R Zn Dust
R NH2 R NH2
N O
Base H
Formation: Cl3CCH2OCOCl, Py or aq. NaOH
Cleavage: Zn, THF, H2O, pH= 4.2

Zn-Pb couple, 4:1 THF/ 1M NH4OAc

Trimethylsilylethyloxycarbonyl (Teoc)
TMS
O TMS
O
Cl O F-
R R NH2
R NH2 N O
Base H
Formation: TMSCH2CH2OCOCl (Teo-Cl) or Teoc-N3

Teoc-OC6H4-4-NO2, NaOH
Teoc-OSu, TEA
Cleavage: TBAF, CH3CN
HF, Py, THF
KF, CH3CN
TAST, CH3CN

Examples
CO2H CO2H
(Boc)2O
NH2 Im, THF NHBoc
Boc OAc H OAc

N AlCl3 N
OTBS DCM OTBS
O
NH2
HN O
Pd(OAc)2
CO2Me
CO2Me
Et3N, Et3SiH

Protectinggroups

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Protectinggroups

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Protecting Groups

10/26/20 CH (401) slides should not be used for commercial purposes

Why do you need protecting groups?

When principles of selectivity can’t be applied, then protection of one

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 2

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 3

1. Two additional steps are required.

3. So, more the number or protecting groups in your synthetic

The best protecting group is “NO PROTECTING GROUP”

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 4

The development of such orthogonal protecting group strategies

This orthogonal protecting group strategy is regularly utilized in the

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 5

Permanent: These are stable protecting groups, survives many steps

Temporary: These protecting groups (as the name suggests) should be

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 6

Should be cheap & commercially available

Should be easily introduced under milder conditions

Should not create any additional stereocenters

Should be stable throughout the reaction, work up and purification

Should be easily removed under milder conditions

Byproducts should be easily separated from the required product

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 7

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 8

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 9

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 10

Aliphatic Secondary Aromatic

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 11

Removal of protecting groups

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 13

Silyl Ethers Alcohols Benzyl Ethers

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 14

ROMe, ROMOM, ROMEM, ROBOM, ROTHP, ROEE

ROBn, ROPMB ROTr

ROTMS, ROTES ROTIPS, ROTBS, ROTBDPS

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 15

EE Ether MOM Ether

THP Ether MEM Ether

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 16

o-NO2Bn Ether PMB Ether

OMe-Tr Ether NAP Ether

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 17

TBDPS Ether TES Ether

TBDMS Ether TIPS Ether

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 18

Pivalate ester Chloroacetate

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 19

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 20

Cyclic carbonate Cycloalkylidene

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 21

NaH, MeI, THF

CH2N2 (Phenols) DIEPA, CH3OCH2Cl, THF

BBr3, DCM HCl, THF

HCl, ROH AcCl, EtOH

Difficult to cleave except for phenols

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 22

Benzyloxymethyl ether (BOM)

ROBOM Alcohols ROMEM

Li, Liq. NH3 TiCl4

CH-401 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan 23

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