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Polar Reaction Under Basic Conditions a.Substitution and Elimination at C(sp 3 )-X σ bonds b.Addition of Nuclephiles to Electrophilic π bonds c.Substitution.

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Presentation on theme: "Polar Reaction Under Basic Conditions a.Substitution and Elimination at C(sp 3 )-X σ bonds b.Addition of Nuclephiles to Electrophilic π bonds c.Substitution."— Presentation transcript:

1 Polar Reaction Under Basic Conditions a.Substitution and Elimination at C(sp 3 )-X σ bonds b.Addition of Nuclephiles to Electrophilic π bonds c.Substitution at C(sp 2 )-X σ bonds d.Base-promoted Rearrangements Chapter Two

2 Nuclephility and Basicity Good nuclephiles and good bases Unhindered RO -, R 2 N -, R 3 N, RC≡C -, Cl - Good nuclephiles and poor bases Br -, I -, R 2 S, RS -, R 3 P, malonate anion, R 2 CuLi Poor nuclephiles and good bases (bulky) t-BuO -, i-Pr 2 NLi(LDA), R 3 N, (TMS) 2 NK, i-Pr 2 NEt, t-BuLi R-R- Nu - B-B- SN2SN2 SN1SN1 E2 E1 TMS: Trimethylsilane S N 2, E2: basic condition S N 1, E1: acidic condition

3 Substitution by the S N 2 Mechanisms a. Back attack b. Sterospecific c. Only 1 o and 2 o C(sp 3 ) undergo S N 2 S R S N Ar How to retent the configuration? S S SP 2 C and 3 o C can’t undergo S N 2 Solvent: Polar Aprotic DMSO, DMF, Acetone, THF, MeCN, EA… Polar solvent can stabilize the intermediate. Aprotic solvent can avoid H + react with Nu -.

4 Loss Configurational Purity by Nuclephilic Substitution Substituted group is good nuclephile, also good leaving group. The leaving group is α or β to a carbonyl group.

5 Elimination by the E2 Mechanisms β hydrogen, Good base, 3 o C Please draw the structure of product. Stereochemistry of E2 E2 a. b. E2 c. Sawhore projection Newman projection d.

6 Syn Elimination If the base were part to the substrate, the acidic hydrogen be removed in an intramolecular reaction(syn elimination). Syn elimination Hofmann Elimination major

7 E1cb and 1,3-Elimination E1cb: β hydrogen is particularly acidic(carbonyl) and leaving group is poor( - OH, - OR) hemiacetal carbonyl 1,3-Elimination(decarboxylation) CH 2 COOH

8 Substitution by the Elimination-Addition Reaction Nu: - OMe E + : carbonyl group, Br No S N 2 due to the steric hindrance. Leaving group: Br, β hydrogen Elimination-Addition Reaction better electrophile than carbonyl group(steric) Please draw the reasonable mechanisms of this reaction

9 Exercises Please draw the mechanisms of following reaction a. b. c. d. e. CO 2

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 carbenes a. b. c. d. - +

11 Reaction of Carbene

12 Exercises Please draw the mechanisms of following reaction a. b. c. d. e.

13 Polar Reaction Under Basic Conditions a.Substitution and Elimination at C(sp 3 )-X σ bonds b.Addition of Nuclepphiles to Electrophilic π bonds c.Substitution at C(sp 2 )-X σ bonds d.Base-promoted Rearrangements

14 Carbonyl Group Under basic conditions, carbonyl compounds are electrophilic at carbonyl C and nuclephilic at α C’s. Arrange the stabilities and reactivities of carbonyl compounds as follow. R is donating group Stabilize the carbocation decrease the reactivity

15 Carbonyl Group As Electrophile a. M-Nu (R-MgBr, NaBH 4, LiAlH 4, R 2 CuLi) 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 Addition Michael 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 reactions a. b. c. d. e.

18 a.Baylis-Hillman reaction: An acrylate ester reacts with an aldehyde in the presence of an amine or phosphine catalyst. b. Robinson annulation Baylis-Hillman Reaction and Robinson Annulation

19 Polar Reaction Under Basic Conditions a.Substitution and Elimination at C(sp 3 )-X σ bonds b.Addition of Nuclephiles to Electrophilic π bonds c.Substitution at C(sp 2 )-X σ bonds d.Base-promoted Rearrangements

20 Substitution at Carbonyl C Draw mechanisms for the following reaction and explain why carbonyl acid can’t undergo similar reaction Reduction of aldehyde, ketone or ester. Organometallic reagents as Nu - (RMgBr, R 2 CuLi…)

21 Claisen condensation: An ester enolate is condensed with a ketone, aldehyde, or ester. Dieckmann condensation: An intramolecuar version of the Claisen condensation Substitution at Carbonyl C Draw mechanisms for the following reactions

22 Substitution at Alkenyl C and Aryl C(S N Ar) α, β-Unsaturated carbonyl compounds with a leaving group in the β position are susceptible to addition-elimination reactions. S N Ar: Aromatic compounds that are substituted with electron-withdrawing groups undergo nuclephilic aromatic substitution. Favor Unfavor

23 Nuclephilic Aromatic Substitution(S N Ar) A B A B Explain the results which was showed below Draw mechanisms for the following reaction

24 Substitution at Aryl C(S N Ar) Aryl halides undergo substitution reactions with very strong base such as – NH 2, terbutyl lithium. Why alkenyl halides such as CH 3 CBr=ChCH 3 don’t undergo substitution upon treatment with a strong base(-NH 2 )? Ans: ring strain. Sandmeyer reaction Nu: CuX, H 2 O, X -, CN -, H 3 PO 2 Ex

25 Polar Reaction Under Basic Conditions a.Substitution and Elimination at C(sp 3 )-X σ bonds b.Addition of Nuclepphiles to Electrophilic π bonds c.Substitution at C(sp 2 )-X σ bonds d.Base-promoted Rearrangements

26 Migration from C to C Favorskii rearrangemet Diazomethane(CH 2 N 2 ) reacts with ketones(R 2 C=O) to insert CH 2 unit between C=O and R Wolf rearrangementPlease draw the mechanisms Baeyer-Villiger rearrangement

27 Curtius rearrangement (acyl chloride to amine) Hofmann rearrangement (amide to amine) Migration from C to O or N Baeyer-Villiger rearrangement base Please draw the mechanisms of Hofmann rearrangement

28 The Swern Oxidation Mechanism 1 o alcohol to aldehyde; 2 o alcohol to ketone

29 The Mitsunobu Reaction A 2 o alcohol and a carboxylic acid are converted to an ester. A poor leaving group is converted to an excellent leaving group. Mechanism S R

30 Draw mechanisms for the following reactions a. b. c. d. e. B

31 Draw mechanisms for the following reactions a. b. c. d. e. f. g. h. i.

32 Thanks For Your Attention

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