Still More Carbonyl Chemistry

Transcription

1 Lecture 17 Still More arbonyl hemistry ' ' A B P( 6 5 ) 3 A P( 6 5 ) 3 B March 22, 2018

2 eaction Theme The most common reaction of a carbonyl group is addition of a nucleophile to form a tetrahedral addition compound Nu - ere it is an acid or electrophile - Nu Tetrahedral carbonyl addition compound

3 The Nobel Prize in hemistry 1979 Georg Wittig University of eidelberg

4 The Wittig eaction ' ( 6 5 ) 3 P ylide A B ' A B ( 6 5 ) 3 P

5 Preparation of Ylides The ylid is made in a two step process. The first step is a nucleophilic substitution reaction that Forms a phosphonium salt A ( 6 5 ) 3 P B A X ( 6 5 ) 3 P X B

6 Preparation of Ylides In the second step, the phosphonium salt is treated with a strong base in order to remove a proton from the carbon bonded to phosphorus. A ( 6 5 ) 3 P B base ( 6 5 ) 3 P base A B

7 Phosphonium ylides esonance stabilized is usually 6 5 (phenyl) arbon is negatively polarized and nucleophilic ( 6 5 ) 3 P A B ( 6 5 ) 3 P A B

8 The Wittig eaction ' ( 6 5 ) 3 P ylide A B ' A B ( 6 5 ) 3 P

9 Mechanism Step 1 ' ' A B P( 6 5 ) 3 A P( 6 5 ) 3 B

10 Mechanism Step 2 A ' B P( 6 5 ) 3 ' A P( 6 5 ) 3 B

11 Example ( 6 5 ) 3 P 2 TF (86%) 2 ( 6 5 ) 3 P

12 Triphenylphosphine oxide P( 6 5 ) 3 P( 6 5 ) 3 This substance is very stable Nearly insoluble in many solvents, i.e. pentane ral, mouse: LD50 = 1380 mg/kg;

13 Wittig eaction More examples 2 3 Ph 3 P 3 TF 87% Z isomer Ph 3 P Don t plan to control the E/Z ratio you get generally get a mixture

14 The Wittig eaction See... sometimes you can control it we won t try to do that in this class The reaction has broad scope 2 Ph 3P 2 3 TF Ph 3 P 100% E isomer

15 An Example: Write the structure of the products

16 xygen Nucleophiles " ' 2" " ' 2

17 Alcohols eact with Aldehydes and Ketones in two steps first ' " " ' Product is called a hemiacetal.

18 emiacetal reacts further in acid to yield an acetal " ' This product is called an acetal., " ' This hemiacetal reacts further.

19 Example l ( 2 3 ) 2 2 Benzaldehyde diethyl acetal

20 Diols Form yclic Acetals 3 ( 2 ) benzene acid catalyst 2 ( 2 ) 5 3

21 Mechanism of Acetal Formation

22 Mechanism esonance stabilized cation

23 Mechanism

24 Mechanism

25 Mechanism

26 Mechanism atalyst regenerated! emi acetal!

27 Mechanism of Acetal Formation Second stage is hemiacetal-to-acetal conversion involves carbocation chemistry

28 emiacetal-to-acetal Stage These are not separate reactions this is all one big equilibrium

29 emiacetal-to-acetal Stage

30 emiacetal-to-acetal Stage ere is the water!

31 emiacetal-to-acetal Stage

32 emiacetal-to-acetal Stage

33 emiacetal-to-acetal Stage The acetal egeneration of catalyst

34 Note that EVEY step is an equilibrium Therefore, the reaction can be pushed forward or backward by appropriate choice of conditions The forward reaction is synthesis The backward reaction is hydrolysis

35 ydrolysis of Acetals " ' 2 2" ' " mechanism: reverse of acetal formation hemiacetal is intermediate. application: aldehydes and ketones can be "protected" as acetals.

36

37 ydrolysis 3

38 Suppose you want to make this compound????? Br2 2?? ydroxy-4-phenylbutanal It s an alcohol. Use the Grignard eaction!!

39 Acetals as Protecting Groups If the Grignard reagent were prepared from 3-bromopropanal, it would self-destruct! First protect the - group as an acetal Br Br

40 Acetals as Protecting Groups Then do the Grignard reaction Br Mg, ether [MgBr] ydrolysis in dilute acid gives the desired product

41 Acetals as Protecting Groups ydrolysis (deprotection) regenerates the - group and the hydroxyl group - [MgBr] l, Valuable and important trick!!

42 For example, the conversion shown cannot be carried out directly..why?? NaN I

43 because the carbonyl group and the carbanion are incompatible :

44 Strategy 1) protect = 2) alkylate 3) restore =

45 Protect benzene 2 S 4, at

46 Alkylate NaN I

47 Deprotect l Desired product

48 Synthesis.. benzene and 3 carbon starting materials

49 Synthesis B r