19 Conclusion
The objective of this chapter has been to present an overview of techniques for the
synthesis of 12- to 16-membered macrocyclic lactones in the total synthesis of
natural products. The careful reader might have recognized that even though many
other efficient macrocyclization methods such as the RCM, intramolecular crosscoupling, Nozaki–Hiyama–Kishi, and HWE methods have been developed over the
years, the lactonization of seco-acids still appears to be one of the most frequently
used approaches to obtain macrocyclic lactones. The need for macrolactonizations
has inspired many clever solutions either by activation of the alcohol or by
activation of the acid moiety and has left synthetic chemists with a variety of
different strategies that allow ample of modifications in their initial retrosynthetic
route.
References
1. Pennella F, Banks RL, Bailey GC (1968) Chem Commun (23): 1548
2. Mortreux A, Blanchard M (1974) J Chem Soc Chem Commun 19:786
3. Fu ¨rstner A, Stelzer F, Rumbo A, Krause H (2002) Chem Eur J 8(8):1856
4. Wengrovius JH, Sancho J, Schrock RR (1981) J Am Chem Soc 103(13):3932
5. Schrock RR, Clark DN, Sancho J, Wengrovius JH, Rocklage SM, Pedersen SF (1982)
Organometallics 1(12):1645
6. Schrock RR (2002) Chem Rev 102(1):145
7. Schrock RR, Czekelius C (2007) Adv Synth Catal 349(1–2):55
8. Furstner A, Davies PW (2005) Chem Commun (18): 2307
9. Beer S, Hrib CG, Jones PG, Brandhorst K, Grunenberg J, Tamm M (2007) Angew Chem Int
Ed 46(46):8890
10. Laplaza CE, Odom AL, Davis WM, Cummins CC, Protasiewicz JD (1995) J Am Chem Soc
117(17):4999
11. Laplaza CE, Cummins CC (1995) Science 268(5212):861
12. Cummins C (1998) Chem Commun (17): 1777
13. Fu ¨rstner A, Mathes C, Lehmann CW (1999) J Am Chem Soc 121(40):9453
14. Zhang W, Kraft S, Moore JS (2003) Chem Commun (7): 832
15. Zhang W, Kraft S, Moore JS (2004) J Am Chem Soc 126(1):329
16. McCullough LG, Schrock RR (1984) J Am Chem Soc 106(14):4067
17. McCullough LG, Schrock RR, Dewan JC, Murdzek JC (1985) J Am Chem Soc 107(21):5987
18. Tsai Y-C, Diaconescu PL, Cummins CC (2000) Organometallics 19(25):5260
19. Heppekausen J, Stade R, Goddard R, Fu ¨rstner A (2010) J Am Chem Soc 132(32):11045
20. Vintonyak VV, Maier ME (2007) Org Lett 9(4):655
21. Vintonyak VV, Maier ME (2007) Angew Chem Int Ed 46(27):5209
22. Vintonyak VV, Cala ` M, Lay F, Kunze B, Sasse F, Maier ME (2008) Chem Eur J 14(12):3709
23. Fu ¨rstner A, Bindl M, Jean L (2007) Angew Chem Int Ed 46(48):9275
24. Bindl M, Jean L, Herrmann J, Mu ¨ller R, Fu ¨rstner A (2009) Chem Eur J 15(45):12310
25. Micoine K, Fu ¨rstner A (2010) J Am Chem Soc 132(40):14064
26. Fu ¨rstner A, Grela K (2000) Angew Chem Int Ed 39(7):1234
27. Fu ¨rstner A, Grela K, Mathes C, Lehmann CW (2000) J Am Chem Soc 122(48):11799
28. Fu ¨rstner A, Larionov O, Flu ¨gge S (2007) Angew Chem Int Ed 46(29):5545
424
M. Cordes and M. Kalesse
The objective of this chapter has been to present an overview of techniques for the
synthesis of 12- to 16-membered macrocyclic lactones in the total synthesis of
natural products. The careful reader might have recognized that even though many
other efficient macrocyclization methods such as the RCM, intramolecular crosscoupling, Nozaki–Hiyama–Kishi, and HWE methods have been developed over the
years, the lactonization of seco-acids still appears to be one of the most frequently
used approaches to obtain macrocyclic lactones. The need for macrolactonizations
has inspired many clever solutions either by activation of the alcohol or by
activation of the acid moiety and has left synthetic chemists with a variety of
different strategies that allow ample of modifications in their initial retrosynthetic
route.
References
1. Pennella F, Banks RL, Bailey GC (1968) Chem Commun (23): 1548
2. Mortreux A, Blanchard M (1974) J Chem Soc Chem Commun 19:786
3. Fu ¨rstner A, Stelzer F, Rumbo A, Krause H (2002) Chem Eur J 8(8):1856
4. Wengrovius JH, Sancho J, Schrock RR (1981) J Am Chem Soc 103(13):3932
5. Schrock RR, Clark DN, Sancho J, Wengrovius JH, Rocklage SM, Pedersen SF (1982)
Organometallics 1(12):1645
6. Schrock RR (2002) Chem Rev 102(1):145
7. Schrock RR, Czekelius C (2007) Adv Synth Catal 349(1–2):55
8. Furstner A, Davies PW (2005) Chem Commun (18): 2307
9. Beer S, Hrib CG, Jones PG, Brandhorst K, Grunenberg J, Tamm M (2007) Angew Chem Int
Ed 46(46):8890
10. Laplaza CE, Odom AL, Davis WM, Cummins CC, Protasiewicz JD (1995) J Am Chem Soc
117(17):4999
11. Laplaza CE, Cummins CC (1995) Science 268(5212):861
12. Cummins C (1998) Chem Commun (17): 1777
13. Fu ¨rstner A, Mathes C, Lehmann CW (1999) J Am Chem Soc 121(40):9453
14. Zhang W, Kraft S, Moore JS (2003) Chem Commun (7): 832
15. Zhang W, Kraft S, Moore JS (2004) J Am Chem Soc 126(1):329
16. McCullough LG, Schrock RR (1984) J Am Chem Soc 106(14):4067
17. McCullough LG, Schrock RR, Dewan JC, Murdzek JC (1985) J Am Chem Soc 107(21):5987
18. Tsai Y-C, Diaconescu PL, Cummins CC (2000) Organometallics 19(25):5260
19. Heppekausen J, Stade R, Goddard R, Fu ¨rstner A (2010) J Am Chem Soc 132(32):11045
20. Vintonyak VV, Maier ME (2007) Org Lett 9(4):655
21. Vintonyak VV, Maier ME (2007) Angew Chem Int Ed 46(27):5209
22. Vintonyak VV, Cala ` M, Lay F, Kunze B, Sasse F, Maier ME (2008) Chem Eur J 14(12):3709
23. Fu ¨rstner A, Bindl M, Jean L (2007) Angew Chem Int Ed 46(48):9275
24. Bindl M, Jean L, Herrmann J, Mu ¨ller R, Fu ¨rstner A (2009) Chem Eur J 15(45):12310
25. Micoine K, Fu ¨rstner A (2010) J Am Chem Soc 132(40):14064
26. Fu ¨rstner A, Grela K (2000) Angew Chem Int Ed 39(7):1234
27. Fu ¨rstner A, Grela K, Mathes C, Lehmann CW (2000) J Am Chem Soc 122(48):11799
28. Fu ¨rstner A, Larionov O, Flu ¨gge S (2007) Angew Chem Int Ed 46(29):5545
424
M. Cordes and M. Kalesse