1.1 introduction - inflibnetshodhganga.inflibnet.ac.in/bitstream/10603/19591/6/06_chapter1.pdf ·...

1.1 Introduction

The oxidative functionalization of olefins is of major importance for

both organic synthesis and the individual production of bulk and fine

chemicals1. Among the different oxidation products of olefins, 1, 2-diols are

used in a wide variety of applications. Ethylene- and propylene- glycol are

produced on a multi-million ton scale per annum, due to their importance as

polyester monomers and antifreeze agents2. A number of 1,2-diols such as 2,3-

dimethyl-2,3-butane diol, 1,2-octane diol, 1,2-hexane diol, 1,2-pentane diol,

1,2- and 2,3-butane diol are of interest in the fine chemical industry. In

addition, chiral 1, 2-diols are employed as intermediates for pharmaceuticals

and agrochemicals. At present 1, 2-diols are manufactured industrially by a

two step sequence consisting of epoxidation of an olefin with a hydroperoxide

or a peracid followed by hydrolysis of the resulting epoxide3. Compared with

Chapter 1 Dihydroxylation of Olefinic Compounds – A Concise Review

Analytical and Synthetic Investigations in Olefinic Compounds 2

this process the dihydroxylation of C = C double bond constitutes a more

atom-efficient and shorter route to 1,2-diols.The dihydroxylation of olefins has

been of value in degradation studies of natural products, synthetic procedures,

and in the characterization of many olefinic compounds.

There are many reagents which can effect the dihydroxylation of

olefins. To be of value, hydroxylation reagents must be stereospecific, leading

entirely, or at least predominantly, to the cis- or trans- addition of the two

hydroxyl groups. The relation between the olefin, which may have a cis- or

trans- configuration, and the resulting glycol, which may be described by the

terms cis- or trans-, erythro or threo, or meso or dl, depending on the nature of

the other groups attached to the glycol system, is set out below:

Glycol cis,meso

Cis- olefin Trans- olefin

Glycol trans,dl

or erythrohydroxylati

onSynTranshydroxylation

Syn

hydroxylation

Trans

hydroxylation

or threo

The chief methods of effecting cis- hydroxylation are by reaction with

potassium permanganate, with osmium tetroxide alone or as a catalyst, or with

silver iodo acetate according to Woodward procedure. The most important

method of trans-hydroxylation is undoubtedly the reaction with per acids,



though the Prevost reaction and oxidation with hydrogen peroxide in alkaline

solution or in the presence of certain oxide catalysts are also useful

procedures.

1.2 Hydroxylation using potassium permanganate

Oxidation by potassium permanganate is one of the simplest and

earliest procedures for effecting dihydroxylation of olefins. Because this

reagent can oxidize olefins in several other ways, and because the desired

glycol may be subject to further oxidation or to acid- or alkali-catalyzed

isomerization,it is necessary to control the reaction conditions carefully if the

yield of glycol is not to be considerably reduced by extensive side reactions.

Best results are usually obtained in alkaline media using water or aqueous

organic solvents; other oxidation products may accompany or replace the diol

in neutral or acid media.

The oxidation of an olefin with potassium permanganate is very facile

in several solvents (aqueous EtOH, acetone, t-BuOH), under acidic, basic or

neutral conditions. Under dilute conditions, permanganate oxidizes olefins to

1, 2-diols. Under vigorous conditions (75oC, 0.2M KOH) extensive carbon-

carbon bond cleavage occurs. In neutral media (and very low hydroxide

concentration) large quantities of α-hydroxy ketones are formed.

The mechanism of the reaction between carbon-Carbon double bonds

and permanganate ion has been a subject of interest for nearly one century4.

Wagner5, noting that the oxidation of unsaturated dicarboxylic acids by basic

permanganate solution resulted in the syn- addition of two hydroxyl groups to

the double bond, suggested that the intermediate in the reaction could be

acyclic manganate (V) diester,1 ,which would undergo hydrolysis with

liberation of a diol in aqueous alkaline solutions (scheme1).



O O

Mn

O O-

H2O

OH OH+ MnO4

- + H2MnO4-

Scheme 1

In more modern times Wiberg and Saegebarth6 substantiated this

mechanism by showing, with the aid of isotropic tracers, that the oxygen in the

diol came from the permanganate and not from the solvent.

This mechanism also accounts for the formation of cleavage products

which are found when the reaction is carried out under acidic conditions7.

Protonation of 1 would increase the oxidation potential of manganate (V)8 and

provoke an oxidative decomposition as depicted in scheme2.

O

Mn

O-

H+

O O

Mn

O OH

O HMnO2

O

O 1

+2

Scheme 2

Wiberg9 and Brownridge10 also observed (independently) that

intermediates can be detected when crotonic or cinnamic acid is oxidized by

permanganate. Although it was initially believed that these intermediates were



the previously proposed cyclic manganese (V) diester, 1, other workers11,12,

subsequently presented evidence which they interpreted as indicating that the

detectable intermediates were actually in a +4 oxidation state. A manganate

(IV) intermediate could be formed in a number of ways, the most direct being

a rapid disproportionation of the manganate (V) diester (scheme3) as

suggested by Wolf, Ingold and Lemieux13.

Mn

O O

Mn

O-O

O O

Mn

O OO O

OO

__

+

1 2 3

2

Scheme 3

The intermediates 2 and 3 could then undergo rapid oxidative

decomposition giving Mn2+ and molecular MnO2 (alleged to be the detectable

intermediate) as in schemes 4 and 5.

O O

Mn

O O

O

__

+ 2 H+ 2 + H2MnO2

2 Scheme 4



O O

Mn

O O

OH+2 + MnO2

3 Scheme 5

Sharpless14 and his co-workers have pointed out that the reaction

mechanism may be further complicated by the intervention of organometallic

complex between the reactants and the first detectable intermediate (scheme6).

MnO

O

O O

Mn

O

O

O

O

OH2

O O

Mn

H2O

_

+MnO4

-

4

5

OO-

Scheme 6

The evidence suggesting this possibility comes from a comparison with

an analogous reaction (between olefins and chromyl chloride) which proceeds



via a similar organometallic intermediate and from a consideration of the fact

that the carbon-carbon double bonds are not usually subject to nucleophilic

attack as implied by scheme 1. Instead it is more likely that the initial interaction

would be between the electropositive metal and the electron-rich double bond as

in scheme615. As this scheme indicates, two possible structures for the

organometallic complex could be considered, a trigonal bypyramid, 4, or an

octahedron, 5. Of these two possibilities there are both theoretical and

experimental evidences favoring the octahedral complex, 5, which incorporates

solvent as an additional ligand. The experimental evidence favoring this

structure comes from work by Wolf and Ingold16, who studied the oxidation of

1,5-hexadiene in oxygen-18 enriched water. From an analysis of the product of

this reaction (scheme7) they found that 17% of the oxygen in the product came

from the solvent and the stereochemistry of the reaction indicated that this

oxygen must have been delivered from the coordination shell of the manganese,

thus establishing that manganese expands its coordination shell by incorporation

of one molecule of water as the reaction proceeds. Furthermore, since 5 is an 18-

electron organometallic system, whereas 4 is a 16-electron system, theoretical

considerations would also favor 5.

Dihydroxylation using potassium permanganate in the presence of

phase transfer catalysts permits non-aqueous solvents such as dichloromethane

to be used, and this generally leads to an increase in the yield of the oxidation

products17. A solution of alkene in dichloromethane and aqueous sodium

hydroxide uses a phase transfer reagent such as benzyl triethyl ammonium

chloride to solubilize the reactants. When potassium permanganate was added

to the mixture, oxidation of cis-cyclooctene to cis-1,2-cyclooctane diol was

observed in significantly higher yields than could be obtained under standard

permanganate oxidation conditions18.



