ENAMINES AND YLIDES

M.SC-II (SEM-III) ORGANIC CHEMISTRY

PREPERATION OF SULFOXIDES:
R S O R
1

(a) Oxidation of alkyl sulphides by

:
O

H2O 2

S O

H2O

H3C

CH3

H2 O 2

H2O

(b) Oxidation of alkyl sulphides using per-acids:

R''COOOH

H3C S

CH3

R''COOH

Generation of carbanion from sulfoxide:

O H3C S CH3

BuLi/LDA/PhLi or MeLi

O H3C S CH2 Li
+

Bu-H

methyl sulphinyl carbanion

1)

O H3C S CH3 n -BuLi

O H3C S
CH2

O
Cl

Li

O S CH3

- LiCl

-keto sulphoxide

Red Al-Hg

O i.e H3C CH3 RCOCH ketone

2)

O H3C S
CH2

R X

H3C
Redn

H3C R

S O

3)

O
NaOH

O S
Redn

OH

O S

S H3C
BrCH2COOMe

CH3

CH3 CH 2COOMe

NaBH4

CH3 CH 2COOMe

-MeOH

O O R Lactone
Redn

O O CH3 R S O

5)

H (CH 2)n

O S Ph
LDA RI

R S (CH 2)n O Ph Ph S (CH 2)n R CH3

HO (CH 2)n

6)

O Ph S
LDA

O S

CH3 CH2 H3C O S Ph

H3C CH3

CH2

H 3C

CH3

CH3 H3C H3C CH3

H2 O

CH3 H3C OH H3C

PREPARATION OF SULPHONES:
R O S R O

(a) Addition of sulphuric acid to polar C=C bonds:

O R O S H O H

+
H
donor or

Z H
acceptor group

H3C

S O H

Here, R=

Z=

withdrawing group

+
O

PhSO 2H O

H SO 2Ph

(b) Addition of sulphuric acid to polar C=O or C=N bond:

R S O

H O

HO H RSO 2 R
1

R S O
O H3C O H3C O

H O

NR''

RSO 2

R' NHR''

O H3C

OH SO 2 CH3

+ H3C

SO 2H

H3C O

Generation of carbanion from sulphones:

O
n -BuLi or LDA orPhLi

H3C

S O CH
-

Carbanion

Now, this carbanion formed can be used in various C-C bond forming reactions. Applications in C-C bond formation: 1) Formation of cyclopropane derivatives:

i)
-

O S
n -BuLi

O S Ar
LDA -

Ar

O Cl

CH

Ar --SO2 Cl Ni -Hg

ii)

O S Ph O O TS
LDA

O S Ph O CH
-

O TS Ph

O S O

n-BuLi

CH3 Ph

O S O H3C
CH3I

O Ph S O C
-

iii) H3C

O S O R

Br

O
LDA

O C
-

H3C

S O

H3C

S O

Br

Br

Br

Ni -Hg

Bamford-Steven Reaction
The BamfordStevens reaction is a chemical reaction whereby treatment of tosylhydrazones with strong base gives alkenes.[1][2][3] It is named for the British chemist William Randall Bamford and the Scottish chemist Thomas Stevens Stevens (1900 2000). The usage of aprotic solvents gives predominantly Z-alkenes, while protic solvent gives a mixture of E- and Z-alkenes.

The treatment of tosylhydrazones with alkyl lithium reagents is called the Shapiro reaction. Reaction mechanism The first step of the BamfordStevens reaction is the formation of the diazo compound 3.[4]

In protic solvents, the diazo compound 3 decomposes to the carbenium ion 5.

In aprotic solvents, the diazo compound 3 decomposes to the carbene 7.

Julia olefination
The Julia olefination (also known as the JuliaLythgoe olefination) is the chemical reaction of phenyl sulfones (1) with aldehydes (or ketones) to give alkenes (3) after alcohol functionalization and reductive elimination using sodium amalgam[1][2] or SmI2.[3] The reaction is named after the French chemist Marc Julia.

