14.8 Organic Synthesis Using Alkynes

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666 CHAPTER 14 • THE CHEMISTRY OF ALKYNES

The reaction of acetylenic anions with alkyl halides or sulfonates is important because it is another method of carbon–carbon bond formation. Let’s review the methods covered so far: 1. cyclopropane formation by the addition of carbenes to alkenes (Sec. 9.8) 2. reaction of Grignard reagents with ethylene oxide and lithium organocuprate reagents with epoxides (Sec. 11.4C) 3. reaction of acetylenic anions with alkyl halides or sulfonates (this section)

PROBLEMS 14.18 Give the structures of the products in each of the following reactions.

(a) ' _ CH3CC Na| CH3CH2 I 3 + L (b) ' _ butyl tosylate Ph C C Na| + L 3 H3O| (c) CH3C' C MgBr ethylene oxide (d) L '+ Br(CH2)5Br HC C_ Na|(excess) + 3 14.19 Explain why graduate student Choke Fumely, in attempting to synthesize 4,4-dimethyl-2-

pentyne using the reaction of H3C C'C_ Na| with tert-butyl bromide, obtained none of the desired product. L 3 14.20 Propose a synthesis of 4,4-dimethyl-2-pentyne (the compound in Problem 14.19) from an alkyl halide and an alkyne. 14.21 Outline two different preparations of 2-pentyne that involve an alkyne and an alkyl halide. 14.22 Propose another pair of reactants that could be used to prepare 2-heptyne (the product in Eq. 14.28).

14.8 ORGANIC SYNTHESIS USING ALKYNES

Let’s tie together what we’ve learned about alkyne reactions and organic synthesis. The solution to Study Problem 14.2 requires all of the fundamental operations of organic synthesis: the formation of carbon–carbon bonds, the transformation of functional groups, and the establish- ment of stereochemistry (Sec. 11.9). Notice that this problem stipulates the use of starting materials containing ﬁve or fewer carbons. This stipulation is made because such compounds are readily available from commer- cial sources and are relatively inexpensive.

Study Problem 14.2 Outline a synthesis of the following compound from acetylene and any other compounds containing no more than ﬁve carbons:

CH3(CH2)6 CH2CH2CH(CH3)2 $

$C A C $ H H cis-2-methyl-5-tridecene

Solution As usual, we start with the target molecule and work backward. First, notice the stereochemistry of the target molecule: it is a cis alkene. We’ve covered only one method of preparing cis alkenes free of their trans isomers: the hydrogenation of alkynes (Sec. 14.6A). This reaction, then, is used in the last step of the synthesis: 14_BRCLoudon_pgs4-2.qxd 11/26/08 9:04 AM Page 667

14.8 ORGANIC SYNTHESIS USING ALKYNES 667

H2 CH3(CH2)6 CH2CH2CH(CH3)2

$ Lindlar catalyst $ CH3(CH2)6 C 'C CH2CH2CH(CH3)2 $C A C $ (14.29a) LL 2-methyl-5-tridecyne H H (target molecule)

The next task is to prepare the alkyne used as the starting material in Eq. 14.29a. Because the desired alkyne contains 14 carbons and the problem stipulates the use of compounds with five or fewer carbons, we’ll have to use several reactions that form carbon–carbon bonds. There are two primary alkyl groups on the triple bond; the order in which they are introduced is arbitrary. Let’s introduce the five-carbon fragment on the right-hand side of this alkyne in the last step of the alkyne synthesis. This is accom- plished by forming the conjugate-base acetylenic anion of 1-nonyne and allowing it to react with the ap- propriate commercially available five-carbon alkyl halide, 1-bromo-3-methylbutane (Sec. 14.7B):

Br CH2CH2CH(CH3)2 L NaNH2 1-bromo-3-methylbutane CH (CH ) C 'CH CH (CH ) C ' C_ 3 2 6 NH (liq) 3 2 6 LL 3 3 1-nonyne

CH3(CH2)6 C 'C CH2CH2CH(CH3)2 (14.29b) LL The starting material for this reaction, 1-nonyne, is prepared by the reaction of 1-bromoheptane with the sodium salt of acetylene itself.

