Jaiwook Park

Dynamic kinetic resolutions and asymmetric transformations by enzymes coupled with metal catalysis

The combination of enzyme and metal catalysis is described as a useful method for the synthesis of optically active compounds. A key feature of this new methodology is the use of metal catalysts for the in situ racemization of enzymatically unreactive enantiomers in the enzymatic resolution of racemic substrates. So far, two combinations - lipase-ruthenium and lipase-palladium - have been developed for the efficient dynamic kinetic resolution of alcohols and amines. The use of these combinations has also been extended to catalysis of the asymmetric transformation of ketones, their enol acetates, and ketoximes. In most cases, enzyme-metal combination catalysis has provided good yields and high optical purities.

Heterogeneous copper catalyst for the cycloaddition of azides and alkynes without additives under ambient conditions.

A new copper catalyst was developed by immobilizing copper nanoparticles in aluminum oxyhydoxide fiber. The catalyst showed high catalytic activity for the (3+2) Huisgen cycloaddition of nonactivated alkynes as well as activated ones with various azides at room temperature. The catalyst was recycled five times without significant loss of activity.

One-Pot Synthesis of Imines and Secondary Amines by Pd-Catalyzed Coupling of Benzyl Alcohols and Primary Amines

Imines and secondary amines were synthesized selectively by controlling reaction conditions for the Pd-catalyzed one-pot reactions of benzyl alcohols with primary amines. The reactions did not require any additives and were effective for a wide range of alcohols and amines.

Dynamic Kinetic Resolution of Amines and Amino Acids by Enzyme–Metal Cocatalysis

Methods for the conversion of racemates to single enantiomers are of great importance in organic and pharmaceutical chemistry. Enzymatic kinetic resolution has been most frequently applied for such a conversion. It is particularly useful in preparing both R and S enantiomers at the same time. However, if one enantiomer is needed, the other should be recycled via racemization to enable high yields. Over the last two decades, in situ racemization of the unwanted enantiomers has been intensively studied with the development of metal‐based catalysts. Metal‐catalyzed racemization can be coupled with enzymatic kinetic resolution for the dynamic kinetic resolution of racemic amines and amino acids, which provides single enantiomeric products with yields approaching 100 %. Recent developments in this field are summarized with focus on metal catalysts for racemization.

Enzymatic resolution of secondary alcohols coupled with ruthenium-catalyzed racemization without hydrogen mediator

Abstract ( η 5 -Indenyl)RuCl(PPh 3 ) 2 was found to catalyze the racemization of secondary alcohols in the presence of triethylamine and oxygen. Unlike previously reported metal-catalyzed racemizations, ketones were not required as hydrogen mediators in our process. The Ru-catalyzed racemization was coupled with enzymatic acetylation for the dynamic kinetic resolution of secondary alcohols to give chiral acetates in good yields (60–98%) with high enantioselectivities (82–99% ee ).

Highly chemoselective aerobic oxidation of amino alcohols into amino carbonyl compounds.

The direct oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has often posed serious challenges in organic synthesis and has constrained chemists to adopting an indirect route, such as a protection/deprotection strategy, to attain their goal. Described herein is a highly chemoselective aerobic oxidation of unprotected amino alcohols to their amino carbonyl compounds in which 2-azaadamantane N-oxyl (AZADO)/copper catalysis is used. The catalytic system developed leads to the alcohol-selective oxidation of various unprotected amino alcohols, carrying a primary, secondary, or tertiary amino group, in good to high yield at ambient temperature with exposure to air, thus offering flexibility in the synthesis of nitrogen-containing compounds.

Dynamic kinetic resolution of secondary alcohols by enzyme–metal combinations in ionic liquid

Dynamic kinetic resolutions (DKRs) of secondary alcohols by lipase–ruthenium or subtilisin–ruthenium combo-catalysis were successfully accomplished in an ionic liquid, [BMIM]PF6 ([BMIM] = 1-butyl-3-methylimidazolium), in the presence of an acyl donor to provide (R)- or (S)-esters of high optical purities in good yields. Ionic liquid as solvent was essential for the successful performance of the DKRs at room temperature since its use enhanced the activity of the racemizing ruthenium catalyst.

EFFICIENT CATALYTIC RACEMIZATION OF SECONDARY ALCOHOLS

Abstract (η5-Indenyl)RuCl(PPh3)2 was found to efficiently catalyze the racemization of chiral alcohols such as (S)-1-phenylethan-1-ol, (S)-1-phenylpropan-2-ol and (S)-4-phenylbutan-2-ol at room temperature in the presence of base. The catalytic activity of five other Ru(II) complexes was also investigated. The effects of varying reaction conditions such as reaction temperature, solvent, and base were investigated as well.

Highly enantioselective dynamic kinetic resolution of 1,2-diarylethanols by a lipase-ruthenium couple.

A practical procedure has been developed for the dynamic kinetic resolution of 1,2-diarylethanols. This procedure employs a highly enantioselective lipase from Pseudomonas stutzeri (trade name, lipase TL) as the resolution catalyst and a ruthenium complex as the racemization catalyst. Sixteen 1,2-diarylethanols have been efficiently resolved to provide their acetyl derivatives with good yields (95-97%) and high enantiomeric excesses (96-99%).

LITHIATION AND PHOSPHORYLATION OF CHIRAL 1,1'-BIS(OXAZOLINYL)FERROCENES

Two chiral 1,1′-bis[(S-2-(4-R-oxazolinyl)]ferrocenes (3) were prepared by condensation of 1,1′-bis(chlorocarbonyl)ferrocene with (S)-valinol and (S)-tert-leucinol, respectively. Lithiation of 3 with n-BuLi followed by coupling with ClPPh2 gave the diphosphorylated product 5 of C2 symmetry as a minor product and the monophosphorylated product 4 as the major product even with using more than 2 equiv of n-BuLi. Use of t-BuLi led to the non-C2 symmetric diphosphorylated product 6, which acted as an N,P-chelating ligand in the palladium complex 7.