14.5 Conversion of Alkynes Into Aldehydes and Ketones 655

Home , Aldehyde, Enol, Hexyne, Ketone, Octyne, Pentyne

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654 CHAPTER 14 • THE CHEMISTRY OF ALKYNES

PROBLEMS 14.7 Give the product that results from the addition of one equivalent of Br2 to 3-hexyne. What are the possible stereoisomers that could be formed? 14.8 The addition of HCl to 3-hexyne occurs as an anti-addition. Give the structure, stereochem- istry, and name of the product.

CONVERSION OF ALKYNES INTO 14.5 ALDEHYDES AND KETONES

A. Hydration of Alkynes Water can be added to the triple bond. Although the reaction can be catalyzed by a strong acid, it is faster, and yields are higher, when a combination of dilute acid and mercuric ion (Hg2ϩ) catalysts is used. O 2 S Hg |, H2SO4 (dilute) C' CH H2O C CH3 (14.4) 0L + 0L L

cyclohexylacetylene cyclohexyl methyl ketone (91% yield)

The addition of water to a triple bond, like the corresponding addition to a double bond, is called hydration. The hydration of alkynes gives ketones (except in the case of acetylene itself, which gives an aldehyde; see Study Problem 14.1, p. 656). Let’s contrast the hydration reactions of alkenes (Sec. 4.9B) and alkynes. The hydration of an alkene gives an alcohol.

H2SO4 R CH CH2 + H2O R CH CH3 (14.5a) an alkene OH an alcohol

Because addition reactions of alkenes and alkynes are closely analogous, it might seem that an alcohol should also be obtained from the hydration of an alkyne:

OH 2 H2SO4, Hg | RCC' H H2O R " C A CH2 (14.5b) LLan alkyne + Lan enol

An alcohol containing an OH group on a carbon of a double bond is called an enol (pronounced en´-ôl).¯ In fact, enols are formed in the hydration of alkynes. However, most enols cannot be isolated because most enols are unstable and are rapidly converted into the corresponding aldehydes or ketones.

OH O S R " C A CH2 R C CH3 (14.5c) L LL an enol a ketone 14_BRCLoudon_pgs4-2.qxd 11/26/08 9:04 AM Page 655

14.5 CONVERSION OF ALKYNES INTO ALDEHYDES AND KETONES 655

Most aldehydes and ketones are in equilibrium with the corresponding enols, but the equilibrium concentrations of enols are in most cases minuscule—typically, one part in 108 or less. The relationship among aldehydes, ketones, and enols is explored in Chapter 22. The impor- tant point here is that, because most enols are unstable, if an enol is formed as the product of a reaction, it is rapidly converted into the corresponding aldehyde or ketone. The mechanism of alkyne hydration is very similar to that of the oxymercuration of alkenes (Sec. 5.4A). In the ﬁrst part of the mechanism, mercuric ion reacts as an electrophile with the p electrons of the triple bond to form a carbocation, which could be in equilibrium with a cyclic mercurinium ion:

R C CH R C CH R C CH (14.6a)

2 .. 2 Hg.. Hg Hg

The carbocation is formed at the carbon of the triple bond that bears the alkyl substituent. (Re- call that alkyl substitution stabilizes carbocations; Sec. 4.7C.) This carbocation reacts with water, and loss of a proton to solvent water gives the addition product. As a result, the oxygen from water ends up on the carbon with the alkyl substituent.

.. ..

.. O H OH

.. OH2 OH2 .. R C CH R C CH R C CH + H3O (14.6b) Hg Hg Hg

In the oxymercuration of alkenes, the reducing agent NaBH4 is the source of hydrogen that replaces the mercury. However, the use of NaBH4 is unnecessary in the hydration of alkynes. The reason is that the presence of a double bond makes possible removal of the mercury by a protonolysis reaction. This protonolysis occurs under the conditions of hydration; a separate procedure is not required. The ﬁrst step in the mechanism of this protonolysis reaction is protonation of the double bond. This protonation occurs at the carbon bearing the mercury because the resulting carbocation is resonance-stabilized.

