DYNAMIC KINETIC RESOLUTION

3rd

PRIYANKA M.M Semester M.Sc Organic Chemistry Reg. no:011013

kR> kS
(R,S)-A Chiral Reagent (R)-A B + (S)-A

Chemical and enzymatic transformation of racemate in chiral environment. One of the enantiomer form product more rapidly

Problems.. Theoretical yield=50% Seperation of product from remaining substrate required In the majority of process ,only one stereoisomer is desired.

DYNAMIC KINETIC RESOLUTION

Highly enantioselective kinetic resolution+ Efficient racemization of unwanted enantiomer

(R) A

kR>kS
Chiral reagent

(S)-A Kinetic resolution

Chemo catalysis Enzyme catalysis

(R )-A

Racemization
1.Thermal racemization 2.Base catalysed racemization 3.Acid catalysed racemization

KINETIC RESOLUTION Chemo catalysis

Reaction
Homogeneous hydrogenation

Catalyst
[Ru(BINAP)(Oac)2]

[(Dipamp)Rh] Isomerization Cyclization [Rh(BINAP)(OCH)] Rh(CHIRAPHOS)Cl

Homogeneous hydrogenation [Ru(BINAP)(Oac)2]

H3C COO OH OH

OH

OH

[(Dipamp)Rh]
CH3 CH3

Isomerization
O O

[Rh(BINAP)(OCH)]

OH

Enzyme catalysis
Lipase and esterase The active site in these enzyme involves a catalytic triad consisting of imidazole ring from a histidine ,the hydroxyl group of serine , and a carboxyl group from aspartic acid. In acylation it is transferred to substrate. In solvolysis active site transferred to solvent

O C

H O
-

N:

HOCH2

N C OH

-OCH2

O C R X

H2C

OO X R H2C O O R

O C

H O-

H N: O R' H2C O O R

CH2 O OR'O R

RACEMIZATION

Acid zeolite,Acid resins(CD550 and CD 8604) Palladium catalyst Shvos catalyst SHVOS CATALYST Applications Reduction of aldehyde and ketones to esters Biomolecular disproportionation of aldehyde to esters Isomerisation of allylic alcohols Oxidation of alcohols Epimerization catalyst in enzyme mediated DKR

O Ph Ph H Ph

O H Ph Ph Ph Ph

Ph OH Ph Ph + Ph

Ph OPh
+

Ru Ph OC CORu Ph CO CO Ph

CO Ru H CO

CO Ru CO

Ph Ph + Ph
+ CO Ru CO

Ph O Ph
-

OH + R H R'

O Ph Ph OH Ph + R R'

CO Ru H CO

Ph OH R' R H Ph + Ph CO Ru CO
+

OPh

One of the oxygen 2absract a proton(removing the need of an external catalyst )and Ruthenium metal acts as a hyride acceptor subsequentely leading to ketone formation .The ketone generated is then reduced in re verse fashion, resulting in an overall epimerization of the corresponding alcohols

Benzoin DKR catalysed by Lipase TL

Lipase TL Trifluoroethyl butyrate

OH

rac-1

SHVO's catalyst THF,600C

O O

(S)-

DKR of BENZOIN catalysed by lypase and Shvos catalyst

OH (R,S)Shvo's catalyst

Pseudomonas stutzeri lipase Vinyl Butyrate THF,rt

O O O + C3H7

(S)-

O O

Shvo's catalyst
OH O

DKR of alcohols

OH

Cl

OAc

OAc

Ru- Catalyst\ CALB

R R' R R'

REFERENCES

Pellissier,H.Tetrahedron 2003,59,8291 Kim,M.J.;Ahn,Y.;PARK,J.Curr.Opin.Biotech,2002,13,587 M.Breuer,K.Ditrich,T.Habicher,B.Hauer,M.Kebeler,R.Sturmer,T.Zelinki,An gew,Chem.INT.Ed.43(2004)788-824 M.Ssingh,A.K.Singh,Synthesis6(2004)837-839 T.Hudlicky,J.W.Reed,Chem.Soc.Rev.38(2009)3117-3132 TH.Akita,Hetrocycles78(2008)1667-1713

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