Jones M., Fleming S.A. Organic Chemistry

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10.5 Dipolar Addition Reactions 439

The overall reaction is a series of three 1,3-dipolar additions (Fig. 10.56). First,

ozone adds to the alkene to give the primary ozonide. Then the primary ozonide

undergoes a reverse 1,3-dipolar addition to give a carbonyl compound and a new

1,3-dipole, the carbonyl oxide. Finally, the carbonyl oxide turns over and re-adds to

the carbonyl compound in the opposite sense to give the new ozonide.The reaction

is a sequence of three reversible 1,3-dipolar additions driven by thermodynamics

toward the relatively stable ozonide.

Now that we have described the reaction, however, the tougher part is to explain

why it runs the way it does. Why does thermodynamics favor the final, more stable

ozonide over the primary ozonide (Fig. 10.57)?

A forward

1,3-dipolar

addition

reaction

A reverse

1,3-dipolar

addition

reaction

A second

forward

1,3-dipolar

addition

reaction

turn

carbonyl

oxide over

–

FIGURE 10.56 In the formation of

the final ozonide from ozone and an

alkene, Steps 1 and 3 are 1,3-dipolar

additions. Step 2 is the reversal of a

1,3-dipolar addition.

Energy

Reaction progress

This energy difference…

…favors this ozonide

FIGURE 10.57 The ozonide contains

fewer weak oxygen–oxygen bonds

than the primary ozonide and is

therefore more stable.

The oxygen–oxygen bond is quite weak ( 40 kcal/mol). Much more stable,

though, is the carbon–oxygen bond (85–90 kcal/mol). The most important factor

that makes an ozonide more stable than a primary ozonide is the difference in the

numbers of weak oxygen–oxygen bonds and strong carbon–oxygen bonds. As long

as the kinetic barriers to the forward and reverse 1,3-dipolar additions are not too

high, thermodynamics favors formation of the stronger carbon–oxygen bonds and

the ultimate result is the final, more stable, ozonide.

PROBLEM 10.18 Use Table 8.2 (p. 337) to do a full calculation of the bond energy

difference between a primary ozonide and an ozonide.

440 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

(75%)

1. O

, –30 C

2. (CH

)

S, ~0 C

(74%)

1. O

, –78 C

2. H

/ Pd

Ketones Aldehydes

reductive

workup

reductive

workup

reductive

workup

One ketone

One aldehyde

1. O

, –78 C, 16 h

(93%)

2. Zn/H

C(CH

)

C(CH

)

O O

SPECIFIC EXAMPLES

FIGURE 10.58 Reductive

decomposition of ozonides leads to

aldehydes and/or ketones.

10.5b The Synthetic Potential of Ozonolysis: Carbonyl Compounds

Why do we spend so much time with this complicated reaction? We have already

mentioned generality. A vast number of 1,3-dipolar agents has been made, and

many of them will add to π bonds to give five-membered rings.

Second, and more important, the ozonides are very useful compounds. Their

further transformations give us entry into new classes of compounds. Ozonides can

be reduced (Fig. 10.58) and, depending on the structure of the starting alkene, the

products can be ketones ( ), which are compounds that have two R groups

attached to the carbonyl carbon; aldehydes ( ), which are compounds

that have an R group and a H attached to the carbonyl; or a mixture of the two. Many

reducing agents are known, among them H

/Pd,Zn, and (CH

)

S (dimethyl sulfide).

RCH

PROBLEM 10.19 Why are oxygen–oxygen sigma bonds so weak? Hint: It is not just

electron–electron repulsion. Do a quick molecular orbital analysis.

PROBLEM 10.20 Complete the Energy versus Reaction progress diagram of

Figure 10.57 to show the conversion of the primary ozonide into the ozonide.

Assign the intermediates to the appropriate points in the reaction pathway.

10.5 Dipolar Addition Reactions 441

Oxidation of the ozonides, usually with hydrogen peroxide (H

), leads either

to ketones or carboxylic acids (see Fig. 10.24). The structure of the product again

depends on the structure of the ozonide, which itself depends on the structure of

the original alkene (Fig. 10.59).

(67%)

1. O

, –78 C

2. H

/CH

COOH

OHH

(85%)

1. O

, –70 C

2. H

/HCOOH

COOH

Ketones

oxidative

workup

One acid One ketone

oxidative

workup

Carboxylic acids

oxidative

workup

GENERAL CASES

SPECIFIC EXAMPLES

HCOOH

FIGURE 10.59 Oxidative

decomposition of ozonides leads to

ketones and/or carboxylic acids.

