Chapter 8 (except 8.10, 8.11) CHM 136H Synthesis and Reactions of Alkenes 1 Chapter 8: Alkene Reactions – alkene synthesis – stereochemistry and regiochemistry of addition reactions – addition of HBr, Br2, Br2/H2O – addition of H2O: 1. oxymercuration 2. hydroboration – hydrogenation: H2 – formation of 3-membered rings: 1. dichlorocarbene 2. Simmons-Smith 3. Epoxidation – formation of 1,2-diols: OsO4 – cleavage of alkenes: O3/Zn, HIO4 1 2 Synthesis of alkenes: elimination reactions addition elimination + A-B Elimination with base: Acid-catalyzed elimination: KOH H2SO4 + Br– + H2O + H2O CH3CH2OH H2O, 3 syn addition: A and B add to same face of alkene anti addition: A and B add to opposite faces of alkene Reactions of alkenes: addition reactions – selectivity in addition: 1. regioselectivity of addition: Markovnikov’s rule 2. stereochemisty of addition: not selective, carbocation intermediate A-B = H-X A-B A-B 4 3 4 Halogenation: What mechanism leads to this anti addition + Br2 CCl4 5 – selectivity in addition: A-B = X2 The mechanism: reaction at either face of alkene equally likely Br- attacks backside of the more substituted carbon anti addition 6 5 6 (Z)-2-butene Addition of Br2 to (Z)-2-butene Stereochemistry of alkene addition reactions (E)-2-butene Addition of Br2 to (E)-2-butene Stereochemistry of alkene addition reactions 7 8 bromonium ion Mechanism very similar to halogenation except nucleophile in second step is H2O ++ Same reaction of cyclohexene and X2 IN H2O: a bromohydrin deprotonation Who wins Br2/H2OCl2/H2O 9 Overall reaction for the formation of a bromohydrin: – water as solvent and reactant! H2O Br2 + racemic mixture + “addition of HOBr” DMSO – anti addition – regioselective: the –OH (from H2O nucleophile) bonds to the more substituted carbon 10Syn products not formed less substituted more substituted 9 10 NBS reacts slowly with water to produce a low constant [Br2]: Bromohydrin formation with NBS H2O + Br2 11 Typical solvents: alkanes, ether, THF, CH2Cl2 not HOH or ROH anti addition Brief summary: X2 X2 = Cl2, Br2 + 12Typical solvent: mixtures of THF/H2O or DMSO/H2O X2 X2 = Cl2, Br2 + anti addition 11 12 Chapter 8: Alkene Reactions – alkene synthesis and stereochemistry and regiochemistry of addition reactions – addition of HBr, Br2, Br2/H2O – addition of H2O: 1. oxymercuration 2. hydroboration – hydrogenation: H2 – formation of 3-membered rings: 1. dichlorocarbene 2. Simmons-Smith 3. Epoxidation – formation of 1,2-diols: OsO4 – cleavage of alkenes: O3/Zn, HIO4, 14 – addition of water to form an alcohol Hydration of alkenes In living cells: fumarase + H2O + H2O cat. H2SO4 D (heat) In (big!) flasks: catalytic amount not useful on the laboratory scale H2O + H2SO4 + HSO4 – 13 14 The acid is a catalyst, being regenerated at the end of the reaction. Markovnikov product 15 Mechanism: + two-step process 1. Oxymercuration: 2. Hydroboration Hydration reactions in the lab two-step process 1. Hg(OAc)2, H2O/THF 2. NaBH4 Markovnikov product + 1. BH3, THF 2. H2O2, OH – non-Markovnikov product syn addition d+ d–d– regioselective reaction: regioselective reaction: 16 15 16 stable compound; can be isolated d+ d– d– Mechanism of oxymercuration: deprotonation 1. Hg(OAc)2, H2O/THF – 3 elementary steps – approach from other face of alkene equally likely 17 H2O H3O + H2O + enantiomer + enantiomer + enantiomer Overall Markovnikov addition of water to C=C: 1. Hg(OAc)2, H2O 2. NaBH4 2. NaBH4Demercuration: + enantiomer 18 + enantiomer + enantiomer 17 18 2. Hydration by hydroboration borane + H2O2, NaOH THF good electrophile 19 BH2 and H add to the same face of the alkene = syn addition…. d+ d ….at the same time. organoborane H2O2, NaOH Mechanism of hydroboration: 20 19 20 Wh
