Pergamon Tetrahedron Letters 40 (1999) 1627-1630 TETRAHEDRON LETTERS Highly Effective Synthesis of 4-1talo-Tetrahydropyrans Via A Highly Diastereoselective in situ Prins-Type Cyclization Reaction Jun Yang, Ganapathy S. Viswanathan and Chao-Jun Li* Department of Chemistry Tulane University New Orleans, Louisiana 70118, USA Received 10 November 1998; accepted 22 December 1998 Abstract: The reaction of aldehyde with homoaUylalcohols mediated by indium trichloride generated 4-chlorotetrahydropyrans in high yields and with high stereoselectivity. The same type of compounds can be generated through a single step, multi-component coupling between aldehyde and allyl bromide mediated by indium O 1999ElsevierScienceLtd. All rightsreserved. The acid-catalyzed olefin-aldehyde condensation, known as the Prins reaction, is a fundamental reaction for carbon-carbon bond formation.1 However, the synthetic application of this important reaction has been underexplored due to the classical conditions of strong acids (e.g., sulfuric acid) and high reaction temperatures, which often generated a range of products. The pyran ring is part of the backbone of various important carbohydrates and natural products. 2 Recently, during our investigation of indium-mediated reactions under neat conditions (Eq. 1),3 we sometimes observed an instant polymerization of the reaction mixture. Although they initially eluded our attention, a subsequent analysis of the mixture revealed the presence of small amount of tetrahydropyran derivatives.4 Br OH o ,n 2 .~ + ~Br " + (1) R H R R R R R= Ph- 54% 25% R= MePh-24% 17% To explain the formation of the tetrahydropyran derivatives, we postulated that the product was generated through a tandem carbonyl allylation-hemiacetal formation-Prins reaction (Scheme 1). In order to test the viability of the proposed reaction pathway, we conceived that the reaction of a homoallyl alcohol with an aldehyde should generate the corresponding tetrahydropyran derivatives in the presence of an indium halide. In addition, the reaction could be pushed to a single 4-halo derivative rather than a mixture of alcohol and 0040-4039/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved. PH: S0040-4039(99)00027-1