(Recall that formation of a resonance-stabilized carbocation also explains the position of protonation in HBr addition; Eq. 14.3b, p. 653.) Dissociation of mercury from this carbocation 2 liberates the catalyst Hg | along with the enol. OH OH A 2 R" C CH2 R" C CH2 Hg | (14.6d) LL L + | an enol Hg" | 14_BRCLoudon_pgs4-2.qxd 11/26/08 9:04 AM Page 656

656 CHAPTER 14 • THE CHEMISTRY OF ALKYNES

Conversion of the enol into the ketone is a rapid, acid-catalyzed process. Protonation of the double bond gives another resonance-stabilized carbocation:

| OH H OH2 OH |OH 3 2 L 3 2 S2 R" CA CH2 2 RCC" H3 RCCH3 OH2 (14.6e) L LL LL + 3 2 |a resonance-stabilized carbocation

This carbocation is also the conjugate acid of a ketone. Loss of a proton gives the ketone product.

H OH2 O| 3 O L 3S 2 3S2 R C CH3 R C CH3 H OH| 2 (14.6f) L L LL + L The hydration of alkynes is a useful way to prepare ketones provided2 that the starting material is a 1-alkyne or a symmetrical alkyne (an alkyne with identical groups on each end of the triple bond). This point is explored in Study Problem 14.1.

Study Problem 14.1 Which one of the following compounds could be prepared by the hydration of alkynes so that it is uncontaminated by constitutional isomers? Explain your answer. (a) O (b) O S CH3CH CH3CH2CCH2CH3 acetaldehyde 3-pentanone

Solution First, what alkyne starting materials, if any, would give the desired products? The equations in the text show that the two carbons of the triple bond in the starting material corre- spond within the product to the carbon of the CAO group and an adjacent carbon. Thus, for part (a), the only possible alkyne starting material is acetylene itself, HC'CH. For part (b), the only

possible alkyne starting material is 2-pentyne, CH3C'CCH2CH3. Next, it remains to be shown whether hydration of these alkynes gives only the products in the problem. Remember, a good synthesis gives relatively pure compounds. The hydration of acetylene indeed gives only acetaldehyde. (In fact, acetaldehyde is the only aldehyde that can be prepared by the hydration of an alkyne.) However, hydration of 2-pentyne gives a mixture consisting of compa- rable amounts of 2-pentanone and 3-pentanone, because the carbons of 2-pentyne both have one alkyl substituent. Thus, there is no reason that the reaction of water at either carbon should be strongly favored.

14.5 CONVERSION OF ALKYNES INTO ALDEHYDES AND KETONES 657

Hence, hydration would give a mixture of constitutional isomers that would have to be separated, and the yield of the desired product would be low. Consequently, hydration would not be a good way to prepare 3-pentanone. (However, 2-pentanone could be prepared by hydration of a different alkyne; see Problem 14.9a).

PROBLEMS 14.9 From which alkyne could each of the following compounds be prepared by acid-catalyzed hydration? (a) O (b) O S S CH3CCH2CH2CH3 (CH3)3CC CH3 L L (c) O S CH3CH2CH2CH2 C CH2CH2CH2CH2CH3 L L 14.10 The hydration of an alkyne is not a reasonable preparative method for each of the following compounds. Explain why.

(a) CH3CH2CH A O (b) O (c) S A O (CH3)3CC C(CH3)3 0 L L 14.11 (a) Draw the structures of all enol forms of the following ketone, including stereoisomers. O S CH3CH2 C CH(CH3)2 L L (b) Would alkyne hydration be a good preparative method for this compound? Explain.

B. Hydroboration–Oxidation of Alkynes The hydroboration of alkynes is analogous to the same reaction of alkenes (Sec. 5.4B).

CH2CH3 % CH3CH2 "C 3CH CH C' CCH CH BH C (14.8a) 3 2 2 3 3 THF ( + B "H 3

As in the similar reaction of alkenes, oxidation of the organoborane with alkaline hydrogen peroxide yields the corresponding “alcohol,” which in this case is an enol. As shown in Sec. 14.5A, enols react further to give the corresponding aldehydes or ketones.

CH2CH3 % CH CH CH CH O 3 2 2 3 S CH3CH2 H O ͞OH "C 2 2 _ A C $CCC ) CH3CH2CH2 C CH2CH3 ( L L B H) $OH "H 3 an enol (14.8b) 14_BRCLoudon_pgs4-2.qxd 11/26/08 9:04 AM Page 658

658 CHAPTER 14 • THE CHEMISTRY OF ALKYNES

Because the organoborane product of Eq. 14.8a has a double bond, a second addition of

BH3 is in principle possible. However, the reaction conditions can be controlled so that only one addition takes place, as shown, provided that the alkyne is not a 1-alkyne. If the alkyne is a 1-alkyne (that is, if it has a triple bond at the end of a carbon chain), a sec-

ond addition of BH3 cannot be prevented.

