Prins reaction yields 1,3-dioxanes

The method ZC3Z + C is used for the preparation of reduced pyrimidines, oxazines and thiazines as well as for dioxanes, dithianes and oxathianes as mentioned above (e.g. 258 — 257, 259 Z, Z = NH, O, S). The Prins reaction yields 1,3-dioxanes (77S661) it involves the acid-catalyzed condensation of alkenes with aldehydes with 1,3-diols as intermediates. 

PdCb-CuCb catalyzes the condensation of branched-chain alkenes with formaldehyde to give the l,3-dioxanes 96a and 96b (Prins reaction)[73]. The yields are much higher than in the conventional acid-catalyzed Prins reaction. 

The limitation on this simple dioxan synthesis is that unbranched olefins are unreactive. Nevertheless, the method offers advantages over the alternative acid-catalyzed (Prins) reaction in regard to both product yield and selectivity. 

Simple mono- and disubstituted alkenes react to yield 1,3-diols, when the Prins reaction is carried out at elevated temperature. Diols originate from the attack of water on carbocation 18, or through the acidolysis of dioxanes under the reaction conditions. When the reaction is conducted in acetic acid, monoacetates are formed by acetate attack on 18. Dienes resulting from the dehydration of intermediate diols are the products of the transformation of more substituted alkenes. Monoacetates and diols may react further to yield 1,3-diol diacetates. When the Prins reaction... 

Dioxacyclohexanes can be produced in excellent yields from aliphatic or aryl-substituted alkenes.64 Dilute sulfuric acid at or above room temperature with paraformaldehyde appears to give the best results. Dioxane-water or acetic acid as solvent was found to afford increased yields in the Prins reaction of arylalkenes. 

Prins reaction (cf 10, 186-187). Dimethylaluminum chloride is an effective catalyst for the ene addition of formaldehyde (as trioxane or paraformaldehyde) to mono- and 1,2-disubstituted alkenes.5 When 1.5-2.0 equiv. of the Lewis acid is used, homoallylic alcohols are obtained, usually in high yield. y-Chloro alcohols, formed by cis-addition of -Cl and -CH2OH to the double bond, are sometimes also observed when only 1 equiv. of the Lewis acid is present. The advantage of this reaction over the Prins reaction (using HC1) is that m-dioxanes are not formed as by-products, because formaldehyde no longer functions as a nucleophile when complexed to the Lewis acid. 

In an early step in an enantioselective total synthesis of certain prostaglandins <88T4989,92T10345>, application of the Prins reaction conditions to an unsaturated bicyclic lactone or ether (Equation (11)) afforded tricyclic heterocycles (31) containing cyclopentane-fused tetrahydrofuran and 1,3-dioxane units in 4-10% yield. The major products in each case were bicyclic diacetate derivatives of the starting material. 

Terpenoid Synthesis from Isoprene.—Interest continues in new syntheses of iso-prene and its derivatives the dioxan (37) is obtained108 in good yield by the Prins reaction of methylallyl chloride with formaldehyde (cf. Vol. 5, p. 8) free-radical addition of isopropyl alcohol to vinyl acetate yields compound (38) which gives isoprene by acid-catalysed reaction over alumina.109 (Z)-2-Methylbut-2-en-l-ol and dimethylallyl alcohol are readily available from frans-crotyl alcohol.110... 

Dioxans - Several syntheses of this ring are notable. In a modification of the Prins reaction, self-condensation of aliphatic aldehydes with styrene has given 4-phenyl-1,3-dioxans [such as ( 195)] in which the alkyl group is in the equatorial position.203 Good yields of the 1,3-dioxin-4-ones (196 R1 and R2 alkyl or aryl) have been obtained by reaction of aldehydes or ketones with diketene and Aliquat 336 (MeN[ (CH2 bMe] 3C1). 20 Condensation of aryl aldehydes with the diol (197) also gave good yields of the... 

Formaldehyde can be coupled to an alkene in the presence of an acid to give a diol (152) or a 1,3-dioxane derivative (154) in what is known as the Prins reaction. l Allylic alcohols such as 153 can also be produced in this reaction. Camphene (155) reacted with formaldehyde and acid to give a 1 1 mixture of allylic alcohol 156 and the acetate 157, in 94% yield. Scandium tiiflate has been used to prepare tetrahydropyran-4-ol derivatives from aldehydes and homoallylic alcohols via a Prins-type cyclization. 3... 

In a fluorous hiphasic system, Hf(OTf)4 has been found to be an efficient catalyst for the Prins reaction of a-methyl styrene with paraformaldehyde using a low catalyst loading. The reaction proceeded smoothly and afforded the corresponding 1,3-dioxane in good yield. The catalyst was selectively soluble in the fluorous phase and could be recovered simply by phase separation and reused three times without decrease of yield (eq 8). ... 

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