Intramolecular Prins cyclisations for the stereoselective synthesis of bicyclic tetrahydropyrans

Methyl (4E,7R)-7-hydroxyoctanoate was prepared in 71% yield from ethyl (R)-3-hydroxybutanoate and on reaction with a series of aldehydes in the presence of TMSOTf gave bicyclic oxygen heterocycles in good yields and with the creation of three new stereogenic centres in a single pot.     

Stereoselective synthesis of 2,4,5-trisubstituted piperidines by carbonyl ene and Prins cyclisations

An approach to 2,4,5-trisubstituted piperidines is reported, in which the key step is the Prins or carbonyl ene cyclisation of aldehydes of the type 1. Prins cyclisation catalysed by concentrated hydrochloric acid in CH(2)Cl(2) at -78 degrees C afforded good yields of two of the four possible diastereomeric piperidines, with the 4,5-cis product 7 predominating in a diastereomeric ratio of up to 94:6. The diastereoselectivity of the cyclisation decreased as the 2-substituent increased in size, becoming unselective for very bulky 2-substituents. In contrast, cyclisation catalysed by MeAlCl(2) in CH(2)Cl(2) or CHCl(3) at temperatures of between 20-60 degrees C, favoured the 4,5-trans diastereomer 8, in a diastereomeric ratio of up to 99:1. The low-temperature cyclisations catalysed by HCl proceed under kinetic control via a mechanism involving the development of significant carbocationic character, in which the 4,5-cis cation is more stable than the 4,5-trans cation as a result of overlap with the neighbouring oxygen. The cyclisations catalysed by MeAlCl(2) proceed under thermodynamic control, affording the product in which both the 4- and 5-substituents are equatorial.     

Stereoselective synthesis of 2,4,5-trisubstituted piperidines by carbonyl ene and Prins cyclisations

Cyclisation of aldehydes 3-e catalysed by concentrated hydrochloric acid affords predominantly the all cis 2,4,5-trisubstituted piperidines 4a-ewhen the 2-substituent is small, while catalysis by MeAlCl2 in refluxing chloroform gives the trans piperidines 5a-e with diastereomeric ratios of up to 99:1.     

Prins cyclizations: labeling studies and application to natural product synthesis

The first syntheses of two natural products, catechols 1 and 2, isolated from Plectranthus sylvestris (labiatae), are reported. Oxygen-18 labeling studies support the proposed intermediacy of a stabilized benzylic cation in the acid-promoted cyclization of an aldehyde and benzylic homoallylic alcohol possessing an electron-rich aromatic ring. In contrast, with an electron-deficient aromatic ring the pathway via a benzylic cation is only minor. [reaction: see text]     

Stereoselective syntheses of (−)-tetrahydrolipstatin via Prins cyclisations

Stereoselective syntheses of (−)-tetrahydrolipstatin have been achieved via two divergent approaches through Prins cyclisations as the key steps. PCC mediated oxidative cleavage, Frater alkylation, Keck allylation, Sharpless asymmetric epoxidation and allylic cleavage were the other key steps employed.     

Oxidative radical cyclisations for the synthesis of gamma-lactones

The use of manganese(III) acetate in combination with copper(II) triflate allows the synthesis of [3.3.0]-bicyclic gamma-lactones from 4-pentenylmalonates in excellent yields.     

Kinetics and mechanism of some vinyl radical cyclisations

The vinyl radicals 2a, 2b, and 11 each undergo fast exo ring closure to give 5a, 5b, and 12, the first two of which readily rearrange to ring-expanded radicals.     

The Prins reaction using ketones: rationalization and application toward the synthesis of the portentol skeleton

We report a TMSI-promoted Prins cyclization reaction with ketones as carbonyl partners to prepare polysubstituted chiral spirotetrahydropyrans. In the presence of racemic 2-methylcyclohexanone a dynamic kinetic resolution occurred affording one stereoisomer. The observed enantiospecificity has been rationalized by DFT calculation.     

Stereoselective synthesis of tetralins using cationic cyclisations

Tetralins, including the terpene calamenene, were prepared by 6-endo cationic cyclisations, effected by addition of an I(I) reagent to alkenylarenes, followed by reductive deiodination. An activating group on the arene was required for efficient cationic cyclisation. Good diastereoselectivity, relative to a chiral centre in the chain linking the alkene to the arene, was observed, with Z-alkenes giving predominantly 1,4-cis disubstituted tetralins, and E-alkenes giving predominantly 1,4-trans derivatives. Analogous 6-exo cationic cyclisations proved very limited in scope.     

Stereoselective synthesis of tarchonanthuslactone via the Prins cyclisation

The stereoselective total synthesis of tarchonanthuslactone, a polyketide natural product, has been achieved. The synthesis exploits the high stereochemical control in the Prins cyclisation along with ring closing metathesis (RCM) as a key step.     

Stereoselective synthesis of anti-1,3-diol units via Prins cyclisation: application to the synthesis of (−)-sedamine

The scope of the Prins cyclisation, the higher stereoselective synthesis of multisubstituted tetrahydropyrans from aldehydes and homoallylic alcohols, is expanded. A new approach for the stereoselective synthesis of polyketide precursors containing anti-1,3-diols, flanked by a variety of alkyl branches and functional groups is described. The approach is successfully exploited for the synthesis of (−)-sedamine.     

Facile synthesis of functionalised spiroethers via radical cyclisations

Alcohols bearing suitable chains for radical initiation are smoothly condensed with cyclic β-diketones to afford systems which undergo radical cyclisation to give various spiroether products.     

Application of Prins cyclization to the total synthesis of (+)-decytospolides A and B

(+)-Decytospolides A and B, natural products containing the tetrahydropyran skeleton, were synthesized via Prins cyclization as the key step.     

Stereoselective synthesis of simplactone B via Prins cyclisation

The synthesis of simplactone B has been achieved through a series of nine steps in 85% overall yield using Prins cyclisation as the key step with high stereochemical control.     

Synthesis of hydrated furans: Analysis of the Prins reaction mechanism

Mechanistic analysis of hydrogenated furan synthesis by the Prins reaction was carried out using mathematical modeling. The direct and inverse chemical kinetic problems are solved for the rate constants of all elementary steps. A probable mechanism is derived from the obtained quantitative kinetic parameters and the kinetic patterns of the reaction. These include kinetic curves from the concentration changes of all species in the reaction.     

Formal synthesis of (+)-SCH 351448: the Prins cyclization approach

The formal synthesis of (+)-SCH 351448 has been accomplished with the catalytic Prins cyclization strategy, yielding the monomeric unit as a single isomer.     

Stereoselective synthesis of basiliskamides A and B via Prins cyclisation

A stereoselective and convergent approach to basiliskamides A and B is achieved through our recently developed strategy for the construction of polyketide precursors via Prins cyclisation. The approach mainly relies upon reductive opening of 1-iodomethyl cyclic ethers, Mitsunobu inversion, Takai olefination and Stille coupling along with Prins cyclisation.     

Strategic use of pinacol-terminated Prins cyclizations in target-oriented total synthesis

An important objective of contemporary synthesis endeavors is the development of new transformations that rapidly evolve molecular complexity in a stereocontrolled fashion. One approach toward this goal is to combine two or more distinct reactions into a single transformation, producing a process often referred to as a sequential, tandem, cascade, or domino reaction. In this Perspective, we discuss the development of one such tandem reaction, the acid-promoted (or catalyzed) Prins-pinacol rearrangement, with particular emphasis on its implementation as the key strategic element in the total synthesis of heterocyclic and carbocyclic natural products.