Synthese von bis(fluorosilyl)anilinen

Fluorosilanes react with $\text{N}$-lithio-2,4,6-trimethyl-aniline with LiF elimination and substitution. Lithium salts are obtained by the reaction of N-(fluoro-diorganylsilyl)-2,4,6-trimethylanilines with butyllithium. Further reactions of these lithium salts with fluorosilanes gives bis(fluorosilyl)-anilines. The ¹⁹F NMR spectra of the N-(fluorosilyl)-N-(di-fluorosilyl)anilines with chiral silicon and bulky substituents show AB systems for the SiF₂ groups. Analyses for C and H, NMR and mass spectra are reported for all compounds.     

Desymmetrization‐Oriented Enantioselective Synthesis of Silicon‐Stereogenic Silanes by Palladium‐Catalyzed C−H Olefinations

A palladium‐catalyzed chelation‐assisted enantioselective C?H olefination of symmetrically diaryl‐substituted tetraorganosilicon derivatives was developed, enabling the generation of nitrogen‐containing silicon‐stereogenic tetraorganosilicon compounds with modest to good yields and good to excellent enantioselectivities (up to 95.5:4.5 e.r.). The Thorpe–Ingold effect exerted by the substituents on silicon was observed to have a profound influence on formation of olefinated products which were further converted into other relevant chiral organosilanes without the loss of enantiomeric purity, thus demonstrating the synthetic utility of the developed enantioselective olefination.     

前手性硅甲基的非等时性, 分子结构对化学位差值的影响

具有手性基团的二甲基二烷氧基硅烷的前手性硅甲基的^1H NMR化学位移有差别, 其差值△γ随着非手性取代基的电负性成比例的改变。△γ与分子结构对Si-O间蝗(p-d)x相互作用的影响, 以及取代芳环的各向异性有关。     

Iron‐ and Bismuth‐Catalyzed Asymmetric Mukaiyama Aldol Reactions in Aqueous Media

We have developed asymmetric Mukaiyama aldol reactions of silicon enolates with aldehydes catalyzed by chiral Fe^II and Bi^III complexes. Although previous reactions often required relatively harsh conditions, such as strictly anhydrous conditions, very low temperatures (?78 °C), etc., the reactions reported herein proceeded in the presence of water at 0 °C. To find appropriate chiral water‐compatible Lewis acids for the Mukaiyama aldol reaction, many Lewis acids were screened in combination with chiral bipyridine L1 , which had previously been found to be a suitable chiral ligand in aqueous media. Three types of chiral catalysts that consisted of a Fe^II or Bi^III metal salt, a chiral ligand ( L1 ), and an additive have been discovered and a wide variety of substrates (silicon enolates and aldehydes) reacted to afford the desired aldol products in high yields with high diastereo‐ and enantioselectivities through an appropriate selection of one of the three catalytic systems. Mechanistic studies elucidated the coordination environments around the Fe^II and Bi^III centers and the effect of additives on the chiral catalysis. Notably, both Brønsted acids and bases worked as efficient additives in the Fe^II‐catalyzed reactions. The assumed catalytic cycle and transition states indicated important roles of water in these efficient asymmetric Mukaiyama aldol reactions in aqueous media with the broadly applicable and versatile catalytic systems.     

Axial chirality in 1,4-disubstituted (ZZ)-1,3-dienes. Surprisingly low energies of activation for the enantiomerization in synthetically useful fluxional molecules

Trialkylsilyltrialkylstannes (R(3)Si-SnR'(3)) add to 1,6-diynes in the presence of Pd(0) and tris-pentaflurophenylphosphine to give 1,2-dialkylidenecyclopentanes with terminal silicon and tin substituents. The (ZZ)-geometry of these s-cis-1,3-dienes, resulting from the organometallic reaction mechanisms involved, forces the silicon and tin groups to be nonplanar, thus making the molecules axially chiral. There is rapid equilibration between the two helical forms at room-temperature irrespective of the size of the Si and Sn substituents. However, the two forms can be observed by 1H, 13C, and 119Sn NMR spectroscopy at low temperature. The rates of enantiomerization, which depend on the Si and Sn substituents, and the substitution pattern of the cylopentane ring can be studied by dynamic NMR spectroscopy using line shape analysis. The surprisingly low energies of activation (DeltaG++ = 52-57 kJ mol(-1)) for even the bulky Si and Sn derivatives may be attributed to a widening of the exo-cyclic bond-angles of the diene carbons.     

