ABSTRACT
An enantioselective method for the synthesis of α-methyl carboxylic acids starting from trans-cinnamaldehyde, a readily available and inexpensive compound, has been developed. Allylic alcohol 1 was obtained via a standard Grignard addition to trans-cinnamaldehyde. Dynamic kinetic resolution was applied to allylic alcohol 1 utilizing a ruthenium catalyst and either an (R)-selective lipase or an (S)-selective protease to provide the corresponding allylic esters in high yield and high ee. A copper-catalyzed allylic substitution was then applied to provide the corresponding alkenes with inversion of stereochemistry. Subsequent C-C double bond cleavage afforded pharmaceutically important α-methyl substituted carboxylic acids in high ee and overall yields of up to 76%.
Subject(s)
Acrolein/analogs & derivatives , Carboxylic Acids/chemical synthesis , Lipase/metabolism , Organometallic Compounds/chemistry , Peptide Hydrolases/metabolism , Propanols/chemistry , Acrolein/chemistry , Carboxylic Acids/chemistry , Catalysis , Fungal Proteins , Kinetics , Lipase/chemistry , Molecular Structure , Peptide Hydrolases/chemistry , Propanols/chemical synthesis , StereoisomerismABSTRACT
No Fe-ar: Iron catalyzes an imine-directed C-H bond activation to introduce an ortho-aryl group to an acetophenone-derived imine using a diarylzinc reagent (see scheme), whereas palladium catalyzes the conventional substitution reaction . The title reaction features mild and selective C-H bond activation in the presence of aryl bromide, chloride, or sulfonate groups, and 1,2-dichloroisobutane is essential to achieve such selectivity.
ABSTRACT
An iron-catalyzed C-C bond formation reaction of a nitrogen-containing aromatic compound with an arylzinc reagent takes place at 0 degrees C in a good to quantitative yield. The reaction involves a C-H bond activation directed by a neighboring nitrogen atom. The important additives in this reaction are 1,10-phenanthroline, tetramethylethylenediamine, and 1,2-dichloro-2-methylpropane, in the absence of which a very low product yield was observed.
ABSTRACT
Dynamic kinetic resolution of allylic alcohols to allylic acetates followed by copper-catalyzed allylic substitution gave alkenes in high yields and high optical purity. Subsequent oxidative C-C double bond cleavage afforded pharmaceutically important alpha-methyl substituted carboxylic acids in high ee.
Subject(s)
Carboxylic Acids/chemistry , Copper/chemistry , Lipase/chemistry , Carboxylic Acids/chemical synthesis , Catalysis , Fungal Proteins , Kinetics , Molecular Structure , Propanols/chemistry , Ruthenium/chemistry , StereoisomerismABSTRACT
Copper-catalyzed alpha-substitution of enantiomerically pure secondary allylic esters with Grignard reagents was studied with the aim to find conditions that give racemic products. It was observed that the degree of chiral transfer is strongly dependent on the temperature. The loss of chiral information is consistent with an equilibration of the Cu(III)(allyl) intermediates prior to product formation. Equilibration of the reaction intermediates is of importance for a possible development of a dynamic kinetic asymmetric transformation (DYKAT) process, in which a chiral catalyst is used to produce an optically active product from a racemic substrate, by means of a dynamic equilibrium of the diastereomeric reaction intermediates.
Subject(s)
Acetates/chemistry , Copper/chemistry , Catalysis , Indicators and Reagents/chemistry , Kinetics , Oxidation-Reduction , Solvents/chemistry , Stereoisomerism , TemperatureABSTRACT
A number of pentasubstituted acylferrocenes were selectively prepared from ferrous chloride, sodium acylcyclopentadienides, and the corresponding pentasubstituted lithium cyclopentadienides in good yields. The selectivity is governed by the different steric and electronic properties of the acylcyclopentadienides vs the pentasubstituted cyclopentadienides.
