Enolizable β-Fluoroenones: Synthesis and Asymmetric 1,2-Reduction

Abstract

The hydrofluorination of enolizable ynones with AgF in t-BuOH/DMF is reported. The formation of furans as side products can be suppressed using 2,2'-biphenol. The corresponding β-fluoroenones were obtained with good Z-selectivity. A variety of functional groups are tolerated. β-Fluoroenones are vinylogous acid fluorides whose hydrolysis to vinylogous acids can be avoided under the reported reaction conditions. The asymmetric 1,2-reduction of β-fluoroenones to 3-fluoroallylic alcohols is possible with pinacolborane and a Ni(0) catalyst prepared from a pyrimidyloxazoline ligand.

Lewis Base Catalyzed, Sulfenium Ion Initiated Enantioselective, Spiroketalization Cascade

“…The washed organic layer was then dried with Na 2 SO 4 (5 g) and concentrated under reduced pressure (25 °C at 100 mmHg) to afford 652.g (91%) of the crude mixture which was taken forward crude. Spectroscopic data for S10 matched the literature values …”

Rhodium‐Catalyzed Regioselective 3‐Fluoroallylic Cyanation

“…In view of the considerably interest in organofluorine chemistry [8–10] and using our recently disclosed entry to Z ‐3‐fluoroallylic alcohols [11] it seemed promising to study the transition‐metal catalyzed 3‐fluoroallylic cyanation. Here we report TMSCN and Rh(I)‐catalysis as solution for this challenge (Scheme 1c).…”

“…The 3‐fluoroallylic carbonate 8 a was chosen as first model substrate to explore suitable reaction conditions for the formation of the 3‐fluoroallylic nitrile 9 (Table 1). Compound 8 a is accessible from the corresponding 3‐fluoroallylic alcohol [11] . Attempts to use CuCN, NaCN or ZnCN as cyanide source for the Pd‐catalyzed reaction ( 8 a → 9 ) gave no conversion of the starting material.…”

“…With respect to stereoselectivity, the absolute configuration of the stereocenter in the allylic alcohol can be controlled as previously reported (Scheme 4). [11] Hydrofluorination of an ynone such as 17 gives the β‐fluoroenone 18 , which can be reduced enantioselectively with pinacolborane and a Ni(0) catalyst prepared from a pyrimidyloxazoline ligand to yield the 3‐fluoroallylic alcohol 19 . For the allylic substitution of the trifluoroacetate 12 a an inversion to give 13 a is expected assuming that cyanide acts as unstabilized nucleophile [16] .…”

DFT mechanistic investigation of the 1,2‐reduction of α,β‐unsaturated ynones

“…[22][23][24][25][26][27] Although, there is evidence of chemoselective reductions at room temperature with easily attainable reagents. [28][29][30] Recently, the mild hydride donor pinacolborane (pinBH, 2) with trialkylphosphane catalyst has been reported to complete the reduction with high yields (Scheme 1). [29,30] According to the pioneer work of the Vilotijevic group, highly nucleophilic, simple phosphane catalysts, such as trialkylphosphanes, provided a high yield at room temperature within 10 minutes in dichloromethane solvent.…”