Stereocontrolled synthesis of tertiary silanes via optically pure 1,3,2-oxazasilolidine derivatives

Optically pure 1,3,2-oxazasilolidine derivatives were synthesized from a chiral 1,2-amino alcohol. These heterocyclic compounds containing a stereogenic silicon atom produced tertiary silanes with excellent optical purity through successive reactions with Grignard reagents and diisobutylaluminum hydride. Stereochemical course of the reactions of the oxazasilolidine at the chiral silicon atom was elucidated based on the absolute configurations of the products and the substrate which were determined by chiral HPLC and X-ray crystallographic analyses.     

Synthesis of d-glucose and l-phenylalanine substituted phenylene-thiophene oligomers

Phenylene-thiophene oligomers bearing peracetylated β-d-glucose or N-BOC-l-phenylalanine as chiral substituents were synthesized in good yields by a versatile protocol based on the Suzuki-Miyaura cross-coupling reaction. Aryl iodides bearing the chiral biomolecules as substituents efficiently reacted with pinacol boronates of bi- or terthiophenes leading to the bio-functionalized oligomers in good yields.     

Planar Chiral,Ferrocene‐Stabilized Silicon Cations

The preparation of a series of planar chiral, ferrocenyl‐substituted hydrosilanes as precursors of ferrocene‐stabilized silicon cations is described. These molecules also feature stereogenicity at the silicon atom. The generation and ²⁹Si NMR spectroscopic characterization of the corresponding silicon cations is reported, and problems arising from interactions of the electron‐deficient silicon atom and adjacent C(sp³)?H bonds or aromatic π donors are discussed. These issues are overcome by tethering another substituent at the silicon atom to the ferrocene backbone. The resulting annulation also imparts conformational rigidity and steric hindrance in such a way that the central chirality at the silicon atom is set with complete diastereocontrol. These chiral Lewis acid catalysts were then tested in difficult Diels–Alder reactions, but no enantioinduction was seen.     

A facile synthesis of enantiopure tricyclic furanyl and pyranyl derivatives via tungsten-mediated cycloalkenation and Diels-Alder reaction

We report the synthesis of chiral furanyl and pyranyl dienes 1 and 2 based on cycloalkenation of chiral tungsten alkynol complexes. These two dienes bear a chiral 1,3-dioxolane group to control diastereoselective Diels-Alder reactions with electron-deficient olefins. The chiral 1,3-dioxolane substituents of the cycloadducts were degraded into hydrogen atoms to make these molecules possess common furan and pyran rings. Dienes 1 and 2 are good building blocks for enantiopure forms of tricyclic oxygen compounds.     

Chirality transfer from silicon to carbon

The exploitation of the asymmetry at silicon in stereoselective synthesis is an exceptionally challenging task. Initially, silicon-stereogenic silanes have been utilized to elucidate the stereochemical course of substitution reactions at silicon. Apart from these mechanistic investigations, only a handful of synthetic applications with an asymmetrically substituted silicon as the stereochemical controller have been reported to date. In these transformations the chiral silicon functions as a chiral auxiliary. Conversely, a direct transfer of chirality from silicon to carbon during bond formation and cleavage at silicon has remained open until its recent realization in both inter- and intramolecular reactions. In this Concept, the pivotal considerations in relation to the nature of suitable silanes as well as mechanistic prerequisites for an efficient chirality transfer will be discussed.     

