Selectivity

Selectivity

Chemoselectivity Regioselectivity (Which) (Where) (How) Chemoselectivity

Preferential selectivity of one functional group over other

Two different functional groups and unequal reactivity

Reaction of one of two identical functional groups

1 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Reaction of a group once, when it may react again Selective Reduction: Chemoselective reduction of C=C over C=O: O O

H 2 /Pd

Chemoselective reduction of C=O over C=C: O OH

NaBH 4 , CeCl3

Chemoselective reduction of α,β-unsaturated over allylic alcohols: O O OH O

2 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity

NaBH 4 , CeCl 3 EtOH, -15 oC

3 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity Selective Reduction: OH O O 1 NaBH 4 (0.25 eq) /3 BH 3

O O HO

Chemoselective reduction of over alkenones:

O ( PPh 3 ) 3 RhCl

H 2 , EtOH O

Chemoselective reduction of alkenones over alkenes:

4 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity K-Selectride O THF or MeCu, DIBAL-H O Chemoselective reduction of alkynes over alkenes: H 2 / Pd-CaCO 3 Quinoline

H 2 / Pd-CaCO 3 Quinoline

5 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity Chemoselective reduction of COOR over CN: CO2R CH2OH

Ca(BH 4 ) 2 MeOH CN CN Chemoselective reduction of α,β-unsaturated in presence of alkenes :

Mg, MeOH

EtOOC EtOOC

Chemoselective reduction of C=O over COOR:

6 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity HO C

NaBH 4 MeOH O CO2Me CO2Me O Clemmensen reduction

HO HO O O Chemoselective reduction of carboxylic in presence of esters, nitro and cyano groups:

7 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity O

HOOC THF O BH3, SMe2 HOH2C O O

Chemoselective reduction of amides in presence of esters: COOMeCOOMe 2 /3 BH 3. THF

N N O Selective Oxidation:

8 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity Chemoselective oxidation of allylic alcohols over other OH OH

MnO 2

HO CHCl 3 O alcohols:

Chemoselective oxidation of secondary alcohols over primary alcohols AgCO3, Celite : OH OH O OH OH NaOCl, AcOH O

9 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity

o H 2 O, 25 C OH OH Selective Oxidation: Chemoselective oxidation of lactols over other alcohols:

O O AgCO 3 , Celite OH Benzene O OH OH

Chemoselective epoxidation of allylic alcohols over unfunctionalized alkenes:

10 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity t -BuOOH O VO(acac) 2 OH OH Chemoselective epoxidation of α,β-unsaturated ketones over alkenes: O O KOH, H 2 O2

O

Chemoselective epoxidation of alkenes over α,β-unsaturated ketones:

11 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity

O m - CPBA DCM

O O Chemoselective acylation of amines over phenols:

NH2 NHAc

Ac 2 O (1 eq) Pyridine

OH OH

Chemoselective alkylation of phenols over carboxylic acids: 12 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity COOH COOH COO I Base

Acid O OH O

Reaction of One of Two Identical Functional Groups: Monoprotection of a diol: NaH, BnBr

HOOHHOOBn

Monohydrolysis of an : 13 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity

CO2Me (1) NaOH, MeOH (1 eq.) CO2Me

CO2Me (2) CO2H

Reaction of A Group Once When It May React Again: Preparation of half esters:

OH OCOCl

COCl 2

Partial reduction of dinitro compounds:

14 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity

NaSH, MeOH

NO2 NH2 NO2NO2

15 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Regioselectivity Preferential reactivity of one site over the other site of the same functional group Addition of HBr to alkenes: Br Br HBr HBr ( PhCOO ) O 2

Hydration of alkenes:

Ph Ph Ph OH OH BH 3 . THF (1) Hg(OAc )2

(2) NaBH 4

16 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Regioselectivity Hydration of alkynes: O (1) HgSO 4 (1) BH .THF 3 H 2 SO 4

CHO (2) NaOH, H2 O 2

Baeyer- Villiger Oxidation:

O CF3 CO 3 H O

Birch Reduction: OMe OMe COOH COOH

17 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Regioselectivity O Diels-Alder Reaction: R R O R

Li, NH 3 Li, NH3 + EtOH EtOH O

major minor

O O

18 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Regioselectivity R R

R O +

O major minor Diels-Alder Reaction: O O

O O OAc O O OAc H H

19 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan H H H Selectivity Opening: Regioselectivity O Me OH H SO O OAc NaOMe O OAc O OAc H Ra Ni, H 2

O O SPh O O SPh O O

HO Me MeH 2 4 Me Me H Me OMe MeMe MeOH MeO Me Aromatic electrophilic substitution:

20 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Regioselectivity

HNO 2

H 2 SO 4 NO2

NO2 Friedel-

Crafts Reaction:

O

RCOCl, AlCl3

O O

21 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Regioselectivity

RCOCl, AlCl3

SiMe3

22 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan