Detailed Course Outline Chem 3A; Fall 2013

Subject to change Revised 9/7/2013

Date 8/29 A Topics Introduction Bond-line notation Functional groups, R and X notation Examples of some interesting molecules Review of bonding I Lewis dot structures, ionic and covalent bonding Electronegativity and bond polarization Formal Charge vs partial charge Review of bonding II Resonance structures, including curved arrow notation VSEPR - Molecular shape and bond angles (review/homework not discussed in lecture) Atomic Orbitals Atomic and Molecular Orbitals Hybridization Sigma bonding and pi bonding Constructing MO diagrams for small molecules Introduction to polar reaction mechanisms Curved arrow notation for reactions Definitions of acid/base/nucleophile/electrophile/leaving group Preview of several polar reactions (SN2, SN1, acyl substitution, E2, E1, electrophilic addition to alkenes, acid-catalyzed alkene isomerization, nucleophilic addition to ketones) Kinetics, thermodynamics, and reaction coordinate diagrams Acid/base reactions: equilibrium and energy Acidity, Basicity, and Structure Definitions of Ka/pKa Trends affecting pKa (electronegativity, charge, hybridization, size, resonance, inductive effects) Nomenclature Constitutional isomerism Basics of IUPAC nomenclature Base chain names (prefixes for 1-10 carbons); common names of branched substituents Naming alkenes, alkynes, haloalkanes, alcohols, ethers, and amines Alkane conformational analysis Single bond rotation in acyclic alkanes Newman projections, wedge-dash notation, Fisher projections equilibrium and free energy (1.36 rule at room temp) Alkane conformational analysis (finish discussion from prev. lecture) Cycloalkanes Ring strain, combustion analysis of alkanes Chair cyclohexane (ring flipping, axial and equatorial) Stereoisomerism (cis/trans) in cyclic systems Stereochemistry I Chirality Optical activity R/S nomenclature Stereochemistry II E/Z nomenclature for alkenes, alkene stereoisomerism Axial chirality Mutiple stereocenters (diastereomers, meso) Resolution of enantiomers Vollhardt text 1.1 1.9 2.3 1.2-1.4

