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Ch.7 : Reactions and Synthesis : versatile function group H OH H H

Alcohol Alkane HO OH X OH

1,2-Diol Halohydrin

CC O X X Carbonyl compound 1,2-Dihalide C H X O Cyclopropane Halide Ch.7 Alkenes: Reactions and Synthesis 7.1 Preparation of Alkenes: A Review of Elimination Reactions

Elimination

addition

X Y CC + XY elimination Ch.7 Alkenes: Reactions and Synthesis

Dehydrohalogenation: -HX under strong basic condition (eg. KOH)

H H Br KOH + KBr + H2O H CH3CH2OH H H Ch.7 Alkenes: Reactions and Synthesis

Dehydration: -H2O under strong acidic condition (eg. H2SO4)

CH3 OH CH3 H2SO4 +H2O H H2O H H THF, 50oC

O THF

Tetrahydrofuran Ch.7 Alkenes: Reactions and Synthesis 7.2 Addition of Halogens to Alkenes

•Cl2, Br2 add readily to alkenes

•F2 is too reactive and difficult to control, and I2 does not react with most alkenes

H H Cl +Cl2 Cl H H 1,2-Dichloroethane Ch.7 Alkenes: Reactions and Synthesis

Bromination mechanism: carbocation intermediate cannot explain the stereochemistry

H H H Br Br Br Br-

H Br Br H H Ch.7 Alkenes: Reactions and Synthesis

Anti stereochemistry: only trans product

Br H trans

Br Br Br H Br Br-

H H H X Br Br H cis

HH

NOT formed Ch.7 Alkenes: Reactions and Synthesis

Bromonium ion: explain anti stereochemistry similarly, chloronium ion

Br Br Br Br

bromonium ion The neighboring bromo substituent stabilizes the positive charge by using two of its electrons to overlap the vacant carbon p orbital, giving a three-membered-ring bromonium ion. Ch.7 Alkenes: Reactions and Synthesis

top side is shielded from attack

Br Br Br Br H

H H H H H Br Br- trans bottom side is open to attack Ch.7 Alkenes: Reactions and Synthesis stable bromonium ion: recently, George Olah has prepared stable bromonium ion solution ; strong evidence for the existence of bromonium ion

H3C Br Br SbF SbF6 H3C 5 CH3 H CCH F liquid SO2 3 3 H H3CH SbF 5 bromonium ion (stable in SO2 solution)

SbF5: strong Lewis , activate C-X bond to generate carbocation Ch.7 Alkenes: Reactions and Synthesis 7.3 Halohydrin Formation

Halohydrin: 1,2-halo

HO X2 H O 2 X halohydrin Ch.7 Alkenes: Reactions and Synthesis

In the presence of an additional nucleophile, the intermediate bromonium ion can be intercepted by the added nucleophile.

Br Br - Br Br Br Br2 H O 2 O H H O 2 H

H2O δ+ δ- Br Br

Br + + H3O OH + Br- a bromohydrin Ch.7 Alkenes: Reactions and Synthesis

In practice, few alkenes are soluble in water, use polar solvent; aqueous dimethyl sulfoxide (DMSO) and NBS (N- bromosuccinimide) as a source of Br+ O

N Br (NBS) OH Br O

H2O/CH3SOCH3 (DMSO) Styrene 76% 2-Bromo-1-phenylethanol

-Br2 is toxic, difficult to handle - NBS is stable, easy to handle Note that the aromatic ring is inert to reaction condition (aromatic ring is more stable than the isolated alkenes) Ch.7 Alkenes: Reactions and Synthesis 7.4 Addition of Water to Alkenes: Oxymercuration

Hydration: addition of water, need a strong acid catalyst, similar mechanism to that of HX addition limitation; strong acid and high temperature

