CHEM 330. Topics Discussed on Oct 16

Size: px

Start display at page:

Download "CHEM 330. Topics Discussed on Oct 16"

Octavia Goodwin
7 years ago
Views:

1 CEM 330 Topics Discussed on ct 16 Deprotonation of,-unsaturated (= conjugated) carbonyl compounds Important: bases cannot abstract protons connected to the olefinic -position of a conjugated carbonyl compound, because resonance interactions force the C= and C=C π-systems to be coplanar As a result, the dihedral angle θ between the axis of the olefinic -C s bond and the axis of the lobes of the π* C= orbital is ca. 90. There is no overlap between σ C and π* C= orbitals à no is possible bases cannot abstract these protons Me Et dihedral angle θ 90 no overlap! axis of the large lobe of the π* C= orbital axis of the C bond Definition of,,, carbons of an,-unsaturated carbonyl compound generic,-unsaturated carbonyl compound Principle of vinylogy (= "vinyl analogy"): the interposition of a C=C unit between the components of a functional group generates a new chemical entity, which retains the chemical characteristics of the original Examples: an enolizable carbonyl compound: is possible because of resonance delocalization of ( ) charge on the eletronegative atom C C 2 : B B : C C=C C 2 a vinylog of the original: resonance delocalization of ( ) charge on the atom still possible through the C=C bond: can undergo an ester: it undergoes hydrolysis to an acid and an alcohol when treated with, e.g. aqueous Cl a vinylogous ester: reacts with aq. Cl like the original C R C C=C R C + R C C=C + R Deprotonation of,-unsaturated esters: conversion of, e.g., ethyl crotonate into a dienolate a base (e.g, ) can remove one of these protons, because... : B Et Et the anion is resonance-stabilized, just like an ordinary enolate Et a dienolate

2 lecture of ct 16 p. 2 Normal -reactivity of dienolates of conjugated esters with, e.g., TMS-Cl: Li TMS-Cl SiMe 3 Et 78 C Et dienolate Et Definition of,,, etc., positions of a dienolate: Li dienolate of a generic,-unsaturated carbonyl compound Potential C-reactivity of a dienolate at the -carbon or at the -carbon, e.g.: Li + C 3 I could R form prod. of -alkylation & / or prod. of -alkylation Principle: the nucleophilic C-reactivity of dienolates is expressed selectively at the -carbon. This is true both for alkylation and for protonation. E.g.: -alkylation of dienolates: Li -protonation of dienolates: formation of deconjugated carbonyl compounds: 3 + Li 3 + Molecular orbital based rationale for selective -carbon reactivity of dienolates: greater electronic density at the -carbon relative to the -carbon, and consequent greater - nucleophilicity relative to - nucleophilicity Principle of least motion: a reaction that could theoretically lead to multiple products tends to form preferentially the product that requires the least amount of internal motion due to the repositioning / displacement of atoms during rehybridization.

3 lecture of ct 16 p. 3 Invoking the principle of least motion to rationalize the selective -carbon reactivity of dienolates: smaller extent of internal motion favored Li C, C remain doubly bonded: no relative motion E + greater extent of internal motion disfavored E E C, C remain singly bonded: no relative motion C, go from singly bonded C, C go from doubly bonded to singly bonded: they move farther from each other C, C go from singly bonded C, go from singly bonded C, C go from doubly bonded to singly bonded: they move farther from each other Deprotonation of,-unsaturated ketones (= enones), e.g., cyclohexenone: potential formation of two regioisomeric dienolates: ' of the ' position thermordynamically disfavored: resonance disperses charge only over the ' carbon cyclohexenone: a typical enone of the position thermordynamically favored: resonance disperses charge over the and carbons Deprotonation of, e.g., cyclohexenone under kinetic (non-equilibrating) conditions (slight excess of, TF, 78 C): occurs selectively at the ' position: proper representation of the half-chair conformation of cyclohexene and of cyclohexenone:

4 lecture of ct 16 p. 4 formation and fate of the enone- complex: only this is properly N aligned for Li kinetic enone Li dienolate. The ( ) charge is delocalized over (excess) one C=C bond Normal - and C-reactivity of kinetic dienolates of enones -reactive E + TMS Li e.g., TMS-Cl (excess) kinetic enone enolate C-reactive E + e.g. C 3 I Me Deprotonation of enones under thermodynamic (equilibrating) conditions: occurs selectively at the position: appropriate conds. (e.g., slight defect of (notes of ct 14) Li thermodynamic enone dienolate: The ( ) charge is delocalized over two C=C bonds Selective -alkylation and protonation of thermodynamic enone dienolates: Li 3 + Li 3 +

5 lecture of ct 16 p. 5 Soft enolization of enones such as cyclohexenone leading directly to regiochemically defined silyl enol ethers TMS-Tf N Et TMS kinetic silyl enol ether faster-forming, but thermodynamically disfavored isomer non-equilibrating conds. TMS-Tf TMS Me 3 Si N SiMe 3 equilibrating conds. thermodynamically favored isomer

Chapter 22 Carbonyl Alpha-Substitution Reactions

John E. McMurry www.cengage.com/chemistry/mcmurry Chapter 22 Carbonyl Alpha-Substitution Reactions The α Position The carbon next to the carbonyl group is designated as being in the α position Electrophilic