Yong-Chun Luo

Multiple-Organocatalyst-Promoted Cascade Reaction: A Fast and Efficient Entry into Fully Substituted Piperidines

Current methods for the synthe-sis of fully substituted, optically active piperidines generallyemploy lengthy routes. Despite the potential utility of thesevaluable compounds, to the best of our knowledge, an enan-tioselective, one-pot catalytic cascade approach to opticallyactive, fully substituted piperidines remains an elusive prob-lem; this is, presumably, due to the challenge of constructingfive contiguous stereocenters around the six-membered-ringheterocycle. In this context, the development of a simple-to-perform and single-operation catalysis cascade to form fullysubstituted piperidines that contain the core structure ofsome anti-cancer compounds would be a timely endeavour.During the last few years, the development of asymmetricorganocatalytic domino/cascade reactions has been hotlypursued.

Highly enantioselective synthesis of polysubstituted tetrahydroquinolines via organocatalytic Michael/Aza-Henry tandem reactions.

Highly enantioselective chiral bifunctional thiourea catalyzed asymmetric tandem reactions for synthesis of substituted tetrahydroquinolines are described. Substituted tetrahydroquinolines were given in good yields (up to 98%), high enantioselectivities (up to >99% ee), and diastereoselectivities (up to 20:1 dr).

TiCl4 Promoted Formal [3 + 3] Cycloaddition of Cyclopropane 1,1-Diesters with Azides: Synthesis of Highly Functionalized Triazinines and Azetidines

A TiCl4 promoted formal [3 + 3] cycloaddition of cyclopropane 1,1-diesters with azides has been developed for the synthesis of highly functionalized triazinines. Both stoichiometric and substoichiometric versions of this reaction were accomplished dependent on the choice of solvent. It is noteworthy that the corresponding products could be easily converted to biologically important azetidines by simple thermolysis.

Organocatalytic Aza‐Michael–Michael Cascade Reactions: A Flexible Approach to 2,3,4‐Trisubstituted Tetrahydroquinolines

Cascading like dominos: An efficient and highly enantioselective synthesis of 2,3,4-trisubstituted tetrahydroquinolines through cascade aza-Michael-Michael reactions was developed. Tetrahydroquinolines were obtained in excellent yields, high enantioselectivities, and good diastereoselectivities, and could be easily transformed into ring-fused tetrahydroquinolines (see scheme).

Hydrogen‐Bond‐Mediated Supramolecular Iminium Ion Catalysis

The manufacture of enantiomerically pure pharmaceuticaland agrochemical products is an ongoing requirement for thechemical industry. As a result, the challenge of significantlyimproving the efficiency of expensive chiral catalysts andexploring their new reactivities has captured the attention ofsynthetic chemists. Over the past decade, iminium ionactivation has been demonstrated to be a powerful strategyfor asymmetric catalysis and many reactions catalyzed byiminium ions have been successfully applied in the synthesisof medicinal agents and natural products.

A powerful cascade approach for expeditious synthesis of trifluoromethylated furans.

A powerful approach to synthesize trifluoromethylated furans has been developed. The method is operationally simple, broad in substrate scope, and amenable to scale-up using trifluoroacetic anhydride. Meanwhile, the strategy not only provided a versatile approach to synthesize trifluoromethylated furans but also provides a new method for exploring the new reactivity of trifluoroacetic anhydride.

Synthesis of α-Amino Acids Based on Chiral Tricycloiminolactone Derived from Natural (+)-Camphor

Amino acids are one of the most important classes of the building blocks of life: they are the structural subunits of proteins, peptides, and many secondary metabolites. In addition to the 20 α-amino acids that constitute the backbone of proteins, hundreds of other natural α-amino acids have been discovered either in free form or as components in natural products. The difference between these molecules is the substituents at the chiral carbon situated between the amino and carboxyl moieties; this carbon (and any atom along a chain attached to it) is thus an important synthetic target. Because tailor-made α-amino acids are increasingly popular in biochemistry and organic synthesis, further refinement in synthetic methods to generate both natural (L-configuration) and unnatural (D-configuration) amino acids is a very active area of current research. In this Account, we examine the tricycloiminolactones, which are versatile glycine equivalents derived from natural camphor. We have developed the tricycloiminolactones in our laboratory and used them in the synthesis of several kinds of enantiopure α-amino acids. As nucleophiles, enolated tricycloiminolactones were shown to successfully participate in alkylations, Aldol reactions, Michael additions, and Mannich reactions. These reactions all gave excellent stereoselectivities and high yields. Simple conversion of the products offered α-alkyl-α-amino acids, α,α-dialkyl-α-amino acids, β-hydroxy-α-amino acids, α,γ-diamino acids, and α,β-diamino acids. One particular advantage is that the same electrophile can react with two chiral templates in the same way, thus affording access to both enantiomeric amino acids. In other words, some natural (L-configuration) α-amino acids and their unnatural (D-configuration) counterparts can be prepared very conveniently. The relation between substrate structures and product stereoconformations derived from our investigations serves as a convenient guide in the synthesis of useful chiral amino acids. In addition, highly stereoselective 1,3-diploar cycloadditions between alkenes and chiral nitrones derived from tricycloiminolactones provide a potential method for the synthesis of γ-hydroxy-α-amino acids. We also discuss applications of our methods in the synthesis of complex natural products, including conagenin, polyoxamic acid, lactacystin, and sphingofungin F. The preparation of some clinically important drug molecules, such as thiaphenicol, florfenicol, and chloramphenicol, was greatly simplified with our methods. The tricycloiminolactones offer a number of advantages in the synthesis of both natural and unnatural α-amino acids and provide many useful building blocks in the synthetic pursuit of complex molecules.

Organocatalyzed Michael–Michael Cascade Reaction: Asymmetric Synthesis of Polysubstituted Chromans

An enantioselective cascade Michael-Michael reaction between chalcones enolates and nitromethane catalyzed by a bifunctional thiourea is developed. This reaction provides a mild but efficient approach to chiral benzopyrans bearing three consecutive stereocenters in high yields with excellent stereoselectivities, and the benzopyrans can be easily transformed to the corresponding tricyclic product.

Organocatalytic asymmetric Michael addition of 1-acetylindolin-3-ones to α,β-unsaturated aldehydes: synthesis of 2-substituted indolin-3-ones.

A highly efficient asymmetric Michael addition of 1-acetylindolin-3-ones to α,β-unsaturated aldehydes is developed to afford 2-substituted indolin-3-one derivatives in high yields (up to 94%) with good stereoselectivities (up to 11:1 dr and 96% ee). The Michael adducts can be transformed into substituted cyclopentyl[b]indoline compounds conveniently without racemization.

Dual C–H functionalization of N-aryl tetrahydroisoquinolines: a highly diastereoselective synthesis of dibenzo[a,f]quinolizines via visible-light induced oxidation and inverse electron-demand aza-Diels–Alder reaction

Described herein is the first example of the application of an iminium intermediate generated by visible-light photocatalyzed oxidation in an inverse electron-demand aza-Diels-Alder reaction. This dual functionalization of both C(sp(3))-H and C(sp(2))-H bonds of N-aryl tetrahydroisoquinolines represents a valuable example for access to polycycles with high diastereoselectivity.