1. Stereoelectronic requirement for Ei-type Elimination: abstraction of  H–atom by leaving group "Cope–elimination" "Chugaev Elimination" “near coplanarity" “near coplanarity"

2. Regioselective Cope-Elimination "Sulfoxide (Selenoxide)–elimination" “Enone Synthesis" “near coplanarity"

3. opportunity Synthesis of  -methylene-  -lactone trans cis

4. “Peterson Olefination"

5. “Nozaki-Yamamoto Elimination for Regio- and Stereo-defined Allylic Alcohol Synthesis from Epoxides" acis-base hybrid reagent (A-B reagent)

6. Stereoelectronic Requirements: SUMMARY sp 3, sp 2, and sp Reaction Centers Attacked by X – Stereoelectronic Requirements: SUMMARY sp 3, sp 2, and sp Reaction Centers Attacked by X –  sp 3 sp 3 sp 2 sp 2    sp sp   Epoxides and related Epoxides and related endo exo X should be second periodical elements

7. Stereoelectronic Control in Nature: Polyene–Epoxide Cyclization squalene squalene epoxide lanosterol cholesterol H+H+

8. Biomimetic Polyene–Alcohol Cyclization: Strategy for Stereoselective Steroid Synthesis: W. S. Johnson H+H+ HOH progesterone Ozone KOH Biomimetic Synthesis: learning from nature

9. Baldwin Rule exo-cyclization endo-cyclization The First Rule:a) 3~7-Exo–Tet Cyclization : favored b) 5~6-Endo–Tet Cyclization : disfavored (a)(b) "3–Exo–Tet" "5–Endo–Tet"

10. The Second Rule: a) 3~7-Exo–Trig Cyclization : favored b) 3~5-Endo–Trig Cyclization : disfavored 6~7-Endo–Trig Cyclization : favored (a) (b)

11. The Third Rule:a) 3~4–Exo–Dig Cyclization : disfavored 5~7–Exo–Dig Cyclization : favored b) 3~7–Endo–Dig Cyclization : favored (a) (b)

12. The Fourth Rule: (Enol...)-Exo-Tet (a) 3~7–(Enolexo)–Exo–Tet: favored (b) 3~5–(Enolendo)–Exo–Tet: disfavored (c) 6~7–(Enolendo)–Exo–Tet: favored (Enolexo)–Exo–Tet The Fifth Rule: (Enol...)-Exo-Trig (a) 3~7–(Enolexo)–Exo–Trig: favored (b) 3~5–(Enolendo)–Exo–Trig: disfavored (c) 6~7–(Enolendo )–Exo–Trig: favored (Enolendo)–Exo–Trig 1(a) 5–Exo–Tet: favored4(b) 5–(Enolendo)–Exo–Tet: disfavored enolate O-alkylation (S N 2)C-alkylation (S N 2)addition

13. 5–(Enolexo)–Exo–Tet 7–(Enolendo)–Exo–Tet The Fourth Rule (a): favored The Fourth Rule (a): favored The Fourth Rule (c): favored The Fourth Rule (c): favored

14. 6–(Enolendo)–Exo–Tet 6–Exo–Tet much faster > The Fourth Rule (c): favored The Fourth Rule (c): favored The First Rule (a): favored The First Rule (a): favored not produced

15. Aryne or Benzyne (Dehydrobenzene) Aryne or Benzyne (Dehydrobenzene) Isolated Carbon-Carbon Multiple Bonds: # very low reactivity toward n-base (very low electrophilicity) # very low nucleophilicity of n-base toward carbon-carbon multiple bonds except for arynes H+H+

16. Evidence in support of non-S N Ar mechanism cine substitution S N Ar Mechamism

17. Preparation of Arynes: Break Through B – slow elimi. fast B – slow excess B - drawback Break Through: K. Suzuki, 1991 BuLi v. fast elimi. fast + 90% [4 + 2] cycloaddition halogen/metal exchange: very fast

18. n-BuLi THF, –78 ℃ <10 min electron withdrawing inductive effect R = Me: 76% R=Bn: 82% K. Suzuki, JACS,1992: Total Synthesis of (+)-Gilvocarcin M Tf 2 O/DIPEA CH 2 Cl 2 99%

19. (+)-Gilvocarcin M