SECTION 6 Stereoelectronic Effects (S.E.) and Reactivity ...Section6)2018.pdf · 2 Esters and...
Transcript of SECTION 6 Stereoelectronic Effects (S.E.) and Reactivity ...Section6)2018.pdf · 2 Esters and...
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SECTION 6
Stereoelectronic Effects (S.E.)
and Reactivity of Esters and Related Functions
(2018)
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Esters and Related Functions
2 conformations
Primary Stereoelectronic Effects
Resonance Structure and
Stereoelectronic Effect in Ester
N. S. True, R. K. Bohn. J. Phys. Chem. 1978, 82, 478-479.
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Secondary Stereoelectronic Effects and Relative Stability of Esters
even t-butyl formate:
N. S. True, R. K. Bohn. J. Phys. Chem. 1978, 82, 478-479.
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Z-esters:
E-esters/lactones:
t versus s-p in Z-ester and E-ester (lactone)
and Justification of the Relative Importance of Resonance
Structures
IR = 1730 cm-1
IR = 1790 cm-1
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Comparison Between Z and E-esters
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LACTONE: RATE OF HYDROLYSIS 1N NaOH / Dioxan-H2O (60:40)
Ring size Rate
5…………………1480
6……………… 55000
7…………………2250
8…………………3530
9…………………..116
10……………………0.22
11……………………0.55
12……………………3.3
13………………..….6.0
14…………………...3.0
16……………………6.5
g-butyro lactone
valero lactone
R. Huisgen and H. Ott. Tetrahedron 1959, 6, 253-267.
…..8.4
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CH Acidity in Z and E-esters
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Meldrum’s Acid
E. M. Arnett, S. G. Maroldo, S. L. Schilling, J. A.
Harrelson,
J. Am. Chem. Soc., 1984, 106, 6759.
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Relative Stability of Dialkoxy-carbonium Ion
C
O CH3
O
R
(NMR)
+
CH3
O O
CH3
+
X-rays
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Experimental Evidence for Secondary Stereoelectronic Effects
Iodide Displacement on Lactonium Salt
SN2 on secondary carbon faster than primary one due to SE control
slowfast
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Resonance Structures in Lactonium Salt
less important more important
lactone (E)lactonium saltiodo ester (Z)
N. Beaulieu, P. Deslongchamps, Can. J. Chem., 1980, 58, 164.
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Stereocontrolled Cleavage of Hemiortoester
Tetrahedral Intermediate
primary (2 A.E.)secondary (1 A.E.)
primary (1 A.E.)secondary (2 A.E.)
primary (2 A.E.)secondary (2 A.E.)
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t Bond and Hemiorthoester Cleavage
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O18-Exchange Concurrent to Hydrolysis in Ester and Lactone
Z-ester undergoes O18 exchange as k2 k3
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O18-Exchange Concurrent to Hydrolysis in Z Ester
In both k2 and k3, cleavage takes place with
2 secondary stereoelectronic effects (or 2 A.E.)
(1) Groupe partant semblable
(2) Transfert de protons à la vitesse de diffusion
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t Bond and Z Ester Hydrolysis
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Lactone (E-ester) do not undergo O18-Oxygen
Exchange Concurrent with Hydrolysis
in k3, cleavage takes place with 2 secondary stereoelectronic effects
in k2, cleavage takes place with 1 secondary stereoelectronic effects
k3 is thus greater than k2
consequently no O18 exchange even if there is conformational exchange (37 to 38)
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Prediction of Hydrolytic Pathway of Lactone
Relative Rate of Hydrolysis of Isomeric Lactones
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t Bond and Lactone Tetrahedral Intermediates
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Reaction of Alkoxide on Lactonium Salt
Experimental proof of stereoelectronic control
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t Bonds – Alkoxide on Lactonium Salt
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Hydrolysis of Cyclic Orthoesters
Possible product formation:
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
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Mild Acid Hydrolysis of Bicyclic Orthoester with Two Different Alkoxy Groups
Kirby
Deslongchamps
Tet. Lett. 1982, 4163-4166.
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Nine Conformers of Cyclic Orthoester
B, D, G, H and I are eliminated because of strong steric effects (>4 kcal).
C is unreactive.
A, E and F should be reactive.
(unreactive)
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C is unreactive in acid
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The Three Reactive 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
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t Bonds and the Three Reactive Conformers
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29N.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 24.
