Selected reactions at ?- and ?-carbons and related reactions O OH O N N 1. RCH2Br 2. H3O+ O O CH2R O R alkylation RCH2R' O RCH2R' HO? or H3O+ X2, H3O+ RCH R' O R R' X Keto-enol interconversion ?-halogenation in acid gives monobrominated product; X2 = Cl2, Br2, or H H+ cat. 1. RCH2COBr 2. H3O+ 1. CH2=CHCHO 2. H3O+ O O H acylation conjugate addition O RCH2R' O X2, HO? X2, HO? R X O O X R' I2 ?-halogenation in base gives perbrominated product; X2 = Cl2, Br2, or I2 HCX3X = halogen R O O R' NuH or Nu? R OH R' Nu O R Nu O H R' 1. Nucleophiles that are weak bases (CN?, RSH, RS?, ROH, RNH2, RO?, Br?, etc.) and R2CuLi add in a conjugate manner. 2. Nucleophiles that are strong bases (RMgX, RLi, H?) add directlyb to C=O. R CH3 O R OH H 1. PBr3 (or P) 2. H2O R O R Br O OH Haloform ?-halogenation of carboxylic acids - Hell-Volhard-Zelinsky Reaction R O Cl NuH or Nu? NuH or Nu? R Nu Nu O HCl Nucleophiles form nucleophilic acyl substitution products with reactive carboxylic acid derivatives R H O R' Base R O R' E+ R E O When??-hydrogen is removed the enolate becomes a R' nucleophile that can react with an electrophile R NHR' R H NHR' Nucleophiles form conjugate addition products with less reactive carboxylic acid derivatives O RCH2R' Br2, H3O+ R Br O R' Nu? R O Nu R' ?-Halogenated Br? compounds can react with nucleophiles O More acidic and more accessible ?-carbon Less acidic and less accessible ?-carbon O Base (catalytic O R H R Br O O R' t-BuO? R R O O R' ?-Halogenated compounds can form ???-unsaturated compounds by dehydrohalogenation kinetic enolate Forms faster from the more acidic and more accessible ??H. But coverts to the thermodynamically more stable product t at equilibrium. excess O amount) Base thermodynamic enolate Thermodynamically more stabe product. => Major product at equilibrium O R H R' 1. LDA, THF 2. R''CH2X R R' CH2R'' Alkylation of preformed enolates using LDA. Applicable to aldehydes, ketones, esters, and nitriles X = halogen (excess) Only the kinetic enolate forms. Reaction is irreversible since the base is in excess; all of the ketone will be converted very fast into the enolate that forms faster. O O O Cl Cl 1. R2CuLI (1 equiv) 2. H3O+ 1. R2CuLI (2 equiv) 2. H3O+ 1. RLI O O R OH R R Cl (2 equiv) 2. H3O+ R R Protection of alcholos O ROH H+ cat O OR acetal Stable to base Cleaved by acid HCl catalyst O ROH Protecytion of ketones and aldehydes O ROH (excess) HCl (cat) O HO OH HCl (cat) O HS SH ZnCl2 Protection of carboxylic acids O O OH RO OR O O S S O O H2 Pd/C H H O O OTHP
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