1.3 Hydroxylation using osmium tetroxide

In general the dihydroxylation of olefins is catalyzed by osmium,

ruthenium or manganese oxo species. Osmium tetroxide (OsO4) is the most

reliable reagent available for the cis hydroxylation of alkene to give the

corresponding cis diols19. It was Hoffmann20, 21 who first showed that

osmium tetroxide could be used catalytically in the presence of sodium or

potassium chlorate for the dihydroxylation of alkenes. The work was later

extended by Milas22,23 who reported osmium tetroxide-catalyzed oxidation of

alkenes by hydrogen peroxide. Other secondary oxidizing agents that have

been used in conjunction with osmium tetroxide for the catalytic oxidation of

alkenes include tert-butyl hydroperoxide, N-methyl morpholine N-oxide,

oxygen, sodium periodate, and sodium hypochlorite.

Although osmium tetroxide had been used previously as a catalyst in

hydroxylation procedures, this compound is itself a most satisfactory

hydroxylating agent. It is suggested that the reaction occurs via the formation

of an intermediate osmium (VI) ester complex which could be hydrolyzed

reductively to give insoluble osmium salts or oxidatively to regenerate

osmium tetroxide, in both cases the corresponding vicinal cis-diol being

formed selectively in good yield. Addition of pyridine to hydroxylation

reaction led to a marked increase in the rate of formation of intermediate ester

complexes.

1.3.1 Non catalytic cis- Hydroxylation of Olefins

1.3.1.1 Formation and structure of oxo osmium (VI) ester complexes

a) In the absence of tertiary amines

When treated at ordinary temperatures with an equivalent quantity of

osmium tetroxide in anhydrous ether; or less frequently in benzene,



cyclohexane22, or dioxane23solution, olefins slowly form addition complexes

which usually precipitate from the solution in an almost quantitative yield

during a period of up to four days.

The cis hydroxylation of olefins by osmium tetroxide is well

established to take place via the formation of an osmium (VI) intermediate

which on reductive or oxidative hydrolysis yields the corresponding cis-diol.

The intermediate osmium (VI) complex is usually written as a tetrahedral

species, 624,25 .

OsO4

O

O

OsO

O

6

+

Structure 6, however, although it may exist as a transient species in

solution, would be unlikely to exist in the solid state since this would be an

example of a tetrahedral d2 complex; no examples of tetrahedral d2

stereochemistry exist for third row transition metals. In addition, the O(ester)- Os-

O(ester) angle for complex 6 would be expected to be highly strained in a

tetrahedral configuration. Criegee26,27, 28 has reported the reaction of osmium

tetroxide with alkenes in non-reducing solvents such as diethyl ether or benzene

to yield dark green to black products of stoichiometry OsO4.R and OsO5.R2;

structures for these complexes were tentatively proposed on the basis of osmium

analyses and hydrolysis of the complexes with sodium sulfite to give the

corresponding cis-diols and the osmium sulfite complex Na4[Os(SO3)3].6H2O,

726. The nature of the osmium(VI) intermediates has been recently

reinvestigated,and they have been formulated as dimeric monoester complexes

syn-29 and anti-[Os2O4(O4R)2]30, 8 and 9, and monomeric diester complexes

[OsO(O2R)2],10,30 respectively. These diamagnetic products have been shown by



X-ray crystallographic studies, in the case of anti-[Os2O4(O2C2Me4)2]31,32 to

contain five-coordinate square-based pyramidal osmium(VI) with cyclic ester

rings.

O

Os

O

O

OO

O

O O

Os OsO

O

OsO

OOO

OO

O

OOs

O

O

O

8 9 10 The formation of dimeric monoester complexes is generally preferred

for reactive alkenes such as cyclohexene, ethylene, and oleic acid, while for

less reactive alkenes (i.e., tetra substituted alkenes or those incorporating

sterically large or electron-withdrawing groups) diester complexes are formed.

This may be partially explained by considering the intermediate tetrahedral

species, 6. If this species is formed in low concentration as in the case of less

reactive alkenes, the formation of dimeric monoester complexes will be

discouraged and the formation of diester complexes preferred. The conversion

of monoester to diester products can be achieved by reaction with ethanolic

hydrochloric acid or with aqueous alcoholic potassium hydroxide. It seems

likely that this reaction occurs via hydrolysis of the monoester to the cis-diol

followed by subsequent reaction of the diol with another molecule of

monoester to yield the corresponding diester species.

b) In the presence of tertiary amines

It was noted by Criegee33 that the rate of formation of osmium (VI)

ester complexes could be dramatically increased by the addition of an excess

of tertiary amine, such as pyridine, to solution of osmium tetroxide and alkene.

Brown diamagnetic products were isolated, and these have been recently

characterized as diolatodioxo bis (amine) osmium (VI) complexes, [OsO2



(O2R)L2],11, (R= alkene, L= pyridine28,30,33,34-42, isoquinoline30, quinoline33, 3-

picoline38-40, 4-picoline38, and 3-chloro pyridine38-40).

O

OOs

O

OL

L

11 The osmium (VI) ester complexes 11 can also be prepared by reaction

of the monoester or diester complexes 8, 9, or 10 with an excess of tertiary

amine26,28,33.

Osmium tetroxide itself reacts with polydentate and monodentate

tertiary amines in non reducing conditions to give the adducts OsO4.L (L=

pyridine33, 43, isoquinoline44, phthalazine44, pyridazine44, hexa methylene

tetramine44,45, triethylene diamine44, and 5-methyl pyrimidine44). These

adducts retain the integrity of the os(VIII)O4 entity and in the case of

hexamethylene tetramine complex can be used as a stabilized, non volatile

form of osmium tetroxide46, the high volatility and toxicity of osmium

tetroxide being considered a great hazard.

1.3.1.2 Hydrolysis of ester complexes

Osmium (VI) ester complexes can be hydrolyzed either reductively or

oxidatively. Reductive hydrolysis is generally carried out using sodium or

potassium sulfite or bisulfite26, 33 , lithium aluminium hydride47,48 or hydrogen

sulfide49 to yield the corresponding cis-diols together with lower forms of

osmium which are removed by filtration. The reduction and possible

hydrolysis of osmium ester complexes by ethylene diamine tetra acetic acid

have been recently reported50. Oxidative Hydrolysis of osmium (VI) ester

complexes is generally carried out by using metal chlorates, N-methyl



morpholine N-oxide, hydrogen peroxide, or tert-butyl hydroperoxide. The cis-

diol is formed together with osmium tetroxide which can react further with

alkene, thus rendering the process catalytic.

1.3.1.3 Mechanism of Cis Hydroxylation

The oxidation of alkenes by osmium tetroxide and other oxo metal

complexes such as chromyl chloride, potassium permanganate, and selenium

dioxide has been thought, in general, to proceed via direct oxygen attack at the

unsaturated centre (12).

Os

OO

O O

Os

O

O

O

O

6e

12 13

The six-electron transition state (13) thus formed will lead to the cis

addition of osmium tetroxide to the alkene. Cyclic transition states such as 13

have been proposed as intermediates in the one-step cis addition of osmium

tetroxide to double bonds50-53. Sharpless and co-workers54 have later suggested

the possibility of indirect attack of alkenes by osmium tetroxide. Their

proposal is based on the observation that nucleophilic attack of the carbonyl

(C=O) function occurs exclusively at the carbon centre and not at oxygen.

Similarly, a C==C bond, although, only a weak nucleophile, would be

expected to attack not at oxygen but at the more electropositive osmium centre

of the Os=O bond, thus forming initially an organometallic intermediate(14).



Os

OO

O O

Os

O

O

O

14 An intermediate involving Os-C bonding has been previously proposed

by Zelikoff and Taylor55. Their proposals were based on the differing

reactivity of osmium tetroxide towards alkenes as compared with

permanganate ion. The intermediate 14 would be considered to rearrange in a

rate-determining step to a five-membered cyclic ester complex, with

subsequent hydrolysis occurring relatively quickly55. It has been observed that

electron-withdrawing groups on the alkene retard its reactivity towards

osmium tetroxide56-58 presumably due to the lowering of the nucleophilicity of

the C = C bond. An opposite effect is noted for permanganate oxidation 56.

