11.1 Ethers, Sulfides and Epoxides - 11 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] O H CH 3 CH 3 H

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

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

11.4 Nomenclature of Ethers trans-2-propoxycyclohexanol 2-methyl-2-methoxypropane (t-butyl methyl ether) OH O H 3 C C H 3 C O CH 3 CH 3

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? Ethers, Sulfides and Epoxides - 11

11.8 Preparation of Ethers O Br + O OCCH 3 CH 3 CH 3 CH 3 Br + CH 3 OCCH 3 CH 3 CH 3 look at Problem 9.49b

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

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

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

11.12 Ether Protecting Groups 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 group characteristics Ethers, Sulfides and Epoxides Pg “Requirements” On efficient Inert to rx Off efficient Problem 6.33: alcohol “interferes” with Br 2 addition. Protecting group (Pg) = blocking group

11.14 Ethers, Sulfides and Epoxides - 11 TMS ethers trimethylsilyl ether or TMS ether

11.15 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

11.16 Ethers, Sulfides and Epoxides – Chapter 11 Structure, nomenclature, properties of Ethers Preparation: Ether synthesis – Williamson Synthesis H+/ROH addition to olefins Reactions - acid catalyzed cleavage of ethers Ethers as Protecting Groups (Gps). Epoxides - nomenclature Preparation: epoxidation, halohydrin Reactions - nucleophilic cleavage O H CH 3 CH 3 H

11.17 Ethers, Sulfides and Epoxides - 11 Nomenclature - epoxy (substituent) or oxirane 4,5-epoxycycloheptene (ignore - not questioned) (4S,5R)-4,5-epoxycycloheptene oxirane ether special 3-membered ring [  (3S,4S)-2-chloro-3,4-epoxyheptane ]

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 H + or Lewis Acid Opening B: or Lewis Base Opening of epoxides :

11.23 Reactions H + or Lewis Acid Opening of epoxides: mechanism?

11.24 Reactions B: or Lewis Base Opening of epoxides: 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 example epoxyresin

11.29 Application of Epoxy Chemistry

11.30 amine epoxide Application of Epoxy Chemistry

11.31 Application of Epoxy Chemistry

11.32 Application of Epoxy Chemistry

11.33 Application of Epoxy Chemistry

11.34 lithium aluminum hydride like sodium borohydride

11.35 O C H H C CH 3 H H

11.36 Ethylene Oxide –ethylene oxide is a valuable building block for organic synthesis because each of its carbons has a functional group