Lecture 9: Addition to σ*

Transcription

1 hemistry 201: rganic eaction chanisms Lecture 9: Addition to σ* B fast A not so fast σ* π* δ - δ δ - E M p Addition to σ* orbital leads to bond cleavage ydrogen atoms are always attached to something. ead: Fleming &S 4.1.2, 4.2.1, 4.2.2

2 Proton Transfer - Geometry 3-Step Eigen mechanism: Step 1 = hydrogen bond N N bond vibration s -1 N - N Eigen, M. in Fast eactions and Primary Processes in hemical Kinetics Nobel Symposium 1967, 5, 245. Arrow-pushers: draw proton transfers as one step. (You can t push arrows with -bonds.) N Linear proton transfers are favored. Transfer protons in 2 steps in tetrahedral intermediates. slow - B fast B fast B - Evidence for linear T.S. (versus bent T.S.) 1. -bonds are close to linear in most crystal structures 2. Largest kinetic isotope effect when proton transfer is linear rystal Structs: N -bonds linear Isotope F: B A vs. B D A Taylor,.; Kennard,. ydrogen-bond geometry in organic crystals. Acc. hem. es. 1984, 17, 320. slows most when T.S. = linear

3 Proton Transfer - Kinetics Look at this data k 1 pk a A A - 2 k -1 rooks, J. E. Proton Transfer to and From Atoms ther Than arbon. omprehensive hemical Kinetics 1977, 8, A F S 2 2 Et N 4 3 N 2 pk a k 1 (M -1 s -1 ) k -1 (M -1 s -1 ) x ~ x10 2 Proton transfers to and from heteroatoms are usually fast An exception in DMS: itchie,. D.; Lu, S. J. Am. hem. Soc. 1989, 111, For N,, S: Acids protonate bases at diffusion-controlled rate if pk a > 3 Ac N - N 3 pk a ' = 5 pk a = -1.7 pk a ' = 9.3 pk a = 9.8 diffusion controlled M -1 s -1.not 10 7 M -1 s -1 This is one of the few cases that where you can predict rate constants. Proton transfers to and from carbon are usually slow pk a ~ 9 2 N Et 10 9 slower!

4 Proton Transfer - Equilibrium You can estimate K eq from pk a s. pk a s are readily available because it is easy to perform titrations. From chemical equations. A 2 A - 3 K a ' = [A - ] [ 3 ] [A] [ 2 ] From math. B B 3 2 K a = [B] [ 3 ] [B ] [ 2 ] K eq = K a' K a A B A - B K eq = [A] [B] [A - ] [B ] (Equilibria and kinetics of proton transfers) Fersht, A. Enzyme Structure and chanism. 2 nd Ed. W.. Freeman, Pp Acid-base equilibria usually precede important rate determining steps. Always try to estimate ratios of relative concentrations of rxn intermediates TP Ar PPTS K eq = 10 (-4 5) = 10-9 Py Py pk a 5 pk a - 4 one out of every billion TP groups is protonated. In organic solvents, the equation is approximate since we rarely know pk a s, but don t be afraid to approximate.

5 S N 2 eactions - Trigonal Bipyramidal T.S. 3 I concerted 3 I- The transition state is trigonal bipyramidal Trigonal bipyramidal molecules: Electronegative substituents want to be axial Electropositive substituents want to be equatorial δ δ δ in the T.S. neg. charge is transferred from equatorial to S N 2 rates: 3 l > 2 l 2 > l 3 > l 4 S N 2 rates: Et- 2 2 l / Et- 2 2 l = 5:1 Lone pair inversion proceeds via tbp T.S. with similar trends sp 3 inversion barrier p F/6-31G* (kcal/mol) E - N s-sp 3 s-sp 2 Si - P S Bader,. F. W, et al. J. Am. hem. Soc. 1990, 112, eteroatom effect: carbanion inversion is slower when heteroatoms are attached - - subst. raises inversion barrier by about 10 kcal/mol ( E = 22.6 kcal/mol)

