Ch.7 Alkenes: Reactions and Synthesis alkene: 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 Epoxide 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 acid, activate C-X bond to generate carbocation Ch.7 Alkenes: Reactions and Synthesis 7.3 Halohydrin Formation Halohydrin: 1,2-halo alcohol 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: Hydrogenation 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 • ketone, aldehyde, ester, nitrile: stable under normal hydrogenation condition.