Chem 634. Pericyclic Reactions. Reading: CS-B Chapter 6 Grossman Chapter 4

Transcription

1 Chem 634 Pericyclic eactions eading: CS-B Chapter 6 Grossman Chapter 4

2 Pericyclic eactions Definition: Continuous, concerted reorganization of electrons cyclic transition state no intermediate, single transition state Bond breaking & bond making occur at the same time. Can be synchronous (equal extent of breaking & making in TS) or asynchronous (unequal extent of breaking & making in TS). Fukui & offmann: Nobel Prize in Chemistry, 1981, for their theories, developed independently, concerning the course of chemical reactions (Woodward dies in 1979)

3 5 Types 1. Electrocyclic 2. Cycloadditions 3. Sigmatropic 4. Chelatropic 5. Group Transfer

4 3 Theories All 3 theories are correct! 1. Woodward offmann: Conservation of rbital Symmetry 1 st historically Uses correlation diagrams 2. Fukui: Frontier Molecular rbital Theory Easier than Woodward offmann (usually) Based on M/LUM interactions 3. Dewar Zimmerman: Aromatic Transition State Easiest to apply for all reaction types, but not intuitive to understand why it s valid

5 3 Things Matter 1. Number of electrons involved 2. Stereospecificity 3. Conditions: heat (Δ) vs. light (hυ)

6 Type 1: Electrocyclic eactions - ing openings and closures - Exchange π-bond for σ-bond - Classified by number of electrons favored by release of ring strain π-bond (~75 kcal/mol) > σ-bond (~88 kca/mol)

7 Diastereoselectivity bservations Case 1: Case 3: Δ 4e- (±) Δ 6e- Case 2: hυ 4e- Case 4: hυ 6e- (±)

8 General Phenomenon Woodward offmann ules Number of electrons Thermal Photochemical 4n Con Dis 4n+2 Dis con (n = integer) 6 points for a touchdown > 6e-, thermal, disrotatory... But why???

9 Theory #1: Woodward offmann Correlation Diagrams Angew. Chem. Int. Ed. 1969, 8, 781. Consider all molecular orbitals (M s) involved Consider symmetry of M s in starting material, product, and transition state. rbitals of different symmetry can cross (orthogonal orbitals). rbitals of same symmetry cannot cross (extreme energetic cost). We are about orbitals where electrons end up.

10 Example of W Correlation Diagrams disrotatory TS conrotatory TS

11 Example of W Correlation Diagrams: Thermal Conditions σ-plane of symmetry C 2 axis of symmetry disrotatory TS conrotatory TS σ SM σ P σ A A Ψ 4 π A S Ψ 3 π S A Ψ 2 σ S S Ψ 1

12 Example of W Correlation Diagrams: Photochemical Conditions σ-plane of symmetry C 2 axis of symmetry disrotatory TS conrotatory TS σ SM σ P C 2-SM C 2-P σ A A A S Ψ 4 π A S S A Ψ 3 π S A A S Ψ 2 σ S S S A Ψ 1 con pathway disfavored

13 W Conservation of rbital Symmetry Shortcut σ-plane of symmetry C 2 axis of symmetry disrotatory TS conrotatory TS Ψ 2 (M)

14 Cycloadditions & Cycloreversions - Union of 2 π-systems - Exchange π-bonds for σ-bonds - Classified by [m+n], m & n = # of conjugated atoms in each π-system [4+2] 4 atoms 2 atoms Diels Alder eaction! Note: 6 e- Great way to make cyclohexenes & cyclohexanes

15 Fukui: Frontier Molecular rbital (FM) Theory The idea: Use FM s (M + LUM) LUM In this case, it doesn t matter M/LUM gaps are the same. LUM E M M nonbonding level Which M & LUM? E E A E B ΔE diene dienophile ΔE orbital overlap E A E B geometrical/spatial overlap If closer in energy, then more stability by forming a covalent bond.

16 Types of Diels Alder eactions Normal electron demand = M of diene + LUM of dienophile Inverse electron demand = M of dienophile + LUM of diene

17 Net Bonding Interaction? The idea: Use FM s (M + LUM) LUM LUM E nonbonding level M M diene dienophile

18 Diastereoselectivity: Endo vs. Exo + [4+2] minor exo + major endo (favored)

19 Why? Secondary rbital Interactions M LUM

20 egioselectivity & ates: Substituent Effects ates depend on M/LUM gap. Perturba4on M LUM extra conjuga7on! " electron- withdrawing group " " electron- dona7ng group!! Effects apply to both dienes & dienophiles. Effect of substitution is biggest if on C1 of diene. 1 bigger effect

21 Examples + rt, 24 h 100% C 12,600 psi 17 h 78%

22 egioselectivity elated to polarization of M and/or LUM + vs. major minor Quick prediction: imaginary intermediate (push arrows to get maximum effect of substituents) more stable C 2 but remember these reactions are concerted!!!

23 Lewis Acid Effects ne of the first Lewis acid-accelerated organic transformations! + C 2 Cl 2 25 C additive none AlCl 3 (1 equiv) t 1/ h < 1 min Ph + Ph Ph + 1,4 1,3 additive none AlCl 3 1,4 : 1,3 80 : : 3 + C 2 endo + exo C 2 additive none AlCl 3 Et 2 (1 equiv) Lewis acid increases rate, endo/exo selectivity & regioselectivity! endo:exo 82 : : 1 Yates, Eaton. JACS 1960, 82, 4436

24 Why??? M perturbation! AlCl 3 AlCl 3 more reactive, more like Explains rates, but what about selectivity issues??? ouk JACS 1973, 95, 4094

25 Why??? Bigger difference in lobe size on C1 vs. C2 = better regioselectivity Lower LUM = faster rate Bigger lobe on C= carbon = bigger 2 orbital interactions = better endo/exo selectivity ouk JACS 1973, 95, 4094

26 ne More Consideration: S-cis vs. S-trans S-cis reactive vs. S-trans not reactive! + k rel

27 [2+2] Cycloadditions FM Analysis: No net bonding forbidden This geometry is suprafacial on both π bonds => [2π s + 2π s ] Suprafacial = same face of π-system Antarafacial = opposite faces of π-system

28 Alternative Transition State Geometry Problem: Steric indrance! Solution: emove steric hindrance!

29 Sigmatropic eactions eorganization of σ and π bonds (migration of a σ-bond) Number of σ and π bonds remains constant Classify by [m,n]-rearrangement or [m,n]-shift (m, n = number of atoms in fragment)

30 [1,3]-Sigmatropic earrangement Does this rearrangement proceed under thermal conditions? Supra- or antara-facial?? For FM, break into M and LUM:

31 [1,3]-Sigmatropic earrangements Alkyl Shift? FM:

32 [3,3]-Sigmatropic earrangements Suprafacial on both components! ighly predictable TS > chair-like (can predict stereochem)

33 Claisen earrangement

34 xy-cope

35 Theory #3: Dewar Zimmerman: Aromatic Transition State Steps: 1. Choose basis set of 2p A s (or 1s for atoms) 2. Assign phases (any phases) 3. Connect orbitals that interact in the starting material 4. Connect lobes that begin to interact in the reaction 5. Count the number of phase inversions 6. Identify topology 1. dd # of phase inversions = Möbius 2. Even # of phase inversions = ückel 7. Assign Transition State as aromatic (thermally allowed) or antiaromatic (photochemically allowed) System/Topology Aroma4c An4aroma4c uckel (4n+2) e- (4n) e- Mobius (4n) e- (4n+2) e-

36 Example of D Z Theory