Similarly aromatic hydrocarbons are oxidized by osmium tetroxide at the sites

of greatest electron density59. Although no direct experimental evidence is

available for the existence of an organometallic intermediate such as 14, the

hypothesis is reasonable on the basis that Os=O bond would be expected to

react with a nucleophile initially at the metal centre and not at oxygen. In

addition, the intermediate 14 may be useful in explaining the dramatic increase

in the rate of formation of osmium (VI) ester complexes on addition of tertiary

amines such as pyridine. Electron donation to the osmium atom may induce

osmium-carbon bond cleavage with a corresponding rate increase in the rate-

determining step leading to the formation of complexes [OsO2 (OR) L] (15)

and finally [OsO2 (O2R)L2](11)54.



Os

O

O O

O Os

OO

O

OOs

O

O

O

O

L:

+L

L

+LL

L

14 1115

The hydrolysis of osmium (VI) ester complexes has been shown to

occur with exclusive Os-O (ester) bond cleavage; hydrolysis in H218O showed

no 18O incorporation into the diol38. Hydrolysis is also found to be catalyzed

by acidic or alkaline media. At high PH (10 M KOH), osmium (VI) ester

complexes are hydrolyzed to give potassium osmate, while at lower PH’s and

in acidic conditions, the disproportionation to osmium (VII) and osmium (V)

occurs38, with the corresponding formation of osmium (VIII) and osmium (IV)

species. The hydrolysis equations are shown below 54, 60-62 .

6 Os(VI) → 3 Os(VII) + 3 Os(V) (7)

3 Os (VII) → 2Os (VIII) + Os (V) (8)

4 Os (V) + 2 Os (VIII) + 6 H2O → 6 Os (IV) + 12H+ + 3 O2 (9)

4 Os (V) + 2 H2O → 4 Os (IV) + 4 H+ + O2 (10)

Schemes 7-10

In general, the hydrolysis of osmium (VI) ester complexes is carried

out reductively with lithium aluminium hydride, potassium sulfite, or

hydrogen sulfide to give reduced forms of osmium which can be removed by

filtration. The oxidative hydrolysis of ester complexes renders the cis-

hydroxylation process catalytic.



1.3.2 Catalytic Cis Hydroxylation of Olefins

Although stoichiometric oxidation of alkenes by osmium tetroxide

usually gives better yields of diol products and are particularly applicable for

small scale oxidation of precious materials it is more usual, for reasons of cost

and convenience, to use osmium tetroxide catalytically. This can be achieved

by using osmium tetroxide in the presence of a secondary oxidant which

hydrolyzes the intermediate osmium (VI) ester complex oxidatively to

generate the tetroxide which can undergo further reduction by the substrate. A

variety of oxidants have been used in conjunction with osmium tetroxide, the

most popular being hydrogen peroxide, metal chlorates, tert-butyl

hydroperoxide, N-methyl morpholine N-oxide, sodium periodate, and sodium

hypochlorite. These catalytic reagents, however, particularly oxygen and

sodium periodate, have the disadvantage that appreciable overoxidation can

occur, leading to the formation of keto or acid products. This can be

minimized by the use of tert-butyl hydroperoxide or N-methyl morpholine N-

oxide. The catalytic use of osmium tetroxide is generally highly successful and

is applicable to many facets of organic synthesis.

1.3.2.1With Hydrogen Peroxide

A catalytic amount of osmium tetroxide in the presence of an excess of

hydrogen peroxide (Milas’ reagent) readily oxidizes alkenes to give the

corresponding cis- diols as the major product63-65. The catalytic reagent is

prepared in tert-butyl alcohol, to which it is inert, and can be used under

anhydrous conditions or with 8% water. Benzene, acetone and diethyl ether

have been used as solvents.

Although hydrogen peroxide has been shown to act as a hydroxylating

agent when irradiated with ultraviolet radiation66, under normal conditions



negligible oxidation of alkenes occurs. On the addition of osmium tetroxide,

however, vigorous reaction takes place with reduction and subsequent re

oxidation of osmium until all the peroxide is consumed. Milas and others have

studied the mechanism of the catalytic process. On addition of osmium

tetroxide to hydrogen peroxide, the formation of a complex67,68 formulated as

peroxy osmic acid, H2OsO6 (16) 69-72, takes place; this rapidly reacts with

alkenes to form ester species. Hydrolysis is thought to occur via cleavage of

the osmium (VIII) ester complex 18 to give osmium tetroxide and the

corresponding cis diol 72.

Os

O

OH

O

OH

O

O

OH

Os

O

O

O

O

OH

Os

O

O

OH

OH

O

O

+

16 17 18

The main disadvantage of this catalytic method is that over oxidation to

give carbonyl products often occurs, thus lowering the final yield of cis-diol.

Potassium osmate73 and osmium trichloride 74 have been also used with

hydrogen peroxide as cis hydroxylating agents. These reagents behave as

nonvolatile sources of osmium tetroxide, the tetroxide being generated in situ

by hydrogen peroxide oxidation.

In spite of the fact that hydrogen peroxide was one of the

stoichiometric oxidants to be introduced for the osmium-catalyzed

dihydroxylation, it was not actually used until recently. When using hydrogen

peroxide as the reoxidant for transition metal catalysts, very often there is the



big disadvantage that a large excess of H2O2 is required, implying that the

unproductive peroxide decomposition is the major process.

1.3.2.2 With Metal Chlorates

It was observed that potassium chlorate in the presence of a catalytic

amount of osmium tetroxide could oxidize a series of alkenes to give the

corresponding cis- diols 75-77. These oxidations presumably occurred via the

formation of an osmium (VI) ester complex which could be hydrolyzed by

chlorate ion to regenerate osmium tetroxide, analogous to that found for

Milas’ reagent. It has been noted, however, that the oxidation potential of

potassium chlorate is raised by the addition of a trace of osmium tetroxide, and

the formation of an addition product has been proposed 75. Alternatively, the

formation of free hypochlorous acid which could act as a source of hydroxyl

radicals has also been thought to occur 78. This would explain the appreciable

amounts of chloro hydroxy products formed when osmium tetroxide is used in

conjunction with sodium or potassium chlorate.

The osmium tetroxide/ sodium chlorate catalytic reagent (Hofmann’s

reagent) is widely used as a cis- hydroxylating agent in spite of the

disadvantage of formation of chloro hydroxy products. In general, silver and

barium chlorates give better yields of cis- diol products and are more easily

removed from solution than the corresponding sodium or potassium salts.

1.3.2.3 With Sodium Hypochlorite

The use of sodium hypochlorite as a secondary oxidant for osmium

tetroxide - cis hydroxylation is presumably linked to the observation that

hypochlorous acid is formed in the reaction between osmium tetroxide and

metal chlorates. Two patents in the early 1970s79 describe the successful



dihydroxylation of olefins to cis- diols using osmium tetroxide in the presence

of sodium hypochlorite.

In 2003 the first general dihydroxylation procedure of various olefins in

the presence of sodium hypochlorite as the reoxidant was described by Uta

Sundermeier and coworkers 80. Using α-methyl styrene as a model compound,

100% conversion and 98% yield of the desired 1, 2- diol were obtained.

1.3.2.4 With tert-Butyl Hydroperoxide

Although the catalytic use of osmium tetroxide with metal chlorates or

hydrogen peroxide is generally successful, these methods have the

disadvantage that over oxidation may occur, leading to high yields of Ketols

and other aldehydic products. In addition, tri- and tetra substituted alkenes are

often difficult to oxidise since their corresponding osmium (VI) ester

complexes are inert towards oxidative hydrolysis. This has led to the search

for more efficient catalytic cis- hydroxylation methods; the development of

tert- butyl hydroperoxide and N- methyl morpholine N-oxide as secondary

oxidants for osmium tetroxide oxidation has been the most successful in this

respect.

