Acid-catalyzed regioselective sulfetherification of alkenols and stereoselective rearrangement of tetrahydrofuran to tetrahydropyran

An efficient acid-catalyzed sulfetherification of various unsaturated alcohols with sulfenamides to form tetrahydrofurans and tetrahydropyrans regioselectively is described. Mechanistic studies have shown that the tetrahydrofurans can stereoselectively rearrange to the corresponding tetrahydropyrans.     

Cu(II)-catalyzed olefin migration and Prins cyclization: highly diastereoselective synthesis of substituted tetrahydropyrans

Metal-ligand complexes of Cu(OTf)(2) with an appropriate bisphosphine ligand have been shown to effectively catalyze the formation of substituted tetrahydropyrans via a sequential olefin migration and Prins-type cyclization. This methodology provides convenient access to a variety of functionalized tetrahydropyrans in excellent diastereoselectivities and good to excellent yields.     

Massenspektroskopiche Fragmentierungsreaktionen, 4. Mitt.: Der Zerfall von 2-Alkoxy-3-hydroxy-tetrahydropyranen

2-Alkoxy-3-hydroxy tetrahydropyrans undergo ring contraction as observed with 3-hydroxy tetrahydropyrans which, however, initiates a series of fragmentation sequences (e.g., ethylene elimination).

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Mit 3 Abbildungen

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3. Mitt. s.     

CeCl3·7H2O/AcCl-catalyzed Prins-Ritter reaction sequence: a novel synthesis of 4-amido tetrahydropyran derivatives

Homoallylic alcohols, carbonyl compounds and nitriles undergo a smooth tandem Prins-Ritter type cyclization in the presence of CeCl₃·7H₂O/AcCl at ambient temperature to produce 4-amido tetrahydropyrans in high yields with all cis-selectivity. Spirocyclic 4-amido tetrahydropyrans are obtained in the case of cyclic ketones.     

Stereoselective synthesis of tetrahydropyrans via formal [4 + 2]-cycloaddition: a comparison of allylsilane and crotylsilane

The reaction of a series of beta-(triethylsilyloxy)aldehydes with several allylsilanes and crotyldimethylphenylsilane is described. Aldehydes possessing an alpha-stereocenter afforded tetrahydropyrans as mixtures of two diastereomers with allylsilane, but only a single diastereomer was observed in the case of crotylsilanes. The reaction time for crotylsilanes was longer than that for allylsilanes likely due to the increased steric hindrance. Allylsilanes afforded tetrahydropyrans in 34-67% yields, and crotylsilanes provided products in 0-62% yields.     

Au-catalyzed cyclization of monoallylic diols

The Ph3PAuCl/AgOTf-catalyzed cyclization of monoallylic diols to form tetrahydropyrans is reported. The reactions proceed rapidly at temperatures as low as -78 degrees C with catalyst loadings as low as 0.1 mol % to provide the products in 79-99% yield. A broad range of structurally diverse substrates perform well in the reaction. When 2,6-disubstituted tetrahydropyrans are produced, the reaction is highly diastereoselective for the 2,6-cis product.     

Acid-promoted Prins cyclizations of enol ethers to form tetrahydropyrans

Trifluoroacetic acid efficiently catalyzes Prins cyclizations of enol ethers 8 to provide tetrahydropyrans 9 and 10. These tetrahydropyrans are isolated with combined yields of 42-85% and stereoselectivities at C(4) ranging from 95:5 to 50:50 depending on the nature of the substituent R. Unique byproducts of these cyclizations that reveal the presence of underlying equilibria have been isolated and identified. [reaction: see text]     

Stereoselective synthesis of 2,6-cis-substituted tetrahydropyrans: Brønsted acid-catalyzed intramolecular oxa-conjugate cyclization of α,β-unsaturated ester surrogates

Intramolecular oxa-conjugate cyclization (IOCC) of α,β-unsaturated carbonyl compounds, triggered by deprotonation with a base, represents a straightforward method for the synthesis of tetrahydropyrans. However, it has been known that stereochemical outcome of IOCC depends on the local structure of substrates and sometimes requires harsh reaction conditions and/or prolonged reaction times for selective formation of 2,6-cis-substituted tetrahydropyrans. These shortcomings limit the feasibility of IOCC in the context of complex natural product synthesis. In this paper, we describe Br?nsted acid-catalyzed IOCC of α,β-unsaturated ester surrogates (e.g., α,β-unsaturated thioesters, oxazolidinone imides, and pyrrole amides) under mild reaction conditions, which affords a series of synthetically versatile 2,6-cis-substituted tetrahydropyran derivatives with good to excellent stereoselectivity (dr from 7:1 to >20:1). These α,β-unsaturated carbonyl compounds were found to be more reactive than the corresponding oxoesters that are generally unreactive toward Br?nsted acid-catalyzed intramolecular oxa-conjugate additions. The product tetrahydropyrans could be transformed into various derivatives in an efficient manner, highlighting the usefulness of our methodology.     

Axial-selective prins cyclizations by solvolysis of alpha-bromo ethers

Prins cyclizations are intramolecular electrophilic additions of oxocarbenium ions. They lead to tetrahydropyrans with a heteroatom at the 4-position, and usually show moderate-to-high selectivity for equatorial substitution. We have found that Prins cyclizations carried out under specific conditions produce tetrahydropyrans with almost exclusive formation of the axial 4-substituent. TMSBr, AcBr, and TMSI all lead to axial-selective Prins cyclizations with alpha-acetoxy ether substrates in the presence lutidine. The mechanism appears to involve solvolysis of the intermediate alpha-bromo ether rather than specific or Lewis acid-catalyzed rearrangement. The scope of the reaction, the high yields, and the stereoselectivity make this a valuable new method for tetrahydropyran formation.     

