Epoxidation of Alkenes - Chemistrychemistry.syr.edu/totah/che676/support/3b1/3-2.C=COx.pdf · Epoxidation of Alkenes Peracids: ! !! • most common reagents • reaction is stereospecific

Epoxidation of Alkenes

Peracids: ! ! !

• most common reagents

• reaction is stereospecific

R O

O

OHO

R OH

O+ +

CH2Cl2

CH3 OOH

O

CF3 OOH

OOOH

OCl

peraceticacid

pertrifluoroaceticacid

m-chloroperbenzoicacid (mCPBA)

increasing reactivity

RmCPBACH2Cl2 R

OR

mCPBACH2Cl2 R

O


• regio- & chemoselectivity

C CH

H

H

HC C

R

H

H

HC C

R

H

R

HC C

R

R

H

HC C

R

R

R

HC C

R

R

R

R< < <≤ <

krel 1 24 500 500 6500 even faster

OMeRO

< <

very slow

OMemCPBA(1 equiv)

OMeOO

mCPBA(1 equiv)

mCPBACHO CHO

O


• diastereoselectivity (cyclic systems)

R R R R R R

+mCPBA

HH

O H

OH

R = HR = CH3

99 : 1 < 10 : > 90

mCPBA

O

OTBSmCPBA OTBSO OTBSO

7 : 1


• diastereoselectivity (cyclic systems) directing effects

OTBSmCPBA OTBSO OTBSO

7 : 1

OHmCPBA OHO OHO

9 : 91

OAcmCPBA OAcO OAcO

43 : 57


Alkyl Hydroperoxides: ! ! !

• common catalysts

• chemoselectivity

OH OHOtBuOOHTM catalyst

R R

VO(acac)2, Mo(CO)6, Ti(OiPr)4

OH tBuOOHVO(acac)2

OH

O

OH

O

mCPBA


• mechanism

HOO V

OR

OROR

tBuOOHO V

OO

RO O tBuO V

O

RO

OO

O V

O

RO

OO

tBu

O VO

OOR tBu

tBu

O

slow

tBuOOHHO

HO O+ tBuOH


• diastereoselectivity

HOH

HOH

HOHO O

mCPBATBHP, V5+

4 : 3100 : 0

+

Me

MeOHHMe

MeOHHMe

MeOHH+

O O

mCPBATBHP, V5+

95 : 5 70 : 30


• diastereoselectivity

Me

H

OVHMeH

Me

MeH OHtBuOOH

(VO(acac)2

Me

MeH OH

Me

MeH OH+

O O

70 : 30

Me

Me

H OV

H

H

OV

MeHMeH

Me

H

H Me

OV

45° ≡≡


• diastereoselectivity – homoallylic alcohols

Ph

OH

OBPS

Ph

OH

OBPS

tBuOOHVO(acac)2

O

VO O OtBuPhMe

OBPS

LL


• Sharpless Asymmetric Epoxidation (SAE)

Empirical Rule:

R2 OH

R1

R3Ti(OiPr)4, (+)-DETtBuOOH, 3Å MSCH2Cl2, -20°C

R2 OH

R1

R3

O

EtO2CCO2Et

OH

OH(-)-DET

(+)-DET

EtO2CCO2Et

OH

OH



R2 OH

R1

R3Ti(OiPr)4, (+)-DETtBuOOH, 3Å MSCH2Cl2, -20°C

R2 OH

R1

R3

O


• Sharpless Asymmetric Epoxidation

OHSAE

(+)-DETSAE

(-)-DET OHOHO O

the following substrate types show excellent selectivity

(Z)-disubstituted olefins are less selective

OH OH

OH

OH OH

OHOH

OH

rxn not compatible with: Ar-OH, CO2H, most amines, phosphines



C8H17

OH

C8H17 OH

C8H17

OH

C8H17 OH

O

OSAE(+)-DET

SAE(+)-DET

78%; 94% ee

63%, 80% ee

OHO

OHOPh OHO

77%; 93% ee 95%; 91% ee 79%; 98% ee


Dimethyldioxirane (DMDO): ! ! !

• prep

• utility

OOK+ -O S OOH

O

O

O

oxone

+ + KSO4H

dimethyldioxirane

CF3

OO

trifluorodimethyldioxirane (TFDO)

O O

DMDOacetone

+

80 : 20

O O

DMDOacetone O O

O


Hydrogen Peroxide: ! ! !

• oxidation of electron deficient alkenes

• chemoselectivity

O

H2O2NaOH

O

O

H

OH2O2NaOH

H

O

O


Other Methods: ! ! !

• From Halohydrins

• From Diols

R OHOH TsCl (1 eq)

pyridine R OTsOH NaH

RO

• Darzon’s Condensation

O Cl OEt

O

KOtBuCO2Et

O

Br2H2O

NaH

OH

BrO

+ regioisomer


Sulfur Ylides (Corey-Chaykovsky Reaction): ! ! !

