Reactions Mechanisms of Electrophiles Addition to Alkenes Based on McMurry’s Organic Chemistry, 7th edition

Reactions of Alkenes Alkenes react with many electrophiles to give useful products

Addition of Halogens to Alkenes Bromine and chlorine add to alkenes to give 1,2-dihaldes, F2 is too reactive and I2 does not add

Addition of Br2 to Cyclopentene Addition is exclusively trans

Mechanism of Bromine Addition Br+ adds to an alkene producing a cyclic ion Bromonium ion, bromine shares charge with carbon Gives trans addition

Bromonium Ion Mechanism Electrophilic addition of bromine to give a cation is followed by cyclization to give a bromonium ion This bromonium ion is a reactive electrophile and bromide ion is a good nucleophile Stereospecific anti addition

Formation of Bromonium Ion Mutual polarization of electron distributions of Br2 and alkene Br 11

Formation of Bromonium Ion d– Electrons flow from alkene toward Br2 Br Br d+ d+ 11

Formation of Bromonium Ion – Br p electrons of alkene displace Br– from Br Br + 11

Stereochemistry – : Br .. + Br .. .. : : Br .. attack of Br– from side opposite C—Br bond of bromonium ion gives anti addition .. Br : .. 12

Cyclopentene +Br2 15

Bromonium ion – 17

Bromide ion attacks the bromonium ion from side opposite carbon-bromine bond – – 17

trans-Stereochemistry in vicinal dibromide 19

Stereochemistry Anti Addition (halogens enter on opposite sides); Stereoselective Syn addition (on same side) does not occur for this reaction.

Mechanism, Step 1 Step 1, formation of cyclic bromonium ion.

Step 2

Stereochemistry, addition of Br2 S,S enantiomers R,R R,R enantiomers Two compounds (R,R and S,S) formed in equal amounts. Racemic mixture. S,S

Attack of the Bromide Ion Inversion. Starts as R Becomes S The carbon was originally R with the Br on the top-side. It became S when the Br was removed and a Br attached to the bottom this is SN2 Mechanism.

Regioselectivity If Br2 is added to propene there is no regioselectivity issue. If Br2 is added in the presence of excess alternative nucleophile, such as CH3OH, regioselectivity may become important.

Regioselectivity - 2 Consider, again, the cyclic bromonium ion and the resonance structures. Stronger bond Weaker bond More positive charge Expect the nucleophile to attack here. Remember inversion occurs.

Regioselectivity, Bromonium Ion Bridged bromonium ion from propene.

Bromination of a substituted cyclohexene Consider the following bromination. Expect to form two bromonium ions, one on top and the other on bottom. Expect the rings can be opened by attack on either carbon atom as before. But NO, only one stereoisomer is formed. WHY?

Addition to substituted cyclohexene The tert butyl group locks the conformation as shown. The cyclic bromonium ion can form on either the top or bottom of the ring. How can the bromide ion come in? Review earlier slide showing that the bromide ion attacks directly on the side opposite to the ring.

Addition to substituted cyclohexene Attack as shown in red by incoming Br ion will put both Br into equatorial positions, not anti. This stereoisomer is not observed. The bromines have not been kept anti to each other but have become gauche as displacement proceeds. Observe Ring is locked as shown. No ring flipping. Be sure to allow for the inversion motion at the carbon attacked by the bromide ion.

Addition to substituted cyclohexene Attack as shown in green by the incoming Br will result in both Br being axial and anti to each other This is the observed diastereomer. We have kept the bromines anti to each other.