This transformation highly favors formation of the trans-alkene. All four steps can be carried out in a single reaction vessel, and use of R3X is optional. However, purification of the sulfone intermediate 2 leads to higher yield and purity. Most often R3 is acetyl or benzoyl, with acetic anhydride orbenzoyl chloride used in the preparation of 2. Several reviews have been published.[4][5]

Reaction mechanism

The initial steps are straightforward. The phenyl sulfone anion (2) reacts with an aldehyde to form the alkoxide 3. The alkoxide is functionalized with R3-X to give the stable intermediate 4. The exact mechanism of the sodium amalgam reduction is unknown but has been shown to proceed through a vinylic radical species (5).[1] Protonation of the vinylic radical gives the desired product (6).

The stereochemistry of the alkene (6) is independent of the stereochemistry of the sulfone intermediate 4. It is thought that the radical intermediates are able to equilibrate so that the more thermodynamically stable trans-olefin is produced most often. Variations Heteroaryl sulfones The replacement of the phenyl sulfones with heteroaryl sulfones greatly alters the reaction pathway.[6] The most popular example is the benzothiazole sulfone.[7] The reaction of the benzothiazole sulfone (1) with lithium diisopropylamide(LDA) gives a metallated benzothiazolyl sulfone, which reacts quickly with aldehydes (or ketones) to give an alkoxides intermediate (2). Unlike the phenyl sulfones, this alkoxide intermediate (2) is unstable and will undergo a Smiles rearrangement[8] to give the sulfinate salt 4. The sulfinate salt (4) will spontaneously eliminate sulfur dioxide and lithium benzothiazolone (5) producing the desired alkene (6).

Since the benzothiazole variation of the Julia olefination does not involve equilibrating intermediates, the stereochemical outcome is a result of the stereochemistry of the initial carbonyl addition. As a result, this reaction often generates a mixture of alkene stereoisomers.

Bestmann-ohira reagent:
Introduction Bestmann-Ohira reagent [(1-diazo-2-oxopropyl)phosphonate] can be prepared by the reaction of dimethyl-2-oxopropylphosphonate, TosN3 [a] or p-acetamidobenzenesulfonyl azide, [b] NaH, tBuOK or Et3N in benzene and THF. An alternative is the preparation using polymer-supported sulfonyl azide and t-BuOK in methylenchloride. [c] The Bestmann-Ohiro reagent is widely used in the conversion of primary alcohols, aldehydes, ketones, and amides into alkynes. Recently, it was employed in the synthesis of pyrazoles as well as 1,3-oxazoles.

Scheme 1

Bestmann modification OhiraBestmann reagent

IUPAC name[hide] dimethyl (1-diazo-2-oxopropyl)phosphonate Dimethyl (diazomethyl)phosphonate can be generated in situ from dimethyl-1-diazo-2oxopropylphosphonate (also called Bestmann's reagent) by reaction with methanol and potassium carbonate. Reaction of Bestmann's reagent with aldehydes gives terminal alkynes often in very high yield.[4][5]

The use of the milder potassium carbonate makes this procedure much more compatible with a wide variety of functional groups. Another modification for less reactive aldehydes is made by replacement of potassium carbonate with caesium carbonate in MeOH and results in a drastic yield increase.[6]

BartonKellogg reaction
The BartonKellogg reaction is a coupling reaction between a ketone and a thioketone through a diazo intermediate forming an alkene.[1][2][3]

This reaction was pioneered by Hermann Staudinger[4], and the reaction also goes by the name Staudinger type diazo-thioketone coupling. Reaction mechanism In the reaction mechanism for this reaction the diazo compound is a 1,3-dipole which reacts with the thioketone in a 1,3-dipolar cycloaddition to a thiadiazoline. This intermediate is unstable and through nitrogen gas expulsion and formation of an intermediate thiocarbonyl ylide it forms a stable episulfide. Triphenylphosphine opens the three-membered ring and then forms a sulfaphosphatane in a manner similar to the Wittig reaction. In the final step triphenylphosphinesulfoxide is expulsed liberating the alkene.

Scope The diazo compound can be obtained from a ketone by reaction with hydrazine to a hydrazone followed by oxidation. Many reagents exist for this conversion for example silver(I) oxide and (bis(trifluoroacetoxy)iodo)benzene [5]. Thethioketone required for this reaction can be obtained from a ketone and phosphorus pentasulfide. Desulfurization of the episulfide can be accomplished by many phosphines and also by copper powder.

