Download Review Chapter 19

ReviewChapter19
Thischapterhighlightssolutionstosyntheticproblemswithnewreactions
ReductionofC=OtoCH2
Carbonylcompoundscanbeusedtobuild(viacarbonyl,aorbcabon)newcarbon-carbonbonds.Once
theframeworkisbuilt,theC=Omaynolongerbeneeded.
ThreereactionscanbeusedtoreplaceketoneoraldehydeC=Owith–CH2-.Thechoicedependsonthe
toleranceofotherfunctionalgroupsinthemolecule.
Wolff-Kishner
H 2NNH 2
DMSO, KOH
O
Clemmensen
Zn(Hg)
or
or
aq. HCl
O
Raney Nickel
1) HS
H
H
SH
2) H 2, Raney Ni
TheWolff-Kishnerisunderstronglybasic/nucleophilicconditionsandwouldnottoleratealkylhalides,
forexample.TheClemmensenisunderstronglyacidicconditionsandwouldnotworkwellwithalcohols
inthemolecule.TheRaney-Nickelreduction,althoughunderneutralconditionswouldhydrogenate
alkenesandalkynesaswell.
TodrawanWolff-Kishner,ClemmensenorRaney-Nickelproduct:
O
Simplyerasethe=O!
Practice:
a.
O
O
b.
H 2NNH 2
H
DMSO, KOH
O
Zn(Hg)
aq. HCl
O
c.
1)
HS
SH
O 2) H 2, Raney Ni
Protectionofalcohols
Alcoholsareacommonorganicfunctionalgroup.Theprevalenceofthisgroupisinnosmallpartdueto
its myriad of reaction pathways. Alcohols are weak acids, weak bases, nucleophiles and electrophiles.
Sometimesitisnecessarytocoveroverthisreactivitytoreactagroupelsewhereinthemolecule.
Simplyconvertingthealcoholstothefarlessreactiveethersmayseemareasonablesolution,butto
converttheetherbacktothealcoholrequiresstronglyacidicconditions.
Thetextreviewsfivemethodsfortheprotectionofalcoholsasethers.Inclasswehighlightedthetwo
mostuseful.Ineachcasethealcoholisconvertedtoanether,butthenatureofthegroupallowsahighly
effectiveandselectivereagentforremoval.
ProtectionwithMOM-Cl
Protection
OH
Reaction
O
1) NaH or NaNH 2
2)
O
O
Deprotection
O
O
Cl
+ formaldehyde
+ methanol
Protection
Reaction
OTBDMS
TBDMS-Cl
imidazole
TBDMS =
OH
dil. H 3O+
ProtectionwithTBDMS-Cl
OH
H 2O
Si
Deprotection
OTBDMS
Bu 4N +F -
OH
+ TBDMS-F
Practice:
a. ShowtheprotectionofthefollowingalcoholwithMOM,reacttheketonewithPhMgBr,anddeprotectandtoaffordfinalproduct:
HO
O
b. ShowtheprotectionofthefollowingalcoholwithTBDMS-Cl,reactthenitrilewithLiAlH4,anddeprotecttoaffordthefinalproduct:
HO
C N
CatalyticHydrogenation
Theconversionofp-bondstos-bondsisahighlyusefulsyntheticprocedurewhereH2isaddedacrossthe
p-bond.Althoughthisconversionisexothermic,acatalystisrequiredtodisruptthedi-hydrogenbond.
Byincreasinghydrogenpressure,reactiontemperatureandthecatalysttype,virtuallyallp-systemscan
bereduced.
reduction with 200 atm., 250C H 2 Pt
reduction with 160 atm., 135 C H 2 Pt
reduction with 75 atm., 80C H 2 Ni
reduction with 3 atm. H 2 Rh
reduction with 1 atm. H 2 Pt
reduces with H 2 Pd/Pt
O
or
O
O
H
C N
NH 2
Undertheconditionsspecifiedallgroupswithintheboxwouldbereduced.
Catalytichydrogenationisstereospecificandoccurssyn.Inthecaseofchaincompounds,thiswillnot
matter.Inthecaseofsubstitutedcycloalkanes,stereochemistrymustberepresentedproperly.
Alkynes under excess hydrogen and catalyst hydrogenate twice to give alkane. If a Lindlar catalyst is
used,hydrogenationisstoppedattheadditionofoneequivalentofH2;acis-alkeneresults.Ifatransalkene is desired, a non-catalytic addition of hydrogen can be used where the alkyne is treated with
Na0/NH3(l).
