Nucleophilic additions to fused bicyclic five-membered ring oxocarbenium ions: evidence for preferential attack on the inside face

Evidence is provided that nucleophilic attack on five-membered ring oxocarbenium ions occurs from the inside face of the envelope. An eight-five fused-bicyclic system in which two substituents are constrained to pseudoequatorial positions underwent nucleophilic addition with selectivity that was comparable to an unconstrained monocyclic system. On the other hand, a bicyclic six-five analogue underwent reaction with low selectivity. This observation indicates that minimization of eclipsing interactions by attacking inside the envelope is not enough to control selectivity, but that the changes in the overall three-dimensional structure of the ring must be favorable as well. In the bicyclic six-five series, the six-membered ring is accommodated in the cation, but it destabilizes the transition state structure leading to the first-formed product of inside attack.     

Copper-catalyzed enantioselective additions to oxocarbenium ions: alkynylation of isochroman acetals

We have developed an enantioselective, copper(I)-catalyzed addition of terminal alkynes to racemic isochroman acetals. This method is one of the first transition-metal-catalyzed approaches to enantioselective additions to prochiral oxocarbenium ions. In this reaction, TMSOTf is used to form the oxocarbenium ion in situ under conditions compatible with simultaneous formation of the chiral copper acetylide. By using a bis(oxazoline) ligand, good yields and enantioselectivities are observed for a variety of enantioenriched 1-alkynyl isochromans.     

Addition of carbon nucleophiles to cyclic N-acyliminium and oxocarbenium ions under solvent-free conditions

The InCl₃-catalyzed addition of carbon nucleophiles to cyclic N-acyliminium and oxocarbenium ions under solvent-free conditions at room temperature is described. The corresponding α-substituted heterocycles were obtained in moderate to excellent yields.     

Investigations into the role of ion pairing in reactions of heteroatom-substituted cyclic oxocarbenium ions

[reaction: see text] The O-to-C rearrangement of vinyl acetals is used to demonstrate that tight ion pairing is not involved in the stereoselective nucleophilic addition reactions of alkoxy-substituted cyclic oxocarbenium ions.     

Inverse stereoselectivity in the nucleophilic attack on five-membered ring oxocarbenium ions. Application to the total synthesis of 7-epi-(+)-goniofufurone

A highly stereoselective nucleophilic substitution at the anomeric position of 1,2-O-isopropylidene furanose derivatives was employed for the synthesis of 7-epi-(+)-goniofufurone and two of its stereoisomers. According to Woerpel's model, the stereoselectivity depends essentially on stereoelectronic factors that lead to a preferred nucleophilic attack on the inside face of the five-membered ring oxocarbenium ion in a folded conformation, whereby the stereochemical outcome generally is controlled by the substituent at the C3 position (OR group). Herein, we developed a strategy for a reverse stereoselective nucleophilic substitution, by placing an acetyl group at the C5 position of the xylofuranose ring, leading now to the nucleophilic approach on the outside face of the respective oxocarbenium ion. With this methodology, starting from diacetone-d-glucose derivative, we were able to achieve in seven steps the total synthesis of the powerful anti-tumor compound 7-epi-(+)-goniofufurone in a remarkable overall yield of 33%.     

An efficient catalytic asymmetric addition of trimethylsilyl cyanide to aldehydes at room temperature

The BINOL-salen compound (S)-5c in combination with Ti(OⁱPr)₄ is found to catalyze the addition of TMSCN to aldehydes to form chiral cyanohydrins with very good enantioselectivity (75-85% ee). The reactions are carried out in one-pot at room temperature without the need to isolate the chiral Lewis acid catalyst.     

Methyltriphenylphosphonium iodide catalyzes the addition of trimethylsilyl cyanide to aldehydes

Methyltriphenylphosphonium iodide catalyzes the formation of cyanohydrin trimethylsilyl ethers of aliphatic, aromatic and heterocyclic aldehydes.     

Catalytic asymmetric addition of aldehydes to oxocarbenium ions: a dual catalytic system for the synthesis of chromenes

A synergistic catalytic system for the first asymmetric addition of aldehydes to in situ generated prochiral oxocarbenium ions has been developed. The dual catalytic protocol allows the simultaneous activation of both electrophile and nucleophile and provides access to a variety of valuable chiral 2H-chromenes with excellent enantioselectivities.     

Nucleophilic additions of lithiated allylphenylsulfone to nitrones: experimental and theoretical investigations

The nucleophilic addition of lithiated allylphenylsulfone to nitrones at −80 °C proceeds exclusively α to the phenylsulfonyl group affording anti adducts in high yield. At 0 °C isoxazolidines are obtained with complete all-trans selectivity. The formation of these compounds involves isomerization of the allylsulphonyl moiety to give a transient vinylsulfone that then undergoes a subsequent intramolecular Michael addition. The addition to several nitrones has been studied and theoretical calculations have been refined to accurately explain the selectivity of the allylation reaction.     

