Bài giảng Organic Chemistry - Chapter 12: Reactions Of Alkenes

Chapter 12: Reactions Of AlkenesTear resistantFundamental building blocks for organic transformations and polymer materials synthesisPolyethyleneAddition Reactions Of Alkenesπ Bond is unsaturated: Reacts by addition.CC+ABCCABexothermic (usually)We can calculate ∆Hº of addition reaction from bond strength data, using DHºπ-bond = 65 kcal mol-1. Note, however: ∆Sº is negative (~ -30 e.u.)Catalyst1. Catalytic HydrogenationCC+HHCCHHTypical catalysts are heterogeneous: insoluble solidsWhy catalysts? Enable a lower Ea mechanism.Alkenes + H2 no reaction without catalystPd/C, PtO2 ( Pt)H2ECatalyzed pathwayUncatalyzed pathwayStereospecific H-H addition from the same side (syn) of double bond.+H2cat.HHCH3CH2CH3cistranscat.D2+ SSDDHHRRStereochemistry+MechanismReversibility causes cis to trans isomerizationHydrogenation “Hardens” Oils, But Generates Trans Fatty AcidsThe fatty acid molecules in butter and hard (stick) margarines are highly saturated, whereas those in vegetable oils have a high proportion of cis-alkene functions (more than 90%). Partial hydrogenation of these oils yields soft (tub) margarine. Conditions of hydrogenation also isomerize cis double bonds to trans. Trans fatty acids are not metabolized in same way as cis counterparts: accumulate in cell membranes Ù increased risk of breast cancer and heart disease.FDA: phase out by 2018.Oleic acid is a cis unsaturated fatty acid making up 55–80% of olive oilElaidic acid is the principal trans unsaturated fatty acid often found in partially hydrogenated vegetable oils.Stearic acid is a saturated fatty acid found in animal fats and is the intended product in full hydrogenation.π Bond is electron-rich. Polar reagents A ―B add to it. +-Mechanism for A = H : Reverse of E1!+CC+ HCCH+:B-CCHB++2. Electrophilic Additions:B-Both syn and anti additionNote: Carbocation intermediate spells trouble  rearrangementsa. Hydrohalogenation H X+ HIH+I--+IHRegioelective: BrHHBr+ HClClMarkovnikov’s RuleH+ (A +) adds to less substituted carbonWhy? Makes the more substituted cationReverse of eliminationVladimir Vasilyevich Markovnikov 1837-19040ºCPropeneHClOrigin Of Markovnikov’s RulePotential Energy DiagramLipshutzBurdonb. Markovnikov Hydration+HOHOHCH3HSolventEquilibrium! Shifted to the right by excess H2OReversible hydration of 2-methylpropene (H+ catalyst):H2SO4H2O, H catalyst+H+ consumedH+ regeneratedAlkenes And Catalytic AcidCatalytic H+ with a nonnucelophilic counter ion (e.g., H2SO4) effects alkene isomerization:H+H+The equilibrium concentrations reflect relative thermodynamic stabilitiesAt equilibrium (0ºC): 2 : 27 : 81125..>99%Mechanism Of EquilibrationReversible E1:+X X gets polarized during approach to alkene.+ Br2BrBrStereospecific : anti (not syn)CCCCorc. Halogenation-Br2RacemicStereospecific 2-Butene BrominationStereospecificityRacemic-BrBr+-CCBr++BrCCBrBranti“Precomplex”LipDjangoImmelcisImmeltransMechanismCCOctetTime Out: Alkenes As Nucleophiles/BasesBase : Nucleophile :General :Halonium Ions Can Be Intercepted By Other Nu+ Br2 + H2OO+NuH+ Or X2, ROH Haloethers (all anti and Markovnikov)+ Cl2 + CH3OHH3CH3CCH3OH-H+ClOCH3Cl++Cf.Br+OH2BrOH-H+CH3CH3CH3HaloetherHaloalcoholGeneral For A ―B Synthetically useful in oxymercuration-demercuration+-d. Oxymercuration-DemercurationA Markovnikov hydration that avoids cations1. Hg(OCCH3)2, HOH2. NaBH4OCH3OH1. Hg(OCCH3)2, ROH 2. NaBH4OCH3ORGoes through radicalsMechanism+3. Hydroboration-OxidationAllows anti-Markovnikov hydration:RCH=CH2 + H2O RCH2CH2OHKey reaction: B H adds to π-bonds.H2B BH2; in THF: H3B OIn hydroboration, all three B-H bonds react:Time out: Borane, BH3, exists as dimer to get octetHH-CCHHHBHCCB3+3TrialkylboraneMechanism Of HydroborationOHBHydroboration Is RegioselectiveSteric control of B-H addition+ BH3less hindered endWhy is hydroboration useful? Oxidation of alkylboranes with H2O2, OH gives ROH [+ B(OH)3]:-+ BH3BR2OHH2O2-anti-Markovnikov hydration + BH3H3CHH3CBCH3CH3OHHH2O2, OH-Hydroboration Is Stereospecific:Syn addition of B—H :CH3CH3Mechanism Of Alkylborane OxidationBH3Negative charge pushesPositive charge pullsLook familiar? Recall:ApplicationsThink