Rhenium(VII) Catalysis of Prins Cyclization Reactions

Abstract

The rhenium(VII) complex O 3 ReOSiPh 3 are particularly effective catalyst for Prins cyclizations using aromatic and α,β-unsaturated aldehydes. The reaction conditions are mild and the highly substituted 4-hydroxy tetrahydropyran products are formed stereoselectively. Rhenium(VII) complexes appear to spontaneously form esters with alcohols and to directly activate electron rich alcohols for solvolysis. Re 2 O 7 and perrhenic acid were equally effective in catalyzing these cyclizations.Osborn reported that the Re(VII) complex O 3 ReOSiPh 3 1 was a highly effective catalyst for allylic alcohol isomerizations. 2 Grubbs studied Osborn's reaction and found that O 3 ReOSiPh 3 isomerizes allylic alcohols stereospecifically. 3 Both Osborn and Grubbs invoked a concerted [3,3] rearrangement of allylic perrhenate esters to explain this very facile and selective isomerization ( Figure 1). 2,3 An alternative mechanism was invoked to explain some of the peculiarities of the reaction. Osborn proposed an ionic mechanism to explain the kinetics for formation of Z-alkenes, 2b and Grubbs invoked a similar mechanism to explain the loss of optical purity with certain electron-rich allylic alcohol substrates (Figure 1). 3 The proposed ionic mechanism attracted our attention because it suggested that Re(VII) complexes might activate and solvolyze electron rich alcohols. We report herein a Prins cyclization initiated by Re(VII) catalysts 4 based on this concept that is both very mild and shows unusual selectivity.Prins cyclization reactions between homoallylic alcohols and aldehydes are generally promoted by strong Bronsted or Lewis acids. 5 If halide counterions are present, they are incorporated at the 4-position of the newly formed tetrahydropyran (THP) ring. 5 Oxygen atoms can be captured at the 4-position of the THP ring, 6 although most acids lead to esters that must be hydrolyzed to form 4-hydroxy THP products. 7 Most Prins cyclizations use superstoichiometric acid to promote the reaction because the acid counterion is trapped in the product, thus consuming the acid. Cyclization and trapping leads to perrhenate ester 6. Ester exchange with Ph 3 SiOH would regenerate the catalyst. The proposed Re(VII) initiated reaction has several potential advantages over traditional Prins cyclization reactions. It avoids the use of strong acid, and the facile transesterification of perrhenate esters with alcohols allows turnover and makes the system catalytic. Additionally, the alcohol product would be produced directly from the reaction rather than requiring a subsequent hydrolysis step. These potentially attractive features led us to explore this reaction. Table 1 presents an initial exploration of the Re(VII) catalyzed Prins cyclization. The aldehyde and homoallylic alcohol were selected with the same substituent to avoid complications from oxonia-Cope induced side-chain exchanges. 8 O 3 ReOSiPh 3 catalyzed the Prins cyclization effectively in most solvents except acetonitrile. Although the reaction was effective using 1 mol % cata...

Contribution to elucidation of the mechanism of preparation of 2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol

“…These two types of product may both be formed during the reaction and the selectivity depends on the reaction conditions, especially the type of catalyst [3]. Lewis [4][5][6][7] or Brønsted acids (inorganic [1,8], organic [9], or ion exchangers [10,11]) may be used as catalysts; occasionally, heteropolyacids [12], organometallic complexes [13] or heterogeneous aluminosilicates [14] are used. The accepted mechanism [15] involves hemiacetal formation in the first step followed by cyclization to form the substituted tetrahydropyranol or dihydropyrans (Fig.…”

“…Sometimes (e.g., condensation of benzaldehyde with isoprenol) it is possible to use a strong acid catalyst to selectively prepare the substituted tetrahydropyranol [1,15]. Substituted tetrahydropyrans may also be prepared selectively by use of strong nucleophiles [2,6,7,13]. If the desired product is a substituted tetrahydropyranol (in this work Florosa), the literature offers only information about changes of the reaction conditions (lower temperature) or addition of water.…”

Synthesis of tetrahydropyranyl diarylheptanoids from Dioscorea villosa

“…15 In 2008, Tadpetch and Rychnovsky reported a variation of the Prins cyclization reaction which was catalyzed by O 3 ReOSiPh 3 or O 3 ReOH as a convenient method to construct 4-OH THPs. 16 This protocol was highly effective with electron-rich aromatic aldehydes. In addition, both equatorial 4-OH and axial 4-OH products are possible using this catalytic system depending on the electronic nature of both the aldehyde and homoallylic alcohol.…”

2.03 Prins Reactions and Carbonyl, Imine, and Thiocarbonyl Ene Reactions

“…225 The rhenium(VII) complex O 3 ReOSiPh 3 is particularly effective for the Prins cyclizations of aromatic and a,b-unsaturated aldehydes leading to 4-tetrahydropyranols. 226 Alkoxonium ion precursors for Prins cyclizations can also be generated by oxidation of homoallylic benzyl ethers with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in the presence of SnBr 4 or In(OTf) 3 . 227 Use of TiF 4 as the Lewis acid leads to 4-fluorotetrahydropyrans.…”