Stereochemistry of nucleophilic substitution reactions depending upon substituent: evidence for electrostatic stabilization of pseudoaxial conformers of oxocarbenium ions by heteroatom substituents

Lewis acid-mediated nucleophilic substitution reactions of substituted tetrahydropyran acetates reveal that the conformational preferences of six-membered-ring cations depend significantly upon the electronic nature of the substituent. Nucleophilic substitutions of C-3 and C-4 alkyl-substituted tetrahydropyran acetates proceeded via pseudoequatorially substituted oxocarbenium ions, as would be expected by consideration of steric effects. Substitutions of C-3 and C-4 alkoxy-substituted tetrahydropyran acetates, however, proceeded via pseudoaxially oriented oxocarbenium ions. The unusual selectivities controlled by the alkoxy groups were demonstrated for a range of other heteroatom substituents, including nitrogen, fluorine, chlorine, and bromine. It is believed that the pseudoaxial conformation is preferred in the ground state of the cation because of an electrostatic attraction between the cationic carbon center of the oxocarbenium ion and the heteroatom substituent. This analysis is supported by the observation that selectivity diminishes down the halogen series, which is inconsistent with electron donation as might be expected during anchimeric assistance. The C-2 heteroatom-substituted systems gave moderately high 1,2-cis selectivity, while small alkyl substituents showed no selectivity. Only in the case of the tert-butyl group at C-2 was high 1,2-trans selectivity observed. These studies reinforce the idea that ground-state conformational effects need to be considered along with steric approach considerations.     

Nucleophilic addition of potassium organotrifluoroborates to chiral cyclic N-acyliminium ions: stereoselective synthesis of functionalized N-heterocycles

The stereoselective nucleophilic addition of potassium aryl- and alkynyltrifluoroborates to cyclic N-acyliminium ion derivatives from N-benzyl-3,4,5-triacetoxy-2-pyrrolidinone, affording the respective 5-substituted 2-pyrrolidinone is described. The products were obtained in moderate to good yields and with preference for the syn diastereomer.     

Silicon in synthesis: The use of trimethylsilyl cyanide for the synthesis of aliphatic cyanomethylethers

The conversion of aliphatic alcohols into cyanomethyl ethers $\text{via}$ treatment of methyl sulfoxymethyl ethers with trimethylsilyl cyanide - zinc iodide is described.     

Formation and reactivity of novel pyranosidic nicholas oxocarbenium ions: access to C-ketosides and branched-chain C-ketosides

[Structure: see text] Dicobalt hexacarbonyl propargyl complexes, prepared from alkynyl ketoses, display an unexpected reactivity when treated with Lewis acids in the presence of nucleophiles and furnish C-ketosides, branched-chain C-ketosides, or branched-chain C-glycals depending on the nucleophile and the carbohydrate starting material.     

Highly stereoselective chlorination of beta-substituted cyclic alcohols using PPh3-NCS: factors that control the stereoselectivity

A variety of trans-beta-substituted cyclic alcohols were stereoselectively chlorinated to either the corresponding cis-chloride or trans-chloride (inversion or retention of configuration) with good to excellent yields; the stereochemical outcome is determined by the size of the ring and the nature of the beta-substituents, especially the electronegativity of the substituted atom.     

Silica-supported heteropoly acids: Highly efficient catalysts for synthesis of α-aminonitriles,using trimethylsilyl cyanide or potassium cyanide

The multicomponent Strecker reaction using trimethylsilyle cyanide or potassium cyanide was performed in very short reaction times and α-aminonitriles were prepared in excellent yields in the presence of a catalytic amount of silica supported dodecatungstophosphoric acid. The simple experimental and product isolation procedure combined with easy recovery and reusability of the catalyst are expected to contribute to the development of clean and environmentally friendly strategy for the synthesis of α-aminonitriles.     

Nucleophilic substitution reactions of sulfur-substituted cyclohexanone acetals: an analysis of the factors controlling stereoselectivity

The reactions of cyclohexanone acetals substituted with thiophenyl groups (and other heteroatoms) at C-2 demonstrate the powerful influence that these substituents have on the stereoselectivity of nucleophilic substitution reactions. The trans selectivities of these reactions correlate with the behavior of the corresponding ketones. These experiments lend support to the possibility that the reactions of the acetals, which proceed via oxocarbenium ions, are operating under Felkin-Anh control.     

Addition of trimethylsilyl cyanide to allenes with the aid of a palladium or nickel catalyst

The reaction of allenes with trimethylsilyl cyanide in the presence of a palladium or nickel catalyst provides functinalized vinylsilanes in good yields.     

Diastereoselective additions of nucleophiles to alpha-acetoxy ethers using the alpha-(trimethylsilyl)benzyl auxiliary

We report the diastereoselective addition of a variety of nucleophiles to alpha-(trimethylsilyl)benzyl-substituted oxocarbenium ions. The oxocarbenium ions are generated from alpha-acetoxy ethers, which are easily prepared via reductive acetylation of esters. The alpha-(trimethylsilyl)benzyl auxiliary produces good to excellent facial selectivity with a variety of nucleophiles, including silyl enol ethers, silyl ketene acetals, allylsilanes, and crotylsilanes. The utility of this auxiliary is further demonstrated in a complex ketone aldol coupling reaction. [reaction: see text]     

Triple nucleophilic additions of (trimethylsilyl)ketene acetals to tropylium derivatives: access to the core nuclei of xanthanolides

The 5,7-fused system of xanthanolides was achieved in three steps from tropylium tetrafluoroborate and ketene acetals via complexes of cycloheptatriene carboxylic acid esters and chromium tricarbonyl.     

Triphenylene based copper ensemble for the detection of cyanide ions

The binding behavior of triphenylene based copper ensemble prepared in situ has been investigated toward various anions (F(-), Cl(-), Br(-), I(-), CH(3)COO(-), H(2)PO(4)(-), NO(3)(-), OH(-), ClO(4)(-), CN(-), CO(3)(-) and SO(4)(-)) by UV-vis and fluorescence spectroscopy. Among various anions tested, 1-Cu(2+) ensemble shows selective and sensitive response towards cyanide ions and responds to CN(-) ions even in the presence of bovine serum albumin and in blood serum milieu. Further, as practical application of compound 1, we utilized the TLC strips coated with THF solution of 1 for the solid state detection of copper and cyanide ions.