Suggested solutions for Chapter 27

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1 uggested solutions for Chapter PRBLEM 1 uggest a mechanism for this reaction, commenting on the selectivity and the stereochemistry. Me 2 1. t-buk 2. Raney Ni Et The opportunity to explore the consequences of the intramolecular version of an important reaction. uggested solution The original work can be found in R.. Matthews and T. E. Meteyer, J. Chem. oc., Chem. Commun, 1971, The ylid forms in the usual way but can t reach across the ring to attack the carbonyl group directly so it has to do conjugate addition instead. It also has to attack from the top face as it is tethered there. Completion of the cyclopropane forming reaction leaves the sulfur still attached to the angular methyl group. Raney nickel reduces the C bond (this reagent is commonly used for this purpose). This reaction shows that simple sulfonium ylids can do conjugate addition they just prefer to add to carbonyl groups if that possibility is available. Me 2 t-buk C 2 Me Me Me

2 2 olutions Manual to accompany rganic Chemistry 2e PRBLEM 2 Explain the regiochemistry and stereochemistry of this reaction.. + Me 2 C 2 Et Et 2 C Exploration of sulfur ylid chemistry. uggested solution tereochemistry and stereoselectivity in fused rings is discussed in detail in chapter 32. The ylid is stabilised by conjugation with the ester group you can think of it also as an enolate. We can expect reversible addition to the carbonyl group and hence conjugate addition under thermodynamic control. The stereochemistry of the ring junction is inevitable: only a cis ring can be made (a trans- fused ring would be too strained). The interesting centre is that of the ester on the three- membered ring. It too is in a more stable configuration: on the outside of a folded molecule. The intermediate is probably a mixture of diastereoisomers, but as the conjugate addition is reversible the cyclopropane may be formed by cyclisation of only the diastereoisomer that can give the more stable product. Et 2 C Et 2 C Et 2 C Me 2 Me 2

3 olutions for Chapter 27 ulfur, ilicon and osphorus in rganic Chemistry 3 PRBLEM 3 Give mechanisms for these reactions, explaining the role of sulfur. Me 1. BuLi 2. MeI Me Cl, CCl 3 3. BuLi 4. gcl 2 2 acetone ulfur acetals as good nucleophiles: in the terminology of chapter 28, acyl anion equivalents or d 1 reagents. uggested solution The first reaction is an acetal exchange controlled by entropy: three molecules go in and four come out (the product, two molecules of methanol and one of water). We show just part of the mechanism. This chemistry was used to make the perfume cis- jasmone by R. A. Ellison and W. D. Woessner, J. Chem. oc., Chem. Commun., 1972, 529. Me Me Me Me Me Me Me Me Me

4 4 olutions Manual to accompany rganic Chemistry 2e continued... etc Me Now the sulfur atoms work to stabilise an anion (organolithium) formed by deprotonation. Alkylation and hydrolysis with a mercury catalyst gives the product. 1. BuLi Li 2. MeI Me 3. BuLi Me 4. RC 2 Me Li R PRBLEM 4 uggest a mechanism by which this cyclopropane might be formed. Me + Me 2 C 2 Me Attempts to repeat this synthesis on the related compound below led to a different type of product. What is different this time? + Me 2 C 2 Can you disentangle a curious variation on a simple mechanism?

5 olutions for Chapter 27 ulfur, ilicon and osphorus in rganic Chemistry 5 uggested solution The first reaction is a straightforward cyclopropane formation with a sulfoxonium ylid and a conjugated ketone. The only unusual feature, the Me group, makes no difference. Me C 2 Me 2 Me Me 2 Me In the second example, the bromine atom and the phenolic evidently do make a difference. No doubt the reaction starts in the textbook. same way and a cyclopropane is formed. Under the reaction conditions, the phenol will exist as an anion and this displaces the bromine. This unusual N2 reaction at a tertiary centre is possible because of activation by the carbonyl group. The accelerating effect of the carbonyl group on N2 reactions is demonstrated on p. 342 of the Me 2 C 2 PRBLEM 5 Deduce the structure of the product of this reaction from the NMR spectra and explain the stereochemistry. Compound A has δ 0.95 (6, d, J 7 z), 1.60 (3, d, J 5), 2.65 (1, double septuplet, J 4 and 7), 5.10 (1, dd, J 10 and 4), and 5.35 (1, dq, J, 10 and 5). 3 P 1. NaN 2 2. i-prc A C 6 12 A simple way to make Z- alkenes, with a bit of NMR revision. uggested solution This is obviously a Wittig reaction and we should expect a Z- alkene as the ylid is not stabilized by further conjugation. The evidence is plain:

6 6 olutions Manual to accompany rganic Chemistry 2e the signals at 5.10 and 5.35 are the alkene hydrogens and the coupling constant between them is 10 z. This is definitely a Z- alkene. 3 P 1. NaN 2 3 P 2. i-prc J 7 δ 0.95 δ 2.65 Me δ 0.95 Me δ 1.60 Me J 5 δ 5.35 J 4 δ 5.10 J 10 PRBLEM 6 A single geometrical isomer of an insect pheromone was prepared in the following way. Which isomer is formed and why? 3 P C Me 2 C C Me Me 2 C A C=CC 3 P 1. NaN 2 2. A Me 2 C C=C C=CEt 1. LiAl 4 2. Ac 2 pyridine Ac C=C C=CEt Testing your knowledge of the stereochemistry of the Wittig reaction. uggested solution The first Wittig with a stabilised ylid gives the E- enal A. The second, with an unstabilised ylid, gives a Z alkene so the final product is an E,Z- diene. Me 2 C A C Ac the insect pheromome

