11.1 Ethers, Sulfides and Epoxides Structure, nomenclature, properties Ether synthesis - Williamson synthesis ( S N 2 ) H + /ROH addition to olefins (chapt 6) Reactions - acid catalyzed cleavage of ethers ( S N 2/S N 1/E1 ) [oxidation out ] Ethers as Protecting Groups (Gps). Epoxides - oxirane nomenclature Preparation: epoxidation, halohydrin Reactions - nucleophilic cleavage ( S N 2/S N 1/E1 ) [sulfides out ] Synthesis (continued) [blue - repeat of earlier chemistry] ss12 19 chapter 11

11.2 Chapter 11 Chapter 15 substitution protecting groups epoxides epoxide reaction sources nomenclature properties reactions

11.3 Structure - tetrahedral (sp 3 ) oxygen & carbon Ethers, Sulfides and Epoxides - 11 diethyl ether tetrahydrofuran or THF dihydropyran

11.4 Nomenclature - ether group is a substituent Ethers, Sulfides and Epoxides cyclopentenol 4-ethoxy-2-cyclopentenol (1S,4R)-4-ethoxy-2-cyclopenten-1-ol

11.5 Properties - polar C-O covalent bonds But low dielectric constant Ethers, Sulfides and Epoxides - 11 Hydrogen bond acceptor (Lewis base)

11.6 Two ways to prep benzyl ethyl ether Ethers, Sulfides and Epoxides - 11 Williamson ether synthesis S N 2 substitution recall similar problems in chapter 9 (9.46, 9.48 and 9.49)

11.7 Two ways benzyl ethyl ether can be prepared Specifically how would each be done? Nucleophic form of the alcohol? Solvent? - alkoxide - polar - aprotic - benzylic substrate Which way should be best? Others? S N 1, some cases Ethers, Sulfides and Epoxides - 11

11.8 H + /ROH addition to olefins, “hydration-like” Ethers, Sulfides and Epoxides - 11 Recall/review addition problems 6.29, 6.34a Familiar?

11.9 Ethers, Sulfides and Epoxides - 11 Reactions - acid catalyzed cleavage of ethers SN2SN2 S N 1/E1

11.10 Chapter 11 substitution protecting groups epoxides epoxide reaction sources nomenclature properties reactions Chapter 15

11.11 Ethers Protecting Groups (ref. problems 6.33) Ethers, Sulfides and Epoxides - 11 Problem 6.33: alcohol “interferes” with Br 2 addition

11.12 Ether Protecting Groups (ref. problems 6.33) Ethers, Sulfides and Epoxides - 11 Problem 6.33: alcohol “interferes” with Br 2 addition protecting group (Pg) = blocking group 1 2 3

11.13 Protecting groups characteristics Ethers, Sulfides and Epoxides On efficient 2.Inert to rx 3.Off efficient Problem 6.33: alcohol “interfers” with Br 2 addition. protecting group (Pg) = blocking group

11.14 Ethers, Sulfides and Epoxides - 11 TMS ethers

11.15 Ethers, Sulfides and Epoxides - 11

11.16 Crown Ethers - Crown Ethers - not covered Cyclic polyethers The parent name is crown, preceded by a number describing the size of the ring followed by the number of oxygen atoms in the ring, e.g 18-crown-6 O O O O O O

11.17 Ethers, Sulfides and Epoxides - 11 Nomenclature - epoxy (substituent) or oxirane 4,5-epoxycycloheptene (4S,5R)-4,5-epoxycycloheptene ether

11.18 Ethers, Sulfides and Epoxides - 11 Prep of epoxides/oxiranes

11.19 Ethers, Sulfides and Epoxides - 11 Prep of epoxides - better mechanistic view stereospecific like bromine addition

11.20 other epoxide sources - halohydrins/base mechanism intramolecular “S N 2” See problem 9.50, same reaction

11.21 chapter 6 Other sources of epoxides - halohydrins/base :B

11.22 Reactions of epoxides: H + or LA Opening B: or LB Opening

11.23 Reactions of epoxides: H + or LA Opening mechanism?

11.24 Reactions of epoxides: B: or LB Opening mechanism?

,2-transdiol Stereochemistry 1,2-cisdiol Recall:

11.26 Regioselectivity 1 o -less hindered 3 o more hindered S N 2 like proton source

11.27 Regioselectivity S N 1 like

11.28 Regioselectivity

11.29 example epoxyresin

11.30 Application of Epoxy Chemistry

11.31 amine epoxide Application of Epoxy Chemistry

11.32 Application of Epoxy Chemistry

11.33 Application of Epoxy Chemistry

11.34 Application of Epoxy Chemistry

11.35

11.36 lithium aluminum hydride like sodium borohydride

11.37 Organometallic Compounds (R-M) Organomagnesium & Organolithium compds 15.1 Lithium Diorganocopper (Gilman) Reagents 15.2 No t covered: Organopalladium reagents, Heck reaction, carbenes, carbenoids, & alkene metathesis. Synthesis, Concepts and the Final