Sodium Alkyl(trimethylsilyl)amides: Substituent- and Solvent-dependent Solution Structures and Reactivities.

The preparation of sodium isopropyl(trimethylsilyl)amide (NaPTA), sodium (1-phenylethyl)(trimethylsilyl)amide (NaPETA), sodium -butyl(trimethylsilyl)amide (NaBTA), and isotopologues [N]NaPTA and [N]NaBTA are described. Solution structural studies using a combination of Si NMR spectroscopy, the Method of Continuous Variations, and density functional theory computations provided insights into aggregation and solvation in a range of solvents including toluene, ,-dimethylethylamine, triethylamine, MTBE, THF, 1,2-dimethoxyethane (DME), diglyme, ,,','-tetramethylethylenediamine (TMEDA), ,,','-tetramethylcyclohexanediamine (TMCDA), ,,',″,″-pentamethyldiethylenetriamine (PMDTA). 12-crown-4, 15-crown-5, and 18-crown-6 revealed solvent- and substituent-dependent dimer-monomer mixtures with affiliated solvation numbers.

Competition between C-C and C-H Bond Fluorination: A Continuum of Electron Transfer and Hydrogen Atom Transfer Mechanisms.

In 2015, we reported a photochemical method for directed C-C bond cleavage/radical fluorination of relatively unstrained cyclic acetals using Selectfluor and catalytic 9-fluorenone. Herein, we provide a detailed mechanistic study of this reaction, during which it was discovered that the key electron transfer step proceeds through substrate oxidation from a Selectfluor-derived -centered radical intermediate (rather than through initially suspected photoinduced electron transfer). This finding led to proof of concept for two new methodologies, demonstrating that unstrained C-C bond fluorination can also be achieved under chemical and electrochemical conditions.

Sodium Isopropyl(trimethylsilyl)amide: A Stable and Highly Soluble Lithium Diisopropylamide Mimic.

The preparation, structure, physical properties, and reactivities of sodium isopropyl(trimethylsilyl)amide (NaPTA) are described. The solubilities at room temperature range from -heptane (0.55 M), -hexane (0.

Ketone Enolization with Sodium Hexamethyldisilazide: Solvent- and Substrate-Dependent - Selectivity and Affiliated Mechanisms.

Ketone enolization by sodium hexamethyldisilazide (NaHMDS) shows a marked solvent and substrate dependence. Enolization of 2-methyl-3-pentanone reveals - selectivities in EtN/toluene (20:1), methyl--butyl ether (MTBE, 10:1), -pentamethyldiethylenetriamine (PMDTA)/toluene (8:1), TMEDA/toluene (4:1), diglyme (1:1), DME (1:22), and tetrahydrofuran (THF) (1:90). Control experiments show slow or nonexistent stereochemical equilibration in all solvents except THF.

Reactions of Sodium Diisopropylamide: Liquid-Phase and Solid-Liquid Phase-Transfer Catalysis by ,,',″,″-Pentamethyldiethylenetriamine.

Sodium diisopropylamide (NaDA) in ,-dimethylethylamine (DMEA) and DMEA-hydrocarbon mixtures with added ,,',″,″-pentamethyldiethylenetriamine (PMDTA) reacts with alkyl halides, epoxides, hydrazones, arenes, alkenes, and allyl ethers. Comparisons of PMDTA with ,,','-tetramethylethylenediamine (TMEDA) accompanied by detailed rate and computational studies reveal the importance of the trifunctionality and κ-κ hemilability. Rate studies show exclusively monomer-based reactions of 2-bromooctane, cyclooctene oxide, and dimethylresorcinol.

Aggregation and Solvation of Sodium Hexamethyldisilazide: Across the Solvent Spectrum.

We report solution structures of sodium hexamethyldisilazide (NaHMDS) solvated by >30 standard solvents (ligands). These include: toluene, benzene, and styrene; triethylamine and related trialkylamines; pyrrolidine as a representative dialkylamine; dialkylethers including THF, -butylmethyl ether, and diethyl ether; dipolar ligands such as DMF, HMPA, DMSO, and DMPU; a bifunctional dipolar ligand nonamethylimidodiphosphoramide (NIPA); polyamines ,,,'-tetramethylenediamine (TMEDA), ,,,,″-pentamethyldiethylenetriamine (PMDTA), ,,,'-tetramethylcyclohexanediamine (TMCDA), and 2,2'-bipyridine; polyethers 12-crown-4, 15-crown-5, 18-crown-6, and diglyme; 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.

Hydrogen Bond Donor Catalyzed Cationic Polymerization of Vinyl Ethers.