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30RESUME: WIth Chair Inversion: pH < 3: more lactone
pH > 3: < 5% lactone
WIthout Chair Inversion: all pH: > 95% hydroxy-ester
Product ratio of lactone (L) and hydroxy-ester (E) from the hydrolysis of cyclic orthoesters as a function of pH*
[ Can.J.Chem. 1985 ]
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Hemiorthoester Mechanism of Fragmentation as a Function of pH
O+
pH 3
pH 3
ORC
O
R
H
O R
HOH
-OH
..
..
+ORC
O
R ROH + H2O + OH-
returnless
favoredless
reactive
ORC
O
R
H
O R
H3O+
ORC
O
R
H
O R
..
+
returnfavored
+ORC
OH
R ROHmore
reactive
+
+ORC
O
R H3O+
H2O
OHO R
H
+O OH
+ ROH biomolecular process:less return
OOH
OR
More Lactone at pH 3
H
+OH
C
OH
OR
+
not a biomolecular process:more return
H
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Small % of Lactone Produced in Cyclic Orthoester Hydrolysis
CONCLUSION
~ 5% LACTONE IS
PRODUCED
VIA 5% COMPETITIVE
BOAT-LIKE TS
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Cyclic Orthoester with Ring Inversion
CONCLUSION
MORE LACTONE IS
PRODUCED
but close back
due to internal
return
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C.A. Bunton, R.H. De Wolfe.
J. Org. Chem. 30, 1371 (1954).
S. Li, P. Deslongchamps.
Tetrahedron Lett. 35, 5641 (1994).
P. Deslongchamps, Y.L. Dory, S. Li.
Tetrahedron 56, 3533 (2000).
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Sinnott Opposition to « Stereoelectronic » Effect
Sinnott1 concluded that there is evidence that neither a steric nor any transition state “stereoelectronic effect” is
responsible for the lower reactivity of the orthocarbonate vs orthoester. This was based on an incorrect statement.2
“In the S4 conformation, each C-O bond is antiperiplanar to an sp3 lone pair of electrons on each of the remaining
three oxygen atoms.” On the contrary, the S4 can have only two such lone pairs.
1 Kandanarachchi, P., Sinnott, M. L. J. Chem. Soc., Chem. Commun. 1992, 777.2 Li, S., Deslongchamps, P. Tet. Lett. 1994, 35, 5641.
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37Shigui LI
RELATIVE RATE OF HYDROLYSIS:
ORTHOESTER VS ORTHOCARBONATE
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ORTHOESTER AND
ORTHOCARBONATE:
RELATIVE RATE,
CONFORMATIONAL ANALYSIS,
AND
STEREOELECTRONIC EFFECTS
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Acid Hydrolysis of Tricyclic Orthoester
P. Deslongchamps, Y.L. Dory, S. Li.
Heterocycles 1996, 42, 617.
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Reaction Pathways of Hydrolysis of Orthoester
P. Deslongchamps, Y.L. Dory, S. Li.
Heterocycles 1996, 42, 617.
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41lower than b attack lower than b attack
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DIFFERENCE OF REACTIVITY BETWEEN OXENIUM AND DIOXENIUM IONS
OR
O
H
ORO
R
H
Oo
O
O
OR
Me
Me
O
O
OR
o
Me
Me* Position of T.S.
oxenium
dioxenium
G* = 0.8 kcal/mol
G* = 1.8 kcal/mol
80%
20%
95%
5%
b
C
O
H
+
R
C
O
O
+
R Me
C
O
H
+
R
O
HMe
T.S.
C
O
H
+
OH
Me
T.S.
O
H
Me
b
C
O
O
+
R Me
O
H Me
T.S.
CO
O
+
R Me
OH Me
T.S.
OR
O
O
Me
Me
b
Me
Me
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ORTHOESTERS REACT WITH GRIGNARD REAGENTS TO YIELD ACETALS AND KETALS
N.B. Leaving OCH3 group and incoming alkyl group prefer axial orientation.
3 and 4 (R1 = R2 = H; R1 = R2 = CH3; R1 = CH3, R2 = H)
Grignard Reagent (R1 = CH3, C2H5, (CH3)2CH, p-RCH6H4)
Orthoester 3 gives 5 with axial R group; 4 is unreactive
Eliel