9/3 B

9/5 C

9/10 D

1.5 1.3 (last part) 1.6 1.7-1.9

9/12 E

2.1-2.2

9/17 F 9/19 G

2.2, 8.3

2.4 2.5, 4.1

2.7-2.8

9/24 H

2.7-2.8 4.2 4.3 4.4 5.1 5.2 5.3 11.1 5.5, 5.6 5.8

9/26 I

10/1 J

10/3 K

10/7 10/8 L

10/10 M

10/15 N

10/17 O

10/22 P

10/24 Q

10/29 R

10/31 S

11/5 T

Overview of Nucleophilic Substitution (SN2 and SN1) nucleophile, electrophile, leaving group Curved arrow notation Kinetics, rate laws, reaction coordinate diagrams Stereochemistry, orbital pictures Midterm Exam #1 7pm Factors that Affect SN2 Reactivity Leaving group ability Sterics Nucleophile strength, reversibility of SN2 reactions, solvation Some specific SN2 examples Alcohol as an electrophile: preparation of haloalkanes from alcohols: HX, PBr3, SOCl2 Alcohol as a nucleophile: Preparation of ethers, cyclic ethers including epoxides Alcohols from SN2 reaction of epoxides with good nucleophiles S-Adenosylmethionine natures alkylating reagent E2 reactions Competition between substitution and elimination (base strength, steric effects) Reactive conformations and stereochemical consequences Orbital description of reaction Kinetic control of product ratio (irreversible reaction) E2 reactions of dihaloalkanes to form alkynes SN1 reactions Solvolysis includes proton transfer step(s) Reaction coordinate diagrams, kinetics Carbocation substitution and stability hyperconjugation Effects of solvent, leaving group, competing nucleophiles Stereochemistry of SN1, ion pairing and its effect on stereochemistry Reactions of epoxides under acidic conditions E1 reaction; Addition to alkenes in acid E1 reaction overview, competition between SN1 and E1 Reversibility of the E1 reaction, LeChateliers principle: -Use of Ag salts with haloalkanes; addition of HX to alkenes -Dehydration of alcohols, hydration of alkenes Alkene isomerization in acidic conditions, alkene stability trends Thermodynamic vs. kinetic control of alkene product ratios Carbocation rearrangements (hydride shift, alkyl shift) Summary/Review (SN2/E2/SN1/E1) - effects of alkyl substitution/branching, solvation, base strength - reversibility, choice of reaction conditions to control product outcome - stereocontrol (concerted vs stepwise reactions); synthetic utility Reactions of alkenes I - reactions with carbocation intermediates Alkene oligomerization/polymerization under acidic conditions Addition of HX or H2O to alkynes under acidic conditions Substitution of allylic halides resonance stabilization of carbocation polyalkenes in nature (polymerization and cyclization examples) Reactions of alkenes II 3-membered rings Addition of Br2 to alkenes anti addition, bromonium ion intermediate Addition of other nucleophiles to bromonium ion intermediate Epoxidation of alkenes with mCPBA Comparison of bromonium ion reactivity to protonated epoxide reactivity cyclopropanation of alkenes (diazomethane, chloroform, Simmons-Smith reagent) Addition of Br2 to alkynes Reactions of alkenes III Hydroboration/oxidation of alkenes and alkynes Dihydroxylation (OsO4, H2O2)

6.2 6.3 6.4 6.5 ---6.7 6.9 6.8 9.2, 9.4 9.6 9.9

7.7 7.8 11.6 13.4 7.1-7.5

9.9 7.6 xx, 12.3 9.2,11.7, 12.4 9.3 7.9

12.14 13.7 14.3 14.10 12.5 12.6 12.10 12.9 13.7 12.8, 13.8 12.11

11/7 U

11/12 V

11/12 11/14 W

11/19 X

11/21 Y

11/26 Z

11/28 12/3 AA

12/5 AB

Ozonolysis (O3, then Me2S) Hydrogenation of alkenes (H2, Pd/C) Multistep Synthesis I Interconversion between alkenes, alcohols, and haloalkanes Comparison of alcohol synthesis methods regioselectivity, stereoselectivity, and synthetic utility Oxidation and Reduction Definitions of oxidation and reduction in the context of organic compounds application of definitions to reactions already discussed. Oxidation of alcohols to carbonyls (CrO3, PCC) focus on elimination step (compare to E2 reaction) Overview of reduction of alcohols by NaBH4 or LiAlH4 NAD+ and NADH for oxidations and reductions in biological systems (see pages 298 and 1186) Midterm Exam #2 7 pm Addition of nucleophiles to aldehydes and ketones Comparison of alkene pi bond to carbonyl pi bond the effect of a strong bond dipole. Details about metal hydrides reductions, compare/contrast with alkene hydrogenation Grignard, and organolithium reagents synthesis, basicity, addition to ketones/aldehydes/epoxides (but not SN2 of haloalkanes) Alkynyl anion as a nucleophile Multistep Synthesis II Utility of carbon nucleophiles to build complexity, oxidation of alcohols as a key step Protecting groups as a synthetic strategy (tert-buyl ether, silyl ether protection of alcohols during Grignard reactions) Reactions with radical intermediates I Homolytic cleavage of bonds, curved arrow notation Structure and stability trends of radicals, BDEs pyrolysis of alkanes halogenation of alkanes radical chain mechanism Reactions with radical intermediates II Radical halogenation of alkanes selectivity Radical allylic halogenation resonance stabilization of the radical intermediate Radical-mediated addition of HBr to alkenes and alkynes Radical initiators: peroxides, AIBN Thanksgiving break Reactions with radical intermediates III Radical polymerization of alkenes Dissolving metal reduction of alkynes Radicals in biological systems Multistep Synthesis III review for final exam

12.12 12.2

8.6

----

8.7 13.5 8.8, 8.9 9.8

3.1 3.2 3.3 3.4-3.5 3.6-3.8 14.2 12.13,13.8 --12.15 13.6