Jones M., Fleming S.A. Organic Chemistry

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10.8 Hydration of Alkynes 449

through ozonolysis of alkenes (p. 436). Here, ketones are the final products of the

hydration reactions of alkynes (Fig. 10.72).The mechanism of their formation from

enols is simple: The alkene part is protonated on carbon and the oxygen of the

enol is deprotonated to generate the compound containing the carbon–oxygen

double bond. Note that this process gives you another synthetic pathway to car-

bonyl compounds. We will see this process many times in the future.

Deprotonate on oxygenProtonate on carbon

Enol Ketone

FIGURE 10.72 Protonation of carbon,

followed by deprotonation at oxygen,

generates the carbonyl compound.

This sequence is a general reaction

of enols.

Nearly all ketones and aldehydes containing a hydrogen on the carbon adjacent

to the carbonyl carbon are in equilibrium with the related enol forms. How much

enol is present at equilibrium is a function of the detailed structure of the molecule,

but there is almost always some enol present.In simple compounds, the ketone form

is greatly favored. This interconversion is called keto-enol tautomerization.

PROBLEM 10.23 Draw a mechanism for the acid-catalyzed hydration of an

alkyne.

WORKED PROBLEM 10.24 Why were we so sure the enol in Figure 10.72 would

protonate to give the cation shown? There is another cation possible. Why is it

not formed?

ANSWER Protonation as shown in Figure 10.72 leads to a resonance-stabilized

carbocation. The adjacent oxygen shares the positive charge. Protonation on the

other carbon of the double bond leads to a carbocation that is not resonance

stabilized, which is therefore of much higher energy.

Not resonance stabilized!

Resonance stabilized!

450 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

PROBLEM 10.25 In general, hydration of unsymmetrical alkynes such as 2-pentyne

is not a practical source of ketones. Why not?

PROBLEM 10.26 Terminal alkynes are certainly unsymmetrical, yet in these

cases hydration is a useful process. In principle, either ketones or aldehydes

could be formed, but in practice only ketones are produced. Write mechanisms

for both ketone and aldehyde formation and explain why the product is always

the ketone. You may write open vinyl carbocations in your answer for simplic-

ity, but be aware that the real intermediates may be more complex cyclic

species.

PROBLEM 10.27 Write a mechanism for the acid-catalyzed conversion of diethyl

ketone into its enol form.

10.9 Hydroboration of Alkynes

Like alkenes, alkynes can be hydroborated by boranes. The mechanism is very sim-

ilar to that for alkenes (p. 390); the stereochemistry of addition of HBH

is syn, and

it is the boron that becomes attached to the less substituted end of a terminal alkyne

(Fig. 10.73).

CCH

Further

hydroborations

Vinylborane

FIGURE 10.73 Hydroboration of

alkynes gives vinylboranes that can

react further (R alkyl).=

Dialkylborane

(100%)

FIGURE 10.74 This sterically hindered dialkylborane reacts only once with alkynes to give an

isolable vinylborane (R alkyl).=

The initial products of hydroboration are prone to further hydroboration

reactions.This complication can be avoided by using a sterically hindered borane

so that further reaction is slowed. A favorite suitably hindered reagent is the

borane formed by reaction of two equivalents of 2-methyl-2-butene with BH

(Fig. 10.74).

10.9 Hydroboration of Alkynes 451

Like alkylboranes, vinylboranes can be converted into alcohols by treatment with

basic peroxide (Fig. 10.75).The products are enols in this case,and they are in equi-

librium with the corresponding carbonyl compounds. Here’s an important point:

The regiochemistry of this reaction is the opposite of the regiochemistry of the

hydration reaction of alkynes.This situation is exactly the same as the one that exists

with the alkenes: Hydration of an alkene gives overall Markovnikov addition,

whereas the hydroboration/oxidation sequence gives the anti-Markovnikov product.

Vinylborane

NaOH/H

AldehydeEnol

(88%)

HOOH

NaOH/H

HOOH

(CH

)

(CH

)

THE GENERAL CASE

A SPECIFIC EXAMPLE

FIGURE 10.75 Oxidation of a

vinylborane leads to an enol that can

be converted into the aldehyde.