6 Substitution at Silicon and Phosphorus: Trigonal Bipyramidal Intermediates Substitution at Si and P always involves two steps; never S N 2 Ac Si Ac Si - Ac Si But siliconate and phosphorane intermediates resemble S N 2 transition states stable tbp intermeds. - Si P better worse F Si - - Si F F F ΔE 8.3 kcal/mol (b3lyp/6-31g*) The nucleophile prefers to attack opposite the most EN group The leaving group always leaves from an axial position - - P P - - P P P For an extensive discussion of phosphorus substitution chemistry. ermann Dugas Bioorganic hemistry: A hemical Approach to Enzyme Action 3rd ed Springer-Verlag: New York, 1995.

7 Steric Effects in S N 2 eactions α-anching slows S N 2 β-anching slows S N 2; most dramatic with neopentyl centers - k rel l - roomy! = neopentyl k rel Ts t-bu t-bu Ts k (S N 2 w/ PhS-) 3.61 x 10-4 M -1 s x 10-4 M -1 s -1 E2 no E2 3-mbered ring onium ions: S N 2 attack at 3 centers only L.G. impossible S N 2 at 3 =, gac, "S N 2" at 3?

8 I- Effects of onjugation on the S N 2 eaction Finkelstein reaction = NaI -l in refluxing acetone l l N l l k rel ompare S N 1 T.S. vs. S N 2 T.S. This is not a oulombic effect π not enough electrons empty p lowers TS energy too many electrons filled p π* = lowers TS energy sp 3 S N 1 2 e- S N 2 filled p empty p sp 3 2 e- aution with neutral nucleophiles: EtN 2 rxn with Ph 2 - is 10x faster than Ph 2 - oss, S. D.; Finkelstein, M.; Peterson,.. ates and salt effects in the reactions of phenacyl bromide with N-ethylaniline and triethylamine in chloroform. J. Am. hem. Soc. 1968, 90, 6411.

9 S N 2 eactions at sp 2 centers S N 2 reactions are only facile at sp 3 centers Nū : way faster Nū: than. Problem if T.S. = planar tetrasubstituted carbon. Planar 4 is 130 kcal/mol higher in energy than tetrahedral 4 Siebert, W.; Gunale, A. hem. Soc. ev. 1999, 28, 367. Some relative rates: L.G. rxn w/ NaI in acetone at 25 3 k (M -1 s -1 ) For - and S-, two-step addition-elimination is faster than S N 2 Kim,. K.; yun, K..; Kim,. K.; Lee, I. J. Am. hem. Soc. 2000, 122, Glukhovtsev, M. N.; Pross, A.; adom, L. J. Am. hem. Soc. 1994, 116, 5961.

10 S N 2' eactions are Uncommon oncerted S N 2' reactions can occur when sterics impedes the S N 2 mechanism S N 2' L.G. cleophile adds syn to the leaving group π* σ* S N 2' is over 1000x slower than S N 2 for allyl chloride Davico, G. E. rg. Lett. 1999, 1,. Be skeptical of most claims of S N 2 unless there is mechanistic evidence. l l harsh conditions neat piperidine 130, h N (Note that the group biases reactivity.) Gilbert Stork, William N. White "The stereochemistry of the S N 2' reaction" J. Am. hem. Soc. 1953, 75, D l neat 2 N rt, 168 h 26% N D syn addition only 99 : 1 D N 2 onald M. Magid,. Stanley Fruchey J. Am. hem. Soc. 1979, 101, 2107.

11 Fallacy of the Leaving Group Analysis Longer bonds are more "polarizable" = higher bonding orbital and lower antibonding orbital Sometimes referred to softness. σ E M σ F l I Longer bonds lead to lower σ*. That is why S N 2 reactions with I are faster than S N 2 reactions with -l Most sophomore texts using "leaving group ability" to explain relative rates of S N 2 reactions, but such effects are better explained as starting material instability. : I l : l I