Montmorillonite K-10 as a mild acid for the Nicholas reaction Fernando R. Pinacho Criso ´stomo, Romen Carrillo, Toma ´s Martı ´n and Vı ´ctor S. Martı ´n * Instituto Universitario de Bio-Orga ´nica ‘‘Antonio Gonza ´lez’’, Universidad de La Laguna C/Astrofı ´sico Francisco Sa ´nchez, 2, 38206 La Laguna, Tenerife, Spain Received 20 January 2005; revised 16 February 2005; accepted 22 February 2005 Abstract—The use of Montmorillonite K-10 as a convenient acid component in the Nicholas reaction is described. Its use permits functional selectivity, inter- and intramolecular reactions and convenience in the experimental conditions. A four-step one-pot [Co 2 (CO) 6 –acetylene complex formation, THP-removal, cyclization and complex cleavage] process permits the direct synthesis of 2-ethynyl-tetrahydrofuran from 6-(tetrahydro-2H-pyran-2-yloxy)hex-1-yn-3-ol. Ó 2005 Elsevier Ltd. All rights reserved. Since its discovery, 1 the Nicholas reaction has gained great significance as a powerful synthetic tool due to its high versatility and because it enables the introduc- tion of different functional groups. It is for this reason that there have been many applications for this reaction varying both the structure of the cation and the nucleo- phile. 1c,2 Hitherto, this reaction implied the use of either a protic acid or a Lewis acid, mainly trifluoromethane- sulfonic acid, HBF 4 ®OEt 2 and BF 3 ®OEt 2 (Fig. 1). How- ever, these are unstable and harsh substances and also complicate the application of this reaction to systems with acid-sensitive functionalities. With these facts in mind and taking into account the use lately of clays as acid, we decided to investigate the use of solid materials as the acid source in order to achieve selectivity, mild- ness and simplicity at the work-up step. After trying different solid acidic materials such as silica gel, Amber- lysts, Ò and Dowex Ò we found Montmorillonite K-10 to be a mild, effective and safe acid for the Nicholas reaction. The use of solid acidic materials such as Montmorillon- ite clays is very attractive since they can easily be recov- ered from the reaction mixture by simple filtration and can be reused after activation, thereby making the pro- cess economically viable. 3 Montmorillonite K-10 has been reported to promote acid-dependent reactions such as the formation of dimethyl acetals 4 and enamines, 5 as well as Ferrier rearrangements. 6 To the best of our knowledge it has never been employed as an acid in the Nicholas reaction. The Co 2 (CO) 6 –propargylic complexes used were easily synthesized via nucleophilic addition of the lithium salt of the alkyne to the corresponding aldehyde, and the resulting propargylic alcohols were complexed with Co 2 (CO) 8 . To a solution of Co 2 (CO) 6 –alkyne complex in CH 2 Cl 2 or toluene was directly added Montmorillo- nite K-10. Once the reaction had finished, it was filtered, the alkyne was decomplexed with CAN in acetone, and the crude product purified by chromatographic column. As shown in Table 1, Montmorillonite K-10 effectively promotes the formation of five- and six-membered cyclic ethers (entries 1–3) in very high yields at room tempera- ture although more slowly than does BF 3 ®OEt 2 . It is worth noting that the presence of a THP-protected alco- hol did not imply a significant decrease in the yield. However, it was necessary to use slightly more energetic conditions, such as refluxing dichloromethane or, even better, toluene at 60 °C (entry 2). 7 This fact suggests that Montmorillonite K-10 also favours the tetrahydropyran- yl ether cleavage, before promoting the Nicholas reaction. 0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.02.118 Keywords: Nicholas reaction; Cyclic ether; Cobalt. * Corresponding author. Tel.: +34 922318579; fax: +34 922318571; e-mail: vmartin@ull.es R 3 R 2 OR R 1 Co(CO) 3 (OC) 3 Co R 3 R 1 Co(CO) 3 R 2 (OC) 3 Co R 3 R 2 Nu R 1 Co(CO) 3 (OC) 3 Co Nu Acid Figure 1. Nicholas reaction. Tetrahedron Letters 46 (2005) 2829–2832 Tetrahedron Letters