Highly Stereoselective Trichloromethylation of N‐(tert‐Butylsulfinyl)aldimines: Facile Synthesis of Chiral α‐Trichloromethylamines

Abstract

The first highly stereoselective and facile synthesis of α-trichloromethylamines is described by using a nucleophilic trichloromethylation strategy. With tetrabutylammonium triphenyldifluorosilicate (TBAT) as the mediator, the tri-

Highly Stereoselective and Practical Synthesis of α‐Trichloromethyl Amines and 2,2‐Dichloroaziridines from Chloroform

“…In view of the generality of this reaction, the ready availability of chloroform, as well as the high diastereoselectivities and good to excellent yields, our herein reported highly diastereoselective trichloromethylation method represents a great advantage compared to the old ones. [11,12,13] The absolute configuration of sulfinamides 3 (except 3e and 3k) were determined to be (Rs, S) by comparison of the NMR spectra with our earlier reported data (see the Supporting Information for details), [13] which indicates that the stereochemistry of the nucleophilic addition was also not chelation controlled. The configurations of 3e and 3k were assigned by analogy.…”

“…Remarkably, the reactions were carried out under strong basic conditions but were still amenable to sulfinylimines bearing a-hydrogen atom(s) (see entries 13 and 14, Table 1), which is in sharp contrast to our reported trimethylA C H T U N G T R E N N U N G (trichloromethyl)silane chemistry. [13] Trichloromethylation reactions of chiral sulfinylimines with TMSCCl 3 were very sensitive to base [for example, tetrabutylA C H T U N G T R E N N U N G ammonium triphenyldifluorosilicate (TBAT), and CsF], and sulfinylimines bearing a-hydrogen atom(s) usually gave lower yields. It is also worthy to point out that, for imine 2e containing a strong electron-withdrawing nitro group, this reaction could proceed smoothly and gave the expected product 3e in high yield (81%), while trichloromethylation of 2e with TMSCCl 3 failed.…”

“…Recently, our research group has described a highly stereoselective method for nuleophilic trichloromethylation of N-(tert-butylsulfinyl)imines with trimethyl(trichloromethyl)silane (TMSCCl 3 ). [13] However, TMSCCl 3 is not commercially available and its storage requires moisture-free conditions. [14] 2,2-Dichloroaziridine represents an important compound from synthetic, mechanistic, and medicinal points of view.…”

Efficient Total Synthesis of Dysidenin, Dysidin, and Barbamide

“…[18,19] The total syntheses of dysidenin (1, 10 steps, 21.5 % overall yield), dysidin (2, 12 steps, 20.2 % overall yield), and barbamide (3, 11 steps, 21.8 % overall yield) have been completed following a robust modular strategy, which allows for the synthesis of large quantities of the natural products and their analogues. [18,19] The total syntheses of dysidenin (1, 10 steps, 21.5 % overall yield), dysidin (2, 12 steps, 20.2 % overall yield), and barbamide (3, 11 steps, 21.8 % overall yield) have been completed following a robust modular strategy, which allows for the synthesis of large quantities of the natural products and their analogues.…”

“…In conclusion, this study further expands the scope of applications of the direct rutheniumcatalyzed radical haloalkylation of N-acyloxazolidinones via titanium enolates for the efficient stereoselective total syntheses of chloroleucine-derived natural products. [18,19] The total syntheses of dysidenin (1, 10 steps, 21.5 % overall yield), dysidin (2, 12 steps, 20.2 % overall yield), and barbamide (3, 11 steps, 21.8 % overall yield) have been completed following a robust modular strategy, which allows for the synthesis of large quantities of the natural products and their analogues.…”