Effect of structure and acidity of acid modified clay materials on synthesis of octahydro-2H-chromen-4-ol from vanillin and isopulegol

The Prins cyclization of (−)-isopulegol with vanillin to form octahydro-2H-chromen-4-ol was studied in the presence of natural layered aluminosilicates modified by 0.5 mol/dm3 HCl, such as montmorillonite, kaolin, and metakaolin obtained by the calcination of kaolin at 650 °C. According to infrared spectroscopy using pyridine as probe molecule, the amount and strength of Brønsted acid sites depend on the type of clay and decrease in the following order HCl-montmorillonite > HCl-kaolin > HCl-metakaolin. The difference in Brønsted acidity and textural properties of clays affected the reaction rate and the selectivity towards octahydro-2H-chromen-4-o

Development and applications of novel HF-based fluorination reagents : DMPU-HF.

The utility of fluorine in medicinal and manufacturing chemistry is undisputed. Despite its usefulness, the incorporation of fluorine in organic molecules is not without challenges. Regardless of their electrophilic or nucleophilic nature, most, if not all, fluorinating reagents derive from HF. Nucleophilic reagents are less expensive compared with their counterparts, and many are not commercially available. The Hammond laboratory is interested in developing and applying HF-based fluorination reagents that are cost effective and capable of enhancing both classical and metal based transformations. The following chapters describe some of the applications of our HF-based reagent. Chapter 2 discusses the preparation and role of DMPU-HF in the fluorination of alkynes in the presence of a metal catalyst. This reaction employs the imidogold precatalyst, which is activated by DMPU-HF to enhance both mono- and di-fluorination of alkynes. Approaches to induce monofluorination and difluorination of terminal alkynes by an HF-based reagent, unprecedented in the literature, are also discussed. In Chapter 3, we describe further the application of DMPU-HF to the diastereoselective synthesis of fluorinated tetrahydropyrans and the N-tosylpiperidine analogues. We also showed that the acidic behavior of DMPU-HF makes it a better fluorinating reagent when compared to existing HF-based reagents in these types of transformations. Further extension of DMPU-HF to the ring opening of aziridines is discussed in Chapter 4. A wide variety of N-tosyl aziridines undergo efficient ring opening in the presence of DMPU-HF at room temperature. The methodology was also extended to some N-substituted aziridines including unactivated substrates, all of which were efficiently fluorinated under these conditions. Chapter 5 gives an overview of some of the applications of DMPU-HF to other known C-F bond formations. Examples of such transformations include but are not limited to the ring opening of epoxides, fluorobromination of unsaturated compounds and the metal free synthesis of fluoroamines. Finally, Chapter 6 provides spectroscopic data for all the new compounds prepared in chapters 2 to 5

Synthesis of octahydro-2H-chromen-4-ol from vanillin and isopulegol over acid modified montmorillonite clays: Effect of acidity on the Prins cyclization

Two calcium-rich natural layered aluminosilicates containing 90–95 wt.% montmorillonite were chemically activated using 0.125–3.0 M HCl solutions. Structural and textural properties were characterized by X-ray diffraction, elemental analysis and N2-adsorption/desorption analyses. According to infrared spectroscopy using pyridine as probe molecule, the amount of Brønsted acid sites increased when increasing HCl concentration. The catalytic performance of these materials was investigated in the Prins cyclization of (−)-isopulegol with vanillin to form octahydro-2H-chromen-4-ol, carried out in toluene at 35 °C. It was found that the amount of Brønsted acid sites and the microporosity of the catalysts are key factors for the control of the reaction rate and the selectivity towards octahydro-2H-chromen-4-o

Diastereoselective synthesis of cis-2,6-disubstituted dihydropyrane derivatives through a competitive silyl-prins cyclization versus alternative reaction pathways

Producción CientíficaA convenient regioselective synthesis of allyl- and vinylsilyl alcohols, from a common precursor, was described, by selecting the appropriate reaction conditions. Allyl- and vinylsilyl alcohols were tested in silyl-Prins cyclizations for the preparation of disubstituted oxygenated heterocycles in a one-pot sequential reaction. The methodology was sensitive to the structure of the starting alkenylsilyl alcohol and reaction conditions, with competitive pathways observed (particularly for allylsilyl alcohols), such as Peterson elimination and oxonia-Cope reactions. However, the use of vinylsilyl alcohols allowed the preparation of differently disubstituted cis-2,6-dihydropyrans in moderate to good yields. Computational studies support the proposed mechanism.Junta de Castilla y León - (grant VA294-P18)Ministerio de Ciencia e Innovación - (PID2020-116076RJI00/AEI/10.13039/501100011033

Enantioselective Prins cyclization: BINOL-derived phosphoric acid and CuCl synergistic catalysis.