Mc Casland and coworkers81 reported the cis dihydroxylation of olefins

using tert- butyl hydroproxide and osmium tetroxide; however, these latter

workers actually used hydrogen peroxide in tert- butyl alcohol (i.e., Milas’

reagent) for their oxidations. Sharpless and co-workers have developed a

catalytic reagent involving osmium tetroxide and tert- butyl hydroperoxide in

the presence of tetra ethyl ammonium hydroxide82 or tetra ethyl ammonium

acetate83 in tert- butyl alcohol or acetone, respectively. The reactions were

suppressed by the addition of excess sodium bisulfite to precipitate lower

forms of osmium.



In general, the use of tetra ethyl ammonium acetate in acetone was

found to give better results than tetra ethyl ammonium hydroxide in tert- butyl

alcohol particularly for the oxidation of base-sensitive alkenes83. In both cases,

however, better yields of cis- diol products were obtained than with Milas’ or

Hofmann’s reagent, the yield of aldehydic products being much reduced. The

problem of hindered and tetra substituted alkenes notwithstanding, the use of

tert- butyl hydroperoxide is probably the most efficient catalytic procedure

available.

1.3.2.5 With N-methyl morpholine N-oxide

Van Rheenan and coworkers at Upjohn84 have shown that a tertiary amine

N-oxide such as N-methyl morpholine N-oxide (NMO) can be used as both a

catalyst for the hydroxylation of alkenes and an agent to decompose the osmylate

ester. Osmylation with NMO can be accomplished with about 1 mol% OsO4 at

ambient temperatures. This procedure is superior to other procedures since only

small amounts of osmium tetroxide are used. The reaction is usually run in aqueous

acetone, THF, or tert- butanol as one or two-phase reaction.

The use of NMO as secondary oxidant for the catalytic oxidation of

alkenes has the advantage that yields of cis- diols are substantially higher than

those obtained with hydrogen peroxide or metal chlorate reagents. The

catalytic reagent, however, like tert- butyl hydroperoxide, is not very efficient

for the cis- hydroxylation of tetra substituted alkenes. In addition, the greater

cost of NMO as compared with tert- butyl hydroperoxide makes the latter

more economical.

1.3.2.6 With Oxygen or Air

In 1999 Krief and coworkers published a reaction system consisting of

oxygen, catalytic amounts of osmium tetroxide and selenides for the



asymmetric dihydroxylation of -methyl styrene under irradiation with visible

light in the presence of a sensitizer85. Here, the selenides are oxidized to their

oxides by singlet oxygen and the selene oxides are able to re-oxidize osmium

(VI) to osmium (VIII). Air can be used instead of pure oxygen.

The reaction was extended to a wide range of aromatic and aliphatic

olefins86. The procedure was applied to practical syntheses of natural product

derivatives87. This version of asymmetric dihydroxylation not only uses a

more ecological co-oxidant, it also requires much less matter; 87 mg. of

matter (catalyst, ligand, base, reoxidant) are required to oxidize 1 mmol of the

same olefin instead of 1400 mg when the AD-mix is used.

1.4 Hydroxylation using Organic peroxy acids

Since the first report of the peroxy benzoic acid oxidation of olefins by

Prileschajew 88, this name has been associated with the epoxidation and

hydroxylation of olefins by peracids generally. This reaction does not require

transition metal catalysis and the yield of epoxide is often high. Peroxy acids

are prepared by reaction of carboxylic acids with hydrogen peroxide. In

general, strong acids such as formic and trifluoro acetic acid generate useful

equilibrium concentrations of the peroxy acids upon reaction with hydrogen

peroxide. Most other alkyl and aryl acids however require catalytic amounts of

strong mineral acids or p- toluene sulfonic acid to give the corresponding

peroxy acid. Several peroxy acids are commercially available, including

peroxy formic, peroxy benzoic, tri fluoro peroxy acetic, and m-chloro peroxy

benzoic. Hydroxylation with 30% hydrogen peroxide in formic acid solution at

400C is considered to be the most efficient peracid hydroxylation procedure.



With all peracids the epoxide 19 is probably formed first and may be

isolated under suitable conditions, but in acidic solution the reactive epoxides

pass more or less readily into the mono acylated derivative 20 of the glycol 21.

O

RCO2H-CH = CH-Cis addition

-CH - CH- -CH(O- CO-R)-CHOH -CHOH - CHOH-

19

20 21

This change may occur spontaneously in the reaction mixture or may

be effected subsequently on the isolated epoxide.

1.4.1 Stereochemistry

Epoxidation is a cis addition, but, as the normal methods of opening the

epoxide ring are accompanied by Walden inversion, the over-all change of

olefin to diol is equivalent to trans addition. This has been confirmed by a

large number of examples89.

1.5 Hydroxylation using hydrogen Peroxide

For economic and environmental reasons, catalytic olefin oxidations

based on oxygen or hydrogen peroxide are preferred over traditional

stoichiometric oxidations, e.g., epoxidations with peracids and cis-

hydroxylation with permanganate90. Whereas currently several catalytic

methods are available for catalytic epoxidation with aqueous hydrogen

peroxide( most successfully with W-, and Mn-based catalysts)91, high

turnover numbers for cis- hydroxylation reactions are only achieved with

osmium19. However, the high cost and toxicity of osmium hamper large scale

application and provide a strong incentive to develop benign Fe- or Mn- based

cis- hydroxylation catalysts.



1.5.1 Iron and Manganese complexes as catalysts for epoxidation

and cis-hydroxylation using H2O2.

Iron porphyrin complexes are potent catalysts for epoxidation reactions

using H2O2 as oxidant92. However, disadvantages of these complexes like the

pure stability under the reaction conditions and the difficult synthesis of the

ligands limit their applicability. Non-heme iron complexes based on tetradentate

nitrogen ligands like 1, 4,8, 11- tetra aza cyclotetra decane, cyclam 22, tris- (2-

pyridyl-methyl) amine, tpa 23 and derivatives of tpa are able to catalyze

epoxidation reactions93,94. These ligands leave two open coordination sites on

the metal. Depending on whether these open sites are located cis or trans to each

other, different types of selectivity were observed. Complexes with two cis-

open coordination sites like [Fe (tpa) (CH3 CN)2 ] (ClO4)2 (24a) and [Fe (6-Me3-

tpa) (CH3 CN)2] (ClO4)2 (24b) catalyze besides the epoxidation of alkene, also

the cis- dihydroxylation reaction93. Employing [Fe (6- Me3- tpa) (CH3 CN)2]

(ClO4)2, containing two cis- coordinated acetonitrile molecules, as catalyst, the

cis- diol was observed as the major product.

NH

NH

NNN

N

NH

NH

22 23

N

NFe

N

N

R

R

R

24 a) R=H[FeII( tpa)(CH3CN)2](ClO4)2

b) R= CH3[FeII(6-Me3-tpa)(CH3CN)2(ClO4)2

Solv. = Solvent = CH3CN

Solv.Solv.



Fe- or Mn-based catalysts are highly attractive for commercial

applications because they are non-toxic and inexpensive. Although the

complex using [Fe (6- Me3 tpa) (CH3 CN) 2] (ClO4)2 shows good diol

selectivities, the catalyst has a rather low activity93. Apart from a high

turnover, there is a need to develop catalytic systems that employ H2O2 very

efficiently, as many Fe- or Mn- catalysts are known to induce efficient

decomposition of H2O2. Recently several research groups found that

decomposition of H2O2 by manganese-1,4,7-trimethyl-1,4,7-tri aza

cyclononane ([Mn2O3 ( tmtacn)2] (PF6)2, Mn-tmtacn, 25) complexes can be

suppressed by addition of co-catalysts like oxalic acid and other bi- or poly

dentate ligands like diketones or diacids.

