Professor David L. Van Vranken Chemistry 201: Organic Reaction Mechanisms I Topic 5: Carbocations π* carbocation carbocation substituent + C pC+ .. n OH EMO π π H σ Reading: I. Fleming Molecular Orbitals and Organic Chemical Reactions, 2.1.3 and 2.2 Carey&Sundberg Advanced Organic Chemistry, 3.4.1 Addition to Empty p Orbitals (and vice versa) ■ If all else is equal, the fastest reactions should involve σ∗ addition of lone pairs to empty p orbitals, not σ* p EMO H H substitution H2N H H H .. .. σ∗ H N B B H N B H H Cl H H H Cl n not so good π∗ ■ Compare 2nd row atoms with empty p orbitals: EMO carbenium nitrenium oxenium fluorenium + .. p C+ H .. H .. H .. p .. H C N O .. F N+ p O+ .. H + H + + Nu p F+ ■ These cations aren’t equally reactive yet they all react at equal rates with water k ~109 M-1 s-1 (diffusion- controlled). ■ It is more insightful to look at the reverse reaction, ionization, because it should proceed through the same transition state. X X X X H X: H C C >> >> : >> : : + H H H : N H O.. H ..F H H Need to PUSH OUT L.G. (usually via R migration) ■ Don’t worry about simple nitrenium ions, oxenium ions, or fluorenium ions. They are too unstable to form in typical organic reactions. Characteristics of SN1 Reactions ■ Two steps via an unstable, planar carbocation + C OH Br X- Nu- LiBr X X- ∆G° Nu + AcOH Nu- configuration? Nu X- ■ Nu can attack either face of empty p orbital ■ First step is slower than 2nd ■ Nucleophile structure is usually NOT important for the overall rate ■ Added X- should slow rate = Common Ion Effect ■ Charged leaving groups - CF3SO3- O2NC6H4CO2 TfO- >> TsO- ≈ MsO- >> I- > Br- > Cl- > PNBO- 104 103 106 ■ Neutral leaving groups + + H Ph P O O OH+ O O+ 3 O SiMe3 SN1 Substrate Reactivity ■ The Hammond postulate Cl δ- - "LATE" + δ HOR "EARLY" • Highly endothermic δ + T.S. MeOCH2 δ T.S. reactions involve late, MeOCH2 product-like transition states + + MeOCH2 Cl- MeOCH HOR ∆G 2 .. • Highly exothermic reactions Cl involve early, starting MeOCH2 Nu–R material-like transition states Cl ■ How to use the Hammond postulate: Cl is fast b/c & carbocation MeO stabilizes + H resembles MeO.. H MeO the carbocation the T.S. MeO (Hammond) Cl ■ The same arguments for Cl is fast b/c similar to MeO donates + p/ * donation into p carbocation stabilization can also σC-Cl H MeO into σ* in S.M. MeO.. in the product MeO .. σ* .. H be applied to T.S. and S.M. C-Cl and T.S. pC+ OH + O O OH + ■ Best substrates for SN1 = good donors next door: 2 + + 2 R2N.. RO.. OH OH or benzyl ■ Since SN1 reactions involve formation of unstable carbocations, we should be able to predict SN1 rates based on carbocation stability. The Best Carbocations are Trigonal Planar ■ Carbocations want to be planar because lower energy orbitals don't want to be empty. 2p most stable sp3 C sp2 C EMO sp C super unstable! 2s ■ Don’t generate sp2 carbocations through SN1 ionization Br + H. Mayr, et al. J. Org. Chem. 1981, 46, 5336. ■ You CAN generate sp2 carbocations by adding electrophiles to alkynes + 30 equiv. Bn NaN3 Bn L.E. Overman, et al. JACS 1988, 110, 612. N +N Nu .. aq. MeOH 75 °C, 3 h (note: Nu is involved in T.S.) Trigonal Planar Carbocations ■ Pyramidalization slows SN1 Br unstable Br Br pyramidal can't cation planarize + + krel 1 0.001 0.0000000001 Carbocation Stability: Donor Effects R OH carbocation reactivity: > > π* harder to add to a + + + H H H H H H carbocation carbocation when carbocation it has a strong substituent donor attached + C ■ Substituents perturb stability and reactivity. pC+ .. n Perturbation theory allows us to predict these OH EMO effects. We can use MO interaction diagrams π π to think about the impact of subsituents in the H same way that we use MO diagrams to σ analyze. + + .. ■ The best resonance structure satisfies octet rule. C NH2 C NH2 The second-best resonance structure predicts reactivity. attack here ■ Compare l.p. donors on carbenium (carbocation) reactivity .. .. .. NH OH F H stability 2 > > > A. M. El-Nehas JOC 1995, 8023 H + H H + H H + H H + H See C&S A Table 5.6 and Table 1.13 Stab. Energy (PM3) 80 51 6 0 kcal/mol ■ Acylium ions are about as stable as t-butyl carbocations; both C and O have filled octets. .. .. .. O O + C + C about as stable as t-Bu Carbocation Stability: Pi Donor Groups ■ Compare: donor energy O NH π C CH O 2 Br < < not good stability: EMO π C NH H + H H + H H + H π C O ■ Note the discrepancy between allyl and benzyl cation stability depending on solvation ■ Benzyl cation is more stable than unsubstituted allyl cation. O O- Ph H N > > > > + H + H H + H H + H H + H H + H Stabilization Energy (PM3/H2O) 23 27 18 0 -28 kcal/mol Stabilization Energy (PM3 gas) 56 43 34 0 -31 ■ Solvation stabilizes carbocations, but solvation of large, delocalized ions isn't always effective ■ In the gas phase, ions with larger alkyl groups are more stable. Carbocation Stability: Sigma Donor Groups CH2 CH3 HC H > > stability: C C C H3C + CH3 H + H H + H ■ Why is the t-butyl carbocation stable? ■ Vicinal bonds stabilize carbocations by donation into the empty p orbital donation weak X 3 + H H H3C H3C C C CH2 H3C + H3C ■ Question: Donation by bond or l.p.? Answer: Lone pairs. .. .. .. .. .. NR NR NR NR OR 2 + 2 2 2 + X -X: X X X YES NO NO ■ Vicinal -OR bond doesn’t stabilize carbocations E .. OR σC-C predicted OR 〉〉 〉 SN1 rates Cl Cl Cl σC-O Winstein, S.; Lindergen, C. R.; Ingraham, L. L. J. Am. Chem. Soc. 1953, 75, 155..