Basic Concepts Of Retrosynthesis (Part 2)

21
RETROSYNTHETIC APPROCH APPROCH TO TO ORGANIC SYNTHESIS ORGANIC SYNTHESIS Dr. Shaikh S. Nizami Dr. Shaikh S. Nizami Department of Chemistry Department of Chemistry University of Karachi University of Karachi

Transcript of Basic Concepts Of Retrosynthesis (Part 2)

Page 1: Basic Concepts Of Retrosynthesis (Part 2)

RETROSYNTHETIC APPROCH APPROCH

TOTOORGANIC SYNTHESISORGANIC SYNTHESIS

Dr. Shaikh S. NizamiDr. Shaikh S. NizamiDepartment of ChemistryDepartment of Chemistry

University of KarachiUniversity of Karachi

Page 2: Basic Concepts Of Retrosynthesis (Part 2)

BASIC BASIC CONCEPTS

(Part 2)

Page 3: Basic Concepts Of Retrosynthesis (Part 2)

CONTENTS

Examples of Retrosynthetic Examples of Retrosynthetic analysis of:analysis of:

1-Phenylhexanol (TM 1.1)1-Phenylhexanol (TM 1.1)

Page 4: Basic Concepts Of Retrosynthesis (Part 2)

RETROSYNTHETIC ANALYSISRETROSYNTHETIC ANALYSIS 1-PHENYLHEXANOL1-PHENYLHEXANOL

Ph CH3

OH

Ph CH3

OFGI

(TM 1.1)(TM 1.1)

Page 5: Basic Concepts Of Retrosynthesis (Part 2)

11stst RETROSYNTHETIC ANALYSISRETROSYNTHETIC ANALYSIS

1-PHENYLHEXANOL1-PHENYLHEXANOL

TM

Path 1

+

+ CH3

?

CH3Br

---------------------------------------------------------------------

Path 2

OH

Ph+

CH3-

+Ph H

O

CH3

BrMg

Ph CH3

OH

-

OH

Ph

Page 6: Basic Concepts Of Retrosynthesis (Part 2)

SYNTHESISSYNTHESIS

CH3Br Mg

Et2OCH3

BrMg

Ph H

O

CH3Ph

OMgBrH+/H2O

TM

Page 7: Basic Concepts Of Retrosynthesis (Part 2)

22ndnd RETROSYNTHETIC RETROSYNTHETIC ANALYSISANALYSIS

1-PHENYLHEXANOL1-PHENYLHEXANOL

Ph CH3

OH

TM

---------------------------------------------------------------------

Path 1

Path 2

Ph+

+

-

OH

CH3

?

Ph-

+

+CH3

OH

PhMgBr

PhBr

CH3H

O

Page 8: Basic Concepts Of Retrosynthesis (Part 2)

SYNTHESISSYNTHESIS

PhBr + Mg Et2O PhMgBr

PhMgBr +CH3H

OH

+/H2O TM

Page 9: Basic Concepts Of Retrosynthesis (Part 2)

33rdrd RETROSYNTHETIC RETROSYNTHETIC ANALYSISANALYSIS

1-PHENYLHEXANOL1-PHENYLHEXANOL

OH

Ph CH3

Ph

OH

+

+

CH3

-

O

Ph

BrMg CH3

TM

Page 10: Basic Concepts Of Retrosynthesis (Part 2)

SYNTHESISSYNTHESIS

O

Ph+

BrMg CH3

Ph CH3

OMgBrH

+/H2O

TM

Page 11: Basic Concepts Of Retrosynthesis (Part 2)

44thth RETROSYNTHETIC ANALYSIRETROSYNTHETIC ANALYSI 1-PHENYLHEXANOL1-PHENYLHEXANOL

Ph CH3

OH

TM

FGI

Ph CH3

O

Ph CH3

O-Ph

O

+

+CH3

Ph CH3

O

Br CH3

Page 12: Basic Concepts Of Retrosynthesis (Part 2)

SYNTHESISSYNTHESIS

Ph CH3

O i) -OEt

ii)Br CH3 Ph CH3

O

LiAlH4

TM

Page 13: Basic Concepts Of Retrosynthesis (Part 2)

55thth RETROSYNTHETIC ANALYSISRETROSYNTHETIC ANALYSIS 1-PHENYLHEXANOL1-PHENYLHEXANOL

Ph CH3

O

+Ph

O

+- CH3

Ph

O

LiCu2)(

CH3

Page 14: Basic Concepts Of Retrosynthesis (Part 2)

SYNTHESISSYNTHESIS

Ph

O

+ CH3( )

2LiCu

Ph CH3

O

TMNaBH4

Page 15: Basic Concepts Of Retrosynthesis (Part 2)

66thth RETROSYNTHETIC ANALYSISRETROSYNTHETIC ANALYSIS 1-PHENYLHEXANOL1-PHENYLHEXANOL

Ph CH3

O

+Ph

O

+

-CH3

Ph

O

LiCu(CH3)2

Page 16: Basic Concepts Of Retrosynthesis (Part 2)

SYNTHESISSYNTHESIS

Ph

O

+

LiCu(CH3)2

Ph CH3

O

MeOH

/CuINaBH4 TM

Page 17: Basic Concepts Of Retrosynthesis (Part 2)

What is the best What is the best synthesissynthesis??

Availability of the reagentAvailability of the reagentSynthetic step should be kept Synthetic step should be kept

minimum unless there is an minimum unless there is an advantage of FGIadvantage of FGI

Disconnection of C-C bond Disconnection of C-C bond should be in the center of a should be in the center of a moleculemolecule

Page 18: Basic Concepts Of Retrosynthesis (Part 2)

Help Tim to get a Help Tim to get a nibble of the Birthday nibble of the Birthday

Cake!Cake!

Page 19: Basic Concepts Of Retrosynthesis (Part 2)

Help Tim get a nibble Help Tim get a nibble of the Birthday Cake!of the Birthday Cake!

Page 20: Basic Concepts Of Retrosynthesis (Part 2)

Help Tim get a nibble Help Tim get a nibble of the Birthday Cake!of the Birthday Cake!

Page 21: Basic Concepts Of Retrosynthesis (Part 2)

Help Tim get a nibble Help Tim get a nibble of the Birthday Cake!of the Birthday Cake!