A Convenient, High-Yielding Copper-Free Synthesis of Skipped 1,4-Diynes

Abstract

Alkynylalanes were found to react efficiently with propargylic electrophiles, such as propargyl mesylates and propargyl diethylphosphates. The reaction proceeds with high regioselectivity and does not require copper or any other transition metal.

Key words

alkynes - alanes - aluminum - cross-coupling - regioselectivity

References

• 1a For a general review, see: Normant JF. Synthesis  1972,  63 
• Exceptions include the use of tris(alkynyl)indiums with benzyl bromide catalyzed by Cl₂Pd(dppf) and the use of alkynylboron dichlorides with benzyl, benzylallyl and benzypropargyl secondary alcohols.
• 1b Perez J. Perez-Sestelo L. Sarandeses A. J. Am. Chem. Soc.  2001,  123:  4155 
• 1c Kabalka GW. Yao M.-L. Borella S. Org. Lett.  2006,  8:  879 
• 2a Durand S. Parrain J.-L. Santelli M. J. Chem. Soc., Perkin Trans. 1  2000,  253 
• 2b Tedeschi C. Saccavini C. Maurette L. Soleilhavoup M. Chauvin R. J. Organomet. Chem.  2003,  670:  151 
• 3a Brandsma L. Synthesis of Acetylenes, Allenes and Cumulenes   Elsevier; Amsterdam: 2003. and references cited therein
• 3b Jeffery T. Guenot S. Linstrumelle G. Tetrahedron Lett.  1992,  33:  5757 
• 3c Hansen TV. Stenstrom Y. Tetrahedron: Asymmetry  2001,  12:  1407 
• 3d Spinella A. Caruso T. Martino M. Sessa C. Synlett  2001,  1971 
• 3e For an exception: Padmanabhan S. Nicholas KM. Tetrahedron Lett.  1983,  24:  2239 
• 4a Mel’nikova VI. Pivnitskii KK. Zh. Org. Khim.  1990,  26:  78 ; Chem. Abstr. 1990, 113, 23031
• 4b Mathai IM. Taniguchi H. Miller SI. J. Am. Chem. Soc.  1967,  89:  115 
• 4c Hungerford NL. Kitching W. J. Chem. Soc., Perkin Trans. 1  1998,  1839 
• 5a Comprehensive Organic Synthesis   Vol. 5:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  p.1543 
• 5b Bohlmann F. Schoenowsky H. Inhoffen E. Grau G. Chem. Ber.  1964,  97:  794 
• 6 Kessabi J. Beaudegnies R. Jung PMJ. Martin B. Montel F. Wendeborn S. Org. Lett.  2006,  8:  5629 
• 7a Shinoda M. Iseki K. Oguri T. Hayasi Y. Yamada S. Shibasaki M. Tetrahedron Lett.  1986,  27:  87 
• 7b Fried J. Sih JC. Tetrahedron Lett.  1973,  14:  3899 
• 7c Fried J. Lin C. Ford SH. Tetrahedron Lett.  1969,  10:  1379 
• 7d Ben-Efraim DA. Sondheimer F. Tetrahedron  1969,  25:  2823 
• 8a Feuvrie C. Blanchet J. Bonin M. Micouin L. Org. Lett.  2004,  6:  2333 
• 8b Wang B. Bonin M. Micouin L. Org. Lett.  2004,  6:  3481 
• 10 Lapitskaya MA. Vasiljeva LL. Pivnitsky KK. Synthesis  1993,  65 
• 12 Yanagisawa A. Nomura N. Yamamoto H. Tetrahedron  1994,  50:  6017 
• 13 White WL. Anzeveno PB. J. Org. Chem.  1982,  43:  2379 
• 14 Tanabe Y. Yamamoto H. Yoshida Y. Miyawaki T. Utsumi N. Bull. Chem. Soc. Jpn.  1995,  68:  297 
• 15 Easton CJ. Ferrante A. Robertson TA. Xia L. Aust. J. Chem.  2002,  55:  647 

9

The need for two equivalents of alkynylalane when employing propargyl phosphates and phosphinates suggests that the reaction proceeds via an alternative mechanism, essentially involving Lewis acid activation prior to coordination and transfer brought on by the second equivalent of alkynylalane.

11

Unpublished results from this laboratory.