CHAPTER 20: CARBONYL REDOX RXNS

Transcription

1 CHAPTER 20: CARBNYL REDX RXNS GENERAL CMMENTS APPLICATINS GENERAL REACTIVITY PATTERN Page 1

2 HYDRIDE REDUCTINS REACTIN PATTERNS With aldehydes or ketones: Lithium aluminum hydride R C H a. LiAlH 4, Et 2 b. H + workup Sodium borohydride NaBH 4 R C H CH 3 CH 2 H REACTIVITY DIFFERENCES LiAlH 4 is more reactive than NaBH 4. NaBH 4 can be in protic solvents while LiAlH 4 cannot. LiAlH 4 + H 2 à MECHANISMS SIMPLIFIED MECHANISM (USE THIS NE) a. LiAlH 4, Et 2 b. H + workup NaBH 4 CH 3 CH 2 H Page 2

3 MRE ACCURATE MECHANISM (FYI) NaBH 4 CH 3 CH 2 H EXAMPLES NaBH 4 CH 3 CH 2 H H a. LiAlH 4 b. H + workup CH 3 a. LiAlD 4 b. H + workup NaBD 4 CH 3 CH 2 D BILGICAL REDUCTINS Under anaerobic conditions (when ATP is scarce) muscle uses this reaction to generate NAD + so they can continue to produce ATP through glycolysis (which uses NAD + ). pyruvic acid Active site of an enzyme NADH Nicotinamide Adenine Dinucleotide Hydride NAD + Nicotinamide Adenine Dinucleotide Page 3

4 ACETYLIDE REACTINS REACTIN / MECHANISM H 3 C C C H a. NaNH 2 b. H c. H + workup EXAMPLES a. NaC CH b. H + workup Devise a synthesis: Page 4

5 RGANMETALLIC REACTINS CHALLENGE F C-C BND FRMATIN Fe 2+ ferrocene RGANMETALLIC REAGENTS rganolithium reagents rganomagnesium reagents rganocuprate reagents H 3 C Li H 3 C MgX (H 3 C) 2 CuLi Francois Grignard (French chemist) Nobel Prize in 1912 PREPARATIN F RGANMETALLIC REAGENTS Prep of rganolithium reagents: Prep of rganomagnesium reagents: Prep of rganocuprate reagents: Page 5

6 PRACTICAL NTES CH 3 MgBr + H 2 à RLi AND RMgX REACTIN WITH CARBNYLS REACTIN PATTERN / SIMPLIFIED MECHANISM With aldehydes or ketones: a. CH 3 Li or CH 3 MgX H b. H + workup EXAMPLES a. MgCl b. H + workup a. Li b. H + workup Br a. Mg b. H 2 C= c. H + workup Page 6

7 RETRSYNTHESIS Design a synthesis of these compounds, using reagents that are 5 carbon atoms or less. MULTI-STEP SYNTHESIS PRBLEMS Design a synthesis of this compound, using reagents that are 5 carbon atoms or less. Page 7

8 Design a synthesis of this compound, using reagents that are 5 carbon atoms or less. RLi AND RMgX REACTIN WITH EPXIDES REACTIN PATTERN / MECHANISM EXAMPLE a. CH 3 CH 2 Li b. CH 3 Br RLi AND RMgX REACTIN WITH DRY ICE REACTIN PATTERN / MECHANISM Page 8

9 PRTECTING GRUPS INCMPATIBLE FUNCTINAL GRUPS PRTECTIN / DEPRTECTIN SEQUENCE PRTECTIN STEP Trimethyl silyl chloride TMSCl DEPRTECTIN STEP Bu 4 N + F - (aka TBAF) Tetrabutyl ammonium fluoride TBAF Page 9

10 EXAMPLE Devise a synthesis of the following, using protecting groups: REACTIN F a - b UNSATURATED CARBNYLS TW d + SITES Page 10

11 1,2 AND 1,4-ADDITIN 1,2-ADDITIN 1,4-ADDITIN 1,2 + 1,4-SELECTIVE REACTINS SELECTIVE 1,2-ADDITINS: LiAlH 4 AND RLI Product ratios 1 a. CH 3 MgBr b. H + Product ratios 2 1 LiAlH4 product ratios from: Jones, M., Fleming, S.A., rganic Chemistry, 4 th ed., Norton, 2010, pp CH3 Li and CH 3 MgBr product ratios from: Solomons, G., Fryhle, C.B., rganic Chemistry, 8 th ed., Wiley, 2004, pp Page 11

12 SELECTIVE 1,4-ADDITINS: RGANCUPRATES EXAMPLES Page 12

13 APPLICATIN: FATTY ACID BISYNTHESIS H Palmitic acid (C 16 ) H NADPH, H + S-CoA S-Protein S-Protein H Acetyl CoA Beginning fatty acid S Adenine N NH 2 N H H NH 2 N N P P N Nicotinamide P H H H NADPH Nicotinamide Adenine Dinucleotide Phosphate Page 13

14 SYNTHESIS STRATEGIES REACTIN PATTERNS EXAMPLES Br CH 3 H Page 14