y non-Markovnikov regioselectivity Transition state for non-Markovnikov addition is more favourable d+ d– and stericallyboth electronically Reaction proceeds by lower energy (more stable) transition state: more steric crowdingless steric crowding partial 3o carbocation partial 2o carbocation → B bonds to the less substituted carbon 21 d+ d– Reaction stereochemistry: d+ d– H2O2, NaOH H2O2, NaOH 22 d+ d– 21 22 Overall reaction: 1. BH3, THF 2. H2O2, NaOH racemic mixture non-Markovnikov and syn addition of H-OH to C=C 23 Chapter 8: Alkene Reactions – alkene synthesis and stereochemistry and regiochemistry of addition reactions – addition of HBr, Br2, Br2/H2O – addition of H2O: 1. oxymercuration 2. hydroboration – hydrogenation: H2 – formation of 3-membered rings: 1. dichlorocarbene 2. Simmons-Smith 3. Epoxidation – formation of 1,2-diols: OsO4 – cleavage of alkenes: O3/Zn, HIO4 23 24 Hydrogenation Addition of H2 gas to alkene C=C forms an alkane H2 catalyst 25 H atoms add to the same face of the alkene from catalyst surface Catalytic hydrogenation Examples: Pt/carbon, Pd/carbon, PtO2 25 26 Polar multiple bonds and aromatic rings are usually unaffected Chapter 8: Alkene Reactions – alkene synthesis and stereochemistry and regiochemistry of addition reactions – addition of HBr, Br2, Br2/H2O – addition of H2O: 1. oxymercuration 2. hydroboration – hydrogenation: H2 – formation of 3-membered rings: 1. dichlorocarbene 2. Simmons-Smith 3. Epoxidation – formation of 1,2-diols: OsO4 – cleavage of alkenes: O3/Zn, HIO4 27 28 Addition of carbenes to alkenes Common features sp2 hybridized carbon one unhybridized p orbital 6 electrons around the C centre 29 CarbocationCarbene two bonds around C atom three bonds around C atom one lone pair of electrons around C atom no nonbonding electrons around C atom Charge: 0 Charge: +1 Differences – – H2O – Cl 1. Dichlorocarbene: – – + HCCl3 KOH E.g. 30 syn addition 29 30 31 Practice: write down the mechanism and the final product of the following reaction. CH2I2 2. Simmons-Smith reaction: + Zn(Cu) + CH2I2 Zn(Cu) ICH2ZnI in the presence of alkenes, can behave as “:CH2” + ZnI2 ICH2ZnI syn addition 32 31 32 3. Epoxidation: a 3-membered ring with an O instead of a C atom MCPBA MCPBA CH2Cl2 epoxide 33 cat. H3O + H2O + 34 Epoxides react with aqueous acid to give trans diols 33 34 Chapter 8: Alkene Reactions – alkene synthesis and stereochemistry and regiochemistry of addition reactions – addition of HBr, Br2, Br2/H2O – addition of H2O: 1. oxymercuration 2. hydroboration – hydrogenation: H2 – formation of 3-membered rings: 1. dichlorocarbene 2. Simmons-Smith 3. Epoxidation – formation of 1,2-diols: OsO4 – cleavage of alkenes: O3/Zn, HIO4 Dihydroxylation using a catalytic amount of OsO4 cat. OsO4 NMO 36 Acetone/H2O + NMO: (N-methylmorpholine N-oxide) m.p. 180-184 °C acetone/H2O mixed solvent 35 36 NMO NMO 37 H2O H2O Mechanism Chapter 8: Alkene Reactions – alkene synthesis and stereochemistry and regiochemistry of addition reactions – addition of HBr, Br2, Br2/H2O – addition of H2O: 1. oxymercuration 2. hydroboration – formation of 1,2-diols: OsO4 – hydrogenation: H2 – formation of 3-membered rings: 1. dichlorocarbene 2. Simmons-Smith 3. epoxidation – cleavage of alkenes: O3/Zn, HIO4 37 38 1. Dihydroxylation and cleavage of 1,2-diol cis-1,2-diol HIO4 H2O/THF 39 cat. OsO4 NMO Alkene cleavage reactions 2. Ozonolysis Reagents: 1. 2. Zn/CH3COOH O3 39 40 Practice: which of the following alkenes will yield the products shown upon epoxidation H2 Pd/C Br2 CH2Cl2 MCPBA H2O THF 1. BH3,THF 2. H2O2, NaOH 1. Hg(OAc)2, H2O/THF 2. NaBH4 42 Summary cat. OsO4 NMO HBr ether NaOH H2O, cat. H2SO4 D (heat) :CR’2 1. O3 2. Zn/H+ HIO4 41 42