Series acetoacetic ester synthesis steps 3 4

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Unformatted text preview: n with allyl bromide 41 Organic Lecture Series Acetoacetic Ester Synthesis – Steps 3 & 4 saponification followed by acidification – Step 5: thermal decarboxylation 42 Organic Organic Lecture Series Acetoacetic Ester Synthesis – to prepare a disubstituted acetone, treat the monoalkylated AAE with a second mole of base, etc 43 Organic Lecture Series Acetoacetic Ester Synthesis The acetoacetic ester (AAE) synthesis is useful for the preparation of mono- and disubstituted acetones of the following types These types of reactions involve active (i.e. acidic) methylene units as the nucleophilic component. 44 Application: Synthesis of 4,4-Disubstituted Piperidines Not exam material Application: Synthesis of 4,4-Disubstituted Piperidines Organic Organic Lecture Series 45 Organic Lecture Series 46 Not exam material Organic Organic Lecture Series Malonic Ester Synthesis – treat malonic ester with an alkali metal alkoxide – alkylate with 1-bromo-3-methoxy propane 47 Organic Lecture Series Malonic Ester Synthesis – saponify and acidify – decarboxylation 48 Organic Organic Lecture Series Addition to α,β-unsaturated Carbonyls α,β When the carbonyl group is conjugated with an alkene, the two groups can act in tandem to expand synthetic utility. α,β-unsaturated carbonyl compounds can exhibit properties of both the carbonyl and alkene group: 49 Organic Lecture Series 50 Organic Organic Lecture Series Michael Reaction • Michael reaction: the nucleophilic addition of an enolate anion to an α,β-unsaturated carbonyl compound (1,4 addition) – Example: 51 Organic Lecture Series Michael Acceptors & Nucleophiles 52 Organic Organic Lecture Series Michael Reaction Example: – the double bond of an α,β-unsaturated carbonyl compound is activated for nucleophilic attack: 53 Organic Lecture Series Michael Reaction • Mechanism Step 1: proton transfer to the base Step 2: addition of Nu:- to the β carbon of the α,β-unsaturated carbonyl compound 54 Organic Organic Lecture Series Michael Reaction Step 3: proton transfer to HB gives an enol Step 4: tautomerism of the less stable enol form to the more stable keto form 55 Organic Lecture Series Michael Reaction A final note about nucleophilic addition to α,β-unsaturated carbonyl compounds: resonance-stabilized enolate anions and enamines are weak nucleophiles, react slowly with α,β-unsaturated carbonyl compounds give 1,4-addition products 56 Organic Organic Lecture Series Retrosynthesis of 2,6-Heptadione MVK is the reagent to add a 2-oxobutyl side chain 57 Organic Lecture Series Michael-Aldol in Combination: The Robinson Ring Annulation O H COOEt O + Ethyl 2-oxocyclohexanecarboxylate O COOEt 1 . NaOEt , Et OH (Michael reaction) 3-Buten-2-one (Methyl vinyl ketone) O O 2 . NaOEt , Et OH (Aldol reaction) COOEt 58...
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