Stereoselective Nucleophilic Monofluoromethylation of N‐(tert‐Butanesulfinyl)imines with Fluoromethyl Phenyl Sulfone.

Abstract

Amines Q 0120Stereoselective Nucleophilic Monofluoromethylation of N-(tert-Butanesulfinyl)imines with Fluoromethyl Phenyl Sulfone. -A highly stereoselective nucleophilic monofluoromethylation of chiral sulfinylimines with fluoromethyl phenyl sulfone is developed. The products are obtained in excellent yield with high stereoselectivity (99:1 or 98:2). Without purification, they are converted into α-monofluoromethylamine salts (VI) via reductive desulfonation and removal of the tert-butanesulfinyl group. The same methodology is also used to synthesize homochiral α-monofluoromethylated cyclic secondary amines using tosylate-bearing (R)-(tert-butanesulfinyl)imine precursors (VII). -(LI, Y.; NI, C.; LIU, J.; ZHANG, L.; ZHENG, J.; ZHU, L.; HU*,

Dynamic Kinetic Resolution-Enabled Highly Stereoselective Nucleophilic Fluoroalkylation to Access Chiral β-Fluoro Amines

“…Hu and co-workers synthesized β-fluoro amines via diastereoselective fluoromethylation of chiral N-tert-butylsulfinyl ketimines, but with a racemic carbon center at the β-position (due to the difficult differentiation of H/F atoms), and the yield is moderate (Figure 1c-ii). 30,31 In addition, an enzyme-catalyzed kinetic resolution was also reported, but the drawback is the limitation of the 50% maximal yield (Figure 1c-iii). 32,33 Our group was recently devoted to the development of nucleophilic fluoroalkylations by employing sulfoximine as the stereocontrol reagent.…”

Selective Fluoroalkylations with Fluorinated Sulfones, Sulfoxides, and Sulfides

“…In 2006, we reported the first highly stereoselective monofluoromethylation of (R)-N-tert-butanesulfinimines using fluoromethyl phenyl sulfone (PhSO 2 CH 2 F, 3) as a novel nucleophilic monofluoromethylating reagent (Figure 13). 64 The reaction has been shown to be highly stereoselective and convenient for the synthesis of enantiomerically pure R-monofluoromethyl amines 71. The same methodology can also be used to synthesize homochiral R-monofluoromethylated cyclic secondary amines 73 by using tosylate (OTs)-bearing (R)-(tert-butanesulfinyl)imine precursors 72 (Figure 13).…”

“…The same methodology can also be used to synthesize homochiral R-monofluoromethylated cyclic secondary amines 73 by using tosylate (OTs)-bearing (R)-(tert-butanesulfinyl)imine precursors 72 (Figure 13). 64 The diastereoselective monofluoromethylation of R-amino Ntert-butanesulfinimine 74 with reagent 3 can afford homochiral R-monofluoromethylated ethylenediamine 77 in good yield (Figure 13). 54 In 2006, we reported a previously unknown compound, fluorobis(phenylsulfonyl)fluoromethane [(PhSO 2 ) 2 CHF, 7] as an excellent monofluoroalkylating reagent.…”

“…For a long time, nucleophilic monofluoromethylation (the transfer of the “CH 2 F” group to carbon electrophiles) has not been studied. In 2006, we reported the first highly stereoselective monofluoromethylation of ( R )- N - tert- butanesulfinimines using fluoromethyl phenyl sulfone (PhSO 2 CH 2 F, 3 ) as a novel nucleophilic monofluoromethylating reagent (Figure ) . The reaction has been shown to be highly stereoselective and convenient for the synthesis of enantiomerically pure α-monofluoromethyl amines 71 .…”

“…The reaction has been shown to be highly stereoselective and convenient for the synthesis of enantiomerically pure α-monofluoromethyl amines 71 . The same methodology can also be used to synthesize homochiral α-monofluoromethylated cyclic secondary amines 73 by using tosylate (OTs)-bearing ( R )-( tert -butanesulfinyl)imine precursors 72 (Figure ) . The diastereoselective monofluoromethylation of α-amino N-tert- butanesulfinimine 74 with reagent 3 can afford homochiral α-monofluoromethylated ethylenediamine 77 in good yield (Figure ) …”