Presentation on theme: "Chapter Two Polar Reaction Under Basic Conditions"— Presentation transcript:
1 Chapter Two Polar Reaction Under Basic Conditions Substitution and Elimination at C(sp3)-X σ bondsAddition of Nuclephiles to Electrophilic π bondsSubstitution at C(sp2)-X σ bondsBase-promoted Rearrangements
2 Nuclephility and Basicity SN2Nu-Good nuclephiles and good basesUnhindered RO-, R2N-, R3N, RC≡C-, Cl-Good nuclephiles and poor basesBr-, I-, R2S, RS-, R3P, malonate anion, R2CuLiPoor nuclephiles and good bases (bulky)t-BuO-, i-Pr2NLi(LDA), R3N, (TMS)2NK, i-Pr2NEt, t-BuLiSN1R-E2B-E1SN2, E2: basic conditionSN1, E1: acidic conditionTMS: Trimethylsilane
3 Substitution by the SN2 Mechanisms Ra. Back attackb. Sterospecificc. Only 1o and 2o C(sp3) undergo SN2SP2 C and 3o C can’t undergo SN2SNArHow to retent the configuration?Solvent: Polar AproticDMSO, DMF, Acetone, THF, MeCN, EA…Polar solvent can stabilize the intermediate.Aprotic solvent can avoid H+ react with Nu-.SS
4 Loss Configurational Purity by Nuclephilic Substitution The leaving group is α or β to a carbonyl group.Substituted group is good nuclephile, also good leaving group.
5 Elimination by the E2 Mechanisms β hydrogen, Good base, 3o CStereochemistry of E2Newman projectionSawhore projectionPlease draw the structure of product.a.b.d.c.E2E2
6 Syn EliminationIf the base were part to the substrate, the acidic hydrogen be removed in an intramolecular reaction(syn elimination).Hofmann EliminationmajorSyn elimination
7 E1cb and 1,3-EliminationE1cb: β hydrogen is particularly acidic(carbonyl) and leaving group is poor(-OH, -OR)hemiacetalcarbonyl1,3-Elimination(decarboxylation)CH2COOH
8 Substitution by the Elimination-Addition Reaction Nu: -OMeE+: carbonyl group, BrNo SN2 due to the steric hindrance.Leaving group: Br, β hydrogenElimination-Addition Reactionbetter electrophile than carbonyl group(steric)Please draw the reasonable mechanismsof this reaction
9 Exercises Please draw the mechanisms of following reaction a. e. CO2 b.c.CO2d.
10 α-Elimination: Generation of Carbene Defination: A carbene is a divalent carbon species link to two adjacent groups by covalent bonds, possessing two nonbonded electrons and six valence electrons.Preparation of carbenesa.-+b.c.d.
12 Exercises Please draw the mechanisms of following reaction a. b. c. d.
13 Polar Reaction Under Basic Conditions Substitution and Elimination at C(sp3)-X σ bondsAddition of Nuclepphiles to Electrophilic π bondsSubstitution at C(sp2)-X σ bondsBase-promoted Rearrangements
14 Carbonyl GroupUnder basic conditions, carbonyl compounds are electrophilic at carbonyl C and nuclephilic at α C’s.R is donating groupStabilize the carbocationdecrease the reactivityArrange the stabilities and reactivities of carbonyl compounds as follow.
15 Carbonyl Group As Electrophile a. M-Nu (R-MgBr, NaBH4, LiAlH4, R2CuLi)b. Amines as nuclephiles (Please draw the mechanism)c. Water and alcohols as nuclephiles under basic conditions.base
16 Carbonyl Group As Nuclephiles (Aldol Reaction) Aldol reaction: Enolates react with ketones and aldehydes.Draw mechanisms for the following aldol reactions
17 Michael AdditionMichael addition: The 1,4-(conjugated) addition of a carbon nuclephile to an α, β-unsaturated carbonyl system is referred to as Michael addition.Draw mechanisms for the following reactionsd.a.b.e.c.
18 Baylis-Hillman Reaction and Robinson Annulation Baylis-Hillman reaction: An acrylate ester reacts with an aldehyde in the presence of anamine or phosphine catalyst.b. Robinson annulation
19 Polar Reaction Under Basic Conditions Substitution and Elimination at C(sp3)-X σ bondsAddition of Nuclephiles to Electrophilic π bondsSubstitution at C(sp2)-X σ bondsBase-promoted Rearrangements
20 Substitution at Carbonyl C Draw mechanisms for the following reaction and explain why carbonyl acid can’t undergo similar reactionReduction of aldehyde, ketone or ester.Organometallic reagents as Nu-(RMgBr, R2CuLi…)
21 Substitution at Carbonyl C Claisen condensation: An ester enolate is condensed with a ketone, aldehyde, or ester.Dieckmann condensation: An intramolecuar version of the Claisen condensationDraw mechanisms for the following reactions
22 Substitution at Alkenyl C and Aryl C(SNAr) α, β-Unsaturated carbonyl compounds with a leaving group in the β position are susceptible to addition-elimination reactions.SNAr: Aromatic compounds that are substituted with electron-withdrawing groups undergo nuclephilic aromatic substitution.FavorUnfavor
23 Nuclephilic Aromatic Substitution(SNAr) Explain the results which was showed belowABABDraw mechanisms for the following reaction
24 Substitution at Aryl C(SNAr) Aryl halides undergo substitution reactions with very strong base such as –NH2, terbutyl lithium.Why alkenyl halides such as CH3CBr=ChCH3 don’t undergo substitution upon treatment with a strong base(-NH2)? Ans: ring strain.Sandmeyer reactionNu: CuX, H2O, X-, CN-, H3PO2Ex
25 Polar Reaction Under Basic Conditions Substitution and Elimination at C(sp3)-X σ bondsAddition of Nuclepphiles to Electrophilic π bondsSubstitution at C(sp2)-X σ bondsBase-promoted Rearrangements
26 Migration from C to C Favorskii rearrangemet Please draw the mechanismsDiazomethane(CH2N2) reacts with ketones(R2C=O) to insert CH2 unit between C=O and RBaeyer-Villiger rearrangementWolf rearrangementPlease draw the mechanisms
27 Migration from C to O or N Baeyer-Villiger rearrangementbaseCurtius rearrangement (acyl chloride to amine)Hofmann rearrangement (amide to amine)Please draw the mechanisms of Hofmann rearrangement
28 The Swern Oxidation 1o alcohol to aldehyde; 2o alcohol to ketone Mechanism
29 The Mitsunobu Reaction A 2o alcohol and a carboxylic acid are converted to an ester. A poor leaving group is converted to an excellent leaving group.SRMechanism
30 Draw mechanisms for the following reactions b.c.d.Be.
31 Draw mechanisms for the following reactions b.g.h.c.d.i.e.