More Carbonyl Chemistry

Transcription

1 Lecture 15 More arbonyl hemistry Shared Nobel Prize with Sabatier in 1912 student of Philippe Barbier François Auguste Victor Grignard March 3, 2016

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

3 arbon Nucleophiles Addition of carbon nucleophiles is one of the most important types of nucleophilic additions to a = group; a new carbon-carbon bond is formed in the process!!!! RMgX A Grignard reagent RLi An organolithium reagent R - An anion of a terminal alkyne - N yanide ion We will study the addition of these carbon nucleophiles

4 Victor Grignard Shared Nobel Prize with Sabatier in 1912 student of Philippe Barbier

5 Grignard Reagents X = l, Br, I Diethyl ether Et 2 Tetrahydrofuran TF

6 rystal Structure of 3 2 MgBr Br Mg L.J. Guggenberger and R.E. Randle, J. Amer. hem. Soc. 90(20) 5357 (1968)

7 Grignard Reagents Given the difference in electronegativity between carbon and magnesium, the -Mg bond is polar covalent, with - and Mg Grignard reagents behave like a carbanions arbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge a carbanions are good nucleophiles and add efficiently to the carbonyl group of aldehydes and ketones

8 Grignard Reagents Addition of a Grignard reagent to formaldehyde followed by 3 gives a 1 alcohol MgBr MgBr 3 2 TF dil. Mg 2 This sequence (mechanism) is general and important!

9 Grignard Reagents Addition to any other R gives a 2 alcohol MgBr MgBr 3 2 TF dil. Mg 2 You may change decorations at will read pages but, be careful of acidic functions like -

10 Grignard Reagents Addition to a ketone gives a 3 alcohol MgBr MgBr TF dil Mg 2 Please try this with other Grignard reagents and other ketones

11 Grignard Reactions MgBr MgBr 3 2 TF dil. Mg MgBr MgBr 3 2 TF dil. Mg MgBr MgBr TF dil Mg 2

12 Grignard Reagents Addition to 2 gives a carboxylic acid MgBr MgBr TF dil. 3 2 Mg 2 This is a great way to add a carbon

13 Grignard Reactions MgBr TF - MgBr 3 Dilute This is a great way to add two carbons These are very valuable and important reactions Please add to your card stock!

14 Grignard reagents react with esters R' R MgX R' diethyl 3 ether R 3 MgX but species formed is unstable and dissociates under the reaction conditions to form a ketone

15 Grignard reagents react with esters R' R MgX R' diethyl 3 ether R 3 MgX this ketone then goes on to react with a second mole of the Grignard reagent to give a tertiary alcohol R R' 3 MgX

16 Example 2 3 MgBr ( 3 ) diethyl ether 2. 3 ( 3 ) (73%) Two of the groups attached to the tertiary carbon come from the Grignard reagent

17 Grignard reagents react with: formaldehyde to give primary alcohols aldehydes to give secondary alcohols ketones to give tertiary alcohols esters to give tertiary alcohols 2 to give acids epoxides give primary alcohols

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19 Grignard Reagents Problem: 2-phenyl-2-butanol can be synthesized by three different combinations of a Grignard reagent and a ketone. Show each combination

20 Practice Problem 1. Starting from benzene, write a synthetic path to the structures below. You are free to use any reagents or reactants you choose, but you must start with benzene. l 0 Br l

21 The Wittig Reaction R R' ( 6 5 ) 3 P ylide A B R R' A B ( 6 5 ) 3 P

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

23 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

24 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

25 Phosphonium ylides Resonance stabilized R is usually 6 5 (phenyl) arbon is negatively polarized and nucleophilic ( 6 5 ) 3 P A B ( 6 5 ) 3 P A B

26 The Wittig Reaction R R' ( 6 5 ) 3 P ylide A B R R' A B ( 6 5 ) 3 P

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

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

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

30 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;

31 Wittig Reaction 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

32 The Wittig Reaction 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

33 An Example: Write the structure of the products P 3

34 To the 328N Band!!