Chapter 5B. Functional Group Transformations: The Chemistry. Related Reactions

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1 Chapter 5B Functional Group Transformations: The Chemistry of fcarbon-carbon C b π-bonds B d and Related Reactions Oxymercuation-Demercuration Markovnikov hydration of a double bond 1

2 Mechanism Comparision between Oxymercuration and Hydroboration 2

3 Epoxidation of Alkenes Epoxides (oxirane) are widely used as versatile synthetic intermediates Because regio- and stereoselective methods exist both for their construction And subsequent reactions. Electrophile vs Nucleophile for the synthesis of α-substituted ketone 3

4 Epoxidation of Alkenes Using Peroxy acids Reactivity order of peroxide for epoxidation of alkenes; CF 3 CO 3 H > mcpba ~ HCO 3 H > CH 3 CO 3 H >> H 2 O 2 > tbuooh stereochemistry 4

5 chemoselectivity The order of alkene reactivity with peroxyacids is as follows: 5

6 Alternatively, epoxy esters may be prepared via the Darzens reaction The reaction of a-chloro esters with aldehyde or ketones. Epoxidation of the electron-deficient double bond in α,β-unsaturated ketones May be complicated by the Baeyer-Villiger reaction. Metal-catalyzed epoxidation of alkenes with H 2 O 2 provides an economical Alternative to oxidations using peroxyacids. 6

7 Baeyer-Villiger Reaction: stereospecific and regiospecific 7

8 The observed relative ease of migration: tert-alkyl > sec-alkyl > phenyl > n-alkyl > methyl Epoxidation of α,β-unsaturated Ketones using Alkaline hydrogen peroxide It should be noted that the inductive electron-withdrawing effect of the neighboring oxygen in HOO - makes it a weaker base than OH - but a better nucleophile than hydroxide. 8

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10 Epoxidation of Alkenes using Dimthyldioxirane Dimethyldioxirane (DMDO) is a mild reagent for epoxidation under neutral Conditions of electron-rich as well as electron-deficient alkenes. oxone The only by-product of the reaction is acetone, making this procedure an environmentally friendly one. 10

11 Methyl(trifluoromethyl)dioxirane (TFDO) is more reactive than DMDO by a factor of ~600. Preparation of Epoxides from halohydrins δ- HO-X δ+ The reaction of chloro- or bromohydrins with bases provides an economical Route for the preparation of epoxides. 11

12 δ- HO-X δ+ Preparation of Epoxides from Ketones instead of alkenes as precursors Dimethylsulfonium methylide 12

13 Dimethyloxosulfonium methylide: much more stable than dimethylsulfonium methylide and may be prepared and used at room temp. p166 nonstabilized stabilized 13

14 Major difference between phorphorus ylide and sulfur ylide Reactions of Epoxides The inherent strain (`27 kcal/mol) of epoxides makes them prone to (1) ring opening by a wide range of nucleophiles, (2) base-induced rearrangement, and (3) acid-catalyzed isomerization. Nucleophilic ring-opening reaction 14

15 stereochemistry 15

16 Collinear S N 2-like displacement: formation of the smaller ring is generally favored. This is because it is difficult to attain the necessary coplanar arrangement at the transition state. In cases involving cyclohexene oxides, the requirement for opening via an anitparallel approach dictates the ring size. 16

17 Inversion of olefin stereochemistry 17

18 Acid-Catalyzed Ring-opening reactions 18

19 Complexaion of epoxide oxygen with the Lewis acid BF3 directs hydride addition to the more substituted carbon. Lewis-acid mediated rearrangement of epoxide 19

20 Epoxidation of Allylic Alcohol Hydroxyl-directed epoxidation with peroxy acids Hydroxy-group directed epoxidation of alkenes using peroxyacids is sensitive To the nature of solvent. 20

21 The Sharpless Asymmetric Epoxidation(SAE) reaction Enantioselectivity 21

22 Jacobsen epoxidation 22

23 Cleavage of Carbon-carbon bonds ozonolysis p188 23

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25 5.2 Reactions of Carbon-carbon Triple Bonds Catalytic semireduction of alkynes Preparation of (Z)-Alkenes using Lindlar-type catalyst 25

26 Preparation of (Z)-Alkenes using Nickel Borides 26

27 Preparation of trans-alkene Reduction of Li or Na in liquid NH 3 27

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