One-Pot Synthesis of Internal Conjugated (Z)-Enynyltrimethylsilanes Possessing Aryl, Cycloalkenyl, (E)- or (Z)-Alk-1-enyl Moieties on the sp Carbon Atom via Two Types of Cross-Coupling Reaction

Abstract

Described herein is an operationally simple and mild method for the stereospecific synthesis of internal conjugated (Z)-enynyltrimethylsilanes whose conjugation is extended away from the distal alkynyl carbon atom. This protocol involves two types of cross-coupling reaction, a Suzuki-type reaction and a sila-Sonogashira reaction, and the desired synthesis can be performed in a one-pot manner. Thus, the copper-mediated cross-coupling reaction of dicyclohexyl[(Z)-1-(trimethylsilyl)alk-1-enyl]boranes with (trimethylsilyl)ethynyl bromide is carried out in the presence of aqueous lithium hydroxide at -15 ˚C to room temperature, resulting in the stereospecific formation of (Z)-1,3-bis(trimethylsilyl)alk-3-en-1-ynes. Subsequent reaction is allowed to proceed without isolation of the enynes. Thus, palladium/copper-catalyzed cross-coupling reactions with aryl iodides, cycloalk-1-enyl triflates, and (E)- and (Z)-alk-1-enyl iodides can be accomplished in the presence of either 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or tetrabutylammonium fluoride (TBAF) at ambient temperature to provide the corresponding internal conjugated (Z)-enynyltrimethylsilanes possessing one more sp-sp^² carbon bond.

Key words

(Z)-enynyltrimethylsilane - (trimethylsilyl)ethynyl bromide - (Z)-1,3-bis(trimethylsilyl)alk-3-en-1-yne - Suzuki-type reaction - sila-Sonogashira reaction

References

• For example, see:
• 1a Fleming I. Dunogues J. Smithers R. Org. React.  1989,  37:  57 
• 1b Blumenkopf TA. Overman LE. Chem. Rev.  1986,  86:  857 
• 1c Babudri F. Fiandanese V. Marchese G. Punzi A. Synlett  1995,  817 ; and references therein
• For example, see:
• 2a Denmark SE. Sweis RF. In Metal-Catalyzed Cross-Coupling Reactions   Vol. 1:  de Meijere A. Diederich F. Wiley-VCH; Weinheim: 2004.  p.163 
• 2b Denmark SE. Tymonko SA. J. Am. Chem. Soc.  2005,  127:  8004 
• 2c Itami K. Yoshida J. Synlett  2006,  157 
• 3 Kusumoto T. Nishida K. Hiyama T. Bull. Chem. Soc. Jpn.  1990,  63:  1947 
• 4 Delas C. Urabe H. Sato F. Chem. Commun.  2002,  272 
• 5 Ogoshi S. Ueta M. Oka M. Kurosawa H. Chem. Commun.  2004,  2732 
• 6 Hoshi M. Kawamura N. Shirakawa K. Synthesis  2006,  1961 
• 7a Hatanaka Y. Hiyama T. J. Org. Chem.  1988,  53:  918 
• 7b Hatanaka Y. Matsui K. Hiyama T. Tetrahedron Lett.  1989,  30:  2403 
• 8a Nishihara Y. Ikegashira K. Mori A. Hiyama T. Chem. Lett.  1997,  1233 
• 8b Nishihara Y. Ikegashira K. Hirabayashi K. Ando J. Mori A. Hiyama T. J. Org. Chem.  2000,  65:  1780 
• 8c Nishihara Y. Ando J. Kato T. Mori A. Hiyama T. Macromolecules  2000,  33:  2779 
• 8d Yang C. Nalan SP. Organometallics  2002,  21:  1020 
• 8e Mio MJ. Kopel LC. Braun JB. Gadzikwa TL. Hull KL. Brisbois RG. Markworth CJ. Grieco PA. Org. Lett.  2002,  4:  3199 
• 9a Mori A. Kondo T. Kato Y. Nishihara Y. Chem. Lett.  2001,  286 
• 9b Bertus P. Halbes U. Pale P. Eur. J. Org. Chem.  2001,  4391 
• 9c Halbes U. Bertus P. Pale P. Tetrahedron Lett.  2001,  42:  8641 
• 9d Halbes U. Pale P. Tetrahedron Lett.  2002,  43:  2039 
• 12 Hoshi M. Nakayabu H. Shirakawa K. Synthesis  2005,  1991 
• 13a Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 
• 13b Suzuki A. In Metal-Catalyzed Cross-Coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; Weinheim: 1998.  p.49 
• 13c Miyaura N. In Metal-Catalyzed Cross-Coupling Reactions, Vol. 1   de Meijere A. Diederich F. Wiley-VCH; Weinheim: 2004.  p.41 
• 15 Cai M. Hao W. Zhao H. Song C. J. Chem. Res., Synop.  2003,  485 
• 16 Hofmeister H. Annen K. Laurent H. Wiechert R. Angew. Chem., Int. Ed. Engl.  1984,  23:  727 
• 17 Zweifel G. Backlund SJ. J. Am. Chem. Soc.  1977,  99:  3184 
• 18a Zweifel G. Whitney CC. J. Am. Chem. Soc.  1967,  89:  2753 
• 18b Hoshi M. Shirakawa K. Chem. Commun.  2002,  2146 
• 19 Hoshi M. Arase A. Synth. Commun.  1997,  27:  567 
• 20a McMurry JE. Scott WJ. Tetrahedron Lett.  1983,  24:  979 
• 20b Ritter K. Synthesis  1993,  735 
• 21a Zweifel G. Brown HC. Org. React.  1963,  13:  1 
• 21b Brown HC. Organic Syntheses via Boranes   Wiley-Interscience; New York: 1975. 

10

Compound 2a was formed in about 90% GC yield based on Me₃SiC≡CBr employed; see ref. 6.

11

Addition of CuI was not necessary because CuI had already been used for the cross-coupling reaction of 1a with Me₃SiC≡CBr.

14

Compound 2a was formed in 82% (0.375 mL of H₂O) or 84% GC yield (0.75 mL of H₂O), based on Me₃SiC≡CBr employed.

22

After column chromatography, the product in eluates should be stored in the refrigerator to avoid decomposition.