H H H3PO4 catalyst CH3CH2OH H H H2O 250oC

suitable for large-scale industrial procedures Ch.7 Alkenes: Reactions and Synthesis

mechanism of the acid catalyzed hydration of an alkene

H H O H C H3C - H3C H H-A 3 OH2 A CH3 CH3 H C H3C H H3C 3 A-

H O H3C CH3 + HA H3C Ch.7 Alkenes: Reactions and Synthesis

Oxymercuration: hydration of alkenes in the laboratory; Hg(OAc)2

1. Hg(OAc) , H O-THF 2 2 OH CH3 2. NaBH 4 CH3 92% electrophilic addition of Hg2+ (mercuric) ion to alkene give mercurinium ion (similar to bromonium ion)

+ - Hg(OAc)2 is ionic salt like Na OAc

2+ - Hg(OAc)2 Hg + 2 OAc

Hg2+ ion is much more electrophilic than H+; reaction can occur at low temperature (rt) Ch.7 Alkenes: Reactions and Synthesis mechanism

OAc OAc OAc Hg Hg OAc Hg OH 2 CH CH3 CH3 3 O H -OAc H -OAc

OAc H Hg H Hg NaBH 4 CH CH3 CH 3 + H-OAc - Hg(0) 3 OH OH OH

- the final reductive demercuration involves radicals Ch.7 Alkenes: Reactions and Synthesis

- the regiochemistry: Markovnikov addition of water (-OH group attaches to the more highly substituted carbon)

OAc - OAc Hg δ+ OAc - CH Hg OAc δ+ 3 CH3

OH Br NBS δ+ Br

H2O Ch.7 Alkenes: Reactions and Synthesis 7.5 Addition of Water to Alkenes: Hydroboration

Hydroboration: addition of B-H bond of borane (BH3) to an alkene; 1959, H.C. Brown

BH3 H2BH

an organoborane Ch.7 Alkenes: Reactions and Synthesis

• borane is highly reactive because the boron atom has only 6 electrons in its valence shell. ; borane accepts an electron pair from a solvent molecule in a Lewis-acid reaction to complete its octet ; commercial borane reagents are available as complexes

HBH + O H H3B O

BH3-THF complex

CH3 H3B N H3B S CH3 BH3-pyr BH3-DMS Ch.7 Alkenes: Reactions and Synthesis

Hydroboration: addition occurs three times to give trialkylborane, R3B

hydroboration / oxydation

BH3 H O 3 2 2 B THF NaOH, H2O

OH 3 + B(OH)3

87% Ch.7 Alkenes: Reactions and Synthesis

mechanism of oxidation

Na+ -OOH R2BR R2BR BR2 B(O-R)3 O OR OH NaOH

B(OH)3 + 3 ROH

• the net result of hydroboration / oxidation is hydration of alkene double bond Ch.7 Alkenes: Reactions and Synthesis

Regiochemistry of hydroboration: syn stereochemistry with boron attaching to the less substituted carbon

H B H OH BH 3 H2O2 H CH3 H THF NaOH CH CH3 3 85% Allkylborane intermediate trans-2-Methylcyclopentanol

• the C-B bond is replaced by the C-OH bond with the retention of stereochemistry Ch.7 Alkenes: Reactions and Synthesis

This stereochemical result is particularly useful because it is complementary to the Markovnikov regiochemistry observed for oxymercuration.

H OH OH 1. Hg(OAc)2 BH3; CH H H O 3 CH3 2 NaOOH CH3 2. NaBH4 Ch.7 Alkenes: Reactions and Synthesis

Mechanism of hydroboration • borane is electron defficient, electrophilic; alkene is nucloephilic • Borane becomes negative in the transition state, as electrons shift from the alkene to boron, but is positive in the product. syn stereoselectivity: concerted mechanism

H2BH BH3 H2BH

Addition of borane to the alkene π-bond occurs in a single step through a cyclic four-membered-ring transition state. Ch.7 Alkenes: Reactions and Synthesis Regiochemical stereoselectivity

electronic factors

H CH3 δ+

H CH3 H B H H2BH - H δ favored partial 3o cation BH 3 (more stable TS)