retrosynthetically:CCH3CCH3CH2CH3HOHCCHCH3HH3CCH3CH2ICH3OHClHCarbenes, :CR2, are 6-electron species, the parent of which is methylene, :CH2. They can be thought of being derived by deprotonating carbocations:4. Electrophilic Carbene AdditionsMethyleneCarbenes are electron deficient: electrophilic.Carbenes As Reactive Intermediatesa. Methylene from diazomethane, CH2N2b. Dichlorocarbene from chloroformc. Simmons-Smith reagent CH2I2 + Zn-Cu  “CH2”Carbenes pick up the two  electrons of alkenes to form cyclopropanes. a.b.Carbene Additions Are StereospecificH3CH3CH3CCH3COOHCyclopropanes are made by nature(+)- Chrysanthemic acid(used by flowers against insects); the “mother” of the Pyrethroids. US market: 1.5 billion $!!c. Simmons-Smith reagent in cyclopropane synthesisCCH3CCH3HH+ CH2I2Zn Cu, (CH3CH2)2O-Metal iodideCCCH3CH2HH3CHas drugs:HOOHAntifungalfor “fun”:Chiral5. Electrophilic Oxidationa. Peroxycarboxylic acidsRCOOHO-+CC+RCOOHOCCO+RCOHOCH3COOH, CF3COOH, Cl“MCPBA”Meta-chloroperbenzoic acidCommonly used peroxycarboxylic acids:COOHOOOPeracetic acidTrifluoro-peracetic acidClCOHOOCHCl390%OClCOHO++Stereospecific: synCCHHDDRCOOHOODHDHRCOHO+95%Aqueous work uptrans-2,3-Di-deuteriooxa-cyclopropane+Examples:Mechanism:CCOOOHCOOOHRRCCC+OH3CCH3:Nu1CC 1.CH3SO2Cl2. :Nu2CH3H3CHNu1HOHCCCH3H3CHNu1HNu2Double nucleophilic syn – addition to double bondApplication:OcacpTurns OH into mesylate leaving groupRates of oxacyclopropanation increase with alkyl substitution:+ CH3COOHO1 equivCHCl310ºCO86%Sequence 1. RCO3H, 2. H+, H2O or –OH, H2O constitutes an anti-dihydroxylation of alkenes.CCHHCH3H3CRCO3HOCH3HH3CHCCCH3H3CHOHHOHmesoH+, H2Oor –OH, H2Ob. OsO4 syn-dihydroxylationOHOH1. OsO42. H2S, H2Ocis-1,2-CyclohexanediolGives complementary stereochemistry to anti-dihydroxylationis reduced to OsVI.OsOOOOVIIIOsO4OMechanism:CCOsOOOOVIIICCOsOOOVIOsmate esterH2OCCOHOH+OsOHOOHOCan be reoxidized by added oxidant, therefore can be made catalytic in OsConditions: stoichiometric H2O2 and catalytic OsO4Good because Os is expensive; OsO4, H2S are toxic. Six electron TSVIc. OzonolysisComplete oxidative cleavage by 1. O3, 2. Reduction of “ozonide”O22-4% in O2OOO+CC1. O32. ReductionCCOO+CCCH3H3CHCH3CH21. O32. Zn, CH3COOHZn2+CH3CH2CCH3 + CH3CHOO90%CH31. O32. H2 , PtH2OOOHRing opening85%Arc discharge-Ozone generator:2. (CH3)2S (CH3)2SOHH3C1. O3HH3COClipped off carbon atom76%)3Recall:+ HBrBrMarkovnikov+ HBrBrAnti-Markovnikov!Mechanism different; goes via faster, radical chain.Popular peroxide radical initiators (the O-O bond is weak, ~39 kcal mol-1):RO-ORBut:6. Radical Hydrobromination70%Mechanism Of Radical HydrobrominationCompare to radical halogenation of hydrocarbons (Chapter 3):RadicalHbrDoes not work for HCl, HI: One of the propagation steps endothermic:Which one?  homework problemHence radical mechanism too slow, and ionic mechanism of Markovnikov addition wins. But works for RSH anti-Markovnikov addition: Initiation:7. Alkene Polymerizationetc.a. Cationic:b. Radical:c. Anionic:d. Metal (Ti, Zr, lanthanides): Ziegler-Natta; now Kaminski-Brintzinger. Organometallic mechanismCCR+ H+CCR+etc.RO +CCRHCCRHROB +CCCNCC-BCNTiRRCH3TiRRCH3TiCH3Insertion-HResonanceetc.a. Acid-catalyzed PolymerizationProceeds through carbocations! Polymerization is yet another complication of carbocations, in addition to SN1, E1, and rearrangements; dominates at high concentrations.At low concentrations: dimerizationoligomerization:Dimerization of 2-methylpropeneContinued oligomerization:Can lead to synthetically useful cyclizations:Mechanism:b. Radical Polymerizationc. Base-catalyzed PolymerizationFacilitated by resonance stabilization of anionic centers:8. Alkenes in Nature: PheromonesSex, war, communication (trail, alarm, defence)NO2Termite defenceBlack tail deer (hoof excretion); recognition and statusOHOO“Queen bee substance”, inhibits ovary development in workers, attracts–excites dronesOOSex pheromone of the western black widow (Latrodectus hesperus)The Holy Grail: Human Sex PheromonesAndrostadienoneComponent of male sweat; has been suggested to be a human sex pheromone. Controversial: the olfactory sense organ responsible for the detection of pheromones as more than just an odor has no active function in humans.