The ultimate formation of a carbonyl compound disguises the matter, but if we look

back one step to the enols, we can see that in alkyne reactions the same regioselec-

tivity holds (Fig. 10.76).Hydration goes through Markovnikov addition to the alkyne

and,ultimately,gives the ketone.The hydroboration/oxidation reaction goes through

anti-Markovnikov addition to the alkyne and, ultimately, gives the aldehyde.

Hydration

O /H

Ketone

Aldehyde

RCH

Hydroboration/oxidation

HOOH

HBR

–

OHH

FIGURE 10.76 It is possible to make

two different carbonyl compounds

from a terminal alkyne. Mercuric

ion-catalyzed hydration gives the

ketone, and hydroboration/oxidation

gives the aldehyde.

Be sure you see the similarities here as well as the mechanistic underpinnings of

the different paths followed. There is too much to memorize. Be sure to annotate

your file cards as you update your catalog of synthetic methods.

452 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

10.10 Hydrogenation of Alkynes: Alkene Synthesis

through syn Hydrogenation

Like alkenes,alkynes can be hydrogenated in the presence of many catalysts.Alkenes

are the first products, but they are not stable under the reaction conditions and are

usually hydrogenated themselves to give alkanes (Fig. 10.77). This reaction is your

second synthetic pathway to alkanes.

THE GENERAL CASE

Pd/C

FIGURE 10.77 Hydrogenation of an

alkyne proceeds all the way to the

alkane stage.The intermediate alkene

cannot usually be isolated.

It would be extremely convenient to be able to stop the alkyne hydrogenation

at the alkene stage,and special,“poisoned”catalysts have been developed to do just

this. A favorite is the Lindlar catalyst (Fig. 10.78), which is Pd on calcium car-

bonate that has been treated with lead acetate in the presence of certain amines

(H. H. M. Lindlar, b. 1909). For many years it was thought that the lead treat-

ment poisoned the palladium catalyst through some sort of alloy formation,

rendering it less active and the reaction more selective. It now appears that the

treatment forms no alloys, but does modify the surface of the palladium.

Regardless, the reaction can be stopped at the alkene stage, and the alkenes formed

by hydrogenation with Lindlar catalyst have cis stereochemistry because the usual

syn addition of hydrogen has occurred.

A SPECIFIC EXAMPLE

Pd/CaCO

/Pb

Lindlar catalyst

(CH

)

(CH

)

(CH

)

(CH

)

96% cis

FIGURE 10.78 If the Lindlar catalyst

is used in hydrogenation of a alkyne,

the cis alkene can be obtained.

10.11 Reduction by Sodium in Ammonia:

Alkene Synthesis through anti Hydrogenation

In a reaction that must at first seem mysterious, an alkyne dissolved in a solution of

sodium in liquid ammonia forms the trans alkene (Fig. 10.79). The practical con-

sequences of this are that we now have a way of synthesizing either a cis (Fig.10.78)

or trans (Fig. 10.79) alkene from a given alkyne. So, update your file cards.

Na/NH

(CH

)

(CH

)

98% trans

FIGURE 10.79 Reduction of an

alkyne with sodium in ammonia gives

the trans alkene.

10.11 Reduction by Sodium in Ammonia: Alkene Synthesis through anti Hydrogenation 453

When sodium is dissolved in ammonia, the sodium atom loses its odd electron

to give a sodium ion and a solvated electron, which is an electron surrounded by

solvent molecules:

–

[NH

]

Na Na

Solvated

electron

This complexed electron can add to an alkyne to give an intermediate called a

radical anion (Fig. 10.80). A radical anion is a negatively charged molecule that has

an unpaired electron.

–

[NH

]

Radical anion

FIGURE 10.80 A solvated electron

can add to an alkyne to generate a

radical anion.

I (MJ) vividly recall being quite uncertain about the structure of the radical anion

when I was first studying organic chemistry. I suspect I solved the problem by mem-

orizing this reaction and hoping that no one would ever ask me to explain what was

happening.But it’s not so hard and you should not repeat my error. First of all, where

is the “extra”electron in the radical anion? It is most certainly not in one of the bond-

ing π orbitals of the alkyne, because they are each filled with two electrons already.

