Download Synthetic Transformations of C=O Compounds Reaction Summary

ReactionSummary
SyntheticTransformationofCarbonylCompounds
Reduction
• Sodiumborohydrideinmethanol(NaBH4,CH3OH)
o Reducesketonesandaldehydestosecondaryandprimaryalcohols,respectively.
O
O
NaBH 4
H
•
OH OH
CH 3OH
Lithiumaluminumhydride(LAH):Conditions=1.LiAlH4,2.H3O+
o LAHisthestrongestofthereducingagentsthatwehavediscussed.
o Reducesketonesandaldehydestosecondaryandprimaryalcohols,respectively.
O
O
OH OH
1) LAH
H
2) H 3O+
o Reducescarboxylicacids,estersandacidchloridestoprimaryalcohols.
O
1) LAH
OH
H 3O+
2)
X
X = OH, OR, Cl, Br
o Reducesamidestoamines.
O
1) LAH
N
H
•
N
H
2) H 3O+
Diisobutylaluminumhydride(DIBAL-H):Conditions=1.DIBAL-H,2.H2O
o Reducesesterstoaldehydes.
O
O
1) DIBAL-H
2) H2O
O
H
o CarboxylicacidsandamidesareunreactivetoDIBAL-H.
o Willreducealdehydesandketonestoalcohols,butgenerallynotusedforthis
purpose.
Oxidation
• Tertiaryalcoholsandcarboxylicacidscannotbefurtheroxidized.
• PCCOxidation
o Primaryalcoholswillbeoxidizedtoaldehydes
o Secondaryalcoholswillbeoxidizedtoketones
o PCCwillnotfurtheroxidizealdehydes
OH O
O
H
H
PCC
O
o Dess-MartinPeriodinaneisanalternativetoPCCthatdoesesspentiallythesame
thing(itisamildoxidizingagent)
HO
O
•
M2Cr2O7,H2SO4,H2O(M=NaorK)]“Activeagent=H2CrO4”andCrO3/H+(Jones)
o Primaryalcoholswillbeoxidizedtocarboxylicacids
o Secondaryalcoholswillbeoxidizedtoketones
o Aldehydeswillbeoxidizedtocarboxylicacids
OH O
O
H
O
OH
Na 2Cr2O7
H 2SO 4
H 2O
HO
O
OH
AdditionofOrganometallicReagentstoCarbonylCompounds
• Reactivity:R-Li>R-MgX>R2CuLi
• Organometallicreagentsactasnucleophilesandbases.Theyareincompatiblewithprotic
solventssuchasalcoholsandwaterbecauseafastacid/basereactionresults.
(i.e.R-Li+H-O-HàR-H+LiOH)
• OrganolithiumReagents(R-Li)
o Preparation:R-X+2LiàR-Li+LiX
o Reactwithaldehydesandketonestoprovide2oand3oalcohols,respectively.
O
O
1.
Li
2. H 3O+
H
OH
OH
H
o TwoequivalentsofR-Liwillreactwithanesteroracidchloridetoprovidea3°
alcohol.
O
Li
2. H 3O+
Z
Z = OR, Cl
•
OH
1.
GrignardReagents(R-MgX)
o Preparation:R-X+MgàR-MgX
o Reactwithaldehydesandketonestoprovide2oand3oalcohols,respectively.
O
O
OH
1.
MgBr
2. H 3O+
H
OH
H
o TwoequivalentsofR-MgXwillreactwithanesteroracidchloridetoprovidea3°
alcohol.
O
•
1.
MgBr
Z
Z = OR, Cl
2. H 3O+
O
1. Ph 2CuLi
OH
OrganocuprateReagents(GilmanReagents)
o Preparation:2R-Li+CuIàR2CuLi+LiI
o Reactswithacidchloridestogiveketones
Cl
2. H 2O
O
Ph •
OrganocuprateReagents(continued)
o Doesnotreactwithcarboxylicacids,esters,amides,aldehydes,orketones(with
theexceptionofα,β-unsaturatedaldehydesandketones).
O
1. Ph 2CuLi
No Reaction
2. H 2O
Z
Z = CH 3, H, OH, OR, NR 2
o Reactswithα,β-unsaturatedaldehydesandketonestogiveβ-substitutedcarbonyl
compounds.Thisprocessiscalled1,4-additionorconjugateaddition.
O
R
α
O
1. Ph 2CuLi
β
2. H 2O
γ
Ph
R
β
1,4-addition only
o OrganolithiumandGrignardreagentsgenerallydonotreactvia1,4-addition
unlessthecarbonylcarbonisespeciallyhindered.
O
1. PhMgBr
or PhLi
2. H 2O
β
α
γ
HO Ph
1,2-addition only ProtectingGroups
• Usedto“protect”analcoholfromreactingwithastrongnucleophilesuchasahydride
reagent,Grignardreagent,ororganolithiumspecies.
• Themostcommonprotectinggroupisanorganosiliconespecies.
• Threesteps:
o A.Protectthealcohol(reactionofalcoholwithR3SiCl).
o B.Performdesiredreaction
o C.Deprotectthealcohol(removetheSigroupbyreactionwithF-).
HO
O
1) LAH
OCH3
A
(H3C)3Si
O
H 3C
HO
2) H3O+
OH
Desired Product
*Note produced because the OH in the
starting material is incompatible with LAH
CH3
Si
H 3C
Cl
Pyridine
C
B
O
1) LAH
OCH3
2) H3O+
(H3C)3Si
TBAF (F- source)
H 2O
O
OH