Epoxide bond formation and cleavage

1

Epoxide Bond Formation and Cleavage

Presented By

Gurudutt DubeyM. Tech. (Pharm.) I Semester

Department of Pharmaceutical Technology (Process Chemistry)National Institute of Pharmaceutical Education and Research, Mohali, Punjab (India)

2

Epoxide Bond Formation

3KATSUKI-SHARPLESS ASYMMETRIC EPOXIDATION

R'

R"R"'

OH

R"

R"'R'

OH

O

R"

R"'R'

OH

O

O

O

Ti(OPri)4

TBHP

(S,S)-(-)-Diethyl tartrate

(R.R)-(+)-Diethyl tartrate

J. Am. Chem. Soc. 1980, 102, 5914

4 OH

TBHP

M(OR)n 2ROH

O

(RO)n-2MO

OBut

O

(RO)n-2MO

OBut

O

(RO)n-2MO

OBut

O

(RO)n-2M

OOBut

O

(RO)n-2M

OBut

O

OH

TBHP

O

OH

tBuOH

1

2 3

45

a

bb

a

Mechanism:

M= Ti R= i-Pr

5

Clayden, J. Warren, S. Greeves, N. Wothers, P. Organic Chemistry, 2001, 1242

Formation of Active Complex

6


Stereoselectivity:

7

J. Am. Chem. Soc. 1962, 84, 867−868

COREY-CHAYKOVSKY REACTION

Mechanism :

8 Preparation of Corey-Chaykovsky Reagent

Dimethyloxosulfonium methylide - known as the Corey Chaykovsky Reagent

s I

B

- BH

HHH

s

H H

s

9

RR'

aq. NaOClMn-salen catalyst

CH2Cl2R

R'

OHH

R = Ar, alkenyl, alkyl< alkynylR' = Bulky Alkyl group

JACOBSEN-KATSUKI EPOXIDATION

O

N

O

NM

HH

X

Salen complex:

(1R, 2R)(t-Bu)2SalenMX

J. Am. Chem. Soc. 1991, 113, 7063-7064

10 PRILEZHAEV REACTIONR

R'R

R'

OHH

R"CO3H

Org. Lett. 2003, 5, 3787-3790

Mechanism :

11

Epoxide Bond cleavage

12


Epoxide ring opening by azide

13

O

RNaN3

[bmim]PF6/H2O(2:1)

65 oC RN3 R

OHOH N3

ONaN3

[bmim]PF6/H2O(2:1)

65 oCn n

OH

N3

n= 1, 2, 4 n= 1, 2, 4

N N PF6n

n= 1= [bmim]PF6 n = 3 = [hmim]PF6 n= 5 = [octim]PF6

Ionic liquids/H2O systems for the reaction of epoxides with NaN3 :a new protocol for the synthesis of 2-azidoalcohols

Tetrahedron Lett. 2005, 46, 6559-6562

14Regioselective Ring Opening of Epoxides Using NaN3

MeO

COOEt

MeO

COOEt

OH

OHMeO

COOEt

OH

OTs

(DHQD)2PHAL, OsO4

t-BuOH/H2O(1:1)0oC, 16h

94%

TsCl, Et3N

CH2Cl2, 5oC, 72h

95%

95% MeO

COOEt

MeO

COOEt

N3

OH

NaN3, 4 oA molecular sieves

CH3CN, rt, 1.6h

95%

(i) PhCOCl, pyridine, CH2Cl2

(ii) PPh3, THF/H2O, 50oC(iii) NaBH4, MeOH, 0oC

67%

O

K2CO3

MeOH, rt, 12h

MeO

HN

O

O

OH

CytoxazoneTetrahedron Lett. 2004, 45, 7355–7358

15Polyepoxide-Opening Cascades Promoted by

Water

Science. 2007, 317, 1189

O

O

O

OHOH

MeHH

HOH

O

O

H

H H H

H2O

70 oC, 24 h

3:1 dr

57%O

H

H

MeO

O

OO

OO

O

O

O

O

O O

O

Me

CHO

H Me H H Me Me HH

H

Me

MeH H H

H H H H

H

H

H

HO

Brevetoxin B

16

O

O

O

O

OMe

H H

HH

HH

O

Me H H

H

OHH O

H

H2O

HO

H

O

H H

O

O

O

O

OMe

H H

HH

HH

O

Me H H

H

OHH O

H

H2O

HO

H

O

H H

OMe

O

H

HOH

OMe

HO

H

OH

OHOH

OH

H

H

Me

H

H2O

H2O

H2O

H2O

-H2O

-H2O

-H2O

-H2O

THF

THF

THF

THF

THF

THF

Minor Major

Mechanism:

17

O

R1

R2

OHR1

R2 NHAr(R)

H2NAr(R)Zn(ClO4)2.6H2O (2 mol%)

neat, rt or 80 oC10 min to 1h

88-100%

Epoxide Ring Opening Catalyzed by Zinc(II) Perchlorate Hexahydrate

O

R2

R1

R4

R3

O

R2

R1

R4

R3

O

R2R1

R4

R3

HO

R2

R1 R4

R3

M(ClO4)x

M(ClO4)x

NH2Ar(R)

NHAr(R)

M(ClO4)x

NH2Ar(R)

O

R2

R1 R4

R3

M(ClO4)xH

NHAr(R)

I

IIIII

Mechanism:

J. Org. Chem. 2007, 72, 10, 3719

18Synthesis of (RS)/(R)-Propranolols and (RS)/(R)/(S)-

Naftopidils

OH O

O

O

O

N

N

NH

OH

H

OH

OCH3

Zn(ClO4)2.6H2O (2 mol%)

Zn(ClO4)2.6H2O (2 mol%)neat, 80 oC, 10 min, 85%

iPrNH2, neat, rt, 1h, 72%MeCN, ref lux, 16 h80%

O

Cl

1-(2-methoxyphenyl)piperazine (RS)-Propranolol

(RS)-Naftopidil

HK2CO3

HN

N

OCH3

1-(2-methoxyphenyl)piperazine

J. Org. Chem. 2007, 72, 10, 3719

19Asymmetric Catalysis with CO2: Direct Synthesis of

Optically ActivePropylene Carbonate from Racemic Epoxides

J. Am. Chem. Soc. 2004, 126, 3733

OMe

H

CO2

O

N

O

NCo

HH

OCOCH3

n-Bu4NBr

OO

O

HOMe

H

HMe

OO

O

HMe

OMe

H

OMe

H

(major)

(minor)

O

N

O

NM

HH

X

Salen complex:

(1R, 2R)(t-Bu)2SalenMX

20Mechanism:

21

Thank You