Prins-type reaction

The synthesis of different substituted finans by cyclization of 4-pentynones using potassium tert-butoxide in DMF was reported <96TL3387>. Dihydrofuran 32 can be prepared by a destannylative acylation of l-[(2-methoxyethoxy)methoxy]-2-(phenylsulfonyl)-2-(tributylstannyl)-cyclopropane. Treatment of 32 with BFj-EtjO yields 3-acyUurans via an intramolecular Prins-type reaction of the resulting oxonium ion intermediate <96TL4585>. 

Cho et al. reported a indium trichloride-catalyzed intramolecular Prins-type reactions of compounds having both the functionalities of homoallyl alcohol and acetal moiety. The intramolecular Prins cycliza-tions were performed using indium trichloride in chloroform or 25%... 

Mascarenas developed a synthetic method to 1,5-oxygen-bridged medium-sized carbocycles through a sequential ruthenium-catalyzed alkyne-alkene coupling and a Lewis-acid-catalyzed Prins-type reaction (Eq. 3.45). The ruthenium-catalyzed reaction can be carried out in aqueous media (DMF/H20 = 10 1).181... 

Another attractive domino approach starts with an aldol reaction of preformed enol ethers and carbonyl compounds as the first step. Rychnovsky and coworkers have found that unsaturated enol ethers such as 2-237 react with different aldehydes 2-238 in the presence of TiBr4. The process consists of an aldol and a Prins-type reaction to give 4-bromotetrahydropyrans 2-239 in good yields, and allows the formation of two new C-C-bonds, one ring and three new stereogenic centers (Scheme 2.56) [131]. In the reaction, only two diastereomers out of eight possible isomers were formed whereby the intermediate carbocation is quenched with a bromide. 

A novel gold catalyzed example of three-component addition was recently reported by Shi et al. (Equation 8.44) [106]. Terminal aryl alkynes, alcohols and 2-(arylmethy-lene) cyclopropylcarbinols provided an intermolecular tandem hydroalkoxylation/ Prins-type reaction to form 3-oxabicyclo[3.1.0]hexanes from simple materials and under mild conditions, catalyzed by the system AuClPPh3/AgOTf. The proposed mechanism for this reaction is shown in Scheme 8.19. 

Formaldehyde reacts with isoeugenol [l-(3-methoxy-4-hydroxyphenyl)propene] in alkaline medium to give a 1,3-dioxane derivative via an unusual Prins-type reaction.192... 

Kinetics of isomerization of glyceraldehyde to dihydroxyacetone—and the formation of pyruvaldehyde from both— have been studied in sub- and super-critical water. Formaldehyde reacts with isoeugenol [l-(3-methoxy-4-hydroxyphenyl)propene] in alkaline medium to give a 1,3-dioxane derivative via an unusual Prins-type reaction. The potential-energy surface for the equihbriimi, HCO - - HCN H2CO - - CN, has been calculated by ab initio methods. 

It may be clear that this reaction involves the formation of one C-C and one C-0 bond during the linking of three molecules I, II, and methanol from the solvent. The combination of an expectedly strong electrophile such as the pyrrolinium ion (I) and a very mild nucleophile represented here by isopropylene, falls within the familiar framework of a Prins -type reaction. That process has a protonated form of a carbonyl derivative as the electrophile, usually an aldehyde of which the iminium ion would be a nitrogen homolog. However, in contrast with the classical Prins reaction whereby 1,3-dioxanes result by the inclusion of a second mole of the electrophile, in the present reaction 1 mol of methanol is incorporated instead. 

Ene reactions are carried out thermally (100-300C,C) or with Lewis acid catalysis under anhydrous conditions. Usually, ene reactions are concerted but recent investigations suggest that some are stepwise processes (Lewis acid catalyzed) and proceed via an intermediate Jt-complex9. In this section only Prins-type reactions will be described ene reactions are discussed in Section D.1.6.2. 

