Highly stereoselective prins cyclization of (Z)- and (E)-gamma-brominated homoallylic alcohols to 2,4,5,6-tetrasubstituted tetrahydropyrans

An efficient method has been developed to construct 2,6-cis-4,5-dibromo-tetrasubstituted tetrahydropyran (THP) rings with well-controlled stereochemistry in moderate to high yields.     

A stereoselective route to multi-substituted tetrahydropyrans by vinyl radical cyclization

The tin-mediated 6-exo-trig radical cyclization of the acetylenic β-alkoxy acrylates proceeded smoothly to give fully substituted tetrahydropyrans in good yields with high equatorial selectivity irrespective of the stereochemistry of the propargylic position.     

Barbier allylation-Prins reaction of PEG-bound aldehydes—soluble polymer-supported synthesis of 2,4,6-trisubstituted tetrahydropyrans

PEG-bound aldehydes undergo zinc-mediated Barbier allylation to form homoallylic alcohols, which on further reaction with various aldehydes in the presence of BF₃·Et₂O through a Prins cyclization afford 4-hydroxytetrahydropyrans and 4-fluorotetrahydropyrans.     

5- And 6-exocyclic products, cis-2,3,5-trisubstituted tetrahydrofurans, and cis-2,3,6-trisubstituted tetrahydropyrans via Prins-type cyclization

Exocyclic products having cis-2,5 and cis-2,6 substitution were synthesized from terminally substituted alkynyl alcohols with various aldehydes via Prins-type cyclization in good yields. It is of interest that synthesized 5- and 6-exocyclic vinyl cations generated as a result of Prins-type cyclization could be trapped as a vinyl triflate in CH2Cl2 to give 3-furanylidenes and 3-pyranylidenes. Those 3-furanylidenes and 3-pyranylidenes underwent hydrolysis to give the corresponding 3-acyl-substituted products having all-cis-configured isomers, such as 2,3,5-trisubstituted tetrahydrofurans and 2,3,6-trisubstituted tetrahydropyrans.     

Synthesis of polyhydroxylated bicyclic tetrahydrofurans and tetrahydropyrans via a stereoselective domino cyclization/reduction reaction

A novel reaction cascade involving a Lewis acid-induced migration of an isopropylidene protecting group followed by the formation of a pyranose or furanose ring and subsequent reduction of the hemiacetal is described. Depending on the reaction conditions, as well as, the stereochemistry of the substrate, polyhydroxylated tetrahydrofurans or tetrahydropyrans can be obtained in reasonable yields. The synthons used in this transformation were prepared via a highly stereoselective one-pot tandem reaction, consisting of a 1,4-Michael addition of vinylmagnesium bromide to d-glucose-derived cyclohexenone followed by aldol reaction with 2,3-O-isopropylidene-d-glyceraldehyde.     

Synthesis of the C22-C26 tetrahydropyran segment of phorboxazole by a stereoselective prins cyclization

[formula: see text] Tetrahydropyran rings are found in many complex natural products, and the segment-coupling Prins cyclization is an effective strategy for their synthesis. We report a four-step, stereoselective synthesis of the C20-C27 tetrahydropyran segment of phorboxazole. The key step is a Prins cyclization induced by catalytic BF3.OEt2.     

Stereoselective synthesis of 4-hydroxy-2,3,6-trisubstituted tetrahydropyrans

[reaction: see text] Reaction of homoallylic alcohols with aldehydes in the presence of TFA gives, after hydrolysis of the ester, 4-hydroxy-2,3,6-trisubstituted tetrahydropyrans with the creation of three new stereocenters in a single-pot process. By varying the aldehyde component, a variety of functionalized side chains are installed at C-2. The utility of this approach is extended to the enantioselective synthesis of tetrahydropyrans with >99% ee.     

Highly stereoselective synthesis of 1,2,3-trisubstituted indanes via oxidative N-heterocyclic carbene-catalyzed cascades

Three stereocenters are formed in the carbene catalyzed cascade reaction of enals with various β-diketones to give the corresponding indane derivatives with excellent stereoselectivities. The products are readily transformed to the corresponding 1,2,3-trisubstituted indane derivatives, which represent privileged substructures in medicinal chemistry.     

Highly stereoselective synthesis of cyclopropyl heterocycles via cyclopropanation of olefin with arsonium salt

An efficient and highly stereoselective approach for the preparation of highly functionalized cyclopropyl heterocycles via the cyclopropanation of olefines with arsonium salts in the presence of KF2H₂O has been developed.     