N

N

Mn

N

O MnO

O

N

NN

IVIV

2+

25

1.6 Hydroxylation using halogens and silver carboxylates

The products of interaction of halogens and the silver salts of

carboxylic acids react with olefins, a fact which underlies the Woodward and

Prevost methods of cis- and trans- dihydroxylations respectively.

1.6.1 Reactions of halogens with silver salts of carboxylic acids

The action of halogens with dry metallic salts, particularly silver salts

of carboxylic acids has been a topic of much interest. It has been pointed out



that the course of action of halogens with silver carboxylates is determined by

the nature of halogens used, the ratio of silver salts to halogen, and the

presence or absence of other active materials, such as olefins, acetylenes, or

readily substituted aromatic rings.

Reaction of silver salt of a carboxylic acid with bromine is called

Hunsdiecker reaction and is a way of producing organic halides containing one

less carbon atom than the original acid95,96 ,97.

RCOOAg + Br2 → RBr + CO2 + AgBr

This reaction in which the molar silver salt-halogen ratio is 1:1 is of

wide scope, producing primary, secondary and tertiary bromides. When iodine

is the reagent, the ratio between the reactants is very important and determines

the product. A 1:1 ratio of salt to iodine gives the alkyl halide, as in

Hunsdiecker reaction. When the silver salt of a carboxylic acid reacts with

iodine in a 2:1 molar ratio an acyl hypoiodite is formed first which coordinates

with excess silver salt to form a complex (Simonini complex) 98,99

2 RCOOAg + I2 → RCOOAg.RCOOI + AgI

The thermal cleavage of the complex leads to the formation of an ester.

RCOOAg.RCOOI → RCOOR + CO2 + AgI

While the Hunsdiecker and Simonini reactions produce halides and

esters respectively, the reaction between silver carboxylate and iodine in a 3:2

molar ratio gives rise to both these products. The iodine triacyl postulated as

an intermediate can be isolated when R is a long-chain alkyl group. Formed by

the action of 2 moles of iodine on 3 moles of the silver salt, such compounds

decompose thermally to yield both alkyl halide and ester.



3 RCOOAg + 2 I2 → I (OCOR)3 + 3AgI

I (OCOR)3 → RCOOR + RI + 2CO2

The fact that triacyls such as iodine tris (trichloro methyl acetate)

conduct electricity with the iodine migrating towards the cathode indicates the

positive nature of the iodine in such materials100.

Reaction between silver carboxylate and halogen in a 1:1 molar ratio

can produce halogenated aromatic compounds if the reaction is carried out in

the presence of a phenyl group which undergoes electrophilic substitution

readily101,102,103 or when R is of such a nature that RCOO- ion is a very weak

base, such as (F3 COO-)104. The substituted products obtained are those

expected through halogenation by an entity which carries a charge. Thus ortho

and para substitutions occur in compounds containing groups known to

activate the aromatic nucleus to electrophilic attack, whereas substitution fails

or occurs in the meta position when the substituent deactivates the nucleus. On

this basis, the fission of the acyl hypohalite would be expected to proceed by

an ionic mechanism. Thus, the acyl hypohalite itself or X+ formed by its

dissociation can serve as the halogenating agent.

RCOOX + C6H6 → C6H5X + H+ + RCOO -

or RCOOX → RCOO - + X+

X+ + C6H6 → C6H5X + H+

1.6.1.1 Hunsdiecker Reaction

Hunsdiecker reaction is a classical transformation that converts

carboxylates to alkyl bromides and it is most useful for preparation of

secondary halides. The silver salt of a carboxylic acid is heated with bromine

to give the bromide via decarboxylation.



It is well established105-107 that the product of the reaction between a

dry silver salt of a carboxylic acid and halogen is an acyl hypohalite.

RCOOAg + X2 → RCOOX + AgX

The thermal decomposition of acyl hypohalite to produce compounds

containing one carbon less than the original acid is one of the most important

of the various silver salt-halogen reactions. The reaction is of general

application in the aliphatic series leading, with simple fatty acids of 2 to 18

carbon atoms, to excellent yields of alkyl halides95,105, 108-114.

Bromine is the most generally used halogen in the Hunsdiecker

reaction. In the few instances in which chlorine has been employed the yields

have been satisfactory115, 116. Iodine was normally used in 1:2 molar ratio with

the silver salts in the early work, and, consequently, the so-called Simonini

ester was the main product. It has been shown that an iodine to silver ratio of

1:1 affords substantial yields of the iodide, though some ester is produced.In

fact, the yield of iodide rises and that of the ester falls as the ratio of iodine to

silver is gradually increased from 1:2 to 1:1. In the presence of excess of

iodine, the silver salts of the long chain acids give good yields of the iodides.

J.Prakash and coworkers have shown that using triethyl amine as

catalyst in Hunsdiecker reaction with N-halo succinimides as Br+ and I+

sources, cinnamic acid and propionic acid are converted to the corresponding

α-halo styrenes and 1-halo 1-alkynes in good isolated yields within 1-5

minutes117.

1.6.1.2 Simonini Reaction

Simonini reaction is carried out with a 2:1 molar ratio of silver

carboxylate to iodine to produce esters. Those silver salts that undergo

Hunsdiecker reaction readily also, in general, undergo the Simonini reaction.



1.6.1.2.1 Simonini Complex

Interaction of a silver carboxylate with a half molar quantity of iodine

at room temperature leads to Simonini complex.

2 R CO2Ag + I2 → (R CO2)2 AgI + AgI

In many cases, especially when R is an aryl group, these complexes are

isolable and their gross constitutions have been confirmed by elemental

analysis. However, their structures have been debated since their first

isolation. Beattie and Bryce- Smith118 noted that silver iodine dibenzoate is

soluble in N, N- dimethyl formamide from which it may be recovered

unchanged. Such solutions precipitate AgI when treated with I-, but not with

Ag+, implying that Ag+ (but not I-) may be made readily available. In accord

with this observation they proposed structure 26 for silver iodine dibenzoate.

PhO

Ag

OC

O

PhI

O-

C

26

Structure 26 for the Simonini complex tends to emphasize the

molecular association between the silver carboxylate and the acyl hypoiodite.

Structures of this type would be expected to exhibit two carbonyl stretching

frequencies, the carboxylate anion near 1600 cm-1 (119) and the acyl hypohalite

at high frequency. Bunce and Hadley120 noted that Simonini complexes show

only one carbonyl absorption. This observation led them to suggest a

symmetrical structure

27

[Ph-C - O - I - O - C - Ph]

O O

Ag+

δ+

δ+ δ‐



for silver iodine dibenzoate. Such a structure would be the analogue of the tri

halide anions such as ICl2– whose chemistry is well known101. The

conductance measurements by Bunce and Hadley demonstrated that Simonini

complexes are at best very weak electrolytes (Kdiss< 10-4 M). This result,

compared with infrared results, prompted them to suggest a more symmetrical

version of Beattie and Bryce- Smith structure 26, such as 28.

Ph CO

O

I

Ag

O

OC Ph

28

Contributing to the lack of dissociation of the complex may be the

presence of silver ion. Quite possibly, silver (I) is an ideal cation to stabilize

the structure 28 with its two- coordinate linear geometry complimenting that

of the linear, two coordinate iodine (I).

1.6.2 Dihydroxylation using halogen and silver carboxylate

Prevost121 showed that the complex formed from silver benzoate reacts

with olefins to give dibenzoate esters of the corresponding 1,2- diols. He

considered that reaction occurred in two stages via the acylated iodohydrin and

the overall reaction is recognized as a trans addition. Woodward122, making

use of earlier studies by Winstein and Buckles123, demonstrated how the

conversion of acylated iodohydrin to acylated 1,2- diol could be made to

proceed with inversion.

