Birch reaction and Michael addition

1. 1
Mr. Rakesh B. Jagtap

2. The Birch reduction reaction was first
reported by Wooster in 1937.
Aromatic Hydrogenation
2
Mr. Rakesh B. Jagtap

3. Birch Reduction
The scientist Birch who explored
the Wooster’s protocol in 1944
3
Mr. Rakesh B. Jagtap

4. 4
Mr. Rakesh B. Jagtap

5. R
•M
R
H
H
..
.
Radical anion
Electron transfer from alkali metal
5
Mr. Rakesh B. Jagtap

6. R
H
H
..
.
R
H
H
H
.
Proton transfer from alcohol
6
Mr. Rakesh B. Jagtap

7. R
H
H
H
.
•M
R
H
H
H
..
Electron transfer from alkali metal
7
Mr. Rakesh B. Jagtap

8. R
H
H
H
..
R
H
H
H
H
1,4-cyclohexadiene
Proton transfer from alcohol
8
Mr. Rakesh B. Jagtap

9. Retention of configuration
at time of
cleavage of bond.
9
Mr. Rakesh B. Jagtap

10. (+)- cepharamine
10
Mr. Rakesh B. Jagtap

11. • The tricyclic sesquiterpene
(-)-longifolene has served as
a vehicle for the illustration
of new strategies for organic
synthesis.
• The hasubanan alkaloids
are of pharmacological
interest because of their
structural resemblance to the
morphine alkaloids. The first
asymmetric synthesis of a
hasubanan alkaloid,
• i.e. (+)-cepharamine 11
Mr. Rakesh B. Jagtap

12. • Reaction temperature (-330 C/-780C)
• Distilled ammonia.
12
Mr. Rakesh B. Jagtap

13. Alternative to
conventional
Birch reduction
13
Mr. Rakesh B. Jagtap

14. 14
Mr. Rakesh B. Jagtap

15. 15
Mr. Rakesh B. Jagtap

16. 16
Mr. Rakesh B. Jagtap

17. O
H
O
O
O
:OH
O
O
O
O
:
Nucleophiles generation
Nucleophile
17
Mr. Rakesh B. Jagtap

18. R
O
O
O
O
O
:
O
R
O
O
O
O
-
Attack of Nucleophile
18
Mr. Rakesh B. Jagtap

19. O
R
O
O
O
O
-
O
O
O
O
H
O
R
O
O
O
OH
Enol
Protonation with simultaneous Nucleophile generation
19
Mr. Rakesh B. Jagtap

20. O
R
O
O
O
OH
Enol
O
O
O
O
R
O
Keto
Tautomerism
Keto-Enol Tautomerism
20
Mr. Rakesh B. Jagtap

21. Stereo-selective synthesis is
possible, but the output depends on
geometry of α,β-unsaturated
carbonyl compound i.e. Michael
acceptor as well as geometry of
Michael donor.
21
Mr. Rakesh B. Jagtap

22. There is retention of configuration.
Three ways for stereo selective synthesis;
1. Addition of chiral donor to achiral acceptor.
2. Use of chiral acceptor with achiral donor.
3. Use of chiral catalyst, if both donor as well as
acceptor are achiral.
22
Mr. Rakesh B. Jagtap

23. Addition of chiral donor to achiral acceptor.
Use of chiral acceptor with achiral donor.
23
Mr. Rakesh B. Jagtap

24. Use of chiral catalyst, if both donor as well as
acceptor are achiral.
A novel synthesis of optically active 2-phenylpropionic acid or esters
which can be used for the synthesis of (S)-naproxen as a non steroidal
anti-inflammatory agent
24
Mr. Rakesh B. Jagtap

25. The Michael reaction has been
used widely in organic synthesis for
its C–C bond-forming ability with
three carbons distance in both
electron withdrawing groups.
25
Mr. Rakesh B. Jagtap

26. Enantio-selective synthesis of
(S)-warfarin
26
Mr. Rakesh B. Jagtap

27. In synthesis of various
polymers
27
Mr. Rakesh B. Jagtap

28. Robinson Annulation
Michael addition followed by Aldol
condensation, gives cyclic product.
28
Mr. Rakesh B. Jagtap

29. Birch reduction:-
1. Wooster, C. B. and Godfrey, K. L.,J. Am. Chem. Soc.,1937,59, 596.
2. Birch, A. J., J. Chem. Soc., 1944, 430.
3. Birch, A. J., J. Chem. Soc., 1945, 809.
4. Loewenthal, H. J. E. and Gottlieb, L., J. Org. Chem., 1992, 57, 2631.
5. Benkeser, Robinson, Sauve, Thomas J. Am. Chem. Soc. 1955, 77, 3230.
6. Greenfield, A. and Schindewolf, U., Ber. Bunsen-Gesellschaft, 1998,102, 1808.
7. Möbitz, H. and Boll, M., Biochemistry, 2002, 41, 1752.
8. Zimmerman, H. E. and Wang, P. A., J. Am. Chem. Soc.,1993,115, 2205.
9. Subba Rao, G. S. R., Pure & Appl. Chem., 2003, 75, 1443.
10. Sinclair, S. and Jorgensen, W. L., J. Org. Chem., 1994, 59, 762.
11. Birch, A. J., and Mukherji, S. M., J. Chem. Soc., 1949, 2531; 1950,867.
12. Corey E. J., Ohno M., Mitra R. B. and Vatakencherry P. A., J. Am. Chem. Soc.,
1964, 86, 478.
13. Huneck S. and Klein S., Phytochemistry, 1967, 6, 383. 29
Mr. Rakesh B. Jagtap

30. 14. Schultz A. G. and Puig S., J. Org. Chem., 1985, 50, 916.
15. Matsui, M., The Alkaloids, ed. A. Brossi, Academic Press, New York, 1988, vol.
33, pp. 307–347.
16. Schultz A. G. and Wang, A., J. Am. Chem. Soc., 1998, 120, 8259.
17. Epling, Flario, Tetrahedron Lett.,1986, 1469-1472.
Michael addition:-
1. Michael, A.J., Prakt. Chem. 1887, 36, 113–114.
2. Brock, W. H., The Chemical Tree—A History of Chemistry; Norton: London,
1992; 517, 518.
3. Oare, D. A., Heathcock, C. H., Topics Stereochem. 1989, 19, 227–407.
4. Heathcock, C. H., Modern Synthetic Methods, 1992, 1–103.
5. Kumar, A., Salunkhe, R. V., Rane, R. A., Dike, S. Y., J. Chem. Soc., Chem.
Commun. 1991, 485.
6. Brown, S. P., Goodwin, N. C., MacMillan, D. W. C., J. Am. Chem. Soc.2003,
125, 1192.
7. Paras, N. A., MacMillan, D. W. C., J. Am. Chem. Soc.2001, 123, 4370.
8. Woodward, R. B., Sondheimer, F., Taub, D., J. Am. Chem. Soc.1951, 73,
4057.
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Mr. Rakesh B. Jagtap

31. 31
Mr. Rakesh B. Jagtap