Chirality Transfer from Silicon to Carbon

The exploitation of the asymmetry at silicon in stereoselective synthesis is an exceptionally challenging task. Initially, silicon‐stereogenic silanes have been utilized to elucidate the stereochemical course of substitution reactions at silicon. Apart from these mechanistic investigations, only a handful of synthetic applications with an asymmetrically substituted silicon as the stereochemical controller have been reported to date. In these transformations the chiral silicon functions as a chiral auxiliary. Conversely, a direct transfer of chirality from silicon to carbon during bond formation and cleavage at silicon has remained open until its recent realization in both inter‐ and intramolecular reactions. In this Concept, the pivotal considerations in relation to the nature of suitable silanes as well as mechanistic prerequisites for an efficient chirality transfer will be discussed.     

Bromoporphyrins as versatile synthons for modular construction of chiral porphyrins: cobalt-catalyzed highly enantioselective and diastereoselective cyclopropanation

5,10-Bis(2',6'-dibromophenyl)porphyrins bearing various substituents at the 10 and 20 positions were demonstrated to be versatile synthons for modular construction of chiral porphyrins via palladium-catalyzed amidation reactions with chiral amides. The quadruple carbon-nitrogen bond formation reactions were accomplished in high yields with different chiral amide building blocks under mild conditions, forming a family of D2-symmetric chiral porphyrins. Cobalt(II) complexes of these chiral porphyrins were prepared in high yields and shown to be active catalysts for highly enantioselective and diastereoselective cyclopropanation under a practical one-pot protocol (alkenes as limiting reagents and no slow addition of diazo reagents).     

Bis(oxazolinyl)phenyl transition metal complexes: synthesis, asymmetric catalysis, and coordination chemistry

Molecular catalysts for organic synthesis should be constructed to be tailored to target reactions and their desirable conditions. In our search for them, we have studied new types of transition metal molecular catalysts dressed with a tridentate N,C,N modular ligand, which consists of a C2-symmetric side-by-side phenyl group with chiral bis(oxazolinyl) substituents. The ligand, 2,6-bis(oxazolinyl)phenyl abbreviated as Phebox, can connect covalently to transition metals by the central carbon atom. Here, we review our recent work on the chemistry of Phebox and its metal complexes, including preparation, structural analysis, asymmetric Lewis acid catalysis, asymmetric hydrosilylation, asymmetric conjugate reduction, asymmetric reductive aldol reaction, and organometallic reactions.     

Radical-clock α-halo-esters as mechanistic probes for bisphosphine iron-catalyzed cross-coupling reactions

The mechanism of chiral bisphosphine iron-catalyzed C(sp²)-C(sp³) cross-coupling reactions has been studied via the synthesis of novel radical-clock α-halo-esters and quantum mechanical calculations. These results provide insights into the role of the substrate (halogen and substituents) in competing in-cage and out-of-cage arylation pathways and provide a basis for the future rational design of novel tandem cyclization-arylation reactions using bisphosphine-iron as catalysts.     

Study on improved diastereoselectivity in photo-induced electron transfer pinacol coupling reactions of substituted acetophenones

Novel diastereoselective photo-induced pinacol coupling reactions of acetophenones by using triethylamine and chiral tertiary amines as electron donating co-sensitizers were studied. Various influence factors including solvents, substituents, and chiral amines on both the diastereoselectivity and yield were examined. The diastereoselectivities were enhanced in supramolecular systems of cyclodextrins and zeolites. The best result of dl/meso up to 82:18 was obtained in combination use of chiral tertiary amine and β-CD.     

Insight into the mechanism of oxidative kinetic resolution of racemic secondary alcohols by using manganese(III)(salen) complexes as catalysts

The oxidative kinetic resolution of various racemic secondary alcohols with PhI(OAc)(2) catalyzed by chiral [Mn(III)(salen)] complexes in the presence of KBr was studied in a water/organic solvent mixture. The dramatic, synergetic effect of additives, organic solvent, and the substituents of chiral salen ligands on the enantioselectivities of the reactions is reported. Results from UV/Vis spectroscopy and ESI-MS studies provide evidence that these reactions are induced by the formation of a high-valent manganese intermediate.     

