Stereoselective Synthesis of α-Silylamines by the Direct Addition of Silyl Anions to Activated Imines

Abstract

[reaction: see text] A highly efficient stereoselective synthesis of unusual alpha-silylamines via a direct silyl anion addition reaction is reported. This approach is convergent and avoids any problematic aza-Brook shifts of the anionic intermediates. The use of enantiopure tert-butanesulfinyl imines as the electrophiles affords exceedingly high levels of diastereocontrol for the newly formed stereogenic carbon.

Reaction prospecting by 31P NMR: enantioselective rhodium-DuPhos catalysed addition of ZnMe2 to diphenylphosphinoylimines

“…4 We were only able to improve on this procedure in two ways. Firstly, the isolated yields of the somewhat hydrolytically labile imines 3b are improved by prompt chromatography in EtOAc/CH 2 Cl 2 compared to just EtOAc, as recommended, due to solubility issues with 3b.…”

Incorporation of β‐Silicon‐β3‐Amino Acids in the Antimicrobial Peptide Alamethicin Provides a 20‐Fold Increase in Membrane Permeabilization

“…The key step of the synthetic route to the siliconcontaining amino acids 10 and 11 was the addition of as ilyl lithium reagent to an Ellman sulfinimine, [17] which is am ethod previously reported by Ballweg et al [18] and later by our group [19] for the preparation of silanediol isosters. [20] This addition reaction generally proceeds with ah igh diastereoselectivity in the order of !…”

Reductive Lithiation and Multilithiated Compounds in Synthesis

“…Indeed, although previous literature reports on this topic indicate hydridosilanes as poor substrates for lithium reduction, Skrydstrup and coworkers accomplished the ready lithiation of a series of alkyldiphenylsilanes, 119, by reacting them with Li metal in THF at room temperature for 18 h. The resulting silyl-lithium intermediates reacted with chiral sulfinimine to afford the desired α-silylsulfinamides, 120, with satisfactory to good yields and, in most cases, with excellent diastereoselectivities (Scheme 12.28) [54][55][56]. Finally, a one-pot hydrosilylation, reductive lithiation, and addition to enantiopure tert-butylsulfinyl imines demonstrated the ready applicability of the whole synthetic protocol (Scheme 12.29).…”