Functional Group Transformations

Transcription

1 Ways to make esters Baeyer-Villiger oxidation Favorskii rearrangement C 2 Et aet/et mcpba Mitsunobu reaction C 2 + ' DEAD, PPh 3 C 2 ' Ph 3 P Et 2 C C 2 Et Ph 3 P Et 2 C C 2 Et Ph 3 P Et 2 C C 2 Et + C 2 PPh 3 PPh 3 + Et 2 C C 2 Et + C 2 ' C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 1

2 Mitsunobu eaction = i Pr, DIAD Diisopropyl azodicarboxylate 2 C C 2 = Et, DEAD Diethyl azodicarboxylate 1 2 C 2 PPh 3, DIAD PPh 3 DEAD Ph 1? Bn Bn +, 2 PPh 3, DEAD Bn C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 2

3 itrogen nucleophile: Mitsunobu eaction 3C Ts Bn PPh 3, DEAD Bn TsC 3 PPh 3 Weak itrogen nucleophile: DEAD Bn Bn Bn PPh 3, DEAD Bn Bn Bn Intramolecular Mitsunobu eaction: PPh Ph 3 Ph C 2 Et DEAD C 2 Et C 2 Et C 2 Et C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 3

4 Azides: Functional Group Transformations + PPh 3 + DEAD Mitsunobu eaction 3 3 PPh 3 + Et 2 C C 2 Et (Ph) 2 P 3 Can be used instead of 3 Ph P Ph + (Ph) 2 P 3 + PPh 3 + DEAD 3 + Ph 3 P Et 2 C C 2 Et (Ph) 2 P 3 Ph P Ph Ph P Ph Et 2 C C 2 Et Et 2 C C 2 Et PPh 3 + Et 2 C C 2 Et PPh 3 PPh PhP C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 4

5 Activation of hydroxyl group Alkyl halides are involved in the formation of C C bond by nucleophilic substitution Preparation of alkyl halides: eaction with S 2 S S + S 2 + Inversion of configuration But, if reaction is taking place in solvent like 1,4-dioxane S etention of configuration C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 5

6 Activation of hydroxyl group eaction with Phosphorous halides P - P 2 P The reaction will stop at this stage if it is carried out in presence of an amine When amine is not present P + P + P Inversion of configuration P + 2? Drawbacks: ot suitable for acid sensitive compounds Amines can not be used C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 6

7 Activation of hydroxyl group eaction with alkoxyphosphonium salts Ph 3 P Ph 3 P + - PPh 3 PPh 3 Formation of strong phosphoryl double bond is the driving force Ph 3 P 2 + PPh 3 + omide source C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 7

8 Activation of hydroxyl group Ph 3 P C C 3 + Ph 3 P PPh 3 C 3 exachloroacetone can be used as chloride source PPh 3 / C 4 3 C PPh 3 C C 3 PPh 3 / I 2 / Imidazole PPh 3 I 2 I Ph 3 P I -I Ph 3 P I I PPh 3 Imidazole I C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan I 8

9 Activation of hydroxyl group eaction with 2-alo-3-alkylbenzoxazolium cation Addition Elimination Mitsunobu reaction Ph 3 P Et 2 C C 2 Et Me I Ph 3 P Et 2 C C 2 Et Me + I I I PPh 3 Et 2 C C 2 Et Me C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 9

10 Activation of hydroxyl group Mild method Ms Py Ms Li MsLi Some other methods 2 C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 10

11 itriles C 2 Dehydration LA 2 / Pd-C 3 + C 2 2 C 2 Abnormal Beckmann earrangement C 'Mg DIBAL- C' Alkylation C X + ac ' ' C C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 11

12 Functional Group Transformations X ac Preparation of itriles C eaction proceed faster in polar aprotic solvents aldoxime p-ts, Py Ac, Py C 2 P 2 5 C Beckmann rearrangenment can also occur C tertiary carbocation C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 12

13 Preparation of itriles C 2 + KC 18-Crown-6 C 3 C 83 o C C 2 C C KC + C stable under mild acidic condition unstable under basic condition - C + C - C TMSC Zn 2 TMS C C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 13

14 Utility of itriles C LA or /Pd-C C 2 2 C partial hydrolysis 2 C 3 + eflux C 2 C Sn 2 / DIBAL- Stephen reaction C 'Mg + / 2 ' C LDA ' 'I C C- 423 Course on rganic Synthesis; Course Instructor: Krishna P. Kaliappan 14