H CH3 + δ H CH3

H CH3 H B H - HBH2 δ H partial 2o cation disfavored (less stable TS) Ch.7 Alkenes: Reactions and Synthesis

Steric factor: explain regioselectivity in hydroboration

steric factors

H CH H CH3 3 H B H H B H H H sterically less hindered sterically more hindered (favored) (disfavored)

Sterically bulky organoboranes (R2BH): high regioselectivity Ch.7 Alkenes: Reactions and Synthesis 7.6 Addition of Carbenes to Alkenes: Cyclopropanation Carbon Species

tetrahedral carbanion radical carbene cabocation carbons

R C R4C 3 R3C R2CR3C - - - 8 e 8 e 7 e- 6 e 6 e-

3 3 2 sp sp sp2 ~ sp3 sp sp2

R R singlet

R planar planar X triplet Ch.7 Alkenes: Reactions and Synthesis

Carbene: neutral, highly reactive, electron-deficient, electrophilic ; generated only in situ

cyclopropanation: concerted one step reaction

RR' R R' + C

carbene cyclopropane Ch.7 Alkenes: Reactions and Synthesis generation of carbene: dichlorocarbene

Cl Cl KOH Cl Cl Cl CH Cl C C + Cl- Cl Cl dichlorocarbene Chloroform (acidic C-H)

vacant p orbital

Cl R 2 R Cl sp R

Dichlorocarbene carbocation Ch.7 Alkenes: Reactions and Synthesis

• carbenes generated in the presence of alkenes add to alkenes

Cl Cl H H KOH H + CHCl H + KCl Et Me 3 Et Me (Z) syn

H Cl KOH + KCl + CHCl3 Cl H Ch.7 Alkenes: Reactions and Synthesis

• carbene addition is a stereospecific reaction: a single stereoisomer is formed

Cl Cl H Me KOH H + CHCl Me + KCl Et H 3 Et H (E) trans Ch.7 Alkenes: Reactions and Synthesis

Stereospecific reaction: generally concerted reactions - stereoisomeric starting materials afford stereoisomerically different products under the same reaction conditions

Cl Cl CCl2

Cl Cl CCl2 Ch.7 Alkenes: Reactions and Synthesis

Stereoselective reaction: a single reactant has the capacity of forming two or more stereoisomeric products in a particular reaction but one is formed preferentially

OH OH BH3; + NaOOH CH 3 Ch3 CH3 major minor

stereospecific: ∆∆G╪ > 25 kcal/mol stereoselective: ~ 1-5 kcal/mol Ch.7 Alkenes: Reactions and Synthesis

Simmos-Smith reaction: involve carbenoid- a metal-complexed reagent with carbene-like reactivity

Et2O "" CH2I2 + Zn(Cu) I-CH2-Zn-I CH2 (Iodomethyl)zinc iodide (a carbenoid)

H Zn(Cu) + CH2I2 + ZnI2 Et2O H 92% Ch.7 Alkenes: Reactions and Synthesis 7.7 Reduction of Alkenes:

Reduction in organic chemistry: addition of hydrogen or removal of oxygen

Oxidation in organic chemistry: addition of oxygen or removal of hydrogen

Hydrogenation: addition of H2 to a unsaturated bond; reduction

HH catalyst + HH

• catalyst: PtO2, Pd/C Ch.7 Alkenes: Reactions and Synthesis

• hydrogenation is heterogeneous reaction and takes place on the surface of solid catalyst • syn stereoselectivity

CH3 CH3 H2, PtO2 H

CH3CO2H CH3 H CH3 82% Ch.7 Alkenes: Reactions and Synthesis

Mechanism

H H HH H2

HH + H H Ch.7 Alkenes: Reactions and Synthesis

• hydrogenation is extremely sensitive to the steric environment around the double bond: reduction from sterically less hindered face

H C CH3 X H C CH3 3 3 H H2 CH Pd/C 3 CH H 3 H Ch.7 Alkenes: Reactions and Synthesis

, , , nitrile: stable under normal hydrogenation condition.

