Unexpected Lewis Acid Mediated Reactions of 1-Arylbut-3-en-1-ols with Trimethyl Orthoformate - A New Synthesis of Homoallyl Ethers and Chlorides

Abstract

L e w i s A c i d M e d i a t e d T r a n s f o r m a t i o n o f 1 -A r y l b u t -3 -e n -1 -o l sAbstract: 1-Arylbut-3-en-1-ols react with trimethyl orthoformate in the presence of Lewis acids like InCl 3 , BiCl 3 , TiCl 4 , or BF 3 ·OEt 2 providing homoallyl ethers or homoallyl chlorides in high yields.Relatively little is known about reactions between ortho esters and alcohols. 1 Among the best known transformations of this kind is the acid-catalyzed transesterification of simple ortho esters with an excess of a less volatile alcohol. The resulting products are higher ortho esters with three identical OR groups. More difficult to achieve is the selective access to mixed ortho esters as no general preparation method is known. Albizati et al. could demonstrate that the synthesis of mono-exchanged products can be achieved by reacting an alcohol with a large excess of an ortho ester in the presence of MgCl 2 . 2 This method has also been applied to the synthesis of a mixed ortho ester of a homoallyl alcohol. Using the substrates in almost equimolar amounts leads, of course, to mixtures of products derived from mono-, bis-and tris-exchange.When the reaction of the homoallyl alcohol with the orthoformate is not performed with MgCl 2 , but in the presence of other Lewis acids like SnCl 4 , 3a,b SnBr 4 , 3a,b ZnBr 2 , 3a,b MgI 2 3b or Mg(CO 2 CF 3 ) 2 , 3b the stereoselective formation of tetrahydropyrans is observed. It can be assumed that the reaction sequence starts with the Lewis acid mediated transformation of the orthoformate A into the electrophilic dioxenium cation B, 4 which in turn is attacked by the allyl alcohol C as a nucleophile to yield the mixed ortho ester D. The latter is transformed into the dioxenium ion E -again in a Lewis acid mediated reaction. The sequence is completed by the intramolecular cationic olefin cyclization of E to give the tetrahydropyran F (Scheme 1). 3,5 Such intramolecular Prins reactions have been developed into an efficient method for the synthesis of tetrahydropyrans. 6 In particular, allylsilanes and related compounds have been employed as intramolecular traps for oxocarbenium ions which are generated in various ways. 7During the course of our studies towards the construction of pyrans and pyrones by means of cationic cyclizations 8 we focused on the development of a general method for the use of ortho esters as precursors for dioxenium ions in intramolecular olefin cyclizations. For this purpose, we chose the reactions between 1-arylbut-3-en-1-ols and orthoformates. To start with, 1-phenylbut-3-en-1-ol (1a) was prepared in 90% yield by reacting benzaldehyde with allylmagnesium bromide in Et 2 O. 9 Subsequently, one equivalent 1a was reacted with one equivalent trimethyl orthoformate (TMOF, 2) in the presence of one equivalent of InCl 3 at room temperature (Scheme 2). InCl 3 is a reagent that has proved to be an efficient Lewis acid in a number of Prins reactions. 10 The transformation proceeded cleanly and without any side reactions. Surprisingly, instead of the expected t...