Journal of Organic Chemistry: 1974 A Brief Synopsis, Lecture notes of Organic Chemistry

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Journal of Organic Chemistry: 1974

A Brief Synopsis

-Mike DeMartino

-Group Meeting: 10-29-

Overview

• Some general observations

• The “prime-time-players”…what were they

doing in JOC? (Thanks Dick Vitale, baby!)

• Some selected total syntheses

E.J. Corey (Harvard)

• Preparation of an optically active intermediate for the prostaglandins (p. 356 )

O

O

• A racemic route had previously been developed from (+/–) 1 to (+/–)- 11 - deoxyprostaglandins

O

O

OH

OH

O

LiOH

(–)- 1 - ( 1 naphthyl)ethylamine

3 recrystalizations

OH

OH

O

• (–)- 1 - ( 1 naphthyl)ethylamine

1. Removal of salt

2. 10 N HCl

• g-Condensation of an allylic Phosphonium Ylide (p. 821 )
  • Generally, allylic phosphorous ylides condense on the a carbon
  • Many geometric isomers usually obtained

CO

2

H Me

Me

P

Ph

Ph

• HBr

Hunig's Base

C

5

H

11

Hexanal

O

O

CO

2

Me

Me

C

5

H

11

Generally, E/Z > 1

90 - 92 %

9 - 10 %

E. J. Corey (p. 256)

Samuel Danishefsky (Univ. of Pitt)

• Furanoid systems by intramolecular homoconjugate addition (p. 2658 )

CO

2

Me

CO

2

Me

O

O O

NaH

PhH

• O-Alkylation was dominant pathway in all systems they tried in this paper

O

MeO

2

C

(CO

2

Me)

2

CO

2

Me

CO

2

Me

O

O

O

NaH

PhH

OR

DMSO

O

(CO

2

Me)

2

O

O

Geometry highly dependent on solvent and

therefore solvation of reaction pathway

Gilbert Stork (Columbia)

• Regiospecific Aldol condensations of the kinetic lithium enolates of methyl ketones (p. 3459 )
  • It had previously been difficult to trap the kinetic enolate with alkyl halides
  • So, used a more reactive electrophile to trap the enolate

O

Li

O

LDA,

THF, – 78 °

Butyraldehyde

O OH

65 % ( 90 % Kinetic enolate)

O

Li

O

LDA,

THF, – 78 °

Benzaldehyde

Ph

O OH

O

Li

O

LDA,

THF, – 78 °

Crotonaldehyde

O OH

Barry M. Trost (Wisconson, Madison)

Alkylations

NaH

CH

3

SO

2

CH

2

CO

2

CH

3

1 , 2 , or 3

H

3

CO

2

S CO

2

CH

3

LiI, NaCN, DMF

130 °C

H

3

CO

2

S

1. HOCH

2

CH

2

OH,

TsOH, PhH, Reflux

2. Li, C

2

H

5

NH

2

, 0 °C

3 .H

2

O, HCl

Barry M. Trost (Wisconson, Madison)

• Alkylation of Lactam Derivatives (p. 2475 )

N

N N

O

O

Li

O

Me

Me

Me

LDA, THF

• 78 °C

N

N N

OMe OMe

Li

LDA, THF

• 78 °C

E

E

OMe

E

E

1

2

• Both of the above examples proceeded with C-alkylation exclusively with alkyl halides,

chlorosilanes.

• For 1 (Stronger enolate), reaction with methyl vinyl ketone proceeds with 1 , 2 addition;

for 2 , (weaker reagent), reaction to MVK proceeded with conjugate addition

This selectivity is due to the less reactive reagent having its charge more delocalized in the

transition state. To test this hypothesis, a controll exmeriment:

MVK

22 hr,

RT

N OMe

Me

N O

Me

O

Exclusively 1 , 4 addition, 29 %

R. F. Heck (Univ. of Delaware :-) )

NH

2

Br

CO

R

R

'

3

N

Pd(Br)

2

(PPh

3

2

100 °C

R

O

N

H

Possible Mechanism:

• Palladium caralyzed Amidation of aryl, heterocyclic, and vinylic halides (p. 3327 )

R. F. Heck (Univ. of Delaware :-) )

• Palladium caralyzed carboalkoxylation of aryl, benzyl, and vinylic halides (p. 3318 )

Br

CO

R

R

2

3

N

Pd(Br)

2

(PPh

3

2

100 °C

R

O

O

R

2

R

1

OH

Possible Mechanism:

(S)-Carlosic Acid

Blommer and Kappler, p. 113

Temple University

MeO

2

C

O O

O

t-BuOK

t-BuOH

O

CO

2

Me

HO

O

O

MeO

2

C

Br

2

AcOH

O

HO

O

MeO

2

C

Br

OH

OMe

MeO

O

O

O

O

Et

3

N (cat), PhH

H

2

, Pd/C

AcOH

O

HO

O

MeO

2

C

Cl

O

TiCl

4

PhNO

2

O

HO

O

MeO

2

C

HCl

NaOH

O

HO

O

HO

2

C

(S)-Carlosic Acid

Note: all yields in the synthesis were 70 - 80 %, except the "key step," the cyclization

Cassamedine

Cava and Libsch, p. 577

UPenn

O

O

OMe

NH

2

O

O

OH

O

Br

Known Compounds

O

O

OMe

H

N O

Br

O

O

PhH, 2 hr

76 %

O

O

OMe

N

O O

Br

POCl

3

CH

3

CN

20 hr, 90 %

O

O

OMe

N

O O

Br O

Ethyl OEt

Chloroformate

Et

3

N, 0 °C

90 %

• HCl

O

O

OMe

N

O

O

O

OEt

t-BuOK

hn, 7 hr

PhH, t-BuOH

32 %

O

O

OMe

N

O

O

Me

LiAlH

4

, AlCl

3

Et

2

O, reflux

1. 5 hr, 87 %

O

O

OMe

N

O

O

Me

O

O

O

H

AcOH

23 %

Cassamedine

• An alkaloid isolated from Cassytha americana

OAc

H

2

, Pd/BaSO

4

Pentane, 84 %

OAc

NaNO

2 (aq)

HNO

3 (aq)

OAc

H

2

, Pd/BaSO

4

Pentane, 80 %

OAc

The Sex Pheramone of the

Pink Bollworm

The Sex Pheromone of the Pink Bollworm

Phillip E. Sonnet, p. 3793

U.S. Dept. of Agriculture, Maryland

• Isolated from the Pectinophora gossypiella, the pink bollworm moth
• Isolated as 1 : 1 mixture of geometric isomers

A Trail Pheromone of the Pharaoh Ant

Sonnet, Oliver, p. 2663

U.S. Dept. of Agriculture, Maryland

• Isolated from the Monomorium pharaonis, the Pharaoh Ant
• It was known that the pheromone had the general structure of 3 - butyl- 5 -

methoctahydroindolizine, but absolute stereochemistry of active pheromone was not

elucidated

• Synthesized all four stereoisomers because they were interested in the

pheromone's utility as a pest control agent

N

C

H

N

C

H

N

C

H

N

C

H

H

H

H

H

A

B

C D

A Trail Pheromone of the Pink Bollworm