; vigorous condition (high T and high pressure of H2) can reduce them

O O H2 Pd/C EtOH

O O H2 OCH3 OCH3 Pd/C EtOH

H2 C C N N Pd/C EtOH

- typical method to reduce double bond only in unsaturated carbonyls Ch.7 Alkenes: Reactions and Synthesis

• commercial saturation of double bonds: unsaturated vegetable oils to saturated fats

O

O Ester of linoleic acid (a constituent of vegetable oil)

H2 Pd/C O

O Ester of stearic acid Ch.7 Alkenes: Reactions and Synthesis 7.8 Oxidation of Alkenes: Hydroxylation and Cleavage

Oxidation in organic chemistry: addition of oxygen or removal of hydrogen

Epoxidation : RCO3H (peroxyacid)

O RCO3H

epoxide Ch.7 Alkenes: Reactions and Synthesis

• concerted formation of epoxide: mCPBA (m-Chloroperbenzoic acid)

mCPBA H O CH2Cl2 CH3

Cl

mCPBA O

O H O Ch.7 Alkenes: Reactions and Synthesis

Alkene Dihydroxylation: 1,2-diol (glycol); use OsO4 ( tetroxide)

HO OH OsO4

NaHSO3 1,2-diol

• concerted formation of osmate

CH3 CH3 CH3 OsO4 O O NaHSO3 OH Os Pyridine O H O CH3 O 2 OH CH3 CH3 87% a cyclic osmate intermediate cis-1,2-Dimethyl-1,2- cyclopentanediol Ch.7 Alkenes: Reactions and Synthesis

Alkene Cleavage: ozonolysis

electric O 3 O2 2 O3 discharge O O ozone

O O O O O OO O3 OO reduction + CH2Cl2 O -78 oC O a molozonide an ozonide

reducing reagent:

Zn, AcOH, H2O Ch.7 Alkenes: Reactions and Synthesis

1. O3 O O + + 2. Zn, H3O

1. O3 CH3(CH2)7CH=CH(CH2)CO2CH3 + 2. Zn, H3O

O O

CH3(CH2)7CH + HC(CH2)7CO2CH3 Ch.7 Alkenes: Reactions and Synthesis

• KMnO4 (potassium , strong oxidant) in neutral or acidic solution can cleave double bonds ; if hydrogens are present on the double bond, carboxylic are produced

KMnO4 O O + + H3O

H KMnO4 O O + + H3O OH

H KMnO4 O +CO2 H + H H3O HO Ch.7 Alkenes: Reactions and Synthesis

Cleavage of 1,2-Diol

HO OH HIO4 O + O H2O, THF 1,2-diol

•HIO4 (periodic acid) or NaIO4 (sodium periodate) cleaves diols

•a mild alternative to direct cleavages of alkenes with KMnO4 or O3

HO OH OsO NaIO4 4 O + O H O, THF NaHSO3 2 1,2-diol Ch.7 Alkenes: Reactions and Synthesis

• C-H is not further oxidized; compare with KMnO4

CH3 CH O OH 3 OH CH HIO4 O 3 I O OH H2O, THF O O H H H O cyclic periodate intermediate

HO OH HIO4 2 O H2O, THF Ch.7 Alkenes: Reactions and Synthesis

•in cyclic diols, only cis-diol is cleaved; trans-diol is not cleaved ; trans-diols cannot form the cyclic periodate

CH3 OH HIO4 No Reaction H H2O, THF OH trans-diol Ch.7 Alkenes: Reactions and Synthesis 7.9 Biological Alkene Addition Reactions • biological reaction: aqueous medium, catalyzed by enzymes • the kinds of biological reactions are similar to laboratory reactions • enzyme catalyzed reactions are highly substrate selective for example, fumarase catalyzes the addition of water to fumaric acid in citric acid cycle, which our bodies use to metabolize food HO HO O O H2O OH O pH 7.4 O OH OH Fumarase Fumaric acid Malic acid