Winstein and Buckles123 have shown that the reaction of silver acetate

and iodine in dry acetic acid with several acetoxy halides proceeds with

retention of configuration whereas the presence of small amount of water in

the solvent causes inversion to occur. The retention of configuration by using

dry acetic acid as the medium and the inversion in the presence of traces of



moisture have been accounted for by the participation in the replacement

process of the acyloxy group on the carbon atom neighboring the seat of

substitution with the production of an intermediate 30. That 30 may the

intermediate has been supported by the isolation of ortho acetate derivative124

in reaction of similar kind. In the presence of dry solvent reaction of this

intermediate with an acyloxy ion gives a product 31 with the same

configuration as the starting material 29. In presence of traces of moisture, 30

gets converted into 32, then rearranges to 33, followed by O-acetylation to 34.

The resultant product assumes a configuration which is the reverse of the

starting material 29.

C C C C

OCOR

C C

O+ O

C(R-CO2)2AgI

C C

OCOR

C C

O OC

R OH

C C

OH OCOR

C CROCO OCOR

- I-

I

R

OCOR

29

30

3132

3334

Scheme 11

Woodward and his colleagues 122, 125 realized that this result could be

used to modify the Prevost reaction so that the trans addition is followed by a

replacement with inversion leading to overall cis addition. The overall reaction

is then equivalent to cis-addition, as summarized in scheme 12.



-CH = CH-R-(CO2)2AgI

CHI - CH(O-CO - R)woodward

Prevost

- CH (O - CO -R) - CH(O -CO -R) -hydrolysis

- CH(OH) - CH(OH) (R is usually C6H5 in the Prevost reaction and CH3 in the Woodward

procedure.) Scheme 12

1.6.2.1 Woodward cis-hydroxylation

The dihydroxylation is effected in three stages. Iodine and silver acetate

first interact to form a product which converts the olefin to an iodoacetate by

trans addition. This occurs when the reactants are shaken in dry acetic acid

solution at room temperature. The second stage, replacement of halogen by a

hydroxyl group which may subsequently be acetylated, is effected by silver

acetate in acetic acid containing the required amount of water by heating for

three hours at 1000 C or for one hour at the reflux temperature. The mixed

mono- and di acetates are finally isolated and hydrolyzed.

1.6.2.1.1 Mechanism of the Woodward reaction

The initial addition of iodine leads to a cyclic iodonium ion, that is

opened through nucleophilic substitution by acetate anion.

R

R'

R'''I -I

- I -

I+

R R' R'' R'''

Ag+O-AcR'''

R''I

RR' O

O

Ag+

R''

Scheme13



A neighboring group participation mechanism prevents the immediate

nucleophilic substitution of iodine by a second equivalent of acetate that

would lead to a syn- substituted product. Instead, a cyclic acetoxonium ion

intermediate is formed.

O/O/

R - AgI +O/

/O/

R

/O/

R

+/O/

Scheme 14

Ag+

IR'''

R'

R' R'''R''

R'' R''R' R'''

In contrast to the course of the Prevost reaction, water appears to add

readily as a nucleophile to the partially positive carbon atom of the

intermediate. The cyclic ortho acetate is then cleaved to a mono acylated diol.

Scheme15

The desired diol can be isolated after hydrolysis.

Woodward122 noted that his modification of the Prevost reaction offers

the opposite facial selectivity as compared to oxidations with OsO4 in the

hydroxylation of synthetic steroid intermediates. Here, the steric approach

factors first direct the stereochemistry of the iodination, which is followed by

hydroxylation from the opposite face, whereas OsO4 leads to the isomeric cis-

diol by direct attack from the most accessible face.



AgOAc/I 2

/H 2OAcO

H O

OsO4

I+

OH

OH

O

O O

O

OOsO2

OH

OH

Scheme 16

The Woodward reaction thus provides a method of cis hydroxylation

additional to the use of potassium permanganate or of osmium tetroxide and

one which does not suffer from the disadvantages associated with these other

methods.

Presence of water has been reported to cause inversion of the

stereochemistry of the products in Woodward reaction. Raman126 has shown

that when erucic acid is oxidised with silver acetae and iodine in dry acetic

acid medium the product is predominantly the lower melting threo-13,14-

dihydroxy behenic acid(equivalent to trans addition) whereas the use of

aqueous acetic acid gives mainly the higher melting erythro dihydroxy acid.

1.6.2.2 Prevost Reaction

The Prevost reaction allows the synthesis of anti- diols from alkenes by the

addition of iodine followed by nucleophilic displacement with benzoate in the



absence of water. Hydrolysis of the intermediate diester gives the desired diol127.

R

PhCOOAg/I2

OCOPh

ROCOPh

R

KOH

H2O

OH

OHR'

R''

R'''R'''

R''R'Benzene

R'''

R''

R'<

Scheme 17

Glycol dibenzoates are formed when mono olefins (1 mole ) are treated with

silver benzoate ( 2 moles ) and iodine ( 1 mole ) in anhydrous benzene solution.

Depending on the reactivity of the olefin, reaction occurs at room temperature or

during a period of refluxing which may extend to 50 hr121. The above reagents are

the most frequently used but iodine may be replaced by chlorine, or bromine, the

silver benzoate by the acetate, propionate or n- butyrate, m-nitro benzoate, or 3,5-

dinitro benzoate, and the benzene by carbon tetra chloride, chloroform, or ether.

The best yields, however, are obtained with silver benzoate, the glycol dibenzoate

crystallizing easily and being readily hydrolyzed.

1.6.2.2.1 Mechanism of the Prevost reaction

Similar to the Woodward reaction, the initial addition of iodine leads to

a cyclic iodonium ion which is opened through nucleophilic substitution by

benzoate anion:

R

R R O

I-I

- I-

I+

Ag+ -O2CPh

I

Ag+

O

Ph

R'

R'''

R' R'R''

R'''

R'''

R''

R''

Scheme 18



A neighboring group participation mechanism prevents the immediate

nucleophilic substitution of iodine by a second equivalent of benzoate that

would lead to a syn- substituted product. Instead, a cyclic benzoxonium ion

intermediate is formed:

R O

I

Ag+

/O/

Ph

O/O+

Ph

R

O

Ph

R

R'

R'''

R''

-AgI

R'''

R''R'

R'''

R''R'

/O/+

Scheme19

Opening this intermediate by a second addition of benzoate gives the

anti- substituted dibenzoate:

O/

Ph

R

-OOCPh

OOCPh

PhCOO

RR'''

R''R'

/O/

R'

R''' R''

Scheme 20

Hydrolysis then delivers the diol.

The use of expensive silver salts, the requirement for a stoichiometric

amount of molecular halogen, and the formation of a relatively large amount

of organic and inorganic wastes are definite drawbacks to this reaction.



Raman128 has shown that though Prevost’s results are true when

absolutely dry benzene is used, in presence of traces of moisture inversion

occurs. Oxidation of erucic acid with silver benzoate and iodine in absolutely

dry benzene gave the lower melting (m.p. 98-990 ) threo- dihydroxy behenic

acid and no trace of the higher melting ( m.p. 129-1300C) erythro- dihydroxy

behenic acid could be isolated. Oxidation using benzene containing a small

quantity of water gave mainly the erythro- dihydroxy behenic acid (m.p.129-

1300C) with a lesser proportion of the lower melting threo- dihydroxy acid

(m.p.98-990C). Repetition of the same experiment with commercial oleic acid

and petroselenic acid also gave analogous results. It was established that even

traces of moisture in the benzene used for the oxidation would affect the

results. These inversions in the presence of moisture can probably be

accounted for on the basis of very extensive work of Winstein and Buckles123

on the role of neighboring groups in replacement reactions.

