Enantioselective Formation of Stereogenic Carbon–Fluorine Centers by a Simple Catalytic Method

Abstract

An easy protocol has been developed for the formation of stereogenic carbon–fluorine centers by the organocatalytic asymmetric α‐fluorination of aldehydes 1. The 2‐fluoroaldehydes 4 are formed with 2 as the fluorinating agent and only 1 mol % of a sterically demanding silylated prolinol 3 as catalyst. The 2‐fluoroaldehydes are subsequently reduced to the corresponding alcohols 5 without loss of enantiomeric excess.

Organocatalytic Domino Michael–Knoevenagel Condensation Reaction for the Synthesis of Optically Active 3‐Diethoxyphosphoryl‐2‐oxocyclohex‐3‐enecarboxylates

“…We anticipated that 2-[bis (3,5-bistrifluoromethylphenyl)trimethyl-silylanyloxymethyl]pyrrolidine 4 should be particularly well suited as a catalyst of our envisioned domino reaction, since its general catalytic activity has been confirmed in numerous aminocatalytic transformations. [9] Cinnamaldehyde 2 a was chosen as a model substrate. To our delight its reaction with ethyl 4-diethoxyphosphoryl-3-oxobutanoate 1 in CH 2 Cl 2 in the presence of 4 (10 mol %) was found to take place efficiently at room temperature and was completed within 24 h (Table 1, entry 1).…”

“…Initially we attempted a hydrolysis-decarboxylation reaction as an entry to 5-substituted-2-(diethoxyphosphoryl)cyclohex-2-enones (11; Scheme 3). Since acid-catalyzed hydrolysis-decarboxylation of tert-butyl 2-oxocyclohex-3-enecarboxylates constitute a well-established strategy to access 2-cyclohexenones, we decided to perform the Michael-Knoevenagel domino reaction of tert-butyl 4-diethoxyphosphoryl-3-oxobutanoate (9) and cinnamaldehyde (2 a) catalyzed by 4 to afford tert-butyl 2-oxocyclohex-3-enecarboxylate (10; Scheme 3). Methanesulfonic acid catalyzed hydrolysis-decarboxylation of 10 conducted in toluene at elevated temperature (90 8C) for 3 h yielded the target compound 2-diethoxyphosphoryl-5-phenylcyclohex-2-enone (11) in 96% ee.…”

An Enantio‐ and Diastereoselective Chemoenzymatic Synthesis of α‐Fluoro β‐Hydroxy Carboxylic Esters

“…[4] Thec ontrolled formation of fluorine-substituted stereocentres,h owever, presents as ignificant challenge.M ost usually,t he challenge is addressed by stereoselective CÀF bond formation. Fore xample,t he fluorination of allylic silanes is often diastereoselective, [5] and organo- [6] and Pd- [7] catalysed methods enable the enantioselective a-fluorination of carbonyl compounds. Stereoselective CÀCbond formation could provide acomplementary approach for controlling fluorine-bearing stereocentres (Scheme 1).…”

Acid-Base Catalysis of Chiral Pd Complexes: Development of Novel Catalytic Asymmetric Reactions and Their Application to Synthesis of Drug Candidates

“…[61][62][63][64] However, continuing exploitation of novel catalysts, including metal complexes and organic catalysts, is necessary to meet the need for various chiral fluorinated compounds, many of which are expected to find applications in the fields of medicinal chemistry, chemical biology, and material sciences. 65) While we could use environmentally friendly solvents, such as EtOH and water, recovery of the Pd complexes from the reaction mixtures was not easy.…”