enantioselective synthesis

1. Enantioselective synthesis of 4H-
pyranonaphthoquinones via
sequential squaramide and silver
catalysis.
BY:
DATTATRAYA GORE
NIPERA1517NP03
MS M.S PHARM(NATURAL PRODUCTS)

2. QUICK OVERVIEW
4H-pyranonaphthoquinones were
previously synthesized by using
bifunctional bis-squaramide catalyst
Catalytic screening for
asymmetric Micheal addition
Optimization studies for
hydroalkoxylation reaction
One pot Michael
addition/
hydroalkoxylation
reaction
One pot Michael
addition/hydroalkoxylation
reaction
Optimized
condition
Substrate scope

3. Recent approaches for the asymmetric
synthesis of pyranonaphthoquinones

4. •Squaramide catalyst
Michael addition
•Metal catalyst
hydroalkoxylation
Synthetic reaction

6. Michael addition
alkyne-tethered
nitroolefins
2-hydroxy-1,4-
naphthoquinones

8. YIELD ENANTIOMERIC EXCESS
Squaramide A 91% 84%
Squaramide B 92% 85%
Squaramide C 99% 82%
Squaramide D 98% 83%
Squaramide E 92% 88%
Squaramide F 94% 68%
Squaramide G 97% 79%
Squaramide H 96% 73%
Squaramide I 97% 71%
Squaramide J 91% 88%
Squaramide K 94% 96%
Squaramide L 98% 81%
Squaramide M 93% 85%
Squaramide N 96% 80%
Squaramide O 94% 90%
Squaramide P traces 10%

9. HYDROALKOXYLATION Through the
π-ACTIVATION of ALKYNE 3a by
late TRANSITION METAL COMPLEX
4H-pyranonaphthoquinones (4a)

11. One pot micheal
addition/hydroalkoxylation
reaction

12. 2-hydroxy-1,4-naphthoquinone alkyne-tethered nitroolefin 4H-pyranonaphthoquinones

13. Substrate scope for the Michael
addition/hydroalkoxylation reaction.
2-hydroxy-1,4-naphthoquinone alkyne-tethered
nitroolefin
4H-pyranonaphthoquinones

14. Substituents on the nitroalkenes
4 R1 R2 R3 Yield(%) Enantiomeric
excess (%)
WEAKLY ELECTRON
DONATING
a H H Ph 93 98
b H H 1-naphthyl 94 96
c H H 2-naphthyl 88 97
ELECTRON WITHDRAWING d H H 2-ClC6H4 81 95
e H H 2-BrC6H4 83 96
f H H 4-CF3C6H4 25 96
ELECTRON RICH g H H 3-MeOC6H4 77 96
h H H 3-MeC6H4 91 96
i H H 2-MeC6H4 93 95
j H H 3,4(-OCH2O-)C6H3 91 92
HETEROARYL k H H 2-furanyl traces -
L H H 2-thienyl 23 99
m H H n-butyl 50 95
n H H cyclopenty 19 97

15. Substituents on naphthoquinone
4 R1 R2 R3 Yield(%) Enantiomeric
excess(%)
o MeO H Ph 84 97
p Me Me Ph 86 96
q MeO H 3-MeC6H4 70 97
r MeO H 1-naphthyl 84 97
s Me Me 3,4(-OCH2O)C6H3 76 89
t F H Ph 70 97

17. • developed an enantioselective one-pot sequential Michael
addition/hydroalkoxylation reaction by combining hydrogen-
bonding catalysis and π-activation.
• This merger provided substituted 4H-pyranonaphthoquinones in
moderate to very good yields and excellent enantioselectivities by
using low catalyst loading of squaramide