RC ' CH + BH3 multiple addition reactions L a 1-alkyne

However, the hydroboration of 1-alkynes can be stopped after a single addition provided that

an organoborane containing highly branched groups is used instead of BH3. One reagent de- veloped for this purpose is disiamylborane, represented with the skeletal structure shown in Eq. 14.9. (How would you synthesize disiamylborane? See Sec. 5.4B.)

CH3 CH3 " " represented as (14.9) H C C BH "" BH L LL LL L LL 2 " "CH3 "H 2 disiamylborane

The disiamylborane molecule is so large and highly branched that only one equivalent can react with a 1-alkyne; addition of a second molecule results in severe van der Waals repulsions. In many cases, van der Waals repulsions, or steric effects, interfere with a desired reaction; in this case, however, van der Waals repulsions are used to advantage, to prevent an undesired second addition from occurring:

CH3(CH2)5 H BH "" LL 2 H2O2 CH (CH ) C ' CH " C A C 3 2 5 THF $ ) OH L _ H B ) $ " " LL 2 " CH3(CH2)5 H

$C A C) CH3(CH2)5 CH2 CH A O (14.10) L L H) $OH octanal (an enol) (an aldehyde; 70% yield)

Notice from this example that the regioselectivity of alkyne hydroboration is similar to that observed in alkene hydroboration (Sec. 5.4B): boron adds to the unbranched carbon atom of the triple bond, and hydrogen adds to the branched carbon. Because hydroboration–oxidation and mercury-catalyzed hydration give different products when a 1-alkyne is used as the starting material (why?), these are complementary methods for the preparation of aldehydes and ketones in the same sense that hydroboration–oxidation and STUDY GUIDE LINK 14.1 Functional Group oxymercuration–reduction are complementary methods for the preparation of alcohols from Preparations alkenes. 14_BRCLoudon_pgs4-2.qxd 11/26/08 9:04 AM Page 659

14.6 REDUCTION OF ALKYNES 659

O 1) BH "" S LL 2 " CH (CH ) CH C H 2) H O ͞OH 3 2 5 2 2 2 _ L L CH3(CH2)5 C ' C H O (14.11) L L 2 S H2O, Hg |, H3O| CH3(CH2)5 C CH3 L L Notice that hydroboration–oxidation of a 1-alkyne gives an aldehyde; hydration of any 1-alkyne (other than acetylene itself) gives a ketone.

PROBLEM 14.12 Compare the results of hydroboration–oxidation and mercuric ion-catalyzed hydration for (a) cyclohexylacetylene and (b) 2-butyne.

14.6 REDUCTION OF ALKYNES

A. Catalytic Hydrogenation of Alkynes Alkynes, like alkenes (Sec. 4.9A), undergo catalytic hydrogenation. The ﬁrst addition of hydrogen yields an alkene; a second addition of hydrogen gives an alkane.

H2, H2, catalyst catalyst RRCC' RRCH A CH RRCH2 CH2 (14.12) LL LL LLL The utility of catalytic hydrogenation is enhanced considerably by the fact that hydrogenation of an alkyne may be stopped at the alkene stage if the reaction mixture contains a catalyst poison: a compound that disrupts the action of a catalyst. Among the useful catalyst poi- 2 sons are salts of Pb |, and certain nitrogen compounds, such as pyridine, quinoline, or other amines.

i ar N N 1 1 pyridine quinoline

These compounds selectively block the hydrogenation of alkenes without preventing the hy-

drogenation of alkynes to alkenes. For example, a Pd/CaCO3 catalyst can be washed with Pb(OAc)2 to give a poisoned catalyst known as Lindlar catalyst. In the presence of Lindlar catalyst, an alkyne is hydrogenated to the corresponding alkene:

Lindlar catalyst or CH3CH2CH2 CH2CH2CH3 Pd/C, pyridine H + CH CH CH C' CCH CH CH C A C (14.13) 2 3 2 2 2 2 3 ethanol $ ) 4-octyne HH) $ cis-4-octene