Todrawtheproductofcatalytichydrogenation
H
O
OH
H
O
H
H2
meso
Lindlar
OH
H
Na
NH 3
O
NH 2
NH 2
H
H
+ enantiomer
N
NH 2
Foralkenes,alkynes,carbonyls Forcycloalkenes,addH2inasyn
andnitrilessimplyerasepmannerinplaceofp-bond
bondsandreplacewith
hydrogens
For alkynes with Lindlar,
replace triple bond with cisdouble bond. With Na0/NH3
replacewithtrans-doublebond.
Practice:
a.
H2
Pt/C
b.
H2
Pt/C
c.
O
O
3 atm H 2
Rh
d.
CN
e.
75 atm H 2
Ni, 80 oC
O
H 2N
160 atm H 2
Pt, 135 oC
f.
H2
Pt, 25 oC
g.
H2
Pt, 25 oC
h.
H2
Lindlar
i.
Na
NH 3, -33 oC
OxidationofAlcoholstoCarbonylCompounds
Theoxidationofalcoholstocarbonylcompoundsisthereverseofnucleophilicaddition(below).Most
oxidantsacceptthealcoholoxygenasanucleophilefollowedbylossoftheacidichydrogen.Theprocess
iscompletedbyanE2-likeeliminationofhydrogenfromtheproto-carbonylcarboninconcertwith
formationoftheC=Op-bondandreductivelossoftheleavinggroup.
B
General
B H
Mechanism
H
H
H
O
H
O Ox
H
Ox
-H +
O
O
Ox
Ox
ChromicAcid
B
O
Cr O
O
H
O
H
H
O
O Cr O
H O
H+
xfer
H
OH
O Cr O
O
B H
O
OH
Cr O
O
ScopeandLimitations
1. Asahydrogenatomisneededfortheeliminationstep,3oalcoholsdonotoxidizetocarbonyl
compounds.
2. Normally1oalcoholsareconvertedtoaldehydesand2oalcoholstoketones.
3. However,inthepresenceofwater,aldehydesformhydratesthatundergomorerapidoxidation
thanthestarting1oalcohols.ThuswithCrO3/H2SO4,Na2CrO7,K2CrO7,H2CrO4,1oalcoholsare
convertedtocarboxylicacids.
B
R
H
O
H 2O
H
R
HO
O
H
O
Cr O
O
H
R
HO
O
O Cr O
H O
H+
xfer
B H
H
R
HO
OH
O Cr O
O
R
O
HO
OH
Cr O
O
4. Thisover-oxidationisavoidedwiththeuseofPCC.
5. Aldehydes treated with with CrO3/H2SO4, Na2CrO7, K2CrO7, H2CrO4 are converted to carboxylic
acids.
Practice:
a.
OH
CrO 3
H 2SO 4, H 2O
b.
Na 2Cr2O7
HO
H 2SO 4, H 2O
c.
OH
HO
H 2CrO4
H 2O
d.
OH
H 2CrO4
H 2O
e.
OH
PCC
CH2Cl2
f.
OH
H
Na 2Cr2O7
H 2SO 4, H 2O
O
g.
OH
H
O
PCC
CH2Cl2
KEY:
ReductionofC=OtoCH2
a.
O
O
H 2NNH 2
H
b.
O
DMSO, KOH
O
Zn(Hg)
aq. HCl
O
c.
1)
HS
SH
O 2) H 2, Raney Ni
Protectionofalcohols
a.
HO
O 1) NaH or NaNH 2
2)
O
Cl
MOMO
O
1) PhMgBr
2) H 3O+
MOMO
OH
H 2O
Ph
dil. H 3O+
HO
OH
Ph
b.
HO
C N
TBDMS-Cl
imidazole
TBDMSO
NH 2
1) LiAlH 4
C N 2) H 3O+
Bu 4N +F -
TBDMSO
HO
NH 2 CatalyticHydrogenation
a.
H2
Pt/C
b.
H2
Pt/C
c.
O
O
OH
3 atm H 2
Rh
O
d.
CN
e.
75 atm H 2
Ni, 80 oC
NH 2
O
H 2N
O
H 2N
160 atm H 2
Pt, 135
oC
f.
H
H
H2
Pt, 25 oC
g.
H
H2
Pt, 25 oC
H
h.
H2
Lindlar
i.
Na
NH 3, -33 oC
OxidationofAlcoholstoCarbonylCompounds
a.
OH
O
CrO 3
H 2SO 4, H 2O
b.
HO
Na 2Cr2O7
HO
H 2SO 4, H 2O
O
c.
OH
HO
O
H 2CrO4
H 2O
HO
d.
OH
O
H 2CrO4
H 2O
OH
e.
OH
O
PCC
CH2Cl2
H
f.
OH
H
Na 2Cr2O7
H 2SO 4, H 2O
O
O
HO
O
g.
OH
H
O
PCC
CH2Cl2
O
H
O