CHAPTER 24 HW: CARBONYL CONDENSATIONS

Transcription

1 CAPTER 24 W: CARBNYL CNDENSATINS ALDL REACTIN 1. Draw the curved arrow mechanism for each aldol reaction. Na 2 product Na Et prod. 2. Give the curved arrow mechanism for this aldol reaction (and dehydration of the aldol product). Na, 2 Page 1

2 3. Give the major organic aldol product for each reaction, along with the dehydration product (if possible) formed after ing. Na 2 Na 2 (same, can't dehydrate) Na 2 4. In the following reaction the aldol product C is difficult to isolate, and even without ing the dehydration product D is formed instead. Explain why this aldol product so readily dehydrates. Na 2 C D This aldol product so readily dehydrates because it forms a highly conjugated system. (The α β unsaturated carbonyl is normally conjugated, but D involves conjugation as well with the lower phenyl group). Thus, there s an enthalpic driving force for dehydration. 5. Draw all possible aldol (non-dehydrated) products from this mixed aldol reaction. Ignore stereoisomers. A + B Na 2 Enolate A + A Enolate A +B Enolate B + B Enolate B + A Page 2

3 CNTRLLABLE MIXED ALDL REACTINS 6. In aldol reactions there is often the possibility of generating a variety of products (see previous problem). For each set of reactions below, give the major expected product. Then explain why the number of side products is minimized in these reactions. + Na Et or (might dehydrate so easily) The first aldehyde is the only one with an alpha, so there is only one possible enolate in this reaction. This removes some possible side products because the second aldehyde (benzaldehyde) can never be the enolate, only the electrophile. Although it s still possible that aldehyde 1 can react with itself (as a side product), at least there are not 4 possible products, as in the previous problem. + NaC 3 Me The alpha between the carbonyls on the first structure is significantly more acidic than the alpha on the aldehyde, so it will be deprotonated exclusively (again there will only be one possible enolate). Additionally, the pk a s are such that reaction of the β-dicarbonyl with Na will deprotonate it fully (100% reaction), so with all the β-dicarbonyl in the enolate form, it cannot react with itself (as long as there are equal moles of β-dicarbonyl and NaC 3 ). The aldehyde will positively be the electrophile, minimizing mixtures. 1 equiv. LDA + LDA is a much stronger base than Na or NaC 3, and the pk a s are such that in the first step, the aldehyde will be deprotonated fully (100% reaction). If there is no unreacted aldehyde from the first aldehyde (butanal), it can t be the electrophile, and the enolate will positively react with the aldehyde in part b (acetaldehyde). Page 3

4 7. Give the major organic product of each reaction. Na, 2 e. 1 equiv. LDA mild + Na, 2, f. 1 equiv. LDA mild + NaEt, Et g. Na, 2 d. Na, Me, h. 1 equiv. LDA mild +, 8. Give the major organic product of each aldol reaction Na, Et Connect C2-C7 NaMe, Me Connect C4-C Na, Connect C2-C6 Page 4

5 ALDL RETRSYNTESIS 9. Propose starting materials needed to synthesize each compound through an aldol reaction. β-hydroxycarbonyl 2 + d. + e. CLAISEN REACTIN 10. Give the curved arrow mechanism for each Claisen reaction. Et NaEt mild + Et Et Et Et Et Et Et + step b Et Et Et Et feels "done" at this point (this is the product), but final deprotonation will happen and also drives the reaction. Continued on next page Page 5

6 10 continued NaEt mild + Et Et Et Et Explain why a Claisen reaction occurs with ester E, but not with ester F. Et E Et F Et from E Et Et from F The Claisen reaction is driven by the final deprotonation of the β-dicarbonyl, which allows the system to lower its energy by transferring charge from the localized Et to the resonance stabilized conjugate base of E (shown above). Ester E can form this resonance stabilized ion, while F cannot (there is no alpha between the two carbonyls). Thus there is no motivation for F product to form. 12. Reaction of the following diester with NaEt followed by mild + makes product G, not product. Explain why there is a preference for forming product G over. Et leads to Et NaEt mild + Et not Et leads to G G Product G forms a β-dicarbonyl, which can be deprotonated to form a highly resonance stabilized ion (see previous problem), which drives the reaction. Product has no alpha- between the carbonyls, so the reaction is not favorable. Page 6

7 13. If a Claisen reaction is expected (in some cases no reaction is expected), give the major organic product. Et NaEt + Et workup e. Me NaMe + workup no reaction Me no alpha- Me NaMe + Me workup f. Me NaMe, Me + workup Me Et NaEt Et + workup Et g. NaEt, Et Et Et + workup Et Et d. Et Cl NaEt Et Et + workup Et Me h. Me NaMe + workup Me DECARBXYLATIN 14. Give the curved arrow mechanism for the decarboxylation and keto-enol tautomerism steps in this reaction (from intermediate J to product K). Et NaEt +, 2, Et I J K J (redrawn) - C K Page 7

8 15. Give the major organic product of each Claisen reaction. Note: each system is ed. Et NaEt +, 2, Et +, 2, Me NaMe +, 2, Me Et NaEt, Et +, 2, Et RBINSN ANNULATIN 16. Give the curved arrow mechanism for each reaction. K, 2 Et Et Et Et Et Michael addition Et Et Et product Aldol reaction Dehydration of Aldol product continued on next page Page 8

9 16 continued Na, Give the major organic product of each annulation reaction. Et Et NaEt, Et + workup Et Et Et Na, 2 Page 9

10 RELATED MECANISM 18. Draw the curved arrow mechanism for this reaction. Et Et NaEt Et + Et Et Et Et Et Et Et Et Et + (step c) Et Et Et Et (Feels done, but a β-dicarbonyl will be deprotonated when in Et-) Page 10

11 SYNTESIS 19. Design a synthesis to perform the following transformations. Show all reagents and synthetic intermediates. Na, 2, a) (C 3 C 2 ) 2 CuLi b) +, 2 Aldol Cuprate 1,4 Addition Et a) NaEt, Et a) C 3 MgI (excess) Et b) + Claisen Et b) +, 2 Grignard Me Me Me Me a) NaMe, Me a) NaMe b) + b) C 3 C 2 C 2 Br Claisen Me Enolate Alkylation Me +, 2, Decarboxylation Page 11