7.3 Addition of Hypohalous Acids to Alkenes: Halohydrin Formation This is formally the addition of HO-X to an alkene to give a 1,2-halo alcohol, called a halohydrin The actual reagent is the dihalogen (Br2 or Cl2 in water in an organic solvent)

Mechanism of Formation of a Bromohydrin Br2 forms bromonium ion, then water adds

Mechanism .. O : Br .. + .. O + bromonium ion is intermediate water is nucleophile that attacks bromonium ion .. Br : .. 12

For unsymmterical alkenes, halohydrin formation is Markovnikov-like in that the orientation of the addition of X-OH can be predicted by considering carbocation stability more + charge on the more substituted carbon H2O adds in the second step and adds to the carbon that has the most + charge and ends up on the more substituted end of the double bond Br adds to the double bond first (formation of bromonium ion) and is on the least substituted end of the double bond

Oxymercuration Intermediates For hydration of an alkene Use mercuric acetate in THF followed by sodium borohydride Markovnikov orientation via mercurinium ion

Mechanism 1 2 3 4

Borane, a digression Isoelectronic with a carbocation

7.5 Addition of Water to Alkenes: Hydroboration Borane (BH3) is electron deficient and is a Lewis acid Borane adds to an alkene to give an organoborane

Hydroboration-Oxidation Forms an Alcohol from an Alkene Addition of H-BH2 (from BH3-THF complex) to three alkenes gives a trialkylborane Oxidation with alkaline hydrogen peroxide in water produces the alcohol derived from the alkene

Orientation in Hydration via Hydroboration Regiochemistry is opposite to Markovnikov orientation OH is added to carbon with most H’s H and OH add with syn stereochemistry, to the same face of the alkene (opposite of anti addition) STEREOSPECIFIC

Mechanism Syn stereochemistry, anti-Markovnikov orientation now established. Two reasons why anti-Markovnikov: Less crowded transition state for B to approach the terminal carbon. A small positive charge is placed on the more highly substituted carbon. Next…

Cont’d

Mechanism of Hydroboration Borane is a Lewis acid Alkene is Lewis base Transition state involves anionic development on B The components of BH3 are added across C=C More stable carbocation is also consistent with steric preferences

7.6 Addition of Carbenes to Alkenes The carbene functional group is “half of an alkene” Carbenes are electrically neutral with six electrons in the outer shell They add symmetrically across double bonds to form cyclopropanes

Formation of Dichlorocarbene Base removes proton from chloroform Stabilized carbanion remains Unimolecular elimination of Cl- gives electron deficient species, dichlorocarbene Orbital picture for the carbene is similar to that of a carbocation

Reaction of Dichlorocarbene Addition of dichlorocarbene is stereospecific cis alkenes give cis cyclopropanes trans alkenes give trans cyclopropanes

Simmons-Smith Reaction Equivalent of addition of CH2: Reaction of diiodomethane with zinc-copper alloy produces a carbenoid species Forms cyclopropanes by cycloaddition

7.7 Reduction of Alkenes: Hydrogenation Addition of H-H across C=C Reduction in general is addition of H2 or its equivalent, or a loss of O from the molecule Requires Pt or Pd as powders on carbon and H2 Hydrogen is first adsorbed on catalyst Reaction is heterogeneous (process is not in solution)

Hydrogen Addition- Selectivity Selective for C=C. No reaction with C=O, C=N Polyunsaturated liquid oils become solids If one side is blocked, hydrogen adds to other STEREOSPECIFIC

Catalytic Hydrogenation Mechanism Heterogeneous – reaction between phases Addition of H-H is syn

Oxidation of Alkenes: Epoxidation and Hydroxylation Oxidation is addition of O, or loss of H Epoxidation results in a cyclic ether with an oxygen atom Stereochemistry of addition is syn MCPBA in CH2Cl2 are the usual conditions Addition of acid results in a trans-1,2-diol meta-Chloroperoxybenzoic acid (mCPBA) Treatment of the epoxide with aqueous acid give a trans diol

Osmium Tetroxide Catalyzed Formation of Diols Hydroxylation - converts to syn-diol Osmium tetroxide, then sodium bisulfate Via cyclic osmate di-ester Osmium is toxic, so catalytic amount and NMO are used

Oxidaton of Alkenes:Cleavage to Carbonyl Compounds Ozone, O3, adds to alkenes to form molozonide Reduce molozonide to obtain ketones and/or aldehydes