Highly stereoselective radical cyclization of haloacetals controlled by the acetal center

A systematic investigation of radical haloacetal cyclizations (Ueno-Stork reaction) where the acetal center is the unique stereogenic element is reported. This highly diastereoselective reaction can be used for the preparation of polysubstituted tetrahydrofurans and gamma-lactones. We report herein the full experimental details of reactions where up to three new chiral centers are created. To demonstrate the potential of this approach, short syntheses of (+)-eldanolide and of tricyclic acetals related to biologically active lignans have been achieved.     

Highly regio- and stereoselective synthesis of indene derivatives via electrophilic cyclization

[reaction: see text] Indene or naphthalene derivatives are readily prepared in moderate to excellent yields with high regio- and stereoselectivity under very mild reaction conditions by the reaction of acetylenic malonates and ketones with I2, ICl, or NIS. The resulting iodides can be further elaborated using palladium-catalyzed coupling reactions.     

Stereochemical Prins cyclization: electronic versus steric effects on the synthesis of 2,4,6-trisubstituted tetrahydropyran rings

A convenient approach towards the synthesis of both syn- and anti-2,4,6-chlorotetrahydropyrans has been developed. The electronic and steric influences on the stereochemistry of the Prins cyclized products were investigated based on the substituents of the homoallylic alcohol.     

Highly stereoselective intramolecular hydroamination/cyclization of conjugated aminodienes catalyzed by organolanthanides

Efficient intramolecular hydroamination/cyclization of primary and secondary conjugated aminodienes can be effected by using organolanthanide precatalysts of the type Cp'2LnCH(TMS)2 (Cp' = eta5-Me5C5; Ln = La, Sm, Y; TMS = SiMe3) and CGCSmN(TMS)2 (CGC = Me2Si(eta5-Me4C5)(tBuN)). The transformation proceeds cleanly (>/= 90% conversion) at 25-60 degrees C with good rates and high regioselectivities, and with electronic effects leading to significant rate enhancements. Some features of the reaction parallel monosubstituted aminoalkene hydroamination/cyclization, including rate law (zero order in [aminodiene]), and rate enhancements observed with larger lanthanide ionic radii and/or more open catalyst ligation structures. Good to excellent diastereoselectivity is obtained in the synthesis of 2,5-trans-disubstituted pyrrolidines (80% de) and 2,6-cis-disubstituted piperidines (99% de) with using the corresponding alpha-methyl aminodiene precursors. Formation of 2-(prop-1-enyl)piperidine with the chiral C1-symmetric precatalyst (S)-Me2Si(OHF)(CpR*)SmN(TMS)2 (OHF = eta5-octahydrofluorenyl; Cp = eta5-C5H3; R* = (-)-menthyl) proceeds with up to 69% ee.     

Highly stereoselective synthesis of 2,5-disubstituted 3-vinylidene tetetrahydrofurans via Prins-type cyclization

[reaction: see text]. A novel synthetic methodology for 2,5-disubstituted tetrahydrofurans having an allenyl group at the 3-position via Prins-type cyclization was developed. The reaction led to excellent selectivity and moderate to high yields.     

Highly stereoselective Friedel-Crafts type cyclization. Facile access to enantiopure 1,4-dihydro-4-phenyl isoquinolinones

The present report describes a stereoselective synthesis of 1,4-dihydro-4-phenyl isoquinolinones 5 based on a stereoselective Friedel-Crafts type cyclization. Cyclization precursors 1 were prepared in two steps, from the readily available (S)-mandelic acid, in 60-80% overall yield. The stereoselective electrophilic cyclization was accomplished in 20-86% yield and with 20-97% ee. In the course of this work, the presence of the amide carbonyl was found to be particularly important to guarantee a stereospecific process during the electrophilic aromatic substitution.     

Formolysis and acetolysis of linear saturated and allylic secondary cyclopropyl carbinols

Simple esterification of a series of secondary aliphatic cyclopropyl carbinols under the influence of concentrated HCO₂H or AcOH without modification of the carbon skeleton is disclosed. Under the same conditions related allyl alcohols undergo stereospecific isomerization to the corresponding esters of 3E,5E-dienols.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 853–856, April, 1991.     

CAN-mediated stereoselective cyclization of epoxypropyl cinnamyl amines to 3,4,5-trisubstituted piperidines and supramolecular assembly of the latter aided by ethyl acetate

The stereoselective intramolecular cyclization of epoxypropyl cinnamyl amines mediated by substoichiometric quantities of CAN leading to the synthesis of functionalized piperidines and the formation of a supramolecular assembly of the latter with ethyl acetate is described.