If it is not there, it must be in one of the antibonding π* orbitals (Fig. 10.81).

An added electron

must go here

One of the π bonds

of the alkyne

CC =

π*

FIGURE 10.81 The electron must go

into an antibonding π* orbital of the

alkyne.

Why should the radical anion put up with this electron in an antibonding orbital?

The answer is twofold. First of all, the intermediate is held together by many elec-

trons occupying bonding orbitals, and a single electron in a high-energy orbital is

not destabilizing enough to overcome all the bonding interactions. Figure 10.82 gives

both molecular orbital and resonance pictures of the radical anion.

An alkyne radical anion

...

π*

.. .

–

FIGURE 10.82 The alkyne radical

anion.

454 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

Radical anion

Vinyl radical

Amide

ion

–

FIGURE 10.83 The radical anion can

abstract a proton from ammonia to

generate a vinyl radical and the amide

ion.The trans form is favored.

Radical

Amide

ion

Anion trans Alkene

–

[NH

]

–

FIGURE 10.84 Transfer of another

electron and protonation completes

the overall trans hydrogenation of

an alkyne.

Second, the radical anion is quite unstable and not much of it is likely formed

at equilibrium. Its very instability contributes to its great base strength,however, and

the small amount present at equilibrium is rapidly protonated by ammonia to give

the amide ion (



) and the vinyl radical (Fig. 10.83).There are two forms of the

vinyl radical, and it will be the trans form, with the alkyl groups as far from each

other as possible, that is the more stable version. A solvated electron can be donated

to this radical forming the vinyl anion, which is rapidly protonated by ammonia to

give the final product, the trans alkene (Fig. 10.84).

PROBLEM 10.28 Devise a synthetic pathway for each of the following com-

pounds, starting in each case with 2-butyne:

(a) (b)

(continued)

10.12 Special Topic: Three-Membered Rings in Biochemistry 455

Summary

Normal hydrogenation of an alkyne adds two equivalents of H

to give the alkane.

Use of a “poisoned” Lindlar catalyst leads to absorption of one equivalent of H

and formation of the cis alkene. The trans alkene can be made by reducing the

alkyne with Na in ammonia.

10.12 Special Topic: Three-Membered

Rings in Biochemistry

Despite the strain inherent in cyclopropanes, Nature finds ways to make them.

Bacteria, in particular, contain surprising amounts of cyclopropanated fatty acids.

Even more remarkable is the conversion of such molecules into cyclopropenes.

The source of the single “extra” carbon is S-adenosylmethionine, the same agent

involved in the methyl transfers discussed in Chapters 3 and 7 (pp. 142, 288;

Fig. 10.85). The mechanism of this intriguing change hasn’t been worked out yet.

COO

S-Adenosylmethionine

A cyclopropanated fatty acid

cyclopropanation

dehydrogenation

A cyclopropene

COOH

WEB 3D

FIGURE 10.85 Cyclopropanation

of a fatty acid is followed by

dehydrogenation.

(e)

meso

CCH

HO OH

456 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

In Chapter 12 we will see other three-membered rings found in Nature.Epoxides

are used as triggers in the construction of the biologically active molecules called

steroids, and, amazingly enough, one of the most prominent molecules in interstel-

lar space is not only a cyclopropene, but a carbene as well.This molecule is known

as cyclopropenylidene:

Pyrethrin I

Cyclopropenylidene

PYRETHRINS

Cyclopropanes are occasionally found in Nature, and one

class of naturally occurring cyclopropanes, the pyrethroids,

are useful insecticides. These compounds are highly toxic to

insects but not to mammals, and because they are rapidly

biodegraded, cyclopropanes do not persist in the environ-

ment. The naturally occurring pyrethroids are found in

members of the chrysanthemum family and are formally

derived from chrysanthemic acid. Many modified pyrethrins

not found in Nature have been made in the laboratory and

several are widely used as pesticides. The molecule known

as pyrethrin I has the systematic name 2,2-dimethyl-3-

(2-methyl-1-propenyl)cyclopropanecarboxylic acid

2-methyl-4-oxo-3-(Z-2,4-dipentadienyl)-2-cyclopenten-

1-yl ester. See why the shorthand is used?

