9.5 Oxymercuration-Demercuration Because rearrangements often produce a mixture of products, the synthetic utility of Markovnikov hydration reactions is somewhat limited Oxymercuration-demercuration is an alternative process that can yeild Markovnikov products more cleanly Copyright 2012 John Wiley & Sons, Inc.

9.5 Oxymercuration-Demercuration Oxymercuration begins with mercuric acetate How would you classify the mercuric cation? As a nucleophile or an electrophile? As a Lewis acid or Lewis base? How might an alkene react with the mercuric cation? Copyright 2012 John Wiley & Sons, Inc.

9.5 Oxymercuration-Demercuration Similar to how we saw the alkene attack a proton previously, it can also attack the mercuric cation Resonance stabilizes the mercurinium ion and the carbocation. Draw a reasonable resonance hybrid Copyright 2012 John Wiley & Sons, Inc.

9.5 Oxymercuration-Demercuration The mercurinium ion is also a good electrophile, and it can easily be attacked by a nucleophile, even a weak nucleophile such as water NaBH4 is generally used to replace the –HgOAc group with a –H group via a free radical mechanism Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation To achieve anti-Markovnikov hydration, Hydroboration-Oxidation is often used Note that the process occurs in two steps Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation Hydroboration-Oxidation reactions achieve syn addition Anti addition is NOT observed To answer WHY, we must investigate the mechanism Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation Let’s examine how this new set of reagents might react The BH3 molecule is similar to a carbocation but not as reactive, because it does not carry a formal charge Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation Because of their broken octet, BH3 molecules undergo intermolecular resonance to help fulfill their octets The hybrid that results from the resonance (diborane) involves a new type of bonding called banana bonds Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation In the hydroboration reaction, BH3•THF is used. BH3•THF is formed when borane is stabilized with THF (tetrahydrofuran) What general role do you think BH3•THF is likely to play in a reaction? Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation Let’s examine the first step of the Hydroboration mechanism on the next slide Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation What evidence is there for a concerted addition of the B-H bond across the C=C double bond? Use sterics and electronics to explain the regioselectivity of the reaction Practice with conceptual checkpoint 9.17 Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation Start Here Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation When ONE chirality center is formed, a racemic mixture results WHY? What is the geometry of the alkene as the borane attacks? The squiggle bond above shows two products, a 50/50 mixture of the R and the S enantiomer Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation When TWO chirality centers are formed, a racemic mixture results Why aren’t the other stereoisomers formed? Practice with SkillBuilder 9.4 Copyright 2012 John Wiley & Sons, Inc.

9.6 Hydroboration-Oxidation Predict the major product(s) for the reactions below Copyright 2012 John Wiley & Sons, Inc.

9.7 Catalytic Hydrogenation The addition of H2 across a C=C double bond If a chirality center is formed, syn addition is observed Draw the other stereoisomers that are NOT produced Copyright 2012 John Wiley & Sons, Inc.

9.7 Catalytic Hydrogenation Analyze the energy diagram below Why is a catalyst necessary? Does the catalyst affect the spontaneity of the process? Typical catalysts include Pt, Pd, and Ni Copyright 2012 John Wiley & Sons, Inc.

9.7 Catalytic Hydrogenation The metal catalyst is believed to both adsorb the H atoms and coordinate the alkene The H atoms add to the same side of the alkene pi system Copyright 2012 John Wiley & Sons, Inc.

9.7 Catalytic Hydrogenation Draw product(s) for the reaction below. Pay close attention to stereochemistry How many chirality centers are there in the alkene reactant above? How does the term, mesocompound, describe the product(s) of the reaction? Practice with SkillBuilder 9.5 Copyright 2012 John Wiley & Sons, Inc.

9.7 Catalytic Hydrogenation If catalysis takes place on the surface of a solid surrounded by solution, the catalyst is heterogeneous. WHY? Homogeneous catalysts also exist What advantage might a homogeneous catalyst have? Copyright 2012 John Wiley & Sons, Inc.

9.7 Asymmetric Hydrogenation In 1968, Knowles modified Wilkinson’s catalyst by using a chiral phosphine ligand A chiral catalyst can produce one desired enantiomer over another. HOW? Why would someone want to synthesize one enantiomer rather than a racemic mixture? Copyright 2012 John Wiley & Sons, Inc.

9.7 Asymmetric Hydrogenation A chiral catalyst allows one enantiomer to be formed more frequently in the reaction mixture Some chiral catalysts give better enantioselectivity than others. WHY? Copyright 2012 John Wiley & Sons, Inc.

9.7 Asymmetric Hydrogenation BINAP is a chiral ligand that gives very pronounced enantioselectivity For any reaction, stereoselectivity can only be achieved if at least one reagent (reactant or catalyst) is chiral Copyright 2012 John Wiley & Sons, Inc.

9.7 Asymmetric Hydrogenation Predict the major product(s) for the reactions below Copyright 2012 John Wiley & Sons, Inc.

9.8 Halogenation Halogenation involves adding two halogen atoms across a C=C double bond Halogenation is a key step in the production of PVC Copyright 2012 John Wiley & Sons, Inc.

