Facile Synthesis of Chiral α‐Difluoromethyl Amines from N‐(tert‐Butylsulfinyl)aldimines

Abstract

Die nucleophile (Phenylsulfonyl)difluormethylierung von (R)‐(N‐tert‐Butylsulfinyl)aldiminen mit (Difluormethyl)phenylsulfon verläuft mit ausgezeichneten Ausbeuten und hoher Diastereoselektivität (siehe Schema). Das unproblematische Entschützen von tert‐Butylsulfinyl‐ und Phenylsulfonylgruppen liefert die gewünschten α‐Difluormethylamine in hoher Enantiomerenreinheit.

Stereoselective Difluoromethylenation Using Me3SiCF2SPh: Synthesis of Chiral 2,4‐Disubstituted 3,3‐Difluoropyrrolidines

“…The reaction mixture was stirred at this temperature for 2 h, and then the temperature was raised to À20 8C and the reaction mixture was stirred for another 4 h. Aqueous saturated NH 4 Cl solution (10 mL) was then added to the mixture at this temperature, and the mixture was extracted with EtOAc (25 mL 3). The combined organic phase was dried over MgSO 4 , and the volatile solvents were removed under reduced pressure.…”

“…[4] Indeed, the present diastereoselective (phenylthio)difluoromethylation of N-(tert-butylsulfinyl)imines 2 provides an alternative approach for the preparation of homochiral a-difluoromethyl amines, which we previously synthesized by using PhSO 2 CF 2 H.…”

“…[4] The pyrrolidine unit is ubiquitous in natural products, and recently it was found that the 3,3-difluoropyrrolidine moiety plays very important roles in a variety of enzyme inhibitors such as coagulation factor Xa (or thrombin) inhibitors [6c] and cathepsin inhibitors, [6d] among others.…”

“…[2a, 3,4] In 2001 Prakash et al reported an elegant diastereoselective nucleophilic trifluoromethylation of N-(tert-butylsulfinyl)imines using the Ruppert-Prakash reagent (TMSCF 3 ), [5] and recently we described highly diastereoselective nucleophilic difluoromethylations and monofluoromethylations using PhSO 2 CF 2 H and PhSO 2 CH 2 F as the di-and monofluoromethylating agents, respectively. [4] The pyrrolidine unit is ubiquitous in natural products, and recently it was found that the 3,3-difluoropyrrolidine moiety plays very important roles in a variety of enzyme inhibitors such as coagulation factor Xa (or thrombin) inhibitors [6c] and cathepsin inhibitors, [6d] among others.…”

Highly Enantioselective Synthesis of β‐Aminophosphinates with Two Stereogenic Atoms and Their Conversion into Optically Pure Ethyl β‐Amino‐H‐phosphinates

“…www.chemeurj.org strates: attempts to remove the tert-butanesulfinyl group from the amino group (4n HCl in dioxane/MeOH) [19] and diethoxyethyl group from the phosphorus atom (TMSCl/ EtOH/CH 2 Cl 2 ) [20] both led to inseparable mixtures. Through several trials, we found that BF 3 ·Et 2 O worked well for the removal of the diethoxymethyl group; however, subsequent attempts to eliminate the tert-butanesulfinyl group proved to be another failure (Scheme 4).…”