Chapter 24 — chemoselectivity

Regioselectivity vs. chemoselectivity vs. stereoselectivity

Carbonyls as electrophiles
Salmefamol synthesis
Reagent control of selectivity: chemoselective carbonyl reductions
More reductions
Oxidizing alcohols
Summary of protecting groups
Carbonyls as electrophiles

more electrophilic… …less electrophilic

O O O O O
R' R'
R H R R' R O R N R O–
R''
Carbonyl reduction by hydride reagents

more electrophilic… …less electrophilic

R'
N O O O O O
R' R'
R H R H R R' R O R N R O–
R''
H2, Pd

NaCNBH3

NaBH4

LiBH4

LiAlH4

BH3
Reductive removal of functional groups

Et3N
TsCl LiAlH4
OH OTs H

Ts =
O O Tosylation is commonly used to convert
S
alcohols to leaving groups

p-toluenesulfonyl "tosyl"

H+
O H2 H
SH H Raney Nickel is great at
HS S S RaNi
catalyzing the cleavage of
C–S bonds

HO–
O H H
H2N NH2 Wolff-Kishner reduction
(see class notes for mechanism)
Alkyne reductions

H2, Pd

still reactive

H2, Lindlar
Poisoned catalyst
Z-selective

Li, NH3 Dissolving metal reduction

E-selective
More dissolving metal reductions

Li, NH3

Li, NH3

MeO MeO
Note regioselectivity effects of
EDG and EWG
Li, NH3

HO2C HO2C
Miscellaneous oxidations

Me KMnO4 CO2H

H OH CrO3 O
R R' R R'

H H CrO3 O CrO3 O
R OH R H R OH

still reactive

H H PCC O
Pyridinium chlorochromate — mild, neutral
R OH R H oxidation that stops at aldehyde
Protecting groups 1.

Name Addition Protects from Removal

OH
HO
O H+, –H2O Protects aldehydes and
acetal
O O ketones from H+, H2O
(dioxolane)
R R R R nucleophiles and bases

R3SiCl protects alcohols from

base bases and nucleophiles, H+ (TMS, TES)
silyl ether R OH R OSiR3 the bulkier versions also F– (all = TMS, TES,
protect from weak acid TIPS, TBDMS, TBDPS)
NaH protects alcohols from
BnBr bases, nucleophiles, H2, Pd/C
benzyl ether R OH R O electrophiles, and all or HBr
but the strongest
acid/nucleophile
combinations

K2CO3
protects amines from H2, Pd/C
BnBr bases, nucleophiles,
benzyl amine R NH2 R N (high pressure)
H some electrophiles,
or PhCHO, and acids
NaCNBH3