Permanganate Oxidation of Alkenes Oxidizing reagents other than ozone also cleave alkenes Potassium permanganate (KMnO4) can produce carboxylic acids and carbon dioxide if H’s are present on C=C

Cleavage of 1,2-diols Reaction of a 1,2-diol with periodic (per-iodic) acid, HIO4 , cleaves the diol into two carbonyl compounds Sequence of diol formation with OsO4 followed by diol cleavage is a good alternative to ozonolysis

Free Radical Polymerization: Initiation Initiation - a few radicals are generated by the reaction of a molecule that readily forms radicals from a nonradical molecule A bond is broken homolytically

Polymerization: Propagation Radical from initiation adds to alkene to generate alkene radical This radical adds to another alkene, and so on many times Chain propagation ends when two radical chains combine Not controlled specifically but affected by reactivity and concentration Termination

6.4: Electrophilic Addition of Hydrogen Halides to Alkenes C-C -bond: H°= 368 KJ/mol C-C -bond: H°= 243 KJ/mol -bond of an alkene can act as a nucleophile!! Electrophilic addition reaction Bonds broken Bonds formed C=C -bond 243 KJ/mol H3C-H2C–H -410 KJ/mol H–Br 366 KJ/mol H3C-H2C–Br -283 KJ/mol calc. H° = -84 KJ/mol expt. H°= -84 KJ/mol 54

Reactivity of HX correlates with acidity: slowest HF << HCl < HBr < HI fastest 6.5: Regioselectivity of Hydrogen Halide Addition: Markovnikov's Rule For the electrophilic addition of HX across a C=C bond, the H (of HX) will add to the carbon of the double bond with the most H’s (the least substitutent carbon) and the X will add to the carbon of the double bond that has the most alkyl groups. 55

Addition Reactions: HX to Alkenes General Order of HX Reactivity: HI > HBr > HCl > HF Usually Dissolved in Solvent (CH3CO2H, CH2Cl2) Can be Bubbled Through Solution as a Gas Addition of HCl not Generally Useful (Works w/ Silica Gel)

Markovnikov’s Rule: Why? Product Distribution Explained When Looking at Intermediates Recall Discussion of Carbocation Stability (2° > 1°) Major Product Formed From More Stable C+ Intermediate

Markovnikov’s Rule: C+ Stability We Know 2° Carbocations More Stable Than 1° Major Product Formed From More Stable C+ Intermediate Means TS in 2° Carbocation Pathway Lower in Energy Lower Energy of Activation Activation Energies in 1° Carbocation Pathways Much Larger

Stereochemistry in Ionic Additions Just as We Saw in SN1: C+ Has TWO FACES Top and Bottom Attack Give Two Stereochemical Products R and S Enantiomers Formed as a Racemic Mixture (50:50)

Regioselectivity (Orientation) The incoming hydrogen attaches to the carbon with the greater number of hydrogens. This is regioselectivity. It is called Markovnikov orientation.

Mechanism Step 1 Step 2

Regioselectivity (Orientation) Primary carbocation Secondary carbocation Secondary carbocation more more stable and more easily formed.

Carbocation Stabilities Order of increasing stability: Methyl < Primary < Secondary < Tertiary Order of increasing ease of formation: Methyl < Primary < Secondary < Tertiary Increasing Ease of Formation

For the electrophilic addition of HX to an unsymmetrically substituted alkene: • The more highly substituted carbocation intermediate is formed. • More highly substituted carbocations are more stable than less substituted carbocations. (hyperconjugation) • The more highly substituted carbocation is formed faster than the less substituted carbocation. Once formed, the more highly substituted carbocation goes on to the final product more rapidly as well. 64

Note that the shifting atom or group moves with its electron pair. 6.7: Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes - In reactions involving carbocation intermediates, the carbocation may sometimes rearrange if a more stable carbocation can be formed by the rearrangement. These involve hydride and methyl shifts. Note that the shifting atom or group moves with its electron pair. A MORE STABLE CARBOCATION IS FORMED. 65