Created by Professor William Tam & Dr. Phillis Chang Ch Chapter 8 Alkenes and Alkynes II: Addition Reactions

Ch Addition Reactions of Alkenes

Ch A.How To Understand Additions to Alkenes  This is an addition reaction: E – Nu added across the double bond. Bonds brokenBonds formed  -bond  -bond 2  -bonds

Ch  Since p bonds are formed from the overlapping of  orbitals,  electron clouds are above and below the plane of the double bond.  electron clouds

Ch  Electrophilic ●electron seeking ●C=C and C ≡ C  bonds are particularly susceptible to electrophilic reagents (electrophiles)  Common electrophile ●H +, X + (X = Cl, Br, I), Hg 2+, etc.

Ch  In an electrophilic addition, the  electrons seek an electrophile, breaking the  bond, forming a  bond and leaving a positive charge on the vacant  orbital on the adjacent carbon. Addition of B – to form a  bond provides an addition product.

Ch

Ch Electrophilic Addition of Hydrogen Halides to Alkenes: Mechanism and Markovnikov’s Rule  Mechanism:

Ch  Mechanism ●Sometimes do not go through a “free carbocation”, may go via:

Ch  Markovnikov ’ s Rule ●For symmetrical substrates, there is no regiochemistry problem.

Ch  Markovnikov ’ s Rule ●But for unsymmetrical substrates, two regioisomers are possible.

Ch  Markovnikov ’ s Rule ●In the electrophilic addition of an unsymmetrical electrophile across a double bond of an alkene, the more highly substituted and more stabilized carbocation is formed as the intermediate in preference to the less highly substituted and less stable one.

Ch  Markovnikov ’ s Rule ●Thus: Note: carbocation stability  3 o > 2 o > 1 o

Ch  Addition of Hydrogen Halides ●Addition of HCl, HBr and HI across a C=C bond. ●H + is the electrophile.

Ch  Energy profile:

Ch A.Theoretical Explanation of Markovnikov ’ s Rule  One way to state Markovnikov ’ s rule is to say that in the addition of HX to an alkene, the hydrogen atom adds to the carbon atom of the double bond that already has the greater number of hydrogen atoms.

Ch ☓ Step 1Step 2

Ch  Energy profile:

Ch  Examples

Ch B.Modern Statement of Markovnikov ’ s Rule  In the ionic addition of an unsymmetrical reagent to an unsymmetrical double bond, the positive portion of the added reagent attaches itself to a carbon atom of the double bond so as to yield the more stable carbocation as an intermediate.

Ch  Examples

Ch  Examples

Ch C.Regioselective Reactions  When a reaction that can potentially yield two or more constitutional isomers actually produces only one (or a predominance of one), the reaction is regioselective.

Ch D.An Exception to Markovnikov ’ s Rule  Only with HBr in presence of peroxide.  Via a radical mechanism (see Chapter 10).  This anti-Markovnikov addition does not take place with HI, HCl, and HF, even when peroxides are present.

Ch Stereochemistry of the Ionic Addition to an Alkene achiral trigonal planar carbocation attack from top attack from bottom racemate

Ch Addition of Sulfuric Acid to Alkenes  Addition of H–OSO 3 H across a C=C bond. more stable 3 o cation less stable 1 o cation

Ch A.Alcohols from Alkyl Hydrogen Sulfates  The overall result of the addition of sulfuric acid to an alkene followed by hydrolysis is the Markovnikov addition of H – and – OH.

Ch Addition of Water to Alkenes: Acid-Catalyzed Hydration  Overall process: ●Addition of H–OH across a C=C bond. ●H + is the electrophile. ●Follow Markovnikov’s rule.

Ch A.Mechanism

Ch B.Rearrangements  Rearrangement can occur with certain carbocations.

Ch Alcohols from Alkenes through Oxymercuration–Demercuration: Follows Markovnikov Addition.  Step 1: Oxymercuration  Step 2: Demercuration

Ch A.Regioselectivity of Oxymercura- tion – Demercuration  Oxymercuration–demercuration is also highly regioselective and follows Markovnikov’s rule.

Ch B.Rearrangements Rarely Occur in Oxymercuration – Demercuration  Recall: acid-catalyzed hydration of some alkenes leads to rearrangement products.

Ch See slide 30 also.

Ch  Rearrangements of the carbon skeleton rarely occur in oxymercuration– demercuration. no rearrangement

Ch C.Mechanism of Oxymercuration There is no “free carbocation”.

Ch  Stereochemistry ●Usually anti-addition.

Ch  Although attack by water on the bridged mercurinium ion leads to anti addition of the hydroxyl and mercury groups, the reaction that replaces mercury with hydrogen (step 2) is not stereocontrolled. This step scrambles the overall stereochemistry.  The net result of oxymercuration– demercuration is a mixture of syn and anti addition of –H and –OH to the alkene.

Ch  Solvomercuration-Demercuration Note: Step 1 with THF-HOH gives an alcohol. Step 1 with THF-ROH gives an ether.

Ch Alcohols from Alkenes through Hydroboration–Oxidation: Anti-Markovnikov Syn Hydration  BH 3 is called borane.  Addition of H–BH 2 across a C=C bond.

Ch  BH 3 exists as dimer B 2 H 6 or complex with coordinative solvent.

Ch syn addition Anti-Markovnikov addition of “H” & “OH”  An anti-markovnikov product results:

Ch anti addition Markovnikov addition of “H” & “OH”  Compare with oxymercuration- demercuration:

Ch Hydroboration: Synthesis of Alkylboranes

Ch A.Mechanism of Hydroboration

Ch  Other examples

Ch B.Stereochemistry of Hydroboration  Syn addition

Ch Oxidation and Hydrolysis of Alkylboranes B always ends up on the least hindered carbon

Ch  Oxidation

Ch ●Via

Ch  Hydrolysis

Ch  Overall synthetic process of hydroboration-oxidation-hydrolysis. ●Overall: anti-Markovnikov addition of H–OH across a C=C bond. ●Forms regioisomer opposite to oxymercuration-demercuration.