C3 and C6 Modification-Specific OYE Biotransformations of Synthetic Carvones and Sequential BVMO Chemoenzymatic Synthesis of Chiral Caprolactones

The scope for biocatalytic modification of non-native carvone derivatives for speciality intermediates has hitherto been limited. Additionally, caprolactones are important feedstocks with diverse applications in the polymer industry and new non-native terpenone-derived biocatalytic caprolactone syntheses are thus of potential value for industrial biocatalytic materials applications. Biocatalytic reduction of synthetic analogues of R-(−)-carvone with additional substituents at C3 or C6, or both C3 and C6, using three types of OYEs (OYE2, PETNR and OYE3) shows significant impact of both regio-substitution and the substrate diastereomer. Bioreduction of (−)-carvone derivatives substituted with a Me and/or OH group at C6 is highly dependent on the diastereomer of the substrate. Derivatives bearing C6 substituents larger than methyl moieties are not substrates. Computer docking studies of PETNR with both (6S)-Me and (6R)-Me substituted (−)-carvone provides a model consistent with the outcomes of bioconversion. The products of bioreduction were efficiently biotransformed by the Baeyer–Villiger monooxygenase (BVase) CHMO_Phi1 to afford novel trisubstituted lactones with complete regioselectivity to provide a new biocatalytic entry to these chiral caprolactones. This provides both new non-native polymerization feedstock chemicals, but also with enhanced efficiency and selectivity over native (+)-dihydrocarvone Baeyer–Villigerase expansion. Optimum enzymatic reactions were scaled up to 60–100 mg, demonstrating the utility for preparative biocatalytic synthesis of both new synthetic scaffold-modified dihydrocarvones and efficient biocatalytic entry to new chiral caprolactones, which are potential single-isomer chiral polymer feedstocks.     

Diastereoselective Coupling of Chiral Acetonide Trisubstituted Radicals with Alkenes

The stereochemical outcome of reactions of chiral nucleophilic trisubstituted acetonide radicals with electron‐deficient alkenes is dictated by a delicate balance between destabilizing non‐bonding interactions and stabilizing hydrogen‐bonding between substituents on the α and β carbons.     

Electronic effects in 1,3-dipolar cycloaddition reactions of N-alkyl and N-benzyl nitrones with dipolarophiles

1,3-Dipolar cycloadditions afforded fast access to isoxazolidines bearing N-alkyl or N-benzyl substituents. The electronic properties of the substituents in the nitrones define the activity of the dipoles and modulate diastereoselectivity in the non-catalyzed reactions. Using a chiral one-point binding ruthenium Lewis acid catalyst, products were obtained in good yields and with excellent regio-, diastereo-, and enantioselectivity.     

Synthesis and application of <Emphasis Type="Italic">N</Emphasis>-hydroxy(tetrahydrofuran-2-yl)amines

Data on synthesis, reactivity and bioactivity of N-hydroxy(tetrahydrofuran-2-yl)amines were discussed in the present review. General approaches to chiral N-glycosylhydroxylamines based on reactions of hydroxylamine with cyclic five-membered hemiacetals or dihydrofurans as well as reactions of tetrahydrofuran-containing nitrones with nucleophiles were systematized. The application of N-hydroxy(tetrahydrofuran-2-yl)amines in the synthesis of chiral heterocycles, aminophosphonic acids, N-hydroxypropargylamines, as well as natural compounds (for example, sieboldin A), pharmaceuticals (Zileuton) and their analogs was demonstrated. It was found that depending on substituents, N-hydroxy(tetrahydrofuran-2-yl)-amines can act as lipoxygenase inhibitors, and show antioxidant, antitumor, antibacterial, and other types of activities.