In addition to providing a synthetic pathway for numerous carbonyl compounds,

ozonolysis has another use for us: The structures of the products of an ozonolysis

reaction can be used to reason out the composition of an unknown alkene. To see

ozonolysis used this way, try Problem 10.21.

1. O

2. workup

PROBLEM SOLVING

Whenever you see ozone (O

) in a problem, you can bet the farm that a double

bond is going to be converted into a pair of carbonyl compounds. The question

may be mechanistic or synthetic in nature, but that processs is going to be

involved. It is not a bad idea at this early point to jot down the general scheme

shown below whenever you see ozone.

442 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

ANSWER (c) Ozonolysis converts a carbon–carbon double bond into two carbon–

oxygen double bonds.

[from two starting materials,

(1) C

(2) C

]

(a)

*(c)

(d)

(b)

WORKED PROBLEM 10.21 Ozonolysis of alkenes can give the carbonyl products

shown below. Supply an alkene structure that can produce the carbonyl compounds

shown.Specify the nature of the workup step in the process (oxidation or reduction).

In this case, both carbon–oxygen double bonds are in the same product molecule,

which means that the starting material must be a cyclic alkene.The product con-

tains carboxylic acids, so we know that an oxidative workup is required. A reduc-

tive workup would give an aldehyde.

1. O

2. oxidative

or reductive

workup

C C

1. O

2. oxidative

workup

HOHHOH

There are several ways to construct an appropriate starting material. Two

possibilities are

1. O

2. HOOH

COOH

1. O

)(C

)

2. HOOH

Summary

Ozonolysis of alkenes breaks both bonds in the carbon–carbon double bond and

generates a pair of carbonyl groups. A double bond carbon bearing two alkyl

groups is transformed into a ketone ( ) regardless of workup conditions.

When a double bond carbon bears one alkyl group and one hydrogen it is trans-

formed into an aldehyde ( ) if the workup is done under reducing con-

ditions and a carboxylic acid (RCOOH) if oxidizing conditions are used.

RHC

10.5 Dipolar Addition Reactions 443

10.5c Oxidation with Permanganate or Osmium Tetroxide Although

they are not 1,3-dipolar reagents, both potassium permanganate (KMnO

) and

osmium tetroxide (OsO

) add to alkenes to form five-membered rings in

reactions that are related to the additions of ozone and other 1,3-dipoles

(Fig. 10.60).

–

Osmate

ester

FIGURE 10.60 Addition of potassium

permanganate or osmium tetraoxide

to alkenes gives five-membered rings.

The cyclic intermediate in the permanganate reaction cannot be isolated and

is generally decomposed as it is formed to give vicinal diols (Fig. 10.61a). Good

yields of cis 1,2-diols can be isolated from the treatment of alkenes with basic

permanganate. The cyclic osmate ester can be isolated, but it, too, is generally

transformed directly into a diol product by treatment with aqueous sodium sul-

fite (Na

) as shown in Figure 10.61b. In both of these reactions it is the

metal–oxygen bonds, not the carbon–oxygen bonds, that are broken. There are

many variations of these reactions, which are among the best ways of synthesiz-

ing vicinal diols.

(a) (b)

(85%)

OH/H

NaOH, 20 ⬚C

(96%) (81%)

MnO

–

Not isolated Can be isolated,

but often is not

Vicinal diol

–

OsO

KMnO

Vicinal diol

OsO

GENERAL CASES

SPECIFIC EXAMPLES

FIGURE 10.61 A five-membered ring containing either (a) Mn or (b) Os can react further to generate vicinal diols.

Dihydroxylation of alkenes

444 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

cis-2-Butene meso-2,3-Butanediol

(shown in eclipsed

conformation for clarity)

1. OsO

2. H

PROBLEM 10.22 What mechanistic conclusions can be drawn from the observa-

tion that reaction of OsO

with cis-2-butene gives this single product?

WEB 3D

–

A vinyl cation

CCH

(60%)

25 °C 25 °C

(Z)-3-Chloro-3-hexene

(the ethyl groups are mostly

trans to each other

in the product)

FIGURE 10.62 Hydrogen halides add

to alkynes as well as to alkenes. Addition

is mostly anti.

The stereochemistry of this addition is mixed, as would be expected from an open

carbocation, although the trans diethyl compound is favored (Fig. 10.62).

