Preparation and Configurational Stability of Chiral Chloro-[D₁]methyllithiums of 98% Enantiomeric Excess

Abstract

Enantiopure stannyl-[D1]methanol was converted to chloro-[D1]methylstannane under complete inversion of configuration using Ph3P/N-chlorosuccinimide in THF. It was transmetalated to stereospecifically give chloro-[D1]methyllithium (ee up to 98%). Its microscopic configurational stability was tested by performing tin-lithium exchange in the presence of benzaldehyde as the electrophile under various conditions. The macroscopic configurational stability was addressed by using the same electrophile but by adding it 30 s after the addition of MeLi used for transmetalation. Chloro-[D1]methyllithium is chemically very labile, however completely configurationally stable on both time scales up to the temperature of rapid decomposition (-78 degrees C).

Synthesis of 2-Aminoazoles from Thioesters via α-Heterosubstituted Ketones by Copper-Mediated Cross-Coupling

“…Performing the cross-coupling with acetylthiomethylstannane 2f , 13 CuDPP was found to be a more effective copper additive compared to CuOAc (entries 11 and 12). Although the coupling reaction with chloromethylstannane 14 or iodomethylstannane 15 did not take place, fluoromethylstannane 2g 16 provided fluoromethyl ketones 15 and 16 (entries 13 and 14). Surprisingly, when CuOAc was used in this fluoromethylation reaction, the formation of the expected ketones ( 15 and 16 ) was accompanied by the formation of α-acetoxymethyl ketone byproducts ( 11 and 12 ).…”

On the Preparation and Determination of Configurational Stability of Chiral Thio- and Bromo[D1]methyllithiums

“…Using NBS/Ph 3 P: 6 A solution of Ph 3 P (772 mg, 2.94 mmol) in dry CH 2 Cl 2 (3 mL) was added dropwise to NBS (523 mg, 2.94 mmol) dissolved in dry CH 2 Cl 2 (5 mL) under argon at −78 °C. After 10 min tributylstannylmethanol ( 2 ) (787 mg, 2.45 mmol) dissolved in dry CH 2 Cl 2 (4 mL) was added, and the reaction mixture was stirred rt for 30 min.…”

“…5 Chloro[D 1 ]methyllithium 1m decomposes quickly but is macroscopically configurationally stable for its short lifetime. 6 …”

Halomethyllithium Carbenoids: Versatile Reagents for the Homologation of Electrophilic Carbon Units

“…(iv) because of the facile decomposition via a-elimination they undergo, reactions are performed in the presence of the electrophile [11] ; (v) the stability of this species is enhanced by both Lewis bases (e.g. THF or diethyl ether) and LiX salts, which, through the coordination to the lithium atom of the carbenoid, disrupt the internal Li-X interaction responsible for a-elimination with consequent decomposition of the carbenoid to the carbene 2 (Scheme 2b).…”

“…n-BuLi) that can further react with the soformed carbenoids. [11] Application of Halomethyllithiums in Organic Synthesis…”