A direct, facile, and highly diastereo- and enantioselective dearomatization reaction of β-naphthol derivatives with aziridines has been developed for the first time. A newly designed Box–OH ligand was employed for an in situ generated magnesium catalyst and proved to be efficient. The corresponding dearomatization product was transformed into a polycyclic scaffold and polyhydroxylated compound. ¹H NMR studies revealed the activation mode of the dearomatization process of β-naphthols, and a clear positive nonlinear effect was observed in the reaction, and provides insight into the coordination environment around the Mg^II center and the possible active species.

A CC bond-forming conjugate reaction was successfully applied to the enantioselective dearomatization of β-naphthols. A C(sp2)C(sp3) bond is formed by using propargylic ketones as reactive partners. Good to excellent Z/E ratios and ee values were obtained by employing an in situ generated magnesium catalyst. Further transformations of the Z-configured CC double bond in the products were achieved under mild reaction conditions. Moreover, the stereocontrolling element of this magnesium-catalyzed dearomatization reaction was explored by computational chemistry.

The asymmetric Michael reaction between 5H-oxazol-4-ones and α,β-unsaturated acyl imidazoles is reported. A novel 2-benzo[b]thiophenyl-modified chiral ProPhenol species is synthesized and used as a ligand, leading to good enantioselectivities in this asymmetric conjugate addition reaction. Furthermore, the introduction of phenol additives as achiral co-ligands is found to improve the reaction’s chemical yields, diastereoselectivities, and enantioselectivities.

A direct, facile, and highly diastereo- and enantioselective dearomatization reaction of β-naphthol derivatives with aziridines has been developed for the first time. A newly designed Box–OH ligand was employed for an in situ generated magnesium catalyst and proved to be efficient. The corresponding dearomatization product was transformed into a polycyclic scaffold and polyhydroxylated compound. ¹H NMR studies revealed the activation mode of the dearomatization process of β-naphthols, and a clear positive nonlinear effect was observed in the reaction, and provides insight into the coordination environment around the Mg^II center and the possible active species.

A CC bond-forming conjugate reaction was successfully applied to the enantioselective dearomatization of β-naphthols. A C(sp2)C(sp3) bond is formed by using propargylic ketones as reactive partners. Good to excellent Z/E ratios and ee values were obtained by employing an in situ generated magnesium catalyst. Further transformations of the Z-configured CC double bond in the products were achieved under mild reaction conditions. Moreover, the stereocontrolling element of this magnesium-catalyzed dearomatization reaction was explored by computational chemistry.

The successful application of imidazole-modified ketones in asymmetric anti-selective Michael reactions with trans-β-nitroalkenes is presented by employing a newly developed 3-bromothiophene-modified chiral diamine ligand. The corresponding conjugate adduct was submitted to further transformations with Grignard reagents to solve the problem of α-site selectivity of simple linear ketones. Additionally, the syn-selective product was obtained by treating the anti-selective adduct with a simple base. In this way, the site-specific products for both diastereomers in the asymmetric conjugate addition of simple ketones to nitroalkenes can be obtained.

The first stereocontrolled cross reaction of enones has been realized. A novel combinational magnesium catalyst was designed to address the enantioselectivity problem between reaction partners with an intermolecular symmetric structure and bearing identical functional groups. This new catalytic strategy was proven to be effective to introduce high levels of enantioselectivity in the cross reaction of enones.

Asymmetric cyanation of trimethylsilyl cyanide (TMSCN) with α,β-unsaturated amides and ketones, respectively, catalyzed by bifunctional mononuclear 1,1′-bi-2-naphthol (BINOL)–Mg and binuclear bis(prophenol)–Mg catalysts was realized. A series of synthetically important 1,4-cyano products were obtained with good to high enantioselectivities (up to 97 % ee).

A magnesium-catalyzed asymmetric ring-opening reaction of aziridine with indole has been realized by employing commercially available chiral ligands. Both of the enantiomers of the ring-opening product could be obtained with good yields and a high level of enantioselectivity. The corresponding ring-opening product could be further transformed to various types of enantioenriched C₃-halogenated-pyrroloindolines.

α-Amino phosphonic acid derivatives are considered to be the most important structural analogues of α-amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2-addition reactions of α-isothiocyanato phosphonate were developed. Through these processes, derivatives of β-hydroxy-α-amino phosphonic acid and α,β-diamino phosphonic acid, as well as highly functionalized phosphonate-substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α-phosphonic acid derivatives.