However, there are problems with this simple extension to alkynes of the mech-

anism for additions to alkenes. Vinyl cations are unusual species and we must stop

for a moment to consider their structures. The positive carbon in a vinyl cation is

attached to two groups: the other carbon in the original triple bond and an R group.

Accordingly, we would expect sp hybridization, and that leads to the structure in

Figure 10.63.

sp Hybridized

carbon

FIGURE 10.63 A vinyl cation

contains an sp hybridized carbon.

10.6 Addition Reactions of Alkynes: Addition

Much of Chapters 9 and 10 has been devoted to the addition of various reagents to

carbon–carbon double bonds. Alkynes contain two π bonds and it would be quite

astonishing if they did not undergo similar addition reactions. If we keep in mind

what we have learned about alkene additions, it is reasonably easy to work through

alkyne additions.The presence of the second double bond will add mechanistic com-

plications, however, and some synthetic opportunities as well.

Addition of or to 3-hexyne gives the corresponding vinyl halides.

It is tempting to begin with a protonation of the π system to give a carbocation

and a halide ion as shown in Figure 10.62. In this case, the positive ion would be

a vinyl cation. Addition of the halide to this cation would give the vinyl halide.

HClHBr

10.6 Addition Reactions of Alkynes: HX Addition 445

Measurements in the gas phase show that vinyl carbocations are very unstable.

Remember that the gas-phase heat of formation values do not include the solvent,

which is very important to any cationic species. Remember also that direct com-

parisons can be made only between isomeric species. Nonetheless, one can get an

approximate idea of the great instability of vinyl carbocations from Table 10.2.The

absolute values of the energy differences are not important, but the relative stability

order of the various carbocations is.

TABLE 10.2 Heats of Formation for Some Carbocations

Cation Substitution (kcal/mol)

Primary vinyl 285

Methyl 261.3

Secondary vinyl 231

Primary 215.6

Primary 211

Primary 203

Secondary 183

Secondary 190.9

Primary allyl 226

(CH

)

Tertiary 165.8

(CH

)

HCH

≤H°

Table 10.2 shows that,just as with alkyl carbocations,secondary vinyl cations are more

stable than primary vinyl cations.However,it also shows that even a secondary vinyl cation

is not even as stable as a primary alkyl carbocation. Primary carbocations serve as a kind

of mechanistic stop sign: They are generally too unstable to be viable intermediates in

most reactions. Presumably, we should treat unstabilized vinyl cations the same way.

What intermediate could we use to replace the highly unstable vinyl cations in

addition reactions involving alkynes? Perhaps cyclic intermediates are involved.

Moreover, alkynes are known to form complexes with HX acids. A cyclic protonium

ion or complex could accommodate the complicated kinetics, which show that more

than one molecule of halide is involved, and also account for the generally observed

predominance of trans addition (Fig. 10.64). We will write cyclic ions in the answers

to problems,but you should know that the intermediacy of vinyl cations in these reac-

tions is not a fully resolved issue. There is still lots to do in organic chemistry.

The modified mechanism shown in Figure 10.64 predicts that Markovnikov addi-

tion should be observed: that the more substituted secondary vinyl halide should be

–

and/or

25 ⬚C

FIGURE 10.64 Possible cyclic

intermediates in the reaction of an

alkyne and hydrogen chloride.

446 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

–

Markovnikov addition

redicted to be favored

Shorter, stronger bond

Longer, weaker bond

FIGURE 10.65 Addition of the

nucleophile to the cyclic ion takes

place at the more substituted position.

formed whenever there is a choice (Fig. 10.65). In the cyclic intermediate, there is a par-

tial positive charge on the carbons of the original triple bond.The partial bond to hydro-

gen from the more substituted carbon of an unsymmetrical alkyne is weaker than the bond

from the less substituted carbon because the partial positive charge is more stable at the

more substituted position. Accordingly, addition of halide would be expected to take

place more easily at the more substituted position, leading to Markovnikov addition.

CCH

(56%)

2-Chloropropene

Propyne

(35%)

2-Iodopropene

H I

HCl

FIGURE 10.66 Markovnikov addition

generally predominates in reactions

of HX with alkynes.

Let’s look at the experimental data.There is no difference in the two carbons of

the triple bond in a molecule such as 3-hexyne, so let’s examine the addition to a

terminal alkyne—a 1-alkyne—to see if Markovnikov addition occurs.Our mechanism

predicts that the more substituted halide should be the product, and it is.The prod-

ucts shown in Figure 10.66 are the only addition products isolated.

