10.1021/jo070337k
The research focuses on the stereoselective total synthesis of (+)-scyphostatin, a potent small molecule inhibitor of neutral sphingomyelinase (N-SMase), which was initially isolated from the mycelial extract of Dasyscyphus mollissima. The purpose of the study was to overcome the compound's instability, particularly in a condensed state, and its highly functionalized nature, to achieve a total synthesis. The synthesis involved the use of L-tyrosine as the starting material, with key reactions including a highly π-facially selective Diels-Alder reaction and a hydroxy group-directed epoxidation. The researchers also corrected a previously mistaken assignment of the relative stereochemistry of the C5-C6 epoxide ring in their model study. The successful synthesis of (+)-scyphostatin was confirmed through spectroscopic data comparison with natural scyphostatin, including 1H and 13C NMR, HRMS, and optical rotation values. Chemicals used in the process included L-tyrosine, spirolactone, cyclopentadiene, and various reagents for the reactions such as LiOH/H2O2, EDCI, SmI2, NaBH4/CeCl3, mCPBA, and TBAF, among others.
10.1016/S0957-4166(98)00087-1
The research focuses on the asymmetric Diels–Alder addition of cyclopentadiene to chiral 1,4-naphthoquinones, with the aim of achieving high levels of diastereomeric excess. The purpose of this study was to develop a method for the stereoselective formation of cyclopentannulated products, which can be further transformed into pyranonaphthoquinones, a class of compounds related to the pyranonaphthoquinone antibiotics. The researchers used various chiral auxiliaries, including (R)-pantolactone, (S)-N-methyl-2-hydroxysuccinimide, and trans-2-phenylcyclohexanol, which when combined with Lewis acid conditions, led to significant asymmetric induction. The conclusions drawn from the study were that the use of chiral auxiliaries at C-2 of 1,4-naphthoquinones enabled up to 96% stereoinduction in Diels–Alder cycloadditions with cyclopentadiene. The chiral auxiliaries could be removed from the fragmented products in acceptable yields, allowing for the formation of cyclopentannulated pyranonaphthoquinone ring systems, similar to those found in nature.
10.1021/ja00029a049
The study explores the use of MAD (a bulky Lewis acid) in Diels-Alder reactions, demonstrating its ability to achieve high regioselectivity, endo selectivity, and diastereoselectivity in reactions involving unsymmetrical fumarates. MAD effectively discriminates between different acrylate carbonyls, such as tert-butyl and methyl acrylates, in chemoselective Diels-Alder reactions with cyclopentadiene. The study also describes an enantiodivergent synthesis of syn-1,3-polyols from a meso precursor through reagent-controlled diastereofacial selective allylation reactions. Key chemicals involved include MAD for asymmetric induction, tert-butyl and methyl acrylates as dienophiles, and cyclopentadiene as the diene. In the synthesis of syn-1,3-polyols, reagents like (+)- or (-)-diisopinylcamphyl allyl borane (Ipc,BAll) are used to introduce chirality, and camphorsulfonic acid is employed for selective acetonide formation. The study highlights the potential of these methods for versatile synthetic applications in organic chemistry.
10.1021/ja068637r
The research focuses on the development of chiral oxazaborolidine-aluminum bromide complexes as effective catalysts for enantioselective Diels-Alder reactions. The study investigates the protonation of oxazaborolidine with triflic acid to form a chiral oxazaborolidinium cation, which is then complexed with aluminum bromide (AlBr3) to create a highly efficient catalyst (complex 3). Various experiments were conducted using cyclopentadiene and diverse dienophiles, demonstrating that only 4 mol % of catalyst 3 yielded excellent reaction yields and enantioselectivity. The effectiveness of the catalyst was analyzed through 1H NMR spectroscopy, optical rotation, and HPLC or GC analysis with chiral columns, confirming that the catalyst significantly outperformed previous catalysts in terms of efficiency and recovery for larger-scale syntheses.
10.1515/znb-2002-1104
The research discusses the synthesis and reactivity of cyclopentadienyl and indenyl ligands bearing fluorinated pendant groups, with a focus on their potential as catalysts for olefin polymerization. The study investigates the stability of cationic complexes formed during catalyst activation and how modifying the ligand environment can influence the physicochemical properties of resulting polymers. The researchers synthesized a series of cyclopentadienes and indenes with fluorinated pendant groups and examined their reactivity towards various metallating agents. The crystal structure of one such complex, 1-trimethylsilyl-3-(diphenyl-ortho-fluorophenyl-methyl)-cyclopentadiene (3), was determined, revealing no interaction between the metal atoms and the fluorine atom due to the bulkiness of the ligand system.
10.1016/S0040-4039(00)88704-3
The research aims to develop a novel method for generating sulfene, a reactive intermediate in organic chemistry, without the use of amines. The traditional method involves using methanesulfonyl chloride with triethylamine, which can lead to complications due to the amine's reactivity. The new procedure involves fluorodesilylation of trimethylsilylmethanesulfonyl chloride in the presence of a trapping agent, such as cesium fluoride, to produce sulfene. This approach avoids the issues associated with amine use and provides better yields of sulfene adducts under mild, neutral conditions. The study demonstrates that this method is superior in terms of yield and selectivity compared to the conventional approach, especially when trapping sulfene with substrates like cyclopentadiene.
10.1021/ol203213f
The study presents a de novo asymmetric synthesis of polyhydroxylated N-alkoxypiperidines and their analogues, including isofagomine, using ring-closing double reductive amination. The synthesis begins with the desymmetrization of cyclopentadiene to produce an optically enriched cyclopentene derivative, which is then oxidatively cleaved to yield the necessary dialdehyde. The key ring-closing double reductive amination involves reacting the dialdehyde with O-substituted hydroxylamines, such as O-benzylhydroxylamine, to form N-alkoxypiperidines. Various functionalized dialdehydes are synthesized to produce a range of N-alkoxypiperidines with different substituents. The final products, including isofagomine, are obtained by deprotecting the synthesized compounds using reagents like BCl3 or BBr3. This method provides a flexible and concise route to produce optically pure polyhydroxylated piperidines and their derivatives, which have potential applications in the development of glycosidase inhibitors.