The main advantage of this reaction over the McMurry reaction is the notion that the reaction can take place with two different ketones. In this regard the diazo-thioketone coupling is a crosscoupling rather than a homocoupling.

Stevens rearrangement
The Stevens rearrangement in organic chemistry is an organic reaction converting quaternary ammonium salts and sulfonium salts to the corresponding amines or sulfides in presence of a strong base in a 1,2-rearrangement.[1]

The reactants can be obtained by alkylation of the corresponding amines and sulfides. The substituent R next the amine methylene bridge is an electron-withdrawing group. The original 1928 publication by T.S. Stevens[2] concerned the reaction of 1-phenyl-2- (N, Ndimethyl) ethanone with benzyl bromide to the ammonium salt followed by the rearrangement reaction with sodium hydroxide in water to the rearranged amine.

A 1932 publication[3] described the corresponding sulfur reaction. Reaction mechanism The reaction mechanism of the Stevens rearrangement is one of the most controversial reaction mechanism in organic chemistry.[4] Key in the reaction mechanism[5][6] for the Stevens rearrangement (explained for the nitrogen reaction) is the formation of an ylide after deprotonation of the ammonium salt by a strong base. Deprotonation is aided by electron-withdrawing properties of substituent R. Several reaction modes exist for the actual rearrangement reaction. A concerted reaction requires an antarafacial reaction mode but since the migrating group displays retention of configuration this mechanism is unlikely. In an alternative reaction mechanism the NC bond of the leaving group is homolytically cleaved to form a di-radical pair (3a). In order to explain the observed retention of configuration, the

presence of a solvent cage is invoked. Another possibility is the formation of a cation-anion pair (3b), also in a solvent cage. Recently the elimination recombination coupling mechanism opens a new approach to understand the formation of normal and abnormal product in the stevens rearrangement[7]

Scope Competing reactions are the Sommelet-Hauser rearrangement and the Hofmann elimination. In one application a double-Stevens rearrangement expands a cyclophane ring.[8] The ylide is prepared in situ by reaction of the diazo compound ethyl diazomalonate with a sulfide catalyzed by dirhodium tetraacetate in refluxing xylene.

HornerWadsworthEmmons reaction
(Redirected from Wittig-Horner reaction) The HornerWadsworthEmmons reaction (or HWE reaction) is the chemical reaction of stabilized phosphonate carbanions with aldehydes (or ketones) to produce predominantly Ealkenes.[1]

In 1958, Leopold Horner published a modified Wittig reaction using phosphonate-stabilized carbanions.[2][3] William S. Wadsworth and William D. Emmons further defined the reaction.[4][5] In contrast to phosphonium ylides used in the Wittig reaction, phosphonate-stabilized carbanions are more nucleophilic but less basic. Likewise, phosphonate-stabilized carbanions can be

alkylated. Unlike phosphonium ylides, the dialkylphosphate salt byproduct is easily removed by aqueous extraction. Several reviews have been published.

Reaction mechanism The HornerWadsworthEmmons reaction begins with the deprotonation of the phosphonate to give the phosphonate carbanion 1. Nucleophilic addition of the carbanion onto the aldehyde 2 (or ketone) producing 3a or 3b is the rate-limiting step.[10] If R2=H, then intermediates 3a and 4a and intermediates 3b and 4b can interconvert with each other.[11] The final elimination of 4a and 4b yield E-alkene 5 and Z-alkene 6.

The ratio of alkene isomers 5 and 6 is dependent upon the stereochemical outcome of the initial carbanion addition and upon the ability of the intermediates to equilibrate. The electron-withdrawing group (EWG) alpha to the phosphonate is necessary for the final elimination to occur. In the absence of an electron-withdrawing group, the final product is the hydroxyphosphonate 3a and 3b.[12] However, these -hydroxyphosphonates can be transformed to alkenes by reaction with diisopropylcarbodiimide. Stereoselectivity The HornerWadsworthEmmons reaction favours the formation of E-alkenes. In general, the more equilibration amongst intermediates, the higher the selectivity for E-alkene formation.

Bibliography:
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AHLUWALIA PS KALSI ADVANCED ORGANIC CHEMISTRY BY BRUCKNER

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