H2O O O No Reaction OHHO pH 7.4 Fumarase Maleic acid Ch.7 Alkenes: Reactions and Synthesis 7.10 Addition of Radicals to Alkenes:

: built up by repetitive bonding of

Many H2CCH2

A section of polyethylene

ethylene : high pressure (1000-3000atm), high temperature (100-250oC) in the presence of a catalyst (eg. benzoyl peroxide) Ch.7 Alkenes: Reactions and Synthesis radical polymerization step 1. Initiation: homolytic cleavage of O-O bond thermally or photolytically

OO O

OO 2 O heat = BzO

Benzoyl peroxide Benzoyloxy radical

- benzoyloxy radical adds to ethylene to generate an alkyl radical;

BzO H2CCH2 BzO H2CCH2

BzO H2CCH2 Ch.7 Alkenes: Reactions and Synthesis step 2. propagation: repetition of radical addition

BzO CH2CH2 H2CCH2 BzO-CH2CH2CH2CH2

BzO-(CH2CH2)nCH2CH2 step 3. termination: two radicals combine to form a stable product

R + R' RR' Ch.7 Alkenes: Reactions and Synthesis other monomers

H2C CHCH3

Propylene Polypropylene

H2C CHPh Ph Ph Ph Ph Styrene Polystyrene Ch.7 Alkenes: Reactions and Synthesis

- unsymmetrically substituted alkene : more stable radical formation is favored - radical species are electron defficient; stabilized by alkyl groups like carbocations

BzO H2C CH BzO H2CCH R R

BzO HC CH2 R

primary radical (less stable) Ch.7 Alkenes: Reactions and Synthesis

Some polymers (Table 7.1)

Ethylene H2CCH2

Propylene H2C CHCH3

Vinyl chloride H2C CHCl PVC

Styrene H2C CHPh

Tetrafluoroethylene F2CCF2 Teflon

Acrylonitrile H2C CH-CN

Methyl methacrylate H2C C CO2CH3 CH3 O

Vinyl acetate H2C CH O CCH3 Ch.7 Alkenes: Reactions and Synthesis

Chain Branching During Polymerization

in practice, polymerization is complicated by several problems

branching: radicals can abstract hydrogen from C-H bond, which can lead branched polymers

Intramolecular C-H abstraction: 1,5-H abstraction

short-chain branching a short chain

H2CCH2 H C H H 2 CH2 CH2 CH2 CH3 branched Ch.7 Alkenes: Reactions and Synthesis

Intermolecular C-H abstraction long-chain branching

H

H2CCH2 CH2 CH3

a long chain

CH2

branched • short-chain branching occurs about 50 times as often as long-chain branching. Why? Ch.7 Alkenes: Reactions and Synthesis

Cationic Polymerization

- initiated by cationic species: strong protic or Lewis acid catalyt - electrophilic addition sequence - stable, tertiary carbocation intermediates are commonly used

acid catalyst

CH3

Polyisobutylene CH2 C

CH3 n Ch.7 Alkenes: Reactions and Synthesis

Anionic Polymerization: (Chapter 31)

H2C CH

- EWG Nu H2C CH Nu H2CCH EWG EWG

H C CH EWG 2 EWG Nu CH2 CH CH2 CH EWG EWG CH2 CH n Chemistry @ Work Natural Rubber

Rubber: natural alkene polymer produced by plants

Isoprene n A segment of natural rubber

• crude rubber: called latex = ~5000 monomers, MW = 200,000 - 500,000 ; too soft, tacky

• vulcanization: hardening and stiffening by heating with elemental sulfur; cross linking between the rubber chain by forming C-S bonds

The remarkable ability of rubber to stretch and then contract to its original shape is due to the irregular shapes of the polymer chains caused by the double bonds.