Finally, Huang and Panek utilized a Prins-type reaction between a crotylsilane and an aldehyde in their total synthesis of callipeltoside A (28).21 22 In the presence of TfOH, crotylsilane 25 and aldehyde 26 underwent mixed acetal formation and subsequent Prins cyclization to generate dihydropyran 27 in 87% yield as a single diastereomer. This intermediate was carried forward to complete a total synthesis of 28.22... 

Cyclocondensation. A Prins-type reaction between aldehydes and 3-butenol leads to 4-tetrahydropyranols and ethers. Sc(OTf)i assists epoxide opening by an intramolecular attack of an enolate, resulting in the formation of three-, four-, and five-membered rings. ... 

Prins-Type Reaction 3.3.1 Five-Membered Rings... 

Tosylhydrazones such as (149), containing a suitably disposed olefinic group, cyclize to bicyclic azo-compounds [e.g. (150)] on treatment with boron trifluoride etherate. The allyl silanes (151) and (152) each undergo a highly stereoselective Prins-type reaction on treatment with trifluoroacetic acid, whereas other acid catalysts give mixtures. ... 

Tian, G-Q., Shi, M. (2007). 2-(Arylmethylene)cyclopropylcarbinols could be converted to the corresponding tetrahydropyrans stereoselectively in the presence of Bronsted acids under mild conditions. A plausible Prins-type reaction mechanism has been proposed, Org. Lett. 9 2405-2408. 

The gold(I)-catalyzed intermolecular addition of carbonyl compounds to 1,6-enyne 1-9 presumably proceeds by trapping rearranged gold carbene intermediate 1-12 with the carbonyl compounds (Scheme 2.4). Thereby forming the oxonium cation 1-13, which undergoes a Prins-type reaction to give I-IO, probably via intermediate 1-14. 

Cyclization via Prins-Type Reactions The intramolecular Prins reaction has been recognized as a powerful method to assemble six- and seven-membered rings from homoallylic alcohols and simple aldehydes under acid catalysis [28]. However, the competing 2-oxo-Cope rearrangement prior to cyclization could lead to a product with partial or total racemization when enantiomerieally enriched secondary alcohols are used [29]. Increasing the nueleophilicity of the alkene reagent... 

Prins-type Reaction. A versatile method for the synthesis of 4-substituted 6-methyl-3-oxabicyclo[3.3.1]non-6-ene-l-methanol derivatives has been developed using Prins-type cycliza-tion reaction between aldehydes and 0-protected/unprotected cyclohex-3-ene-1,1-dimethanol. The optimized reaction conditions used Hf(OTf)4 and various substrates including functionalized benzaldehydes and heteroaromatic carbaldehydes, to afford the cyclization products in high yields (eq 7). Among various metal triflates tested, Hf(OTf)4 provided the best results. 

Styrenes are activated in this fashion toward intermolecular Prins-type reaction with 1,1-diaryl alkenes, although at high temperatures (eq 37). ... 

The putative metal cationic intermediates can be interconnected into a series of cationic processes such as Friedel-Crafts, pinacol, Nazarov, Prins-type reactions. In Scheme 7.28, the gold-catalyzed cycloisomerization of 1,6-enynes is followed by an intramolecular nucleophilic attack by the proximate carbonyl to generate the tetrahydro-pyranyl cation, which participate in a Prins-type reaction to produce tricyclic compounds resembling the core structures of several terpenoids [52]. 

Very recently, Shi and co workers have shown that methylenecyclopropanes such as (29) react with aldehydes (Equation 20) and acetals (Equation 21) in the presence of Bp3 OEt2 to give the corresponding indenyl products (30) and (31) [25]. Based on deuterium labeling experiments, the authors invoke a Prins-type reaction mechanism with Lewis acid activation of the aldehyde (acetal). 

Allylsilanes react with two molar equivalents of aldehydes in the presence of AICI3 or AlBrs catalyst to give 4-halotetrahydropyrans through conventional allylation followed by formation of oxonium species and their intramolecular Prins-type reaction... 

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