STEREOELECTRONIC EFFECTS (S.E.) IN ORGANIC CHEMISTRY

Transcription

1 STEEELECTNIC EFFECTS (S.E.) IN GANIC CEMISTY Pierre Deslongchamps (version du 3 février 2010) Cf. pour le livre: 1

2 SECTIN 5 Stereoelectronic Effects (S.E.) and eactivity of Esters and elated Functions 2

3 Esters and elated Functions 2 conformations Primary Stereoelectronic Effects esonance Structure and Stereoelectronic Effect in Ester 3

4 Secondary Stereoelectronic Effects and elative Stability of Esters even t-butyl formate: C C Z 90% E 10% 4

5 elative Stability of Dialkoxy-carbonium Ion C 3 C 3 + C + C 3 X-rays (NM) 5

6 Experimental Evidence for Secondary Stereoelectronic Effects Iodide Displacement on Lactonium Salt fast slow SN 2 on secondary carbon faster than primary one due to SE control 6

7 Stereocontrolled Cleavage of emiortoester Tetrahedral Intermediate primary (2 A.E.) secondary (2 A.E.) primary (1 A.E.) secondary (2 A.E.) primary (2 A.E.) secondary (1 A.E.) 7

8 18 -Exchange Concurrent to ydrolysis in Ester and Lactone Z-ester undergoes 18 exchange as k 2 k 3 8

9 18 -Exchange Concurrent to ydrolysis in Z Ester In both k 2 and k 3, cleavage takes place with 2 secondary stereoelectronic effects (or 2 A.E.) 9

10 Lactone (E-ester) do not undergo 18 -xygen Exchange Concurrent with ydrolysis in k 3, cleavage takes place with 2 secondary stereoelectronic effects in k 2, cleavage takes place with 1 secondary stereoelectronic effects k 3 is thus greater than k 2 consequently no 18 exchange even if there is conformational exchange (37 to 38) 10

11 Prediction of ydrolytic Pathway of Lactone elative ate of ydrolysis of Isomeric Lactones 11

12 eaction of Alkoxide on Lactonium Salt Experimental proof of stereoelectronic control 12

13 ydrolysis of Cyclic rthoesters The formation of esters from the mild acid hydrolysis of orthoesters proceeds through the formation of a hemi-orthoester tetrahedral intermediate as described by the following equation hemi-orthoester Possible product formation: 13

14 Mild Acid ydrolysis of Bicyclic rthoester with Two Different Alkoxy Groups Deslongchamps C 3 C 3 + CD 3 CD 3 C 3 clear preference for the exchange of the axial C 3 group (100/1) Kirby 14

15 Nine Conformers of Cyclic rthoester B, D, G, and I are eliminated because of strong steric effects (>4 kcal). C is unreactive. A, E and F should be reactive. 15

16 C is unreactive in acid 16

17 The Three eactive Conformers and their Corresponding Dialkoxy Carbonium Salt (1) E cleaves with no secondary S.E. (2) A and F cleave with one secondary S.E. (3) F yields one molecule (ring is cleaved) (4) A yield two molecules (favored entropically) A is thus the favored cleavage 17

18 N.B. ~5% lactone in case of no ring inversion is explained by cleavage of the boat form of 20. >5% lactone in case of ring inversion is explained by cleavage as above and by cleavage of 23 and

19 Product ratio of lactone (L) and hydroxy-ester (E) from the hydrolysis of cyclic orthoesters as a function of p* ESUME: WIth Chair Inversion: p < 3: more lactone p > 3: < 5% lactone WIthout Chair Inversion: all p: > 95% hydroxy-ester [ Can.J.Chem ] 19

20 emiorthoester chanism of Fragmentation as a Function of p p 3 -. C.. return less favored C less reactive p 3 C 3 +. C + return favored C C more reactive + More Lactone at p biomolecular process: less return + + C not a biomolecular process: more return 20

21 Small % of Lactone Produced in Cyclic rthoester ydrolysis CNCLUSIN ~ 5% LACTNE IS PDUCED VIA 5% CMPETITIVE BAT-LIKE TS 21

22 Cyclic rthoester with ing Inversion CNCLUSIN ME LACTNE IS PDUCED 22

23 S. Li, P. Deslongchamps. Tetrahedron Lett. 35, 5641 (1994). P. Deslongchamps, Y.L. Dory, S. Li. Tetrahedron 56, 3533 (2000). C.A. Bunton,.. De Wolfe. J. rg. Chem. 30, 1371 (1954). 23

24 BIMLECULA PCESS: ELATIVE ATE rthoester of formic acid el. rate: Entropy: 6.4 x x x cleavage 3 cleavages 3 cleavages Leaving group: C 3 C 3 C 2 5 rthoester of acetic acid el. rate: Entropy: 8.4 x x cleavage 3 cleavages Leaving group: C 3 C

25 ELATIVE ATE F YDLYSIS: TESTE VS TCABNATE Shigui LI 25

26 TESTE AND TCABNATE: ELATIVE ATE, CNFMATINAL ANALYSIS, AND STEEELECTNIC EFFECTS 26

27 lower than β attack lower than β attack 27

28 DIFFEENCE F EACTIVITY BETWEEN XENIUM AND DIXENIUM INS C + + C oxenium 80% α α T.S. + 20% β C G* = 0.8 kcal/mol o T.S. β C + 95% α C T.S. + G* = 1.8 kcal/mol dioxenium β 5% C + o T.S. * Position of T.S. 28

29 TESTES EACT WIT GIGNAD EAGENTS T YIELD ACETALS AND KETALS rthoester 3 gives 5 with axial group; 4 is unreactive 3 and 4 ( 1 = 2 = ; 1 = 2 = C 3 ; 1 = C 3, 2 = ) Grignard eagent ( 1 = C 3, C 2 5, (C 3 ) 2 C, p-c 6 4 ) Eliel N.B. Leaving C 3 group and incoming alkyl group prefer axial orientation. 29