Pentafluorophenyl Esters: Highly Chemoselective Ketyl Precursors for the Synthesis of α,α-Dideuterio Alcohols Using SmI₂ and D₂O as a Deuterium Source

Abstract

We report the first highly chemoselective synthesis of α,α-dideuterio alcohols with exquisite incorporation of deuterium (>98% [D2]) using pentafluorophenyl esters as ketyl radical precursors, SmI2 as a mild reducing agent, and D2O as the deuterium source. This system tolerates a variety of functional groups, offering rapid entry to valuable α,α-dideuterated alcohol building blocks. More generally, this report introduces pentafluorophenyl esters as the most reactive O-ketyl precursors reported to date.

Pentafluorophenyl Group as Activating Group: Synthesis of α‐Deuterio Carboxylic Acid Derivatives via Et3N Catalyzed H/D Exchange

“…Pfp ester is very reactive compared with most other aliphatic and aromatic esters [5] . It reacts with amines to give amide at mild conditions without the addition of any other reagents [6] .…”

“…Therefore, the H/D exchange process can be achieved under mild reaction conditions using Et 3 N as the catalyst and D 2 O as the deuterium source. Pfp ester is an active precursor prone to nucleophilic attack [4] and reduction [5] . They can be easily converted into deuterated carboxylic acids, amides, [6] alcohols [5] or polymers [7] (Figure 4).…”

“…Pfp ester is an active precursor prone to nucleophilic attack [4] and reduction [5] . They can be easily converted into deuterated carboxylic acids, amides, [6] alcohols [5] or polymers [7] (Figure 4).…”

Catalytic Asymmetric C(sp3)H Carbene Insertion Approach to Access Enantioenriched 3Fluoroalkyl 2,3-Dihydrobenzofurans

“…NaH (12.0 mmol, 480 mg, 60% wt) was added under 0 o C in portions and stirred for 15 min. Then MeI (20 mmol, 2.84 g) was added and stirred at rt for 1.5 h. After the reaction was complete, the reaction mixture was treated with aqueous NH 4 Cl and quenched with CH 3 COOEt.…”

“…To a N 2 filled sealed reaction tube was added ethyl trifluoroacetate (30.0 mmol) and dry THF (15.0 mL). The corresponding Grignard reagent was added to the mixture at -40 o C, then the reaction was stirred at rt for 2 h. The reaction mixture was then treated with aqueous NH 4 Cl and quenched with CH 3 COOEt. The organic layer was washed with brine and dried over anhydrous Na 2 SO 4 .…”