Asymmetric hydrogenation of unprotected NH imines catalyzed by rhodium/bis(phosphine)-thiourea provided chiral amines with up to 97 % yield and 95 % ee. ¹H NMR studies, coupled with control experiments, implied that catalytic chloride-bound intermediates were involved in the mechanism through a dual hydrogen-bonding interaction. Deuteration experiments proved that the hydrogenation proceeded through a pathway consistent with an imine.

α-Amino phosphonic acid derivatives are considered to be the most important structural analogues of α-amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2-addition reactions of α-isothiocyanato phosphonate were developed. Through these processes, derivatives of β-hydroxy-α-amino phosphonic acid and α,β-diamino phosphonic acid, as well as highly functionalized phosphonate-substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α-phosphonic acid derivatives.

Asymmetric hydrogenation of unprotected NH imines catalyzed by rhodium/bis(phosphine)-thiourea provided chiral amines with up to 97 % yield and 95 % ee. ¹H NMR studies, coupled with control experiments, implied that catalytic chloride-bound intermediates were involved in the mechanism through a dual hydrogen-bonding interaction. Deuteration experiments proved that the hydrogenation proceeded through a pathway consistent with an imine.

A metal-free intramolecular oxidative cross-coupling reaction for the constructing C_sp3C_sp3 bonds mediated by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) under mild conditions was realized for the first time. This novel strategy provides a simple, efficient, and environmentally friendly access to diverse ring-fused tetrahydroquinoline derivatives.

The asymmetric organocatalysis is definitely one of the most powerful and versatile tools for the rapid construction of various spirocyclic oxindoles. In the past few years, a number of successful strategies based on organocatalysis have been developed for the construction of 3,3′-spirocyclic oxindoles in high yields and excellent enantioselectivities under mild conditions. In this review, recent advances in this area are summarized and classified according to the spiro ring fused at the 3-position of the oxindole core.

We present a bifunctional catalytic, chemo-, regio- and enantioselective inverse electron demand Diels–Alder reaction (IEDDAR) cascade of a variety of methylenebut-3-enoates with azlactones at high levels of yield and enantioselectivity (up to 99% yield, and >99% ee) via a dual HOMO_dienophiles and LUMO_dienes activated pathway using a heterogeneous catalytic system. Meanwhile, a novel MNPs-supported chiral thiourea was developed for economical and environment-friendly purposes. The catalyst can be conveniently recycled and reused for 10 runs with only a slight loss of yield and enantioselectivity.

Due to the lack of tumor-specific anticancer agents, the discovery and development of new types of highly selective anticancer agents is still a very urgent topic. Herein, we present our contribution to concise construction of novel chiral spirooxindole-type pyranopyrimidines exhibiting a unique profile of biological activities. We have found that this new type of spiro alkaloid could inhibit the proliferation of various cancer cells in a preliminary biological evaluation. These findings suggested that spirooxindole-type pyranopyrimidines, developed by an asymmetric Michael/cyclization strategy, can potentially serve as a new kind of anticancer candidate.

The highly diastereo- and enantioselective relay cascade Michael/Michael/Henry reaction catalyzed by combination of readily available diphenylprolinol silyl ether and the quinine thiourea in a one-pot fashion has been developed. Up to 70% yield and up to >99% enantioselectivity of the single major isomer were obtained from the cascade reactions.

We present a highly efficient strategy for obtaining a series of chiral 2,4-disubstituted thiazolone derivatives with excellent diastereo- and enantioselectivities through the creation of carbon- and nitrogen-substituted quaternary carbon stereocenters. With the chiral tertiary amine-thiourea catalyst developed by our group, the reactions could be performed smoothly at 1 mol-% catalyst loadings without any additive. Preliminary biological evaluation demonstrated that these analogues could inhibit cell proliferation in vitro significantly.

We have performed the first bifunctional organocatalytic highly enantioselective inverse-electron-demand hetero-Diels–Alder reaction of cyclic ketones with enones to afford densely functionalized bicyclic skeletons that contain three stereocenters (up 82 % yield, 10:1 d.r., and 97 % ee). Unlike the previous IEDDAR catalytic strategy, this method features a double HOMO_dienophile/ LUMO_diene-activated pathway. Moreover, this process provides a promising method for the construction of enantioenriched macrolides.