An Enamide‐Based Domino Reaction for a Highly Stereoselective Synthesis of Tetrahydropyrans

A novel method for the highly stereoselective synthesis of tetrahydropyrans is reported. This domino reaction is based on a twofold addition of enamides to aldehydes followed by a subsequent cyclization and furnishes fully substituted tetrahydropyrans in high yields. Three new σ‐bonds and five continuous stereogenic centers are formed in this one‐pot process with a remarkable degree of diastereoselectivity. In most cases, the formation of only one out of 16 possible diastereomers is observed. Two different stereoisomers can be accessed in a controlled fashion starting either from an E‐ or a Z‐configured enamide.     

Stereoselective Synthesis of 2,3,4,6-Tetrasubstituted Tetrahydropyrans

The construction of stereodefined, highly substituted tetrahydropyrans has attracted a lot of interest over the years since they constitute ubiquitous fragments of numerous biologically active natural products.[1] During the course of our synthetic studies toward ambruticin, a fascinating antibiotic[2] which came back in the front scene with three recent total synthesis, [3] we have been interested in the synthesis of 2,3,4,6-tetrasubstituted tetrahydropyrans 5 (Scheme 1). [4] Moreover, this kind of subunit is found to be embedded in several other natural products such as lasonolide A, polycavernoside A, ratjadone, or concanamycin A.     

Cycloshydratation de dios in presence D'HMPT

1,4 and 1,5-diols heated with 0.3 equivalent of HMPA undergo cyclodehydration leading to tetrahydrofurans and tetrahydropyrans.     

Highly stereoselective prins cyclization of silylmethyl-substituted cyclopropyl carbinols to 2,4,6-trisubstituted tetrahydropyrans

The homoallyl cation formed from a cyclopropyl carbinol that was vicinally substituted by a silylmethyl function underwent smooth Prins cyclization with aldehydes and ketones to form 2,4,6-trisubstituted tetrahydropyrans with very high stereoselectivity.     

Synthesis of novel 2,6-disubstituted-3,4-dimethylidene tetrahydropyrans via Prins-type cyclization

Synthesis of novel substituted tetrahydropyrans with adjacent exo-methylene groups at the C3 and C4 positions via Prins-type cyclization has been described.     

Improved multicomponent,one-pot synthesis of functionalized tetrahydropyrans cardiovascular dysfunction regulators

A simple, efficient, and straightforward one-pot three-component synthesis of functionalized tetrahydropyrans ( 6a-l ) is carried-out in the presence of an inexpensive and environmentally benign Eaton's reagent as a catalyst to discover some ACE inhibitors and anti-inflammatory agents. Angiotensin-converting enzyme (ACE) is highly involved in the renin-angiotensin system and often directly associated with cardiovascular dysfunction via inflammation. Thus, the cardiovascular protective effect of newly synthesized tetrahydropyrans ( 6a-l ) was evaluated through ACE inhibition, human red blood cell (HRBC) membrane stabilization, and molecular docking studies. As the results complied, compounds 6e and 6f were identified as effective ACE inhibitors. Docking studies, HRBC based anti-inflammatory assay, and SAR studies revealed that compounds 6e and 6f could be good anti-inflammatory agents apart from ACE inhibitors.     

Cationic cyclizations initiated by electrocyclic cleavage of cyclopropanes. Synthesis of lactones,tetrahydropyrans, and tetrahydrofurans

The electrocyclic opening of cyclopropane derivatives containing internal nucleophilic groups provides a new route to vinyl lactones, tetrahydropyrans, and tetrahydrofurans.     

Formal [4 + 2] cycloaddition of alkoxy-substituted donor-acceptor cyclobutanes and aldehydes catalyzed by Yb(OTf)3

The cycloaddition between 2-alkoxy-1,1-cyclobutane diesters and aromatic, heteroaromatic, or aliphatic aldehydes under Yb(OTf)(3) catalysis generates tetrahydropyrans in high yields with exclusive cis-stereochemistry.     

A convergent route to β-hydroxy δ-lactones through Prins cyclisation as the key step: synthesis of (+)-prelactones B, C and V

Reactions of homoallylic alcohols with aldehydes in the presence of acid catalysts gave multisubstituted tetrahydropyrans with the creation of one to three new stereogenic centres in a single-pot process. The utility of this approach is extended to the enantioselective syntheses of (+)-prelactones B, C and V.     

Synthesis of oxygen-containing heterocyclic compounds via α-chloro-δ-(trimethylsilyloxy)imines

Treatment of α-chloro-δ-(trimethylsilyloxy)ketimines, obtained by regiospecific alkylation of α-chloroketimines with 3-bromo-1-(trimethylsilyloxy)propane, with bases and nucleophiles leads to a variety of oxygen-containing heterocycles, including tetrahydrofurans and tetrahydropyrans.     

Lewis Acid-Promoted Mukaiyama Aldol-Prins (MAP) Cyclizations of Acetals, Ketals, α-Acetoxy Ethers, and Orthoformates

The Mukaiyama aldol-Prins (MAP) cyclization of acetals stereoselectively provided substituted tetrahydropyrans. The scope of the reaction has been expanded to include other electrophiles, including ketals and α-acetoxy ethers. Finally, a double MAP cyclization with orthoformates is described.