Short Syntheses of (-)-( R )-Pyrrolam A and (1S)-1-Hydroxyindolizidin-3-one

Abstract

(-)-(R)-Pyrrolam A was prepared in five steps, 95% ee and 25% yield, from (R)-benzyl prolinate. Closure of the pyrrolidine ring was effected by a domino addition-Wittig alkenation reaction with ylide Ph₃PCCO, immobilized on a polystyrene resin. An indolizidinone was obtained likewise from (R)-benzyl pipecolate. The reduction of 1-ketopyrrolizidinones and 1-ketoindolizidinones is described.

domino reactions - solid-phase organic synthesis - indolizidines­ - pyrrolam A - heterocycles

References

1 Liddell JR. Nat. Prod. Rep.  2000,  17:  455 ; and references cited therein

2 Grote R. Zeeck A. Stümpfel J. Zähner H. Liebigs Ann. Chem.  1990,  525 

3 Aoyagi Y. Manabe T. Ohta A. Kurihara T. Pang G. Yuhara T. Tetrahedron  1996,  52:  869 

4 Murray A. Proctor GR. Tetrahedron  1996,  52:  3757 

5 Giovenzana GB. Sisti M. Palmisano G. Tetrahedron: Asymmetry  1997,  8:  515 

6 Huang PQ. Chen FC. Chen CL. Zhang HK. Tetrahedron: Asymmetry  1999,  10:  3827 

7 Watson RT. Gore VK. Chandupatla KR. Dieter RK. Snyder JP. J. Org. Chem.  2004,  69:  6105 

8 Ramachandran J. Li CH. J. Org. Chem.  1963,  28:  173 

9a Löffler J. Schobert R. J. Chem. Soc., Perkin Trans. 1  1996,  2799 

9b Schobert R. Gordon GJ. Curr. Org. Chem.  2002,  6:  1181 

10 Schobert R. Jagusch C. Melanophy C. Mullen G. Org. Biomol. Chem.  2004,  2:  3524 

11 Galeotti N. Poncet J. Chiche L. Jouin P. J. Org. Chem.  1993,  58:  5370 

12a Cieplak AS. J. Am. Chem. Soc.  1981,  103:  4540 

12b Paddon-Row MN. Wu YD. Houk KN. J. Am. Chem. Soc.  1992,  114:  10638 

13 Lennartz M. Steckhan E. Tetrahedron  2001,  57:  675 

14 According to the synthesis of ent-8 by: Boger DL. Chen J.-H. Saionz KW. J. Am. Chem. Soc.  1996,  118:  1629 

15 Rodwell VW. Methods Enzymol.  1971,  17B:  174 

16 Pyne SG. Tang TM. Curr. Org. Chem.  2005,  9:  1393 

17 Heimgärtner G. Raatz D. Reiser O. Tetrahedron  2005,  61:  643 

18 Corey EJ. Helal CJ. Angew. Chem. Int. Ed.  1998,  37:  1987 ; Angew. Chem. 1998, 110, 2092

19 Mathre DJ. Thompson AS. Douglas AW. Hoogsteen K. Carroll JD. Corley EG. Grabowski EJJ. J. Org. Chem.  1993,  58:  2880 

20 Szeto P. Lathbury DC. Gallagher T. Tetrahedron Lett.  1995,  36:  6957 

21 Hanson GJ. Baran JS. Lindberg T. Tetrahedron Lett.  1986,  27:  3577 

22 Beckett RP. Davies SG. Mortlock AA. Tetrahedron: Asymmetry  1992,  3:  123 

23 Rasmussen MO. Delair P. Greene AE. J. Org. Chem.  2001,  66:  5438 

24 Pourashraf M. Delair P. Rasmussen MO. Greene AE. J. Org. Chem.  2000,  65:  6966