Additions of HX to alkynes are mechanistically complex. Also, they are usually not

practical sources of vinyl halides because the vinyl halides also contain π bonds and often

compete favorably with the starting alkyne in the addition reaction. The vinyl halide

products are not symmetrical and two products of further reaction are possible (p.367).

It makes a nice problem to figure out which way the second addition of

should go. As always in a mechanistic problem of this sort, the answer only appears

through an analysis of the possible pathways for further reaction.Draw out both mech-

anisms, compare them at every point, and search each step for differences.We will use

the reaction of propyne with hydrogen chloride as a prototypal example. The initial

product is 2-chloropropene,as shown in Figure 10.66.There are two possible ions from

the reaction of this vinyl halide with additional hydrogen chloride. Structure A in

Figure 10.67 has the positive charge adjacent to a chlorine, but structure B does not.

–

Two possible

carbocations

2,2-Dichloropropane

2-Chloropropene

HH C

1,2-Dichloropropane

–

HCl

FIGURE 10.67 2-Chloropropene can

protonate in two ways.

10.7 Addition of X

Reagents to Alkynes 447

There is a way for the chlorine in structure A to share the positive charge.The

charge is shared by the two atoms through 2p/3p overlap as shown in Figure 10.68.

In molecular orbital terms, we see that a filled 3p orbital on chlorine overlaps

with the empty 2p orbital on carbon, and this orbital overlap is stabilizing. The

primary carbocation B in Figure 10.67 is much less stable, and products from it

are not observed.

HCl

–

2,2-Dichloropropane

Resonance-stabilized cation

3p/2p Overlap

FIGURE 10.68 The carbocation

adjacent to chlorine is stabilized by

resonance.

excess

HCl

2,2-Dichloropropane2-Chloropropene

2-Iodopropene

Propyne

2,2-Diiodopropane

(56%) (44%)

(

65%

)

(

35%

)

FIGURE 10.69 Addition of excess

hydrogen halide to an alkyne gives

a mixture of products of mono- and

di-addition.

So, addition of a second halogen will preferentially result in formation of the

geminal dihalide (geminal means groups substituted on the same carbon) not

the vicinal (groups substituted on adjacent carbons) compound because the cation

with chlorine attached is lower in energy, and leads inevitably to the observed

geminal product. The reactions of Figure 10.66 are complicated by the for-

mation of compounds arising through double addition in the presence of

excess hydrogen halide. The double addition always gives the geminal dihalide

(Fig. 10.69).

10.7 Addition of X

Reagents to Alkynes

The pattern of alkene addition is also followed when X

reagents add to alkynes,

although the mechanism of the alkyne reaction is not well worked out. Both ionic

and neutral intermediates (i.e., radicals, which are discussed in Chapter 11) are

448 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

involved. Alkynes add Br

or Cl

to give vicinal dihalides. A second addition can

follow to give the tetrahalides (Fig. 10.70).

WEB 3D

(15–20%) (60–65%)

excess

CCH

65–70 ⬚C

excess

CRR

THE GENERAL CASE

A SPECIFIC EXAMPLE

FIGURE 10.70 Addition of Cl

(or Br

) to alkynes gives both vicinal

dihalides and tetrahalides.

10.8 Hydration of Alkynes

Like alkenes, alkynes can be hydrated. The reaction is generally catalyzed by mer-

curic ions in an oxymercuration process (Fig. 10.71), although simple acid catalysis

is also known. In contrast to the oxymercuration of alkenes, no second, reduction

step is required in this alkyne hydration. By strict analogy to the oxymercuration of

alkenes, the product should be a hydroxy mercury compound, but the second dou-

ble bond exerts its influence and further reaction takes place. The double bond is

protonated and mercury is lost to generate a species called an enol. An enol is part

alkene

and part alcohol, hence the name.

(+)

–

O /H

Hg(OAc)

HgOAc

An enol

Resonance

stabilized cation

RHC RHC

CHR CHR

Oxymercuration of alkenes

An alcohol

Oxymercuration of alkynes

RHC

Hg(OAc)

FIGURE 10.71 The oxymercuration of alkynes resembles the oxymercuration of alkenes. In the alkyne case,

the product is an enol, which can react further.

Enols are extraordinarily important compounds, and more than one chapter

will mention their chemistry. Here their versatility is exemplified by their conver-

sion into ketones. We have already seen a synthesis of ketones in this chapter