Total Syntheses of Phomallenic Acids B and C Utilizing Palladium-Catalyzed Coupling of Propargylic Tosylates with Terminal Alkynes

Abstract

Total syntheses of (±)-phomallenic acids B and C, potent FAS II inhibitors, have been achieved by a palladium-catalyzed coupling of propargylic tosylates and terminal alkynes. Attempts to find an enantiospecific coupling using optically active propargylic compounds resulted in racemization of the products.

Key words

alkynes - allene - coupling - palladium - phomallenic acid

References

• 1 Ondeyka JG. Zink DL. Young K. Painter R. Kodali S. Galgoci A. Collado J. Tormo JR. Basilio A. Vicente F. Wang J. Singh SB. J. Nat. Prod.  2006,  69:  377 
• 2 Young K. Jayasuriya H. Ondeyka JG. Herath K. Zhang C. Kodali S. Galgoci A. Painter R. Brown-Driver V. Yamamoto R. Silver LL. Zheng Y. Ventura JI. Sigmund J. Ha S. Basilio A. Vicente F. Tormo JR. Pelaez F. Youngman P. Cully D. Barrett JF. Schmatz D. Singh SB. Wang J. Antimicrob. Agents Chemother.  2006,  50:  519 
• 3 Very recently Wu and co-workers reported the first total synthesis of phomallenic acid C: Jian Y.-J. Tang C.-J. Wu Y. J. Org. Chem.  2007,  72:  4851 
• 4a Yoshida M. Hayashi M. Shishido K. Org. Lett.  2007,  9:  1643 
• 4b Dixneuf PH. Guyot T. Ness MD. Roberts SM. Chem. Commun.  1997,  2083 
• The enantiospecific synthesis of 1,3-disubstituted allenes by palladium-catalyzed coupling of optically active propargylic compounds with organoboron compounds has been reported:
• 5a Yoshida M. Okada T. Shishido K. Tetrahedron  2007,  63:  6996 
• 5b Molander GA. Sommers EM. Baker SR. J. Org. Chem.  2006,  71:  1563 
• 5c Yoshida M. Gotou T. Ihara M. Tetrahedron Lett.  2004,  45:  5573 
• 6 Tueting DR. Echavarren AM. Stille JK. Tetrahedron  1989,  45:  979 
• 7 Ohtani I. Kusumi T. Kashman Y. Kakisawa H. J. Am. Chem. Soc.  1991,  113:  4092 
• 8 Condon-Gueugnot S. Linstrumelle G. Tetrahedron  2000,  56:  1851 
• 9 Mandai T. Nakata T. Murayama H. Yamaoki H. Ogawa M. Kawada M. Tsuji J. Tetrahedron Lett.  1990,  31:  7179 
• 10 Ogoshi S. Nishida T. Shinagawa T. Kurosawa H. J. Am. Chem. Soc.  2001,  123:  7164 
• 11 Horváth A. Bäckvall JE. Chem. Commun.  2004,  964 
• 13 Seigel K. Brückner R. Chem. Eur. J.  1998,  4:  1116 

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Molander et al. reported the racemization of chiral alkenylallenes in the palladium-catalyzed coupling of propargylic phosphates with alkenyl trifluoroborates; see ref. 5b.