10.13 Summary

New Concepts

This chapter continues our discussion of addition reactions, and

many of the mechanistic ideas of Chapter 9 apply. For example,

many polar addition reactions start with the formation of

the more stable carbocation. The most important new concept

in this chapter is the requirement for overall anti addition

introduced by three-membered ring intermediates. This

concept appears most obviously in the trans

bromination and chlorination of alkenes.

The openings of the intermediate bromonium

and chloronium ions by nucleophiles are S

reactions in which inversion is always

required.This process insures anti addition

(Fig. 10.13).

Remember also the formation of epoxides,

stable three-membered rings containing an

oxygen atom, and cyclopropanes, formed by carbene additions

to alkenes (Fig. 10.86).

Alkenes and alkynes react in similar fashion in most

addition reactions, although additional complications and

opportunities are introduced by the second π bond in the

alkynes.

COOOH H

Oxirane Alkene Cyclopropane

hν

FIGURE 10.86 Stable three-membered rings can be formed in some alkene

addition reactions.Two examples are epoxidation and carbene addition.

10.13 Summary 457

Reactions, Mechanisms, and Tools

Key Terms

aldehydes (p. 440)

alkene halogenation (p. 414)

bromonium ion (p. 415)

carbene (p. 431)

carbonyl compound (p. 438)

carboxylic acid (p. 424)

diazo compounds (p. 431)

1,3-dipolar reagents (p. 436)

1,3-dipoles (p. 436)

diradical (p. 434)

enol (p. 448)

epoxidation (p. 424)

geminal (p. 447)

halohydrin (p. 419)

heterogeneous catalysis (p. 411)

homogeneous catalysis (p. 411)

hydrogenation (p. 411)

ketone (p. 440)

molozonide (p. 437)

organocuprate (p. 430)

oxymercuration (p. 421)

ozonide (p. 437)

ozonolysis (p. 437)

primary ozonide (p. 437)

radical anion (p. 453)

singlet carbene (p. 433)

solvated electron (p. 453)

tautomerization (p. 449)

triplet carbene (p. 433)

vicinal (p. 414)

In this chapter, a series of ring formations is described: the

three-membered oxiranes, cyclopropanes, bromonium, chlor-

onium, and mercurinium ions, as well as the five-membered rings

formed through 1,3-dipolar additions, ozonolysis, and the addi-

tions of osmium tetroxide and potassium permanganate. Many

of these compounds react further to give the final products of

the reaction (Fig. 10.87).

Cyclopropanes and oxiranes can be isolated, but the other

rings react further under the reaction conditions to give the

final products. Oxiranes can be opened in either acid or base

to give new products. Additions to alkynes resemble those of

alkenes, but the second π bond adds complications, and

further addition reactions or rearrangements occur. Alkynes

can be reduced in either cis or trans fashion (Fig. 10.78 and

Fig. 10.79).

Both homogeneous and heterogeneous catalytic hydrogena-

tion are syn additions, because both added hydrogens are trans-

ferred from the metal surface to the same side of the alkene.

Alkene

KMnO

OsO

Hg(OAc)

X = Br or Cl

HgOAc

–

hν

FIGURE 10.87 Ring formation through addition across the double bond.

458 CHAPTER 10 Additions to Alkenes 2 and Additions to Alkynes

Syntheses

This chapter provides many new synthetic methods.

Via ozonide intermediates

1. O

2. H

2. Alcohols

Markovnikov addition, no rearrangements, anti addition

Organocopper reagents also work

1. Hg(OAc)

2. NaBH

1. RMgX

2. H

ROH

1. LiAlH

2. H

3. Aldehydes

A vin

l borane and an enol are intermediates

CCH

1. O

2. (CH

)

1. R

2. H

/NaOH

4. Alkanes

CHR

/Pt

RCH

/Pt

syn Addition, many catalysts possible

5. Alkenes

syn Addition

anti Addition

Lindlar catalyst

Na/NH

6. Halohydrins

anti Addition, X = Br or Cl

7. Bromo Ethers and Chloro Ethers

anti Addition, X = Br or Cl

/ROH

8. Cyclopropanes

cis Addition for singlet carbene, but both

cis and trans addition for triplet carbene

hν or Δ

1. Carboxylic Acids