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Nucleophilic Addition of Enol to Iminium Cation — Mannich Reaction —

Nucleophilic Addition of Enol to Iminium Cation — Mannich Reaction —. Mechanism. - H +. Mannich Reaction in Asymmetric Synthesis: Proline-promoted Robinson Annelation. L-proline recycled as cat. Opportunities. Mannich reaction in nature. Mannich reaction in natural product synthesis.

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Nucleophilic Addition of Enol to Iminium Cation — Mannich Reaction —

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  1. Nucleophilic Addition of Enol to Iminium Cation —Mannich Reaction— Mechanism - H+

  2. Mannich Reaction in Asymmetric Synthesis: Proline-promoted Robinson Annelation L-proline recycled as cat.

  3. Opportunities Mannich reaction in nature

  4. Mannich reaction in natural product synthesis L. E. Overman, 1983, 1987: (+)-Streptazolin charge accelerated cationic aza-Cope rearr. Mannich (a) 1. NaBH4, MeOH, 0℃,98%, 2. Ac2O, NEt3, DMAP, CH2Cl2, rt,95%; (b) BF3, CH2Cl2, rt,99%; (c) CH2O, camphorsulfonic acid

  5. Benzoin Condensation Mechanism Realization of Cross benzoin condensation

  6. Nucleophilic Reactivity toward a,b–Unsaturated Carbonyl Compounds A) reaction to C=O :electric charge control N– or O–nucleophile (hard nucleophiles ) B) reaction at b-carbon : orbital control (LUMO and nucleophile HOMO) stable carbanions, enamines, or thiolate (soft nucleophiles) Li+ coordination

  7. 1,2-addition 1,4-addition kinetic control : –78℃ 88% 8% not formed 84% Thermodynamic control : 25℃ 1) THF/–78 ℃ 2) H2O no additive >99% 0% added HMPA <2% >98%

  8. soft base hard base soft acid hard acid electronegativity Small large positive charge density low high polarizability large small atomic radius large small oxidation easy difficult n-electron yes no carbanion the larger p-orbital %, the softer (p-orbital: higher energy lebel; easy to oxidize) the higher the oxidation state, the harder it will be. exceptions : Hg (II) < Hg (I) ; Tl(II) < Tl (I) vertical series in P.T. the heavier, the softer the more carbocation character a center Attains during reaction, the harder it will be. horizontal series in P.T. the lighter, the softer

  9. [4 + 2]Cycloaddition Reactions: Diels-Alder reaction HOMO LUMO LUMO HOMO "favorable" "unfavorable"

  10. Lewis Acid Catalysis in Diels–Alder Reaction AlCl3 (1.0 equiv): t1/2 < 1 min without AlCl3: t1/2≒ 2400 h LUMO LUMO HOMO HOMO

  11. Regioselectivity of D—A Reaction "favourable” "x" = electron-donating "favourable”

  12. FMO of Olefins

  13. FMO of Dienes

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