Synthesis of Chlorophyll A

C55H72MgN4O5
Principal investigator | Robert B. Woodward |
---|---|
Publication year | 1960 |
Synthesis type | Formal |
Number of steps | 49 (7 parts) |
References |
Part 1 of 7
Part 2 of 7

H2SO4
40 °C, 20 min, 90%

HO(CH2)2NH2
170 °C, 60 min, 84-87%



Br2
H2O, MeOH
Reflux, 4 min, 68-70%

NaOH
H2O
100 °C, 3.5 h, 83%


NaHCO3,
NaBH4
H2O
RT, 40 min, 87%

NaOAc.3H2O,
KOAc
100-135 °C, 25 min, 50-58%

H2,
PtO2
3 atm
MeOH
RT, 3 h, 85-93%

Part 3 of 7

AcCl,
AlCl3
CH2Cl2
Reflux, 2 h, 86%
See the Friedel-Crafts Acylation
"The starting material is an intermediate of the second part of this synthesis."




SO2Cl2
AcOH
55 °C, 90 min, 84%

Part 4 of 7

- Br2 , SO2Cl2
- H2O
AcOH
0 to 60 °C, 6.5 h, 70-75%

Cu-Bronze
230-240 °C, 60 min, 72%

KOH
EtOH, H2O
Reflux, 2.5 h, 90%

Cu-Bronze
220-240 °C, 60 min, 80%

Part 5 of 7

Malonic Acid,
PhNH2
EtOH
Reflux, 8 h, 70-75%
See the Knoevenagel Condensation
"The starting material is an intermediate of the second part of this synthesis."

Ni (Raney),
NaOH,
H2
2 atm
H2O
RT, 12 h, 90-92%

- SO2Cl2
- H2O
Et2O
-15 °C to RT, ON, 85-90%

NaOH
H2O
180 °C, 90 min

CH2N2
Et2O, MeOH
RT, 75-80% (2 steps)


Part 6 of 7
+
+





NaOH
H2O
95 °C, 15 min

CH2N2
H2O, MeOH
RT, 90 min, 84% (2 steps)

EtNH2,
HBr
AcOH, H2O
0 °C, 45 min, 94%

H2S,
NaOMe
MeOH, PhH
RT, 5 min, 86%

Part 7 of 7
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+


HBr
Et2O, H2O, MeOH
-25 to 0 °C, 56%

NaBH4
H2O
RT


- HCl
- I2
CH2Cl2, MeOH, PhH
RT, 60 min

Ac2O
Pyr
50-55 °C, 60 min, 48% (3 steps)

O2
AcOH
95 °C, 60 min, 91%

AcOH
Reflux, 31.5 h, 59%

HCl
H2O, MeOH
Reflux, 18 h, 75%


O2
hν
CH2Cl2
0 °C, 35 min, 59%

KOH
CH2Cl2, MeOH
RT, 60 min, 22%

NaOH
Dioxane , H2O
RT, 12 h
"The enantiomers were resolved with (-)-Quinine (4 % yield)."

CH2N2
Et2O, MeOH
RT, 20 min, 60% (2 steps)
"Relay point."

HCN,
Et3N
CH2Cl2
0 °C to RT, 5 min, 78%

Zn
AcOH, CH2Cl2
RT, 1 min

CH2N2
Et2O, MeOH
RT, 10 min, 9% (2 steps)

HCl
MeOH
0 °C to RT, 16 h, 36%

Remaining...
23% (4 steps)
"See: Fortschr. Chem. Forsch. 1952, 2, 538 and
Tetrahedron 1981, 37, 399."