7 olutions for Chapter 27 ulfur, ilicon and osphorus in rganic Chemistry 7 PRBLEM 7 ow would you prepare samples of both geometrical isomers of this compound? C 2 A simple stereocontrolled alkene synthesis but both isomers are needed. uggested solution There are many methods that can be used to tackle this question. The only snags are protecting the group if necessary and care in isolating the Z- compound as it may isomerise easily to the E- compound by reversible conjugate addition. ne way to the Z- alkene uses reduction of an alkyne to control the stereochemistry. The group is protected as a benzyl ether removed by hydrogenation, perhaps under the same conditions as the reduction of the alkyne. 1. BuLi 2. Bn Bn 1. BuLi 2. C 2 Bn C 2 2, Pd Lindlar catalyst C 2 The E- alkene might be produced by reduction of the alkyne with an alkali metal in liquid ammonia but a Wittig reaction is probably easier. Either a phosphonium ylid or a phosphonate ester could be used. Protection of the alcohol as an ester allows hydrolysis of both esters in one step. 3 P 1. Me 2. Ac C 2 Me C Ac C 2 Me Na 2 C 2

8 8 olutions Manual to accompany rganic Chemistry 2e PRBLEM 8 Which alkene would be formed in each of these elimination reactions? Explain your answer mechanistically. 3 P base? 2 R 2 Na/g R 1? Ac Me 3 i base? Me 3 i acid? Revision of the three main methods for stereoselective (or stereospecific) alkene bond formation. uggested solution The first is sort of a Wittig reaction (the starting material is made by opening an epoxide with 3P), the second a Julia reaction and the third and the fourth are Peterson reactions under different conditions. Each is described in detail in chapter 27 of the textbook. The Wittig reaction is under kinetic control and is a stereospecific cis elimination. In this case the product is a Z- alkene. 3 P base 3 P R 1 R 2 3 P R1 R 2 R 1 3 P R P The Julia reaction is under thermodynamic control as equilibration occurs under the reaction conditions. The stereoselective product is the E- alkene. 2 Ac Na/g R 2 R 1 Ac Ac

9 olutions for Chapter 27 ulfur, ilicon and osphorus in rganic Chemistry 9 The Peterson reaction is a syn elimination under basic conditions, giving the Z- alkene from this starting material, but an E2 anti- elimination under acidic conditions, giving the E- alkene from this starting material. syn Me 3 i Me 3 i R 1 elimination base R 2 acid R 1 R 1 R 2 Z-alkene R 2 Nu Me 3 i 2 E-alkene PRBLEM 9 Give mechanisms for these reactions, explaining the role of silicon. 1. Na, Me 3 i Ms 2 2. Bu 4 NF 2 Reminder of the anion- stabilizing role of sulfones and the excellence of the mesylate leaving group plus the special role of fluoride as a nucleophile for silicon. uggested solution odium hydride removes a proton from the sulfone to give an anion that can act as a nucelophile. Displacement of mesylate gives an allyl silane, which is converted into an allylic anion by fluoride. Addition to the ketone gives a 5/5 fused system with the more stable cis ring junction. ime 3 Na ime Ms ime 3 F

10 10 olutions Manual to accompany rganic Chemistry 2e PRBLEM 10 Give mechanisms for these reactions, explaining the role of silicon. Why is this type of lactone difficult to make by ordinary acid- or base- catalysed reactions? Et 2 C Me 3 i MgCl Cl Et 2 C + ime 3 R R Lewis acid Basic organosilicon chemistry: the Peterson reaction and allyl silanes as nucleophiles. uggested solution Acylation of the Grignard reagent is followed by a second attack on the ketone as expected but the tertiary alcohol is a Peterson intermediate and eliminates to give the alkene. Et 2 C MgCl ime 3 Cl Et 2 C ClMg ime 3 ime 3 Et 2 C ime 3 ime 3 ime 3 Et 2 C ime 3 Et 2 C ime 3 Now a Lewis acid catalysed reaction of the allyl silane via a β- silyl cation gives the lactone. The double bond in these exo- methylene lactones easily moves into the ring in acid or base so mild conditions are ideal for these reactions. R LA = Lewis acid LA R R R R Et 2 C ime 3 ime 3 X cyclisation on work-up R Et R Et

11 olutions for Chapter 27 ulfur, ilicon and osphorus in rganic Chemistry 11 PRBLEM 11 ow would you carry out the first step in this sequence? Give a mechansims for the second step and suggest an explanation for the stereochemistry. You may find that a Newman projection helps.? EtAlCl 2 C ime 3 An important way to make an allyl silane and an important reaction of the product. uggested solution The best route to the allyl silane is the Wittig reaction (p. 675). The ylid is not stabilised by and extra conjugation so the Z- isomer is favoured. 3 P ime 3 C ime 3 The reaction with EtAlCl 2 is a Lewis acid- catalysed conjugate addition of the allyl silane to the enone. Conjugate addition is preferred because the nucleophile (the allyl silane) is tethered to the electrophile (enone) and the five- membered ring is preferred to a seven- membered ring. Cl Et Al ime 3 ime 3 The stereochemistry comes from the way the molecule prefers to fold and the Newman projection below should make that clear. The hydrogen atom on the allyl silane tucks underneath the six- membered

12 12 olutions Manual to accompany rganic Chemistry 2e ring while the double bond of the allyl silane projects out into space to give the stereochemistry found in the product. The ratio between this diastereoisomer and the other varies from 2:1 to 7.5:1 depending on conditions so the preference is really quite weak. ClEtAl ime 3 ime 3