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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 Ref. "Comprehensive Organic Transformations" by Lorock, 1999 1) Alcohol Activation a. Sulfonation + Pry.HCl pyridine Generates non-nucleophilic byproducts via
** 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
iii) Through activating agents 1. ROH + PPh3 + Br2 RBr • ROH+ PPh3+ CCl4RCl or
3. MitsunobuReaction : Synthesis, 1 (’81) ROH+ PPh3+ DEAD + Nu-RNu + Activates PPh3 POPh3 + EtOOCNHNHCOOEt
3. MitsunobuReaction : inversion of stereochemistry 4. Others
2) reactions of activated alcohols a. one carbon homologation NaCN DMSO, 100oC LiCN THF b. Nitrogen nucleophiles Possible impurities Gabriel synthesis
NaN3 DMF NaN3 THF w/ R4PBr Phase transfer catalyst CH2Cl2 ROH+ PPh3+ DEAD + DPPARN3
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
3) Nucleophilcreactions of ethers & esters -- deprotectionmethods BF3 BBr3 MgBr2 TMS-I R’’SH
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.
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'
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
d. activation of caboxylicacids Alternatives to DCC DPC (Kim’s reagent) BOP-Cl
e. From ester to amide RCOOR' + R2Al-NHR'' RCONHR'' Pyrophoric!! Homework Chapter 3 : 1, 3, 5, 6, 13, 17 Due :