9.8 Halogenation Halogenation with Cl2 and Br2 is generally effective, but halogenation with I2 is too slow and halogenation with F2 is too violent Halogenation occurs with anti addition Given the stereospecificity, is it likely to be a concerted or a multi-step process? Copyright 2012 John Wiley & Sons, Inc.

9.8 Halogenation Let’s look at the reactivity of Br2. Cl2 is similar It is nonpolar, but it is polarizable. WHY? What type of attraction exists between the Nuc:1- and Br2? Does the Br2 molecule have a good leaving group attached to it? Copyright 2012 John Wiley & Sons, Inc.

9.8 Halogenation We know alkenes can act as nucleophiles Imagine an alkene attacking Br2. You might imagine the formation of a carbocation However, this mechanism DOES NOT match the stereospecificity of the reaction. HOW? WHY? Copyright 2012 John Wiley & Sons, Inc.

9.8 Halogenation Mechanism continued on next slide Copyright 2012 John Wiley & Sons, Inc.

9.8 Halogenation Only anti addition is observed. WHY? Prove to yourself that the products are enantiomers rather than identical Copyright 2012 John Wiley & Sons, Inc.

9.8 Halogenation Only anti addition is observed Can you design a synthesis for ? Practice with conceptual checkpoint 9.26 Copyright 2012 John Wiley & Sons, Inc.

9.8 Halogenation Predict the major product(s) for the reactions below Copyright 2012 John Wiley & Sons, Inc.

9.8 Halohydrin Formation Halohydrins are formed when halogens (Cl2 or Br2) are added to an alkene with WATER as the solvent The bromonium ion forms from Br2 + alkene, and then it is attacked by water Why is the bromonium attacked by water rather than a Br1- ion? Is water a better nucleophile? Copyright 2012 John Wiley & Sons, Inc.

9.8 Halohydrin Formation A proton transfer completes the mechanism producing a neutral halohydrin product The net reaction is the addition of –X and –OH across a C=C double bond Copyright 2012 John Wiley & Sons, Inc.

9.8 Halohydrin Regioselectivity The –OH group adds to the more substituted carbon The key step that determines regioselectivity is the attack of water on the bromonium ion Copyright 2012 John Wiley & Sons, Inc.

9.8 Halohydrin Regioselectivity When water attacks the bromonium ion, it will attack the side that goes through the lower energy transition state Water is a small molecule that can easily access the more sterically hindered site Practice with SkillBuilder 9.6 Copyright 2012 John Wiley & Sons, Inc.

9.8 Halohydrin Regioselectivity Predict the major product(s) for the reactions below Copyright 2012 John Wiley & Sons, Inc.

Study Guide for sections 9.5-9.8 DAY 25, Terms to know: Sections 9.5-9.8 Oxymercuration-Demercuration, Hydroboration-Oxidation, hydrogenation, halogenations, halonium ion, bromonium ion, halohydrin DAY 25, Specific outcomes and skills that may be tested on exam 4: Sections 9.5-9.8 Be able to give reasonable reagents and conditions including an alkene that could be used to produce a desired addition product. Given an alkene and reaction conditions, be able to predict the product of an addition reaction including the proper stereochemistry and regiochemistry. Be able to explain why borane conditions yield anti-Markovnikov hydration products using sterics and electronics to explain regioselectivity and stereoselectivity. Be able to give the mechanism for each step of the Hydroboration-Oxidation reaction. Be able to explain the role of the metal catalyst in hydrogenation reactions. Be able to predict region- and steroselectivity in hydrogenation reactions. Be able to predict region- and steroselectivity in halogenation reactions. Be able to predict region- and steroselectivity in halohydrin reactions. Be able to draw a reasonable mechanism for each addition reaction mechanism covered in class. Klein, Organic Chemistry 2e

Practice Problems for sections 9.5-9.8 Complete these problems outside of class until you are confident you have learned the SKILLS in this section outlined on the study guide and we will review some of them next class period. 9.15 9.16 9.17 9.18 9.19 9.20 9.21 9.23 9.24 9.25 9.26 9.27 9.28 9.52 Klein, Organic Chemistry 2e

Prep for Day 26 Must Watch videos: Other helpful videos: https://www.youtube.com/watch?v=KfTosrMs5W0 (anti dihydroxylation) https://www.youtube.com/watch?v=76KtDSfWnkw (syn dihydroxylation) https://www.youtube.com/watch?v=bFj3HpdC4Uk (ozonolysis) https://www.youtube.com/watch?v=k-gd5-4wglQ (naming alkynes) https://www.youtube.com/watch?v=_-I3HdmyYfE (reactions of alkynes) Other helpful videos: http://ps.uci.edu/content/chem-51b-organic-chemistry (lecture 9) Read sections 9.9-9.13, 10.1-10.3 Klein, Organic Chemistry 2e