Selectivity Selectivity Chemoselectivity Regioselectivity Stereoselectivity (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 ketones 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 alkenes 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 esters 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 acids 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 Benzene 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 ester: 13 CH-­­423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan Selectivity Chemoselectivity CO2Me (1) NaOH, MeOH (1 eq.) CO2Me CO2Me (2) Acid 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 Epoxide Opening: Regioselectivity O Me OH H SO O OAc NaOMe O OAc O H OAc Ra Ni, H 2 SPh O O 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 .