• dimethylsulfonium methylide

preparation

reactivity

irreversible addition to carbonyl

CH3SCH3

MeICH3

SCH3

MenBuLiI

CH3SCH2

Me

OS

Me

Me

O

CH3S CH3+

O SMe2



• dimethylsulfoxonium methylide

preparation

reactivity

reversible addition to carbonyl

CH3S CH3

MeICH3

S CH3

OnBuLiI

CH3S CH2

OO

Me Me

Me SO

Me

O O

CH3S CH3+

O



• mechanistic consquences

stereoselectivity

cyclopropanation of enones

tBu

O

tBu tBu+

Me2S=CH2Me2S(O)=CH2

87 : 13 0 : 100

OO

O OMe S

O

Me

SO MeMe

O


Further Digression: Simmons Smith Reaction ! ! !

• cyclopropanation

• selectivity

OTMS OTMS

Zn(Cu)CH2I2

HClMeOH

O

Zn(Cu)CH2I2

R RZn(Cu)CH2I2

OH

Zn(Cu)CH2I2

OH

-NR2, -CO2R also direct

Dihydroxylation of Alkenes

Osmium Tetraoxide (OsO4) ! ! !

• reactivity

• mechanism

OOs

O

OO

OOsO O

O

VIVII

OH

OH

OOs

O

O

N+NMe Me O-

VI

OsO4NMO

OH

OH

stoichiometric or catalytic in the presence of a reoxidant e.g. NMO; UpJohn Process)



• diastereoselectivity (cyclic systems)

OsO4NMO

OH

OH

MeH

E

Me

H

OsO4NMO

OH

OH

EOH

H

OH

OH



• diastereoselectivity (acyclic systems)

BnOBnO

OsO4NMO

BnOBnO

BnOBnO

+

OH

OHOH

OH

9 : 1

HBnO

BnO

L

M

OsO4

HBnO

BnOHO OH


Sharpless Asymmetric Dihydroxylation (SAD) ! !

Empirical Rule:

HRMRS

RL

AD-mix β

AD-mix α

Ph CO2Et AD-mix αtBuOH/H2O

AD-mix βtBuOH/H2O Ph CO2Et

OH

OHPh CO2Et

OH

OH 97% ee 95% ee


Sharpless Asymmetric Dihydroxylation ! !

alkaloid ligands:

• AD-mix: K3Fe(CN)6 K2OsO2(OH)6 K2CO3 alkaloid ligand

(DHQD)2-PHALligand for AD-mix β

(DHQ)2-PHALligand for AD-mix α

these substrates do not work well:

R1 R2 R2 R4

R1 R3


Epoxide Opening ! !

O

MeH

Me

H

MeH

Me

HO

Nu (axial attack)

OH

OH

mCPBA H3O+

or NaOH

Oxidative Cleavage of Alkenes

Ozonolysis ! ! ! • reactivity

O3;DMS or Zn/AcOH or PPh3

O3;H2O2

O3;NaBH4

OO

OH

CO2H CHO

OH

R R

O OO

OO

O

R R

OO

O

R RO

OO

R

R

OO

O

R

R

Criegeeintermediate ozonidemolozonide

products

mechanism:


Ozonolysis ! ! ! • reactivity differentiated products

O3;ROH, NaHCO3

O3;ROH, pTsOH

OOHCHO

OR

Ac2OEt3N O

CHO

OR

OOH

OR

OR

ORNaHCO3DMS

Ac2OEt3N O

OR

OR

OR

CHO

OR

OR

best used on symmetrical olefins


KMnO4 or RuO4, NaIO4 ! ! ! • reactivity

KMnO4 orRuO4, NaIO4

OH

OH CO2HCO2H

note:

OH OH

O

OH OH

O

R

OH

OH

R' R

O

O

R' R

OH

O

R' not R

OR"

O

R'


OsO4 / NaIO4 ! ! !

• reactivity

Johnson-Lemieux Procedure:

OsO4 (cat)NaIO4, tBuOH/H2O O

O

H H+

notHOO

R2NO

OO OH OH

OH

OH

CHOOsO4O

NaIO4

Allylic Oxidation

Selenium Dioxide (SeO2) ! ! !

• reactivity

OHSeO2

• regioselectivity SeO2

HO

HO+

SeO2HO

SeO2OH

then prefered order of reactivity is CH2 > CH3 > CH

Epoxidation of Alkenes - Chemistrychemistry.syr.edu/totah/che676/support/3b1/3-2.C=COx.pdf · Epoxidation of Alkenes Peracids: ! !! • most common reagents • reaction is stereospecific

Documents