Prins-type cyclization

In the case of terminal alkynes having oxygenated functions in the linear chain (Scheme 10, route D), Martin, Padron, and coworkers found that homopropargylic alcohols reacted properly, yielding 2-substituted dihydropyrans as sole products, probably via a Prins-type cyclization. This cyclization provides a new approach toward 2-alkyM-halo-5,6-dihydro-2//-pyrans through a concomitant C-C and C-O bond formation (Scheme 21) [35]. 

Scheme 21 Plausible mechanism for Prins-type cyclization promoted by iron(III) halides...

Scheme 28 Halide exchange with halogenated solvents during the acetylenic Prins-type cyclization...

Whereas the Prins-type cyclizations reported in this and the preceeding chapter were performed using stoichiometric amounts of Fe salts as Lewis acids, a breakthrough in the field of catalysis was reported in 2009 when the first iron-catalyzed Prins- and aza-Prins cyclization was reported. The catalytic system, which is obtained by combining catalytic amounts of an iron salt with trimethylsilyl halides as a halide source, is widely applicable and promotes the construction of substituted six-membered oxa- and aza-cycles (Scheme 33) [44]. 

A fourfold anionic sequence which is not initiated by a Michael but an aldol reaction has been reported by the group of Suginome and Ito (Scheme 2.129) [295]. In this approach, the borylallylsilane 2-573 reacts selectively in the presence of TiCl4 with two different aldehydes which are added sequentially to the reaction mixture. First, a Lewis acid-mediated allylation of the aldehyde with 2-573 takes place to form a homoallylic alcohol which reacts with the second aldehyde under formation of the oxenium ion 2-574. The sequence is terminated by a Prins-type cyclization of 2-574 and an intramolecular Friedel-Crafts alkylation of the intermediate 2-575 with formation of the fraws-1,2-be rizoxadeca lines 2-576 as single diastereomers. 

Tetrahydropyrans hydroxylated at the 4-position have good synthetic value [113]. Although many synthetic methods have been reported [17-23,114,115], the search for potential alternate approaches and the development of eco-friendly and high-yielding reactions resulted in the development of a method that poses less problems for the environment. Synthesis of tetrahydropyranol derivatives can be achieved through the Prins-type cyclization reaction of homoallylic alcohols with aldehydes using bismuth triflate as catalyst in [bmim]PF6 solvent system [108] (Fig. 22). 

An intramolecular Prins-type cyclization of a-acetoxy acetals 239 is catalyzed by (7-PrO)2Ti(NTf)2 and provides a stereoselective route to 2,6- A-substituted 3,6-dihydropyrans 240 (Equation 107, Table 5) <2004BKC1625>. 

An iron(m)-catalyzed Prins-type cyclization between a homopropargylic alcohol and an aliphatic aldehyde provides 2-alkyl-3-halo-3,6-dihydropyrans in excellent yield (Equation 113). The solvent and the catalyst equally contribute to the halogen observed in the product therefore, a straightforward choice of catalyst and solvent provides a route to either monochlorinated 252 or monobrominated 3,6-dihydropyrans 253 (Equation 113). Indium compounds have also shown potential as catalysts for this process, with high yields also obtained <20030L1979>. 

An acid-mediated Prins type cyclization of enol ether 328 followed by basic hydrolysis of the intermediate trifluoro-acetate provides a key step during synthetic studies toward leucascandrolide A (Equation 139) <20010L755>. The acid-promoted Prins cyclization of enol ethers attracts much attention <20030L1499, 2004HCA2750, 2005OL2683>. 

Yang, J., Viswanathan, G. S., Li, C.-J. Highly effective synthesis of 4-halotetrahydropyrans via a highly diastereoselective in situ Prins-type cyclization reaction. Tetrahedron Lett. 1999,40,1627-1630. 

Lopez, F., Castedo, L. and Mascarenas, J.L. (2002) Atom-efficient assembly of 1,5-oxygen-bridged medium-sized carbocycles by sequential combination of a Ru-catalyzed alkyne-alkene coupling and a Prins-type cyclization. Journal of the American Chemical Society, 124, 4218-4219 Lopez, F., Castedo, L. and Mascarenas, J.L. (2005) Practical asymmetric approach to medium-sized carbocycles based on the combination of two Ru-catalyzed transformations and a Lewis add-induced cydization. Organic Letters, 7, 287—290. 

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 separate investigation by Porco, Jr. and coworkers, the isatin derivative 134 (R = H) was converted to spirooxindole pyran 141 in 13 1 dr and 99% ee by means of a Prins-type cyclization involving homoaUyhc alcohol 140 [79]. The diastereos-electivity of the transformation has been proposed to arise from a preferred chairlike transition state with the benzenoid ring of oxindole in a pseudoequatorial orientation. Spirooxindole oxepenes also were prepared via diastereoselective spiro-annulation of isatins with bis-homoallyhc alcohols. 

Prins-type cyclization reactions in natural product synthesis 12COC1277, 13EJ01193. 

Cyclizations. In addition to the use of SEM-Cl as a means of one-carbon homologation, it has also been employed in the generation of acetals capable of undergoing a variety of cy-clization events. Alkylation of allylic alcohols with SEM-Cl permits haloacetalization to afford di- and trisubstituted 1,2-dioxanes (eq 28). Alternatively, homoallylic alcohols permit Prins-type cyclizations (eq 29) to furnish 2,4,5-trisubstituted tetrahydro-pyrans. Transition metals can also be employed to promote the formation of substituted benzofurans (eq 30). ... 

This formal [2h-2h-2] alkyne/alkene/carbonyl cycloaddition proceeds through the opening of the cyclopropyl carbene intermediate 1-4 by the carbonyl group to form oxonium cation 1-5, which undergoes nucleophilic attack by the vinylgold intermediates in a Prins-type cyclization to give tetrahydropyranyl cation 1-6. 

Barluenga J, Fernandez A, Di6guez A, Rodriguez F, Fananas FJ (2009) Gold- or platinum-catalyzed cascade processes of alkynol derivatives involving hydroalkoxylation reactions followed by Prins-type cyclizations. Chem-Eur J 15 11660-11667. doi 10.1002/ chem.200900856... 

---