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Functional Group Conversion : nucleophilic

Functional Group Conversion : nucleophilic. Ref. "Comprehensive Organic Transformations" by Lorock, 1999. 1) Alcohol Activation. a. Sulfonation. + Pry.H Cl. pyridine. Generates non-nucleophilic byproducts. via. b. Halides. ** Through activation of alcohols **. i) from sulfonate.

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Functional Group Conversion : nucleophilic

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  1. Functional Group Conversion : nucleophilic Ref. "Comprehensive Organic Transformations" by Lorock, 1999 1) Alcohol Activation a. Sulfonation + Pry.HCl pyridine Generates non-nucleophilic byproducts via

  2. b. Halides

  3. ** Through activation of alcohols ** i)from sulfonate Acetone DMF DMSO NMP Alcohol LiBr NaI LiCl ii)from other halides ---- FinkelsteinReaction excess Equilibrium control ppt formation helps ! NaCl addition of water needed

  4. iii) Through activating agents 1. ROH + PPh3 + Br2 RBr • ROH+ PPh3+ CCl4RCl or

  5. 3. MitsunobuReaction : Synthesis, 1 (’81) ROH+ PPh3+ DEAD + Nu-RNu + Activates PPh3 POPh3 + EtOOCNHNHCOOEt

  6. 3. MitsunobuReaction : inversion of stereochemistry 4. Others

  7. 2) reactions of activated alcohols a. one carbon homologation NaCN DMSO, 100oC LiCN THF b. Nitrogen nucleophiles Possible impurities Gabriel synthesis

  8. NaN3 DMF NaN3 THF w/ R4PBr Phase transfer catalyst CH2Cl2 ROH+ PPh3+ DEAD + DPPARN3

  9. c. sulfur nucleophile : cf. Selenium, Phosphorous Reactivity of the Electrophiles benzyl > allyl > methyl > primary > secondary sulphonates > iodidie > bromide > chloride Phase transfer catalyst can enhance the reactivity when any of the reagents are not quite soluble

  10. 3) Nucleophilcreactions of ethers & esters -- deprotectionmethods BF3 BBr3 MgBr2 TMS-I R’’SH

  11. 4) Esters & Amide formation a. Classics RCOOH+ R'OHacid RCOOR' b. through activation of alcohols -- Mitsunobu reaction ROH+ PPh3+ DEAD + R'COO-ROOCR' -- Imidate intermediate TL, 39, 1557(1998) cf.

  12. c. unusual way RCOOH+ CH2N2RCOOCH3 or TMSCHN2 d. activation of caboxylicacids * acid halides : RCOOH+ SOCl2RCOCl + (COCl)2+DMF(cat.) RCOOH+ PPh3+ BrCCl3RCOBr RCOOH+ CDIRCO-Im Reaction: RCOCl+ R'OH+ DMAP(cat.) RCOOR' RCOCl+ R'NH2RCONHR'

  13. d. activation of caboxylicacids • in situ activation to esters & amides • DCCcoupling RCOOH+ DCC+ R'OH+ DMAPRCOOR' RCOOH+ DCC+ R'NH2 (+ HOBT) RCONHR' to ester prevent ketene formation racemization to amide EDC Water soluble DCC

  14. d. activation of caboxylicacids Alternatives to DCC DPC (Kim’s reagent) BOP-Cl

  15. e. From ester to amide RCOOR' + R2Al-NHR'' RCONHR'' Pyrophoric!! Homework Chapter 3 : 1, 3, 5, 6, 13, 17 Due :

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