CEM 109A 1. Predict the products of the following reactions (a-c E2, d-f E1 KEY focuses only on elimination products, in most cases there will also be substitution products.) a. - LG must be axial - are the same - - b. - (E > Z and more substituted over less substituted alkene) - - c. - LG must be axial (more substituted alkene) - d. I I I - 3 + Page 1 of 7
CEM 109A e. Me shift 2 o carbocation 3 o carbocation 3 + - f. ydride shift 2 + C 3-2. Which reactant in each of the following pairs will undergo an elimination reaction more rapidly? Explain your choice and show the mechanism. - 2 a. or E2 conditions and better LG so more rapid reaction. - 2 Page 2 of 7
CEM 109A b. C 3 - C 3 or E2 conditions and LG must be axial for E2 reaction. C 3 - C 3 3. For each of the following, give the major elimination product; if the product can exist as stereoisomers, indicate which stereoisomer is obtained in greater yield. a. (R)-2-bromohexane + high concentration - - 2 - trans is (cis and monosub alkene are minor) E2 b. (R)-2-bromohexane + 2 3 + - trans is (cis and monosub alkene are minor) E1 c. trans-1-chloro-2-methylcyclohexane + high concentration C 3 - -C 3 Will remove on C6 b/c it is axial E2 d. trans-1-chloro-2-methylcyclohexane + methanol Page 3 of 7
CEM 109A ydride shift 2 + C 3 - e. (R)-2-bromohexane + high concentration sodium tert-butoxide - Na + E1 (R)-2-bromohexane Na + - E2 f. (2-omo-3-methyl-butyl)-benzene/2-bromo-3-methyl-1-phenylbutane + high concentration methoxide - C 3 (2-omo-3-methyl-butyl)-benzene - C 3 (dbl bond is less substituted, conjugated with benzene ring) E2 Additional Information: Definitions Elimination rxn: in general, removal of -X molecule and formation of double bond (alkene). A.K.A. β-elimination, 1,2-elimination Zaitsev s (Saitseff s) Rule: The more substituted alkene is obtained when a proton is removed from the β-c w/fewest s. EXCEPTINS: If R has double bond or benzene ring, the conjugated alkene (NT more sub) will be more stable/. If bulky B is used, alkene w/ bulky groups opposite each other (NT more sub) will be the more stable/. Page 4 of 7
CEM 109A E2 Mech: Bimolecular, 1 step/concerted reaction: B removes proton from β-c, e- go to form double bond and α-c X bond breaks heterolytically so LG leaves as X-. 2 - - Rel Reactivity: Based on LG: RI > R > R > RF Based on R: 3 o > 2 o > 1 o Regioselectivity: Usu. follows Zaitsev s rule - unless opportunity for formation of conjugated double bonds, more substituted alkene I, conjugated diene minor P, more substituted, but isolated diene Page 5 of 7
CEM 109A, dbl bond conjugated w/ benzene ring R steric hinderence for B reacting w/ on β-c (i.e. bulky base) minor P, more substituted, but dbl bond isolated from benzene ring -, b/c less steric hinderence Tbl 9.1 If alkyl halide (R) is NT sterically hindered and Base is Little/Moderately hindered Very hindered More sub P Less sub P W/ alkyl fluoride is the less substituted alkene b/c F is such a poor LG that a neg charge develops on the α-c in the T.S. ~ carbanion (1 o > 2 o > 3 o, carbanion stability b/c destabilized by e- donating alkyl groups). Stereoselectivity: Since elimination of and X occurs in 1 step, the -C and X-C bonds have to be in the same plane (a.k.a. periplanar) Syn-elimination (from eclipsed conformer) front attack Anti-elimination (from staggered conformer) back attack, favored b/c it is the more stable conformer & allows for back-side attack so base doesn t feel the LG as much get more E than Z. E1 Mech: 2-step rxn 1) LG leaves to form carbocation (r.d.s.) 2) B removes from β-c (delocalization of e- b/c of hyperconjugation dec B.D.E. of attached to sp 3 C). 3 + - *WATC for 1,2-hydride shifts, 1,2-methyl shifts (carbocation rearrangements) to form more stable carbocation before deprotonation. Page 6 of 7
CEM 109A Rel Reactivity: Based on LG: RI > R > R > RF Based on R = rel stability of carbocations: 3 o benzylic ~ 3 o allylic > 2 o benzylic ~ 2 o allylic ~ 3 o > 1 o benzylic ~ 1 o allylic ~ 2 o > 1 o > vinyl Regioselectivity: Same as E2 Stereoselectivity: W/ carbocation intermediate, both anti and syn elim possible has bulkiest substituents opposite each other rel to the double bond. Cyclohexanes E2 and X must be axial (more stable conformer will NT go E2) E1 carbocation intermediate w/ possibility of rearrangement, usually follows Zaitsev s Rule. Substitution and Elimination Compete So look at rxn conditions Tbl 9.4, 9.5and 9.6 S N 1 vs. E1 S N 2 vs. E2 Rxn Conditions Poor Nuc/wk B Strong Nuc/strong B Alkyl alide 1 o N/A Favored W/ sterically hindered R or Nuc/B 2 o Both Both W/stronger B, bulkier B, higher T 3 o Both N/A nly Rel Reactivity 3 o > 2 o > 1 o 3 o > 2 o > 1 o 1 o > 2 o > 3 o 3 o > 2 o > 1 o Stereochemistry Both E & Z Both R & S (more w/ Both E & Z (more w/ bulky groups Inverted bulky opposite, unless β-c bound to 1 and only groups then only single stereoisomer formed) opposite) Page 7 of 7