NaNH2 CH3(CH2)6Br HCHC ' Na C_ ' C H CH3(CH2)6 C 'CH (14.29c) NH3 (liq) | LL(large excess 3 L LL relative to NaNH2)

The large excess of acetylene relative to sodium amide is required to ensure formation of the monoanion—that is, the anion derived from the removal of only one acetylene proton. If there were more sodium amide than acetylene, some dianion C_ 'C_ could form, and other reactions would occur. (What are they?) Because acetylene is cheap3 and 3is easily separated from the products (it is a gas), use of a large excess presents no practical problem. Because the 1-bromoheptane used in Eq. 14.29c has more than ﬁve carbons, it must be prepared as well. The following sequence of reactions will accomplish this objective.

Mg H2C$ CH2 H O CH CH CH CH CH Br 3 | 3 2 2 2 2 ether L L 1-bromopentane conc. HBr H2SO4 CH3CH2CH2CH2CH2CH2CH2 OH CH3CH2CH2CH2CH2CH2CH2 Br (14.29d) L L 1-heptanol 1-bromoheptane

The synthesis is now complete. To summarize:

NaNH2 CH3(CH2)6Br (Eq. 14.29d) NaNH2 HC' CH (excess) CH3(CH2)6C' CH NH3 (liq) NH3 (liq)

H2 CH3(CH2)6 CH2CH2CH(CH3)2 BrCH CH CH(CH ) Lindlar catalyst 2 2 3 2 CH (CH ) C' CCH CH CH(CH ) 3 2 6 2 2 3 2 $CCC A ) HH) $ (14.29e) 14_BRCLoudon_pgs4-2.qxd 11/26/08 9:04 AM Page 668

668 CHAPTER 14 • THE CHEMISTRY OF ALKYNES

PROBLEM 14.23 Outline a synthesis of each of the following compounds from acetylene and any other compounds containing ﬁve or fewer carbons.

(a) CH3CH2CH2CH2CH2CH2CH2CH2CH2 OH (b) O S 1-nonanol H3CC (CH2)8CH3 L L 2-undecanone

14.9 PHEROMONES

As Problems 14.24 and 14.25 on p. 664 illustrate, the chemistry of alkynes can be applied to the synthesis of a number of pheromones—chemical substances used in nature for communi- cation or signaling. An example of a pheromone is a compound or group of compounds that the female of an insect species secretes to signal her readiness for mating. The sex attractant of the female Indian meal moth (Plodia interpunctella, a common pantry moth in the United States) is such a compound: O

H CH2 CH2CH2CH2CH2CH2CH2CH2CH2 O C CH3 CC CC

H3C HH H

(9Z,12E)-9,12-tetradecadienyl acetate (mating pheromone of the female Indian meal moth)

Pheromones are also used for defense, to mark trails, and for many other purposes. It was dis- covered not long ago that the traditional use of sows in France and Italy to discover buried truffles owes its success to the fact that truffles contain a steroid that happens to be identical to a sex attractant secreted in the saliva of boars during premating behavior! About three decades ago, scientists became intrigued with the idea that pheromones might be used as a species-specific form of insect control. The thinking was that a sex attractant, for example, might be used to attract and trap the male of an insect species selectively without af- fecting other insect populations. Alternatively, the males of a species might become confused by a blanket of sex attractant and not be able to locate a suitable female. When used success- fully, this strategy would break the reproductive cycle of the insect. The harmful environmen- tal effects and consequent banning of such pesticides as DDT stimulated interest in such highly specific biological methods. Although experimentation has shown that these strategies are not successful for the broad control of insect populations, they are successful in specific cases. For example, local infestations of the common pantry moth can be eradicated with commercially available traps that uti- lize the female sex attractant (Fig. 14.7). In large-scale agriculture, traps employing mating pheromones are useful as “early-warning” systems for insect infestations. When this approach is used, conventional pesticides need be applied only when the target insects appear in the traps. This strategy has brought about reductions in the use of conventional pesticides by as much as 70% in many parts of the United States. Sex pheromones, aggregation pheromones (pheromones that summon insects for coordinated attack on a plant species), and kairomones (plant-derived compounds that function as interspecies signals for host plant selection) are used commercially in this manner. Attractants for more than 250 different species of insect pests are now available commercially.