1 nucleophilic additions of hard anions to aldehydes and ketones … nucleophi… · ·...

©Kevin Burgess, March 27, 2017 1

NucleophilicAdditionOfHardAnionsToAldehydesAndKetonesfrom chapter(s) _______ in the recommended text

A. Introduction


B. Types Of Additions To Carbonyls PolarityOfCarbonyls. positively polarized. to carbonyl carbons oxygen. ReactivityOfNucleophilesAndCarbonylsAtDifferentpHValues

more reactive more reactive than ones that are not. hard because are likely to cannot be used completely wrong to show neutral or basic conditions. cannot be reversible.

CH3- NH3O O+H

O

A

drawarrowhere


FormationOfTetrahedralIntermediates

sp3 hybridized. give alcohols. (this is kinetics), (thermodynamics).

tetrahedral intermediate

O-OEt

H

-O OEt


O-H

H

-O H


O-CH3

H

-O CH3


O-

H

-O


one C–O bond(s) one bond(s) the starting materials. it will be ie irreversible addition.

reversibly to ketones

C. Reactions of Aldehydes And Ketones With Hydridic Reducing Agents

relatively stable relatively unstable

MeO-Cl- Br- CN- Me- Ph- CH2CH-


OH-

H+

product

H

-O HH

HO H

O

PhH-

H+

Ph H

-O HPh

OH

OH-

H+

H

-O H OH


does not do

OH-

H+-O H OH

O

H-H+-O H OH

NaBH4 NaH LiAlH4

nucleophilc basic nucleophilc

name: Sodium Borohydride Sodium Hydride Lithium Aluminium Hydride


reduction processes.

O

NaBH4 H2O

-O H OH

two diastereomers

O

(i) NaBH4

(ii) H++

OH OH

O

(i) LiAlH4

(ii) H+OH

O (i) NaBD4

(ii) H++

two diastereomers

H

HO DH

D OH


because:

Lithium aluminium hydride can reduce ester to alcohol, but sodium borohydride cannot.

OH O

OH O

OHOH OHO

MeO2COH

MeO2CO


D. Addition Of Carbanions reactive carbonyls irreversibly. is stronger than under anhydrous conditions. alkoxide does not

OH OH

H

OHOH

OHCN CCl3

EtHO OOH

OHOH OH

OH OH

OH

OHOH

OMe-


H+-O Me HO Me


O Et-


H+-O Et HO Et

O


H+-

H

-O PhPh

OH

O


H+Ph-

H

-O PhPh

OH

O


H+-

H

-O HO H


O


H+Ph- -O Ph HO Ph

O


H+Et-

H

-O EtEt

OH

O


H+O-H

-O OOH

O

O Et-


H+-O Et HO Et


E. Reactions Of Carbonyl Compounds With Acetylide Anions NEt3 NaNH2 MeMgBr HO- LiNiPr2 LiBu Na2CO3

secondary or tertiary

Ph

O Li Ph H3O+

Ph

O-Li

PhPh

OH

Ph

OLi(i)

(ii) H+HO

H2CO(i) H2C2, excess NaH

(ii) H+

OH


EtO (ii) H+

two diastereomers

+Li(i)

EtOH

EtOH

OH O

OH HO O

Ph

OH

Ph

O

Ph

two diastereomers

OH OH OO


F. Si And Re Faces Revisited enantiomers. Re-face attack Si -face attack.

OHO

OO

Ph

OEt-

Re-faceaddition

Si-faceaddition

Et-

PhHO Et

PhEt OH

LiAlH4O

Re-face

OH

Me-

Si-face

O OHMe


(R)-Alcohols are not (S)-alcohols are not

2 Et-

twoSi-faceadditions

O O HO Et Et OH

Ph

O-OMe

Re-faceaddition

Si-faceaddition

-OMe

PhHO OMe

PhMeO OH

R S

Ph

OLiAlH4

Re-faceaddition

Si-faceaddition

PhHO H

PhH OHLiAlH4

S R

1 nucleophilic additions of hard anions to aldehydes and ketones … nucleophi… · ·...

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