A series of macrocycles were successfully prepared using electrophilic halogen-mediated semipinacol rearrangement under mild conditions. Although the expansion from small ring to medium ring is an energetically unfavorable process, the electrophilic halogenation was found to be powerful enough to override such an energy barrier. The rearranged products could further undergo Dowd–Beckwith rearrangement to give the corresponding one-carbon ring-expanded ketones. This approach has been applied to the total synthesis of the natural product (±)-muscone, which is widely used in modern perfumery and medicines, in a two-step sequence.

We have developed a synthetic strategy to access axially chiral biaryls through a dynamic-kinetic resolution-semipinacol rearrangement process. The axial chirality together with a sp3 quaternary carbon can be introduced in a single chemical operation. The products can be further ring-expanded to yield biologically relevant seven-membered dibenzolactams with inverted axial chirality.Keywords: axial chirality; biaryl; dynamic-kinetic resolution; organocatalysis; semipinacol rearrangement;

A zwitterionic-salt-catalyzed electrophilic monobromination of arenes with high regioselectivity has been developed. Under mild reaction conditions, a wide range of monobrominated aromatic compounds can be obtained in excellent yields. The reaction can be operated using an extremely low catalyst loading (0.05 mol %) with the inexpensive brominating agent N-bromosuccinimide. The versatility of this catalytic protocol has been demonstrated by the scale-up reaction with a 0.01 mol % catalyst loading to provide the selectively halogenated compound in quantitative yield.

We have developed ring-strain dictated divergent diastereoselective fluorinating Prins cyclization reactions or semipinacol rearrangement reactions to access tetrahydropyrans containing a fluorohydrin or a carbonyl moiety at quaternary carbon centers under mild conditions, respectively.

We developed a simple and efficient method to construct a variety of α-ester bromolactones in good to excellent yields with high diastereoselectivies. The protocol uses readily prepared malonate ester derivatives as substrates, water as an additive and inexpensive N-bromosuccinimide as the halogen source; no catalyst or toxic additive is required. The resulting substituted bromolactones are the fundamental units of many useful molecules.

A trifluoroacetic acid catalyzed highly 6-endo regioselective bromocyclization of styrene-type carboxylic acid has been developed. The resulting 3,4-dihydroisocoumarines are valuable building blocks in organic synthesis.

How can high enantioselectivity be achieved when the racemic background reaction proceeds at a rate comparable to that of the catalytic asymmetric reaction? We attempted to rationalize this counterintuitive observation by studying the effect of (1) catalyst structure, (2) temperature and addition sequence of components, (3) catalyst loading, and (4) Brønsted acid additives. In the course of our investigation, it was found that increasing the amount of catalyst used led to inhibition of the stoichiometric reaction. Olefinic 1,3-diol 1, 5 mol % of catalyst 3a, 1 equiv of MsOH, and NBS were added at low temperature in a specific sequence to provide the best performance for the enantioselective bromoetherification.

Reaction between (N,N-dimethylamino)pyridine and isocyanate unexpectedly produced a three-component mixture. By using this mixture as an unprecedented three-component catalyst system, a facile and selective bromolactamization of olefinic amides has been developed. The protocol confers enhanced selectivity of N- over O-cyclization, leading to the formation of a structurally diverse range of lactams including both small and medium ring sizes.

A Lewis basic sulfide catalyzed electrophilic bromocyclization of cyclopropylmethyl amide has been developed. The catalytic protocol is applicable to both 1,1- and 1,2-substituted cyclopropylmethyl amides, giving oxazolines and oxazines in good yields and excellent diastereoselectivity.

We developed a simple and efficient method to construct a variety of α-ester bromolactones in good to excellent yields with high diastereoselectivies. The protocol uses readily prepared malonate ester derivatives as substrates, water as an additive and inexpensive N-bromosuccinimide as the halogen source; no catalyst or toxic additive is required. The resulting substituted bromolactones are the fundamental units of many useful molecules.

A trifluoroacetic acid catalyzed highly 6-endo regioselective bromocyclization of styrene-type carboxylic acid has been developed. The resulting 3,4-dihydroisocoumarines are valuable building blocks in organic synthesis.