Drug lead synthesis by the rapid construction of chiral molecular complexity around the biologically relevant framework using a highly efficient strategy is a key goal of organic synthesis. Herein, a highly efficient and convenient strategy that allows the rapid synthesis of highly optically active methylthioimidazolines through the novel rosin-derived thiourea-catalyzed asymmetric synthesis of cyclic thioureas with high levels of enantio- and diastereoselectivity (up to 99% ee, and 20:1 dr) via Mannich reaction is described fior the first time. Several of the new methylthioimidazolines showed extremely promising antipyretic activity in the development of neuroinflammation through preliminary biological studies. Additionally, to gain a better understanding of the structural stability-activity relationships, explicit molecular dynamics (MD) simulations in water at room temperature and at body temperature were investigated.

Although the organocatalytic direct asymmetric Michael reactions of carbonyl compounds to nitroalkenes have been investigated intensely, the Michael reaction of the thioether-based donors remains a rather undeveloped field. This work concerns the asymmetric Michael addition of aryl sulfanyl-propan-2-one to nitroalkenes with benzoic acid as an additive, and chiral amine-thiourea as a bifunctional organocatalyst. The reactions provided the highly functionalized chiral adducts with excellent enantioselectivities (up to 96% ee) and good yields. Moreover, the further transformed products exhibited excellent diastereoselectivity. Chirality, 2010. © 2010 Wiley-Liss, Inc.

The doubly stereocontrolled organocatalytic aza-Henry reaction of nitroalkanes to N-Boc-imines generated in situ from a variety of substituted α-amido sulfones was investigated for the first time, in general, affording the corresponding products with high to excellent yields (up to 93% yield) and enantioselectivities (up to 98% ee), and satisfactory diastereoselectivies (anti/syn up to 98:2). Furthermore, these organocatalysts based on rosin have been proved to be the very effective promoters for this catalytic asymmetric process along side the Cinchona alkaloid-derived catalysts.

A new synthetic methodology for the preparation of optically active propargylamines is described. The alkynylation of aromatic, heteroaromatic, aliphatic and α,β-unsaturated N-(diphenylphosphinoyl)imines was investigated by using diethylzinc and a proline-derived β-amino alcohol. N-(Diphenylphosphinoyl)-protected propargylic amines can be synthesized in high yields and with good to excellent enantioselectivities. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The first highly enantioselective phosphonylation of α,β-unsaturated N-acylpyrroles has been developed. Excellent yields (91–99 %) and enantioselectivities (up to >99 % enantiomeric excess (ee)) were observed for a broad spectrum of both phosphites and N-acylpyrroles under mild conditions. In particular, when diethyl phosphite was employed to test the scope of the N-acylpyrroles, almost optically pure products (98 to >99 % ee) were obtained for 20 examples of N-acylpyrroles. Moreover, optically pure α-substituted β- or γ-amino phosphonates can be obtained by several simple transformations of the pyrrolyl phosphonates. The versatility of the N-acylpyrrole moiety makes the phosphorus adducts powerful chiral building blocks that enable the synthesis of various phosphonate-containing compounds. Finally, the present strategy can also be applied to the asymmetric hydrophosphonylation of N-acylimines with high enantioselectivities (93 to >99 % ee).

A new catalytic system, generated from the readily available and inexpensive β-sulfonamide alcohol L*, Ti(OⁱPr)₄, Et₂Zn, and tertiary amine base (R₃N), effectively catalyzes the enantioselective addition of various terminal alkynes including some quite challenging alkynes to aldehydes in good yields and excellent enantioselectivities. Up to 96% yield and >99% enantioselectivity were achieved with the use of N,N-diisoproylethylamine (DIPEA) as an additive in this asymmetric addition. Chirality, 2009. © 2008 Wiley-Liss, Inc.

Various new chiral hydroxysulfonamide ligands (3a–3n, 4a–4d) were prepared. Compounds 3a, 3g, 3i, 3k–3n, 4a–4d could accelerate the reaction and reduce reaction time, and 3a, 3g, 3i, 3k–3n catalyzed the reaction without titanium. The results obtained were promising in terms of yields and enantiomeric excesses (3k up to 85% ee, 4a up to 83% ee). Chirality, 2009. © 2008 Wiley-Liss, Inc.

A mild method for the asymmetric synthesis of quaternary and tertiary carbon centers has been developed through Michael addition of trisubstituted carbon nucleophile to nitroalkenes catalyzed by low loading sodium demethylquinine salt in water. Chirality, 2008. © 2009 Wiley-Liss, Inc.