Pei Juan Chua

Organocatalytic asymmetric tandem Michael-Henry reactions: a highly stereoselective synthesis of multifunctionalized cyclohexanes with two quaternary stereocenters.

A novel organocatalytic asymmetric tandem Michael-Henry reaction catalyzed by 9-amino-9-deoxyepiquinine (VI) has been developed. The reaction was efficiently catalyzed by catalyst VI to give highly functionalized cyclohexanes with four stereogenic carbons including two quaternary stereocenters in excellent enantioselectivities (97 to >99% ee) and high diastereoselectivities (93:7-99:1 dr). Thus, the first organocatalytic asymmetric Henry reaction of common ketones as acceptors is shown.

Rational design of organocatalyst: highly stereoselective Michael addition of cyclic ketones to nitroolefins.

A remarkable organocatalyst that facilitates the asymmetric Michael addition of cyclic ketones to nitroolefins in excellent stereoselectivities (98:2 to >99:1 dr, 92% to >99% ee) has been developed and afforded various types of optically active nitroalkane derivatives of synthetic and biological importance. The extremely simple and practical operational procedure at room temperature increases the attractiveness of this reaction.

Control of four stereocenters in an organocatalytic domino double Michael reaction: efficient synthesis of multisubstituted cyclopentanes.

A highly enantioselective and diastereoselective domino organocatalytic double Michael reaction which provides expedited access to multifunctionalized five-membered rings catalyzed by 9-amino-9-deoxyepiquinine (V) has been developed. Simple operational procedures, high yields (81-92%), excellent enantioselectivity (90-97% ee), diastereoselectivities (95:5->99:1 dr), and immense potential of synthetic versatility of the products render this new methodology highly appealing for asymmetric synthesis.

Facile Domino Access to Chiral Bicyclo[3.2.1]octanes and Discovery of a New Catalytic Activation Mode

A highly enantio- and diastereoselective organocatalytic domino Michael-Henry process for the preparation of synthetically unique and medicinally important bicyclo[3.2.1]octane derivatives with four stereogenic centers including two quaternary stereocenters has been developed. Theoretical DFT calculations on the transition states have been carried out to reveal origins of the excellent stereoselectivities. A novel dual model was thus proposed.

A Highly Diastereo- and Enantioselective Synthesis of Multisubstituted Cyclopentanes with Four Chiral Carbons by the Organocatalytic Domino Michael−Henry Reaction

Highly functionalized cyclopentanes with four stereogenic carbons including two quaternary stereocenters have been synthesized in excellent yields (90-95%) with complete diastereoselectivities and excellent enantioselectivities (88-96% ee) by the organocatalyzed asymmetric domino Michael-Henry reaction.

N-heterocyclic carbene (NHC)-catalyzed highly diastereo- and enantioselective oxo-Diels-Alder reactions for synthesis of fused pyrano[2,3-b]indoles.

A chiral N-heterocyclic carbene (NHC)-catalyzed Diels-Alder reaction of 2-oxoindolin-3-ylidenes and α-chloroaldehydes was developed for the synthesis of fused pyrano[2,3-b]indoles in good to excellent yields (up to 99%) with high cis-diastereoselectivities (>99:1 dr) and enantioselectivities (up to >99% ee).

A Highly Stereoselective Organocatalytic Tandem Aminoxylation/Aza-Michael Reaction for the Synthesis of Tetrahydro-1,2-Oxazines

A facile stereoselective synthesis of multifunctionalized tetrahydro-1,2-oxazines (THOs) has been achieved by the organocatalyzed asymmetric tandem alpha-aminoxylation/aza-Michael reaction for the C-O/C-N bond formations in moderate to good yields with excellent diastereo- (>99:1 dr) and enantioselectivities (92% to >99% ee).

Unusual Domino Michael/Aldol Condensation Reactions Employing Oximes as N‐Selective Nucleophiles: Synthesis of N‐Hydroxypyrroles

As one of the most important classes of heterocycles, pyrroles are not only important building blocks in the synthesis of natural products, but also key structural units in compounds with interesting biological activities. Pyrroles have also found broad application in materials chemistry. Accordingly, substantial attention has been paid to develop efficient methods for their synthesis. One of the common approaches to pyrrole synthesis is the Paal–Knorr reaction, in which 1,4dicarbonyl compounds are converted into pyrroles by acidmediated dehydrative cyclization. However, this approach is usually subject to significant limitations in terms of substituents introduced, substitution patterns, or regioselectivities. Although several novel synthetic strategies have been described in recent years, 6] a general facile and regioselective approach to generate pyrroles with a wide functionalgroup tolerance from readily available precursors is still lacking. Over the past few years, organocatalytic domino reactions have emerged as a powerful synthetic paradigm to make diverse molecules. The operational simplicity, readily available catalysts, and low toxicity associated with organocatalysis make it an attractive method in organic synthesis. Herein, we report a catalytic synthesis of multisubstituted N-hydroxypyrroles by the domino reaction of a-carbonyl oxime compounds and a,b-unsaturated aldehydes in the presence of secondary amine catalysts through the iminium activation strategy. 9] This approach is differs from previously reported strategies, as oximes were employed as Nselective nucleophiles in the Michael addition step instead of the more commonly used O-selective nucleophiles in organocatalysis. To our knowledge, the formation of pyrrole derivatives through this simple and mild domino strategy has not been reported to date. Amine catalysts perform efficient iminium activation by lowering the LUMO of a,b-unsaturated aldehydes. Thus, we set out to investigate the use of IV as a catalyst for a domino reaction involving sequential Michael addition and intramolecular aldol condensation (Scheme 1, Table 1). Ini-

Water—More Than Just a Green Solvent: A Stereoselective One‐Pot Access to All‐Chiral Tetrahydronaphthalenes in Aqueous Media

A facile and highly stereoselective construction of heavily functionalized chiral tetrahydronaphthalene skeletons fused with an oxazolidine moiety has been developed. The process involves an organocatalytic tandem Michael/nitrone formation/intramolecular [3+2] nitrone-olefin cycloaddition in aqueous media. Using rationally designed substrates, the reaction conditions have been optimized and the one-pot process has been applied to a series of nitroolefin acrylates and aldehydes. The N-hydroxyphenylamine component used in the second step has also been varied. The stereochemistry of one product has been verified by an X-ray crystal structure determination. The water used in the strategy not only constitutes an environmentally benign solvent, but also helps to improve the reactivity and stereoselectivity.

Chiral Brønsted Acid Catalyzed Enantioselective Addition of α-Isocyanoacetamides to Aldehydes

A clean and highly efficient enantioselective addition of alpha-isocyanoacetamides to aliphatic aldehydes catalyzed by chiral phosphoric acid in the presence of MS 5 A in toluene at -40 degrees C was developed. Excellent yields (85-98%) and good to excellent enantioselectivities (up to >99% ee) were achieved.