Carbonyl Chemistry Survey of Reactions and Mechanisms Part 5

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Simon Gilbert
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1 arbonyl hemistry Survey of Reactions and Mechanisms Part xaloacetate AD Malate AD arbonyl Reduction Reactions Generalized transformation: electrons Reduction Add one bond xidation Add one bond electrons = reduction important in synthesis and biology But how is this reduction? Reduction = gain electrons...? Reduction: Increase in the number of bonds between and elements less electronegative than (often ). xidation: Increase in the number of bonds between and elements more electronegative than (often ). arbonyl hemistry Survey of Reactions and Mechanisms Part 5 Lecture Supplement Page1

2 Reactants for arbonyl Reduction ow? uc So for carbonyl reduction, nuc = : ydride ion uc a : A strong base but not nucleophilic B a Sodium borohydride A good hydride source Example: ab 4 3 Reactants for arbonyl Reduction ab 4 3 Mechanism: First step... Protonate =? Yes o Enolate formation? ot yet... Therefore start with nucleophilic attack at = 3 3 B Tetrahedral adduct... B 4 is **not** source What will ab 4 reduce? Aldehyde Ketone Thioester Ester Amide arboxylate Student exercise: Draw mechanisms and products of these reduction reactions. arbonyl hemistry Survey of Reactions and Mechanisms Part 5 Lecture Supplement Page2

3 Reactants for arbonyl Reduction What will ab 4 reduce? Aldehyde Ketone Thioester Ester Amide arboxylate ow to reduce these less reactive =? B 3 Boron loses formal charge 3 B Something with stronger drive to lose formal charge? Less electronegative atom... X X 3 ": " B E = Al E = Al Li Lithium aluminum hydride LA Reactants for arbonyl Reduction Ketone reduction by LiAl 4 : 1. LiAl LiAl 4 = strong base Do not mix with acid Mechanism: 2 Just another = addition reaction. 3 Al FAQ: Protonate before Al 4 attack? Yes o o strong acid present at this point. arbonyl hemistry Survey of Reactions and Mechanisms Part 5 Lecture Supplement Page3

4 Reactants for arbonyl Reduction LiAl 4 reduction of an ester: 3 1. LiAl ??? Predict product(s) via mechanism. Mechanism: First step... Protonate =? Yes o o strong acid present Enolate formation? ot yet... Therefore start with Al 3 Al Tetrahedral adduct... Aldehyde more electrophilic than ester Tetrahedral adduct... verall reaction: 3 1. LiAl Reactants for arbonyl Reduction LiAl 4 reduction of an amide: 1. LiAl 4 2. ( 3 ) 2 2 ( 3 ) 2 LiAl 4 reduction of a carboxylic acid and carboxylate: LiAl 4 1. LiAl 4 You are not responsible for the mechanisms of these reductions What will LiAl 4 reduce? Aldehyde Ketone Thioester Ester Amide arboxylate Student exercise: Draw mechanisms and products of these reduction reactions. arbonyl hemistry Survey of Reactions and Mechanisms Part 5 Lecture Supplement Page4

5 arbonyl Reductions in Biology Reduction xidation ommon in living systems Example: In gluconeogenesis (biosynthesis of glucose from noncarbohydrate precursors) 2 2 xaloacetate AD Malate AD ote selectivity: Reduction of ketone versus carboxylate AD/AD equilibrium balanced by changes in aromaticity, formal charge Student exercise: Draw curved arrows for both sides of equilibrium The hichibabin Reaction verall reaction: a 2 Mechanism? Substitution on aromatic ring... 2 Pyridine Aromatic EAS? Yes o 2 is nucleophile 2 is nucleophile so pyridine is ucleophilic attack on polar pi bond ydride ejection assisted by restoration of aromaticity arbonyl hemistry Survey of Reactions and Mechanisms Part 5 Lecture Supplement Page5

ALCOHOLS: Properties & Preparation

ALCOHOLS: Properties & Preparation ALLS: Properties & Preparation General formula: R-, where R is alkyl or substitued alkyl. Ar-: phenol - different properties. Nomenclature 1. ommon names: Name of alkyl group, followed by word alcohol.