Ch  Example anti-Markovnikov syn addition This oxidation step occurs with retention of configuration

Ch Summary of Alkene Hydration Methods Summary of Methods for Converting Alkene to Alcohol ReactionRegiochemistryStereochemistry Occurrence of Rearrangements Acid-catalyzed hydration Markovnikov addition Not controlledFrequent Oxymercuration- demercuration Markovnikov addition Not controlledSeldom Hydroboration- oxidation Anti-Markovnikov addition Stereospecific: syn addition of H – and –OH Seldom

Ch  Examples With rearrangement Markovnikov addition of H 2 O, no rearrangement anti-Markovnikov, syn addition of H 2 O No rearrangement

Ch Protonolysis of Alkylboranes  Protonolysis of an alkylborane takes place with retention of configuration; hydrogen replaces boron where it stands in the alkylborane.  Overall stereochemistry of hydroboration– protonolysis: syn.

Ch  e.g.

Ch Electrophilic Addition of Bromine and Chlorine to Alkenes  Addition of X–X (X = Cl, Br) across a C=C bond.

Ch  Examples

Ch A. Mechanism of Halogen Addition Br–Br bond becomes polarized when close to alkene. (vincinal Dibromide) (cyclic bromonium ion)

Ch  Stereochemistry ●Anti addition

Ch Stereospecific Reactions  A reaction is stereospecific when a particular stereoisomeric form of the starting material reacts by a mechanism that gives a specific stereoisomeric form of the product.

Ch ●Reaction 1 ●Reaction 2

Ch  Addition of bromine to cis-2-Butene (a)(b)

Ch  Addition of bromine to trans-2-Butene (a)(b)

Ch Halohydrin Formation  Addition of –OH and –X (X = Cl, Br) across a C=C bond.  X + is the electrophile.  Follow Markovnikov’s rule.

Ch  Mechanism

Ch  Other variation ●If H 2 O is replaced by ROH, RÖH will be the nucleophile.

Ch Divalent Carbon Compounds: Carbenes 15A. Structure and Reactions of Methylene

Ch (Resonance forms)

Ch B. Reactions of Other Carbenes: Dihalocarbenes  :CX 2 (e.g. :CCl 2 = dichlorocarbene).  Generation by  -elimination of chloroform.  Note: E1 & E2 are β-eliminations.

Ch  :CCl 2 usually gives a syn (cis) addition across a C=C bond.

Ch  Stereospecific reactions

Ch C. Carbenoids: The Simmons-Smith Cyclopropane Synthesis  I-CH 2 -ZnI is the Simmons-Smith reagent.

Ch  I-CH2-ZnI gives a stereospecific syn (cis) addition across a C=C bond.

Ch Oxidation of Alkenes: Syn 1,2-Dihydroxylation  Overall: addition of 2 OH groups across a C=C bond giving a vicinal diol.  Reagents:dilute KMnO 4 / OH ⊖ / H 2 O / cold or OsO 4, pyridine then NaHSO 3, H 2 O.

Ch A. Mechanism for Syn Dihydroxylation of Alkenes

Ch  Both reagents give syn dihydroxylation.

Ch  Comparison of the two reagents ●KMnO 4 : usually lower yield and possibly side products due to over- oxidation. ●OsO 4 : usually much higher yield but OsO 4 is extremely toxic. (oxidative cleavage of C=C)

Ch Oxidative Cleavage of Alkenes 17A. Cleavage with Hot Basic Potassium Permanganate

Ch  Other examples

Ch B. Cleavage with Ozone

Ch  Examples

Ch  Mechanism

Ch Electrophilic Addition of Bromine & Chlorine to Alkynes

Ch Addition of Hydrogen Halides to Alkynes  Regioselectivity ●Follow Markovnikov’s rule.

Ch  Mechanism

Ch  As with akenes, Anti-Markovnikov addition of hydrogen bromide to alkynes occurs when peroxides are present in the reaction mixture.

Ch Oxidative Cleavage of Alkynes  Example OR

Ch How to Plan a Synthesis: Some Approaches & Examples  In planning a synthesis we often have to consider four interrelated aspects: 1.Construction of the carbon skeleton. 2.Functional group interconversions. 3.Control of regiochemistry. 4.Control of stereochemistry.

Ch  How to synthesize ? ●Retrosynthetic analysis 21A. Retrosynthetic Analysis

Ch ●Synthesis Markovnikov addition of H 2 O

Ch  How to synthesize ? ●Retrosynthetic analysis ●Synthesis anti-Markovnikov addition of H 2 O

Ch  One approach to retrosynthetic analysis is to consider a retrosynthetic step as a “disconnection” of one of the bonds.  In general, we call the fragments of a hypothetical retrosynthetic disconnection Synthons. 21B. Disconnections, Synthons, and Synthetic Equivalents

Ch  Example ●Retrosynthetic analysis (gem-dibromide came from addition of HBr across a C ≡ C bond.)

Ch ●Retrosynthetic analysis disconnection synthons synthetic equivalent

Ch ●Synthesis

Ch C. Stereochemical Considerations

Ch  Retrosynthetic analysis ●The precursor of a vicinal dibromide is usually an alkene. ●Bromination of alkenes are anti addition. (rotate 180 o ) (anti addition of Br 2 ) (anti addition of H 2 )

Ch ●Synthesis (anti addition of Br 2 ) (anti addition of H 2 )

Ch  END OF CHAPTER 8 