Lecture 23 Two Germans and an Englishman Robert Robinson Otto Paul Hermann Diels Kurt Alder 1886-1975 1876-1954 1902-1958 Nobel Laureate Nobel Laureates 1947 1950 April 16, 2018 Chemistry 328N Exam III - Wed April 24 • PAI 3.02 • 7-9 PM • Covers thru 4/18 • Homework • Hydrolysis • Reactions • Synthesis • Get an A!!! Chemistry 328N Review Session ⚫ Where: Here ⚫ When: Tuesday April 23 at 5PM ⚫ Bring questions from your studies Chemistry 328N Kinetic Control ⚫ When a reaction is under kinetic control, the composition of the product mixture is determined by the relative rates of formation of each product Thermodynamic Control ⚫ When a reaction is under thermodynamic control, the composition of the product mixture is determined by the relative stabilities of each product Chemistry 328N Recall the relative Stability of 1,2 vs 1,4 adducts Chemistry 328N Conjugate Addition Chemistry 328N Michael Reaction O EtOC O - + Et O Na CH2 + CH2 =CHCCH 3 EtOH EtOC 3-Buten-2-one O (Methyl vinyl ketone) Diethyl propanedioate O (Diethyl malonate) EtOC O CH CH2 CH2 CCH 3 EtOC O Chemistry 328N Michael Reaction O O CH3 C - + EtO Na CH2 + EtOC EtOH O 2-Cyclohex- O enone O Ethyl 3-oxobutanoate (Ethyl acetoacetate) CH3 C CH EtOC O Chemistry 328N Michael Addition ⚫ The Michael reaction is a useful method for forming carbon-carbon bonds….1,5 dicarbonyls O O 2 1 3 4 5 Chemistry 328N The Robinson Annelation: 1. Michael addition O O CH3 + H2C CHCCH3 O KOH, methanol O CH3 O CH2CH2CCH3 O Chemistry 328N Robinson annelation: 2. aldol condensation O O CH3 CH3 O NaOH heat CH2CH2CCH3 O O OH not isolated; dehydrates under reaction conditions Chemistry 328N Robinson annelation: 3. elimination O O NaOH CH CH O 3 3 heat CH2CH2CCH3 O O OH O CH3 O Chemistry 328N Testosterone Cortisone Chemistry 328N The Signature Page Claisen Condensation: -ketoesters Dieckmann: Cyclic -ketoesters Aldol: , -unsaturated aldehydes and ketones Acetoacetic ester synthesis: decorated acetones Malonic ester synthesis: decorated acetic acids Michael Reaction: 1-5 dicarbonyl compounds Grignard Reaction: Alcohols Wittig Reaction: Alkenes. …, etc Chemistry 328N The Diels-Alder Reaction Otto Paul Hermann Diels Kurt Alder 1876-1954 1902-1958 Chemistry 328N Diels-Alder Reaction: • The Diels-Alder reaction is an addition reaction between a 1,3-diene and an alkene (called a dienophile), that forms a new six-membered ring. Chemistry 328N Predict the products Chemistry 328N All Diels-Alder reactions: 1. are initiated by heat; that is, the Diels-Alder reaction is a thermal reaction. 2. form new six-membered rings. 3. involve breaking three bonds and making two new bonds and one new bond. 4. are concerted; that is, all bonds are broken and new bonds formed in a single step. Chemistry 328N 4 Rules that govern the Diels-Alder reaction 1. The diene can react only from the s-cis conformation. Chemistry 328N 2. Electron-withdrawing substituents in the dienophile increase the reaction rate. • The conjugated diene acts as a nucleophile and the dienophile acts as an electrophile. • Electron-withdrawing groups make the dienophile more reactive • If Z is an electron-withdrawing group, then the reactivity of the dienophile increases as follows: Chemistry20 328N Common dienophiles The carbonyl group is electron-withdrawing and activates dienophiles Chemistry 328N Example O + H2C CHCH CH2 H2C CH CH benzene 100°C via: O O CH CH (100%) Chemistry 328N 3. The stereochemistry of the dienophile is retained. Chemistry 328N Chemistry 328N Example O C6H5 COH + H2C CHCH CH2 C C H H H C6H5 COH only product H O Chemistry 328N Example O H COH + H2C CHCH CH2 C C C6H5 H C6H5 H COH only product H O Chemistry 328N O H COCH3 + C C H CH3OC O H O COCH3 H COCH3 O Chemistry 328N H O O COCH COCH 3 is the 3 H H same as H COCH COCH3 3 O O Chemistry 328N 4. When endo and exo products are possible, the endo product is preferred. endo and exo indicate the orientation of Z. endo = on the side of the big bridge exo = on the side of the small bridge Chemistry 328N The endo product is preferred! Chemistry 328N Some nomenclature Chemistry 328N Nomenclature of Bicyclic Systems Bicyclo [#.#.#]alkane Where # is the number of carbons on the bridges (in decreasing order) and the alkane name includes all the carbons in the compound. Chemistry 328N Nomenclature of Bicyclic Systems Numbering begins at a bridgehead, goes around the largest ring first, to give the lowest number to any functionality on the ring. 5 4 6 7 8 O 3 1 2 7-Methyl-bicyclo[4.2.0]octan-3-one Chemistry 328N Some nomenclature If substituents are present, number the bridge ring system beginning at on bridge-head, proceeding first along the longest bridge to the other bridge-head. The shortest bridge is named last Chemistry 328N Practice Aldol products from what ?? O H H CH 3 CH 3 O O CH 2 H3C H H H3C CH3 H3C O Chemistry 328N Practice Exercises Disguised signatures!? show how the following compounds could be synthesized by a path that Includes an aldol or mixed aldol condensation, O OH OH Don’t let disguises fool you! Chemistry 328N Make these starting with ethyl acetate or diethyl malonate and anything else O H O O HO Chemistry 328N How far can you expand this web? O ? O O C C NaBH OH O 4 O O LiAlH4 C C NH Cl + R H3O O O C C O CH3NH2 Chemistry 328N Interconversions ⚫ Problem: show reagents and experimental conditions to bring about each reaction O PhCH CCl 2 5 1 O O 4 PhCH2 COH PhCH2 CNH2 2 O 6 7 3 PhCH2 COCH3 PhCH2 CH2 NH2 9 8 O 10 11 PhCH2 CH2 OH PhCH2 CH Chemistry 328N Next……. POLYMERS Jöns Jacob Berzelius Hermann Staudinger Wallace Hume Carothers (1779-1848) (1881-1965) (1896-1937) Chemistry 328N.