The synthesis of high-molecular-weight poly(vinyl ethers) under mild conditions is a significant challenge, since cationic polymerization reactions are highly sensitive to chain-transfer and termination events. We identified a novel and highly effective hydrogen bond donor (HBD)-organic acid pair that can facilitate controlled cationic polymerization of vinyl ethers under ambient conditions with excellent monomer compatibility. Poly(vinyl ethers) of molar masses exceeding 50 kg mol can be produced within 1 h without elaborate reagent purification.

Sodium Hexamethyldisilazide: Using N-Si Scalar Coupling to Determine Aggregation and Solvation States.

Si NMR spectroscopy, the method of continuous variations, and density functional theory computations show that sodium hexamethyldisilazide (NaHMDS) is a disolvated dimer in toluene, a mixture of disolvated dimer and tetrasolvated monomer in THF/toluene, and exclusively monomer in neat THF. The dioxane-solvated NaHMDS only partially deaggregates to monomer even in neat dioxane. N-Si coupling constants and Si chemical shifts show a high and dependable correlation with the aggregation state.

Structure, Reactivity, and Synthetic Applications of Sodium Diisopropylamide.

The 60-year history of sodium diisopropylamide (NaDA) is described herein. We review various preparations, solvent-dependent stabilities, and solution structures. Synthetic applications of NaDA reported to date are framed by a mechanism-driven approach, emphasizing selectivities when appropriate.

Enantioselective Alkylation of 2-Alkylpyridines Controlled by Organolithium Aggregation.

Direct enantioselective α-alkylation of 2-alkylpyridines provides access to chiral pyridines via an operationally simple protocol that obviates the need for prefunctionalization or preactivation of the substrate. The alkylation is accomplished using chiral lithium amides as noncovalent stereodirecting auxiliaries. Crystallographic and solution NMR studies provide insight into the structure of well-defined chiral aggregates in which a lithium amide reagent directs asymmetric alkylation.

Sodium Diisopropylamide-Mediated Dehydrohalogenations: Influence of Primary- and Secondary-Shell Solvation.

Eliminations of alkyl halides by sodium diisopropylamide (NaDA) in tetrahydrofuran (THF)/hexane or THF/-dimethylethylamine (DMEA) solutions are facile and complementary to analogous reactions of lithium diisopropylamide in THF. Rate studies show a dominance of monomer-based metalations and prevalent secondary-shell solvation effects overlaid on primary-shell effects. 1-Halooctanes exclusively undergo elimination rather than substitution.

Aryl Carbamates: Mechanisms of Orthosodiations and Snieckus-Fries Rearrangements.

Aryl carbamates are orthometalated by sodium diisopropylamide (NaDA) in tetrahydrofuran. The resulting arylsodiums undergo Snieckus-Fries rearrangement to give orthoacylated phenols in good yield. The intermediate arylsodiums and resulting orthoacylated phenolates are suggested to be monomeric.

Triethylborane-initiated radical chain fluorination: a synthetic method derived from mechanistic insight.

We offer a mild, metal-free sp(3) C-H fluorination alternative using Selectfluor and a substoichiometric amount of triethylborane--an established radical initiator in the presence of O2. This radical-chain-based synthetic method is particularly noteworthy as an offspring of the insight gained from a mechanistic study of copper-promoted aliphatic fluorination, constructively turning O2 from an enemy to an ally. Furthermore, BEt3/O2 is a preferred initiator in industrial processes, as it is economical, is low in toxicity, and lends way to easier workup.

Direct, catalytic monofluorination of sp³ C-H bonds: a radical-based mechanism with ionic selectivity.

Recently, our group unveiled a system in which an unusual interplay between copper(I) and Selectfluor effects mild, catalytic sp(3) C-H fluorination. Herein, we report a detailed reaction mechanism based on exhaustive EPR, (19)F NMR, UV-vis, electrochemical, kinetic, synthetic, and computational studies that, to our surprise, was revealed to be a radical chain mechanism in which copper acts as an initiator. Furthermore, we offer an explanation for the notable but curious preference for monofluorination by ascribing an ionic character to the transition state.

Iron(II)-catalyzed benzylic fluorination.

Direct C-F functionalization of benzylic sp(3) C-H bonds is a synthetic challenge that has yet to be propitiously overcome. A mild, one-pot synthesis of monofluorinated benzylic substrates is reported with commercially available iron(II) acetylacetonate and Selectfluor in good to excellent yields and selectivity. A convenient route to β-fluorinated products of 3-aryl ketones is also highlighted, providing a synthetic equivalent to the difficult to accomplish conjugate addition of fluoride to α,β-unsaturated ketones.