Jung Woon Yang

Proline-catalysed Mannich reactions of acetaldehyde

Small organic molecules recently emerged as a third class of broadly useful asymmetric catalysts that direct reactions to yield predominantly one chiral product, complementing enzymes and metal complexes. For instance, the amino acid proline and its derivatives are useful for the catalytic activation of carbonyl compounds via nucleophilic enamine intermediates. Several important carbon–carbon bond-forming reactions, including the Mannich reaction, have been developed using this approach, all of which are useful for making chiral, biologically relevant compounds. Remarkably, despite attempts, the simplest of all nucleophiles, acetaldehyde, could not be used in this way. Here we show that acetaldehyde is a powerful nucleophile in asymmetric, proline-catalysed Mannich reactions with N-tert-butoxycarbonyl (N-Boc)-imines, yielding β-amino aldehydes with extremely high enantioselectivities—desirable products as drug intermediates and in the synthesis of other biologically active molecules. Although acetaldehyde has been used as a nucleophile in reactions with biological catalysts such as aldolases and thiamine-dependent enzymes, and has also been employed indirectly, its use as an inexpensive and versatile two-carbon nucleophile in asymmetric, small-molecule catalysis will find many practical applications.

Switching regioselectivity in crossed acyloin condensations between aromatic aldehydes and acetaldehyde by altering n -heterocyclic carbene catalysts

An unprecedented high level of regioselectivities (up to 96%) in the intermolecular crossed acyloin condensations of various aromatic aldehydes with acetaldehyde was realized by an appropriate choice of N-heterocyclic carbene catalysts.

Efficient and practical polymeric catalysts for heterogeneous asymmetric dihydroxylation of olefins

Abstract High enantioselectivity (>99% ee) and reactivity in heterogeneous catalytic asymmetric dihydroxylation (AD) of olefins have been achieved using new polymeric cinchona alkaloids containing 1,4-bis(9- O -quininyl)phthalazine ((QN) 2 -PHAL), which can be synthesized more economically than their homogeneous analogue, 1,4-bis(9- O -dihydroquininyl)phthalazine ((DHQ) 2 -PHAL).

Hydrotrifluoromethylation and iodotrifluoromethylation of alkenes and alkynes using an inorganic electride as a radical generator

The trifluoromethyl (CF3) group is a staple synthon that can alter the physical and chemical properties of organic molecules. Despite recent advances in trifluoromethylation methods, the development of a general synthetic methodology for efficient and selective trifluoromethylation remains an ongoing challenge motivated by a steadily increasing demand from the pharmaceutical, agrochemical and materials science industries. In this article, we describe a simple, efficient and environmentally benign strategy for the hydrotrifluoromethylation of unactivated alkenes and alkynes through a radical-mediated reaction using an inorganic electride, [Ca2N](+) · e(-), as the electron source. In the transformation, anionic electrons are transferred from [Ca2N](+) · e(-) electrides to the trifluoromethylating reagent CF3I to initiate radical-mediated trifluoromethylation. The role of ethanol is pivotal in the transformation, acting as the solvent, an electron-releasing promoter and a hydrogen atom source. In addition, iodotrifluoromethylation of alkynes proceeds selectively upon the control of electride amount.

SILICA GEL SUPPORTED BIS-CINCHONA ALKALOID : A HIGHLY EFFICIENT CHIRAL LIGAND FOR HETEROGENEOUS ASYMMETRIC DIHYDROXYLATION OF OLEFINS

Abstract Comparable reactivity and enantioselectivity to those in homogeneous solution have been achieved in heterogeneous catalytic asymmetric dihydroxylation (AD) of olefins using a new silica gel supported cinchona alkaloid containing 1,4-bis(9- O -quininyl)phthalazine ((QN) 2 -PHAL). Moreover, the silica supported alkaloid exhibited much greater binding ability for OsO 4 than its homogeneous analogue.

Practical Proline-catalyzed asymmetric Mannich reaction of aldehydes with N-Boc-imines

This protocol describes a procedure for the synthesis of α, β-branched-b-amino aldehydes via Proline-catalyzed asymmetric Mannich reaction of aldehydes with N-tert–butoxycarbonyl-imines. The crystalline β-amino aldehydes are formed in good yields and extremely high levels of diastereo- and enantioselectivities without the need for chromatographic purification and are readily oxidized to the corresponding β-amino acids. The protocol can be completed in approximately 14 h on small scales or up to 30 h on larger scales.

Transition-Metal-Free and Chemoselective NaOtBu–O2-Mediated Oxidative Cleavage Reactions of vic-1,2-Diols to Carboxylic Acids and Mechanistic Insight into the Reaction Pathways

A method for efficient oxidative cleavage of vic-1,2-diols using a NaO(t)Bu-O2 system resulted in the formation of carboxylic acids in high yields. The present protocol is an eco-friendly alternative to a conventional transition-metal-based method. This new strategy allows large-scale production with nonchromatographic purification while also suppressing competitive reaction pathway such as benzilic acid rearrangement.

Transition metal-free, NaOtBu-O2-mediated one-pot cascade oxidation of allylic alcohols to α,β-unsaturated carboxylic acids

We developed a protocol for the transition metal-free, direct oxidation of allylic alcohols using the simple base NaOtBu under an oxygen atmosphere. The NaOtBu–O2 system exhibited unprecedented activity and selectivity in this oxidation reaction. In particular, a competing epoxidation reaction was suppressed under these conditions.

Acetaldehyde: a small organic molecule with big impact on organocatalytic reactions

Stereocontrolled formation of carbon-carbon and carbon-heteroatom bonds through asymmetric organocatalysis is a formidable challenge for modern synthetic chemistry. Among the most significant contributions to this field are the transformations involving the use of acetaldehyde or α-heteroatom-substituted acetaldehydes for constructing valuable synthons (e.g., amino acid derivatives and hydroxycarbonyl). In this Minireview, versatile (enantioselective) organocatalytic transformations are discussed.

Enantioselective Organocatalytic Cyclopropanation of Enals Using Benzyl Chlorides.

Herein, we describe the first enantioselective cyclopropanation of enals using benzyl chlorides as bifunctional (nucleophilic and electrophilic) reagents. The reaction is simply catalyzed by chiral secondary amines to afford the formyl cyclopropane derivatives in good yields with moderate to excellent stereoselectivities.