TETRAHEDRON LETTERS Tetrahedron Letters 43 (2002) 2091–2094 Pergamon Synthesis and structure of 2-aryl-5,5-disubstituted-1,3-dioxanes and conversion into chiral (1,1,1-trishydroxymethyl) methane derivatives John M. Gardiner, a, * Paul Mather, a Ramy Morjan, a Robin G. Pritchard, a John E. Warren, a Malcolm L. Cooper, a Abd El-Rahman S. Ferwanah b and Omar S. Abu-Tiem b a Department of Chemistry, UMIST, Manchester M60 1QD, UK b Department of Chemistry, Al -Azhar University of Gaza, PO Box 1277, Gaza, Palestine Received 6 November 2001; revised 4 January 2002; accepted 24 January 2002 Abstract—Pentaerythritol, (1,1,1-trishydroxymethyl)methyl methane and (1,1,1-trishydroxymethyl)nitromethane are converted into 2-aryl-5,5-bis(hydroxymethyl), 2-aryl-5-hydroxymethyl-5-methyl- or 2-aryl-5-hydroxymethyl-5-nitro-1,3-dioxanes and a range of derivatives. X-Ray and NMR analysis establishes that the latter is obtained as a single diastereomer whose structure is unambiguously determined. These materials can be elaborated to chiral derivatives of the starting (1,1,1-trishydroxymethyl) methanes. © 2002 Elsevier Science Ltd. All rights reserved. Pentaerythritol (1), (1,1,1-trishydroxymethyl)methyl methane (2) and (1,1,1-trishydroxymethyl)nitromethane (3) are readily available and inexpensive materials. They have numerous potential uses for synthesis. 1 We have been interested in elaborating these materials to fully differentiated multifunctional intermediates, spe- cifically of type 6 (i.e. with at least two of R 1 –R 3 being protected with orthogonal protecting groups), with at least three differentiated functionalities for further elab- oration. We report here the conversion of 2 and 3 into such chiral derivatives and provide structural proof of the diastereochemical outcomes of intermediate dioxane formation with 3. All approaches used the potential of benzylidene or p -methoxybenzylidene acetals to select two hydroxy- methyl groups, with subsequent reductive acetal half- opening to differentiate the two acetal oxygens. Pentaerythritol has four equivalent groups and so an initial further differentiation is required. Although it is possible to obtain monoacetals by direct reaction of pentaerythritol, and subsequently to differentiate the two remaining hydroxyls, product separations due to the over-protection potential at each step are generally required. 2 The obvious strategy is initially to derivatize one group, and thus work proceeded by preparation of the known 3 orthoformate 7 (using triethyl orthofor- mate). The one remaining free hydroxyl was derivatized as its acetate or as a t -butyldiphenyl silyl ether, and in each case the orthoformate was removed using water to give 4 or 5, respectively. 4 In both cases, the main issue was the incomplete removal of the orthoformate pro- tecting group. We ascertained that this could be largely controlled in the case of acetate 4. The monoacetyl pentaerythritol (4) could be obtained in about 80% yield on prolonged warming during hydrolysis. How- ever, previously when we conducted the aqueous cleav- age reaction without heating, the unknown formyl derivative 8 was obtained in 90% yield. In the case of the silylated derivative 5, however, even on prolonged heating, a mixture of triol 5 and the novel formyl diol 9 was always obtained. Purified 4 and 5 were converted to the corresponding benzylidene acetals 10 and 12, respectively, but yields were variable, around 30–40% after purification. In the case of the reaction forming 10, this was in part due to concomi- * Corresponding author. Tel.: +44 (0)161 200 4530; fax: +001 (510) 217 2371; e-mail: john.gardiner@umist.ac.uk 0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0040-4039(02)00176-4