International audienceThe first catalytic enantioselective Prins cyclization is disclosed. The reaction is catalyzed by the combination of a chiral BINOL-derived bis-phosphoric acid and CuCl. The process consists of a tandem Prins/Friedel-Crafts cyclization that affords the hexahydro-1H-benzo[f]isochromenes products with three new contiguous stereogenic centers in high yields, and good enantio- and excellent diastereoselectivities

Use of bis-phosphine platinum-dications as highly electrophilic catalysts for generation of intermediate carbocations in catalysis

Chiral Pt-dicationic catalysts capable of C-C bond formation with the intermediacy of carbocations were developed. Similar carbocations are key intermediates in the biosynthesis of terpenoid natural products, and are normally generated by protonation of an alkene or an epoxide under careful enzymatic guidance. Under non-enzymatic conditions such activations of alkenes are much more difficult to control. Synthetic Ptdicationic complexes were developed for selective generation of these key intermediates in two specific types of processes. One, the asymmetric Prins cyclization reaction, and second an asymmetric oxidative cation-olefin cascade cyclization reaction that converts polyolefin substrates into complex polycyclic products, an analogy to steroid biosynthesis. Highly electrophilic P2Pt2+ catalysts proved to be uniquely able to catalyze a Prins cyclization reaction in the reaction of alkenyl phenols and glyoxylate esters. Other chiral Lewis acids provided the products of a concerted glyoxylate-ene reaction. The uniqueness of the reactivity to Pt-dicationic catalysts suggested that they were able to access trappable ionic intermediates. This reaction was made highly enantioselective by employing (tol-BINAP)Pt2+ catalysts and tBu glyoxylate with various phenol substrates. The P2Pt2+ catalysts also proved capable of mediating regio- and diastereoselective oxidative polycyclization reactions of dienol and trienol susbtrates. This biomimetic cyclization is initiated by Pt(II) activation of a less substituted alkene at the terminus of a polyene susbtrate and is terminated by <-hydride elimination. This transformation was rendered catalytic by employing trityl cation to abstract hydride from the putative cationic Pt-hydride to regenerate the Pt2+ catalyst. Good enantioselectivity could be achieved in this reaction by employing xylyl-PHANEHPOS as the bisphosphine ligand

ZnAlMCM-41: a very ecofriendly and reusable solid acid catalyst for the highly selective synthesis of 1,3-dioxanes by the Prins cyclization of olefins

The Prins cyclization of styrene (SE) with paraformaldehyde (PFCHO) was conducted with mesoporous ZnAlMCM-41 catalysts for the synthesis of 4-phenyl-1,3-dioxane (4-PDO) using a liquid phase heterogeneous catalytic method. For a comparison study, the Prins cyclization reaction was also conducted over different nanoporous catalysts,e.g.mesoporous solid acid catalysts, AlMCM-41(21) and ZnMCM-41(21), and microporous catalysts, USY, Hβ, HZSM-5, and H-mordenite. The recyclable mesoporous ZnAlMCM-41 catalysts were reused in this reaction to evaluate their catalytic stabilities. Since ZnAlMCM-41(75) has higher catalytic activity than other solid acid catalysts, washed ZnAlMCM-41(75)/W-ZnAlMCM-41(75) was prepared using an efficient chemical treatment method and used with various reaction parameters to find an optimal parameter for the highly selective synthesis of 4-PDO. W-ZnAlMCM-41(75) was also used in the Prins cyclization of olefins with PFCHO and formalin (FN, 37% aqueous solution of formaldehyde (FCHO)) under different reaction conditions to obtain 1,3-dioxanes, which are widely used as solvents or intermediates in organic synthesis. Based on the nature of catalysts used under different reaction conditions, a reasonable plausible reaction mechanism for the Prins cyclization of SE with PFCHO is proposed. Notably, it can be seen from the catalytic results of all catalysts that the W-ZnAlMCM-41(75) catalyst has higher 4-PDO selectivity with exceptional catalytic activity than other microporous and mesoporous catalysts

Changing the reaction pathway of Silyl-Prins cyclization by switching the lewis acid: Application to the synthesis of an antinociceptive compound

Producción CientíficaDeveloping new procedures for the synthesis of tetrahydropyrans in a very stereoselective manner is of great importance for the synthesis of THP-containing natural products. Here, we report an interesting protocol for the synthesis of polysubstituted halogenated tetrahydropyrans by silyl-Prins cyclization of vinylsilyl alcohols, in which the nature of the Lewis acid determines the outcome of the process. The methodology has been applied to the synthesis of a known antinociceptive.Junta de Castilla y León (VA294P18

Total Synthesis of (+)-Dactylolide. Studies on the Cascade Cyclization Reactions of Epoxides/Polyepoxides Initiated by Single Electron Transfer

The total synthesis of the marine macrolactone (+)-dactylolide was achieved in a highly convergent and efficient way (Scheme I). The route involves the coupling of two functionalized fragments of the molecule, an ¦Á,¦Â-unsaturated aldehyde and a 1,3-syn-diol, to form a cyclic ¦Á,¦Â-unsaturated cyclic acetal. Both enantiopure fragments arise from asymmetric vinylogous Mukaiyama aldol reactions. The key transformations in this synthesis include a sequential Peterson olefination/Prins cyclization reaction to construct the 2,6-cis-disubstituted-4-methylenetetrahydropyran core efficiently and stereoselectively, a Mislow-Evans selenoxide-selenate [2,3] sigmatropic rearrangement to transpose allylic alcohol transposition and an intramolecular Horner-Emmons macrocyclization.A systematic study on the cascade cyclizations of epoxides/polyepoxides initiated by single electron transfer has been carried out (Scheme II). Four monoepoxides and six diepoxides were tested. The results showed that the bicyclo[3.1.0] epoxonium ion intermediates formed in the cyclization favor 5-exo-cyclization in the nonpolar solvent (1,2-dichloroethane) while in the polar solvent (CH3CN), they prefer 6-endo-selectivity. However, the bicyclo[4.1.0] epoxonium ion intermediates usually give 7-endo regiochemical selectivity in the presence of substitution-induced bias. However, without the substituent effect, 6-exo and 7-endo-cyclizations are two competitive pathways