1.6.3 Cis-hydroxylation of olefinic compounds using silver succinate

and iodine

Mathew and Raman129 have shown that the use of silver succinate and

iodine in molecular proportion in dry benzene medium is a very efficient

method of preparing 1, 2-dihydroxy acids from olefinic acids. Oxidation of

oleic acid (octadec-cis-9-enoic acid) and of erucic acid (docos-cis-13-

enoicacid) thus has given 9, 10-dihydroxy stearic acid and of 13, 14-dihydroxy

behenic acid respectively in very good yields.. The hydroxylation using silver

succinate and iodine in dry benzene involves cis-addition of hydroxyl groups,

whereas, hydroxylation using silver benzoate and iodine in dry benzene

involves trans- addition of hydroxyl groups.

An exhaustive investigation of this silver succinate-iodine

hydroxylation was conducted later by Ashrof130. Various structural types of



olefinic compounds including typical aliphatic and aromatic terminal olefins,

1,2-disubstituted, trisubstituted and tetrasubstituted olefins, cyclic olefins,

natural long chain fatty acids and their esters were hydroxylated by this

method. The study revealed that all structural types of olefins could be

hydroxylated using silver succinate and iodine in yields ranging from 4.5% to

78% (Table 1)

Table 1 Olefinic compound hydroxylated Yield(%) of diol

Ethyl undec-10-enoate 32 Undec-10-enoic acid 32 Styrene 63 1,1-Diphenyl ethylene 15 Oleic acid 72 Methyl oleate 70 Ethyl oleate 72 Erucic acid 78 Ethyl fumarate 4.5 Anethole 42 2-methyl but-2-ene 62 2,3-Dimethyl but-2-ene 37 Cyclohexene 72

In all cases studied where stereochemistry is relevant, hydroxylation

involved cis-addition of hydroxyl groups. Unlike in Prevost reaction, no

inversion was observed when hydroxylation was carried out in presence of

water.

1.6.3.1 Nature of silver succinate-iodine complex

Silver succinate-iodine complex was prepared by reacting

equimolecular amounts of silver succinate and iodine in dry benzene. The

cream colored compound could be readily hyrolysed by water to succinic acid,

silver iodide and silver iodate.



The silver succinate-iodine complex was assigned the structure

CH2-COOI

,CH2-COOAg

CH2-COOAgCH2-COOI

on the basis of a study of its chemical properties and analytical results. Thus,

the formation and hydrolysis of the complex can be represented as

CH2-COOI

,

CH2-COOAg

CH2-COOAg CH2COOH

CH2COOH

CH2 -COOI ,+ 6 H2O + 4 AgI + 2 AgIO33 6

1.6.3.2 Nature of the intermediate in hydroxylation of olefins using silver

succinate and iodine

The products of the reaction of the silver succinate-iodine complex

with oleic acid, methyl oleate, ethyl oleate, ethyl erucate, ethyl undec 10-

enoate, styrene, 1,1-diphenyl ethylene and 2-methyl but-2-ene were

investigated in detail130. The dominant intermediate involved in the

hydroxylation was isolated and purified by column chromatography to obtain

it in a high state of purity as colorless, thick syrupy liquid. A mechanism was

proposed for the hydroxylation which incorporated a general structure 37 for

the intermediate involved.

CH2-COOI,

CH2-COOAg

CH2-COOAg

CH2-COOAg

CH2-COOAg+

CH2 -COOI2 I22 + 2AgI



C C

O O

CO CO

CH2 CH2

CH2 CH2

CO CO

O O

C CR

R R2

R3R1

R2

R3R1

37 1.6.3.3 Mechanism of hydroxylation using silver succinate and iodine

Reaction of equimolecular amounts of silver succinate and iodine in

dry benzene leads to the formation of a complex 35. A trans-addition of this

complex to 2 molecules of olefin yields an intermediate species 36. Reaction

of 36 with silver succinate by SN2 mechanism leads to replacement of iodo

group resulting in the formation of a cyclic intermediate 37. Hydrolysis of 37

yields the diol 38. Thus the overall reaction is equivalent to addition of two

hydroxyl groups to the olefinic bond. The sequence may be represented as

follows.

CH2-COOI

,

CH2-COOAg

CH2-COOAg

CH2-COOAg

CH2-COOAg+

CH2 -COOI+ 2AgI2 I22

35



C C

RCH2-COOI CH2-COOAg

C CR

OCOCH2

COO

CR

CH2

CH 2-C

OOAg

CH 2-COOAg

I

C CR

O

CO

CH2

CO

OC C

R

CH2

COCH2

CO

O

CH2

O

C CR

OH OH

R1 R3

R2

Trans-addition

hydrolysis

R3

R2

R3

R2

36

R1

R2

R3

R1

R2

R3

37

R3

R2

R1

CH2- COOI , CH2COOAg

R1

35

38

I

C

R1

1.6.4 Cis-hydroxylation of olefins using silver phthalate and iodine

It has been shown130 that silver phthalate can be used in place of silver

succinate for hydroxylating olefinic compounds along with iodine in dry

benzene medium. Hydroxylations of oleic acid, ethyl oleate, cyclohexene and



trans-stilbene were attempted and, all compounds except trans-stilbene could

be hydroxylated in yields of 69%, 69% and 44% respectively. Trans-stilbene

was recovered unchanged. Hydroxylation involved cis-addition of hydroxyl

groups and no inversion occurred when the reaction was carried out in the

presence of moisture.

The silver phthalate- iodine complex was assigned a structure 39

similar to that of silver succinate-iodine complex.

COOI

COOI ,

COOAg

COOAg

39

1.6.4.1 Mechanism of hydroxylation using silver phthalate and iodine

The mechanism of hydroxylation using silver phthalate-iodine complex

was shown to be similar to the one proposed for hydroxylation using silver

succinate and iodine. The reaction proceeds by a trans-addition of the complex

39 , formed by the reaction of equimolecular amounts of silver phthalate and

iodine in dry benzene, to two molecules of olefin leading to the formation of a

diiodo ester, 40. A bimolecular nucleophilic attack by the silver phthalate

gives the cyclic ester, 41, the hydrolysis of which gives the diol, 42. This may

be represented as shown below.



COOI

COOI ,

COOAg

COOAg

2 +2

COOAg

COOAg

+ 2AgI

C C

R1

R

R2

R3

COOI

COOI ,COOAg

COOAg,

Trans-addition

C C

O

CO

CO

O

C CR

R1

R2

R3

R

R1

R2

R3

I

COOAgCOOAg

C C

O

CO

CO

O

C CR

R1

R2

R3

R

R1

R2

R3

O

OC

OC

O

hydrolysisC C

R

R1

OH OH

R2

R3

40

41

42

2I2

I



1.7 Hydroxylations Using Metal Carboxylates Other than

Silver Carboxylates

The dihydroxylation of olefins using the Prevost’s or Woodward’s

method involves the use of silver carboxylates and halogen. Silver

carboxylates have the disadvantages of being expensive, frequently unstable

and difficult to dry. The use of silver salts, a stoichiometric amount of

molecular halogen, and formation of large amount of organic and inorganic

wastes resulted in a search for simpler systems.

1.7.1 Cis- Hydroxylation of olefins using iodine, potassium iodate

and potassium acetate

The reaction of olefins with iodine and silver acetate in moist acetic acid

(Woodward’s procedure) is a method for the preparation of cis- diols with the

hydroxyl groups on the more hindered side of the molecule. In this procedure,

the silver carboxylate is assumed to have a double function:

i. to give hypoiodite that serves as a source of electrophilc iodine;

ii. to facilitate the conversion of the acetylated iodohydrin, formed in the

addition step, into a dioxolenium ion that then leads to the cis- diol131.

L. Mangoni and coworkers 132 have shown that silver salt is not

essential for either i) or ii) and have developed a convenient procedure that

does not require this expensive reagent. Thus, when reacted with iodine and

potassium iodate in acetic acid at 600C for 3 hr and then refluxed with

potassium acetate for 3 hr, 5-α-cholest-2-ene gave (after hydrolysis with

alkali) 5α- cholestan-2β,3β- diol (70% yield). Analogous results were obtained

when the above procedure was essayed on cyclohexene and oleic acid.



1.7.2 Dihydroxylation with Thallium Acetate and Iodine

R.C.Cambie and P.S.Rutledge133 have suggested a procedure which

offers a convenient alternative to the Prevost reaction and the Woodward

modification of the Prevost reaction, in which thallium carboxylates are used

instead of silver carboxylates. Thallium salts have the advantage of being

generally stable crystalline solids that can be readily prepared in high yield by

neutralization of the appropriate carboxylic acid with thallium (I) ethoxide.

Silver salts, on the other hand, are frequently unstable and difficult to dry.

Thallium acetate and iodine can be used to effect both cis- and trans-

dihydroxylation of olefins. Thus when reacted with iodine and thallium acetate

in dried acetic acid under reflux conditions for 10 hr, cyclohexene gave (after

hydrolysis with alkali) trans-1,2-cyclo hexane diol (m.p. 103-1040). When

hydroxylation was carried out using the same reagent in presence of water,

cyclohexene gave cis-1,2- cyclo hexane diol (m.p. 97-980).

The mechanism of these reactions are presumably analogous to those of

the Prevost and Woodward reactions122,134 . In the first step of the reaction of

iodine and thallium (I) acetate with cyclohexene, both in the presence and

absence of water, produces trans-2- iodo cyclohexyl acetate. The second

equivalent of thallium (I) acetate scavenges iodide ion during formation of the

1, 3- dioxolan-2- ylium ion intermediate. Under the anhydrous conditions, the

carbonium ion reacts with acetate ion at a ring carbon with inversion to give

the diacetate. In the presence of water, the ion is captured by water, and the

resulting ortho ester undergoes ring opening to the cis- diol mono acetate.



OCOCH3

I

O

OCH3

CH3CO2- OCOCH3

OCOCH3

H2O

O

O

OHCH3

OCOCH3

OH

OTl+OCH3CO2Tl/ I2

Scheme 21

Vicinal iodocarboxylates may also be prepared from reaction of olefins

with thallium (I) benzoate and iodine in benzene.

1.7.3 Cobalt (II) Acetate- Catalyzed Woodward- Prevost Reaction

Yi Yi Myint and M.A.Pasha135 have reported Woodward- Prevost

reaction of alkenes with iodine and cobalt (II) acetate in acetic acid.

C C C C

I

OAc

R1 R2

R3

R4

15-55 min.

, 250C R1

R2

R3

R4

+ I2 + Co(Ac)2

Scheme 22

The reaction is facile and α- iodo acetates are obtained from both

acyclic and cyclic olefins in high yields within 15-55 min.



1.7.4 Hydroxylation using Lead Acetate and Iodine

Raman and Ashrof136 have shown that lead acetate may be used in the

place of silver acetate in the Woodward procedure for the hydroxylation of

oleic acid.

1.8 Ruthenium-Catalyzed Dihydroxylation of olefins

Transition – metal - Catalyzed oxidations of C=C double bonds have

become one of the most commonly used transformations in organic synthesis.

Among these reactions, the osmium- catalyzed dihydroxylation in its

asymmetric version represents a benchmark when it comes to generality and

selectivity. Despite its success, some problems still need to be solved. The

oxidation is limited to electron-rich or mono-, di-, and in some cases tri –

substituted olefins. Furthermore, the osmium catalyst is toxic and very

expensive. Alternative oxidants have been described for this reaction. Among

these, RuO4 is most promising as a dihydroxylation catalyst. In ethyl acetate/

acetonitrile/water a very fast dihydroxylation of olefins using 7 mol % of

RuO4 was observed137.

Plietker and Niggemann138 have described the beneficial influence of

protic acids in ruthenium-catalyzed dihydroxylations of olefins. In the

presence of 20 mol % sulfuric acid, they were able to decrease the amount of

catalyst from originally 7 mol% to only 0.5mol% without loss of activity. The

reaction is very fast and clean. This reaction represents an efficient, less toxic

alternative to the dihydroxylation using osmium or manganese reagents.

Plietker and coworkers have also recently described a RuCl3 - catalyzed

dihydroxlation of olefins139. In this report, the treatment of an olefin with

RuCl3 and NaIO4 in the presence of either a Bronstead or Lewis acid provided

the desired cis- diols in good yield.



1.9 NaIO4/ Li Br- mediated Dihydroxylation of olefins

L. Emmanuel and coworkers140 have reported a new “transition-metal-

free” procedure for the dihydroxylation of alkenes, catalyzed by LiBr using

commercially available NaIO4 or diacetoxy iodo benzene [PhI(OAc)2] as

oxidant in acetic acid to produce syn- or anti-diols, respectively. The

simplicity, environmental friendliness and readily accessible reagents make

this system superior to other expensive and toxic Tl (I), Ag (I), Bi (III), and

Hg (II) reagents.

Emmanuel and coworkers envisioned to prepare diol directly from

styrene using a catalytic amount of LiBr (20 mol %) and NaIO4 (30 mol %) in

AcOH at 950C and indeed obtained regio- isomers of styrene mono (43a, 43b)

and diacetates (44) with the ratio 87: 5 in 92% combined yield. The mixture

was subjected to basic hydrolysis (K2CO3, MeOH, 250C) without separation to

furnish 1- phenyl-1,2- ethane diol in 87% yield (scheme 23).

OAC OH

OH OAc

OAc

OAc

OH

OH

++NaIO4(30mol%)

LiBr(20mol%)

AcOH,950C,18hr.

K2CO3(1.5equiv.)

MeOH,rt,24hr.

43a

43b44

Scheme 23



Control experiments indicated that no hydroxylation occurred in the

absence of either LiBr or NaIO4.

Several alkenes (aliphatic, styrenic, allylic, disubstituted alkenes, α, β-

unsaturated alkenes, etc.) with electron-donating and –withdrawing groups

underwent dihydroxylation and produced the corresponding diols in excellent

yields with syn- diastereoselectivity. The syn- selectivity is controlled by

water formed in situ from NaIO4 and AcOH, which attacks 1,3- dioxolon-2-

ylium ion (C) at C - 2 position (scheme 24)

Interestingly, anti- diols were obtained when acetoxy iodo benzene [PhI

(OAc)2] was employed as the oxidant in stoichiometric amounts under the

same reaction conditions. Since no water is formed, acetic acid acts as the

nucleophile and opens up the intermediate C at C-4 position to result in trans-

diastereoselectivity.

From the above facts and other evidences provided by the cyclic

voltammetry study, the proposed catalytic cycle for the LiBr catalyzed

dihydroxylation is shown in scheme 24.



Br2

O O

OO

Br

LiBr

Br-

Br2(O)

A

Br

B

Br-

C

OAc

OH

OAc

OAc

+

NaIO4 + AcOH

IO3- + LiOAc + H2O R2

R1

R2

R1

R1 R2

+

R2

R1

R2

R1

R2

+

+ AcOH

[O,Nu]

Nu=H2O,AcOH

R1

Nu=H2O Nu= AcOH

[O] = NaIO4 or IO3 -

Scheme24

The halogens (X= I, Br, Cl), generated in situ from alkali metal halides

by oxidation with NaIO4 or PhI(OAc)2 rapidly undergo bromo acetoxylation

with alkenes via bromonium ion A to produce trans- 1,2- bromo acetate

derivative B, which was isolated and characterized. The intermediate C,

formed from B in the presence of NaIO4, assisted anchimerically by the acetate

group, is opened either by water to give the cis-hydroxy acetate or by acetic

acid to give the trans -di acetate with concomitant liberation of Bromine.

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