The Chemistry of Enolates and Enols May 3, 2013 • The acetoacetic and malonic ester syntheses. • A few other things you can do with LDA… • Additions to ,-unsaturated aldehydes & ketones. – Conjugate addition. – Michael addition & the Robinson annulation.

Announcements

Suggested Problems for Chapter 22: 22.50, 22.55, 22.59, 22.61, 22.62, 22.66, 22.69, 22.70(a), 22.71, 22.73(a,c,d,f), 22.75(a,e,j), 22.76, 22.80(a,f), 22.81(a,j), 22.83(a), 22.84(d), 22.85(a).

TA Office Hours: Mon 7‐8 pm: Rob Craig ‐ 302 Schlinger (x4056); Tue 3‐4 pm: Kelly Kim ‐ 302 Schlinger (x4047); Tue 7‐8 pm: Corey Reeves ‐ 302 Schlinger (x4056); Wed 5‐6 pm: Adam Boynton ‐ 139 Noyes (x3202); Wed 8‐9 pm: Ben Suslick (UTA) ‐ Lloyd Lounge (CANCELLED); Thu 8‐9 pm: Evan Zhao (UTA) ‐ Fleming Lounge (CANCELLED); Thu 9‐10 pm: Crystal Chu ‐ 202 Schlinger (x3634); Sun 3‐4 pm: Chung Wan Lee ‐ 302 Schlinger (x4056).

41c Ombuds seeks course feedback by noon on Friday May 3: email Ricky Barz ([email protected]).

Midterm exam review session: Friday, May 3, 4:30 PM, May 3, 153 Noyes. Review documents on website: 1. practice problems 2. topic review sheet.

Midterm examination: Monday, May 6, 9:00‐9:55 AM, 153 Noyes. Chemistry of the Acetoacetic Ester Dianion

Spartan images of the dianion The Michael Addition Reaction (conjugate addition of an enolate):

O O Active hydrogen O O compounds: NaOEt + O EtO OEt EtOH Z Z' OEt H H O OEt Mechanism:

O O O O Z, Z' = + OEt + HOEt EtO OEt EtO OEt O O H H H R H O O O HOEt OEt O O O O O O + EtO OEt OR NR2 OEt OEt H O OEt O OEt CN NO2

O O O S S -note base is catalytic. EtOH R R -driving force is formation of a C-C single bond at the expense of a C-C bond.

O O O O Decarboxylation reaction yields 1,5-dicarbonyl compound: S S OR NR 2 O O O CO2 O O H3O+ OEt O H O OEt HO O HO O Who will be your academic grandparents?

Conjugate addition: Frank Anet UCLA O OH O CH NMR pioneer CH3MgBr H2O 3 + (my academic dad)

major H3C minor

O O Sir Robert Robinson HCN Oxford major 1947 Nobel Prize NC (my academic grand dad)

Michael addition (conjugate addition with an enolate anion): O

O O CH 3 O KOEt CH3 aldol rxn. Me H + CH Me EtOH 3 O

Such a ring-f orming reaction (Michael f ollowed by an aldol) is called a Robinson annulation. Frank Anet UCLA

Loudon, Figures 7.5 and 13.19. The Stork Enamine Synthesis Preparation of tertiary enamines:

O H N N N N cat H+ + +H2O

pyrrolidine resonance picture This mechanism was discussed earlier--recall imine & enamine preparations.

Reaction of tertiary enamines:

[electrophile should be Me, primary, allylic, benzylic; acyl-Cl are OK, Michael acceptors,too.] N O H2O + Br Spartan views of an enamine

iminium This mechanism was discussed earlier-- ion recall imine hydrolysis.

N O O O H O N O 2 + Cl

N O O O O H2O +

this last reaction category--the Michael reaction--is discussed in Chapter 19 of 10E. The Umpolung Concept: Polarity Reversal!

O traditional view: HS SH R H SS H+ R H pK = 32

Li

R'-X (methyl or primary) Spartan images of SS SS the anion (R = H) R R' R

note: the charge is HgCl2 (hydrolysis of dithioketal) now negative on the CH3OH H O aldehyde-derived carbon 2 atom. Umpolung! O

R R'