Granular Indium Barbier Allylation of Carbonyl Compounds: A More Economical Protocol

Abstract

A new protocol, amenable to be used in large-scale preparations, using a cheaper form of indium metal and mild warming is reported for the Barbier allylation of aldehydes and ketones with allyl bromide in N,N-dimethylformamide.

Key words

indium - carbonyl complexes - allylation - homoallylic alcohols - addition reactions

References and Notes

• 1a Nair V. Ros S. Jayan CN. Pillai DS. Tetrahedron  2004,  60:  1959 
• 1b Poddlech J. Maier TC. Synthesis  2003,  633 
• 1c Cintas P. Synlett  1995,  1087 
• 2 Lin CJ. Tetrahedron  1996,  52:  5643 
• 3 Preite MD. Cuellar MA. Chem. Commun.  2004,  1970 
• 6 It was previously reported that when a THF suspension of In powder and allyl bromide was stirred for 90 min, and then allowed to react with a ketone, a yellow-green color developed: Capps SM. Clarke TP. Charmant JPH. Höppe HAF. Lloyd-Jones GC. Murray M. Peakman TM. Stentiford RA. Walsh KE. Worthington PA. Eur. J. Org. Chem.  2000,  963 
• 8 Das S. Hung CH. Goswani S. Inorg. Chem.  2003,  42:  5153 ; and references cited therein
• 9a Finet JP. Ligand Coupling Reactions with Heteroatomic Compounds   Pergamon Press; Oxford: 1998. 
• 9b Donnelly DMX. Finet JP. Guiry PJ. Nesbitt K. Tetrahedron  2001,  57:  413 
• Radical reactions initiated by In:
• 10a Miyabe H. Naito T. Org. Biomol. Chem.  2004,  2:  1267 
• 10b Miyabe H. Ueda M. Nishimura A. Naito T. Org. Lett.  2002,  4:  131 ; and references cited therein
• For a study on the direct binding of carbonyl compounds to the In surface, see:
• 11a Tachikawa H. Kawabata H. J. Mater. Chem.  2003,  13:  1293 
• 11b Tachikawa H. Kawabata H. J. Organomet. Chem.  2003,  678:  56 
• 11c Tachikawa H. Kawabata H. Phys. Chem. Chem. Phys.  2003,  5:  3587 
• 12 Araki S. Ito H. Butsugan Y. J. Org. Chem.  1988,  53:  1831 
• 13 Chan TH. Yang Y. J. Am. Chem. Soc.  1999,  121:  3228 
• 14 For a similar study on the indium-mediated Reformatsky reaction, see: Babu SA. Yasuda M. Shibata I. Baba A. Org. Lett.  2004,  6:  4475 
• 15 For a similar NMR analysis of Ga and Al allyl derivatives, see: Takai K. Ikawa Y. Org. Lett.  2002,  4:  1727 
• It is also possible that no actual organometallic compounds form under Barbier conditions, but rather a series of single electron-transfer processes occur at the metal surface, as previously proposed for other metals:
• 16a Molle G. Bauer P. J. Am. Chem. Soc.  1982,  130:  3481 ; and references cited herein
• 16b Li CJ. Zhang WC. J. Am. Chem. Soc.  1998,  120:  9102 
• 17 Chen W. Liu Y. Chen Z. Eur. J. Org. Chem.  2005,  1665 
• 18 Solin N. Kjellgren J. Szabò KJ. J. Am. Chem. Soc.  2004,  126:  7026 
• 19 Huang Y. Liao Y. J. Org. Chem.  1991,  56:  1381 
• 20 Doucet H. Santelli M. Tetrahedron: Asymmetry  2000,  11:  4163 

4

Purchased from Alfa Aesar Chemical Co. A somewhat more expensive indium wire, 99.99% pure, purchased from Indium Corporation of America, also gave identical results.

5

Indium is so soft that an ingot of metal can be easily flattened by pressing with a spatula (or even strong fingernails) between two pieces of clean filter paper, and then cut into small pieces of a few square millimeters with scissors.

7

If the reaction is run in water instead of DMF, only a slightly greenish yellow color is observed in the reaction suspension that turns to an orange-ocher color when the reaction is complete. In this case, a better indication of reaction progress is to observe the metal surface, dark at the beginning, and shiny at the end.