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The first Lewis acid mediated stereoselective removal of an anomeric chiral urea group or an electron deficient nitrogen substituent is described here. The ability to remove this urea group which had served as a chiral auxiliary, along with stereoselective hydroboration-oxidation of the endocyclic olefin renders the pyranyl cycloadduct from hetero [4+2] cycloadditions of chiral allenamides a useful chiral template. This represents a new approach to synthesis of complex pyranyl heterocycles or C-glycoside derivatives.

Evidence is described here to support that a highly stereoselective 6pi-electron electrocyclic ring closure of 1-azatrienes is a key step in formal [3 + 3] cycloaddition or annulation reactions of chiral vinylogous amides with alpha,beta-unsaturated iminium salts. This would represent the first highly stereoselective 6pi-electron electrocyclic ring closure of 1-azatrienes. We have also unambiguously demonstrated that these specific ring closures are reversible, leading to the major diastereomer that is also thermodynamically more stable, and that a rotation preference likely also plays a role. A synthetic application is illustrated here to stereoselectively transform the resulting dihydropyridines to cis-1-azadecalins with unique anti relative stereochemistry at C2 and C2a, leading to synthesis of epi isomers of (-)-pumiliotoxin C.

Highly stereoselective formal [3 + 3] cycloaddition reactions of chiral vinylogous amides with α,β-unsaturated iminiums are described. A mechanistic model is proposed to rationalize the observed stereoselectivity. The 6π-electron electrocyclic ring closure appears to be reversible, and a preferred rotation of the alkenyl group, one of the three 2π-components, during the ring closure step provides the thermodynamically favored diastereomer as the major product.

A general approach to synthesis of dihydroxanthone derivatives is described here. In vitro evaluation of these dihydroxanthones demonstrated that some derivatives possess moderate anti-cholinesterase activities and better selectivities than tacrine for acetylcholinesterase over butyrylcholinesterase. Structural effects on anti-cholinesterase activities were also examined, and docking experiments were carried out to provide preliminary understandings of these experimental observations.

Complex piperidinyl heterocycles (for example, 2) were accessed by using a novel intramolecular formal [3+3] cycloaddition reaction of vinylogous amides tethered with enals (for example, 1). This method has been applied to a formal total synthesis of (+)-gephyrotoxin (3).

A formal [3 + 3] cycloaddition strategy for constructing piperidinyl heterocycles from vinylogous amides and α,β-unsaturated iminiums is described here. These reactions proceed well, leading to various heterocycles that could serve as useful synthetic building blocks. Comparative studies between the reactivities of vinylogous amides and other 1,3-diketo systems have also been examined. Preferences for the nitrogen atom during the electrocyclic ring closure step are noted in these reactions, and preliminary calculations suggest that these preferences could result from electronic factors.

Complex piperidinyl heterocycles (for example, 2) were accessed by using a novel intramolecular formal [3+3] cycloaddition reaction of vinylogous amides tethered with enals (for example, 1). This method has been applied to a formal total synthesis of (+)-gephyrotoxin (3).

We describe here an inherent problem in direct epoxidation of the endocyclic olefin in 2H-pyrans fused to 2-pyrones. Such difficulties led to the development of highly stereoselective trans- and cis-dihydroxylations of these olefinic systems in both 2H-pyrans and dihydropyridines fused to a 2-pyrones or a 2-cyclohexenone. Protocols for the removal of the activated allylic hydroxyl group are also reported.

Endeavors including an unexpected retro-aldol–aldol process that proved to be critical for our eventual total synthesis of arisugacin A are described here.

The first regioselective α-deprotonation and functionalization of electron-deficient allenamines are described here. The acidities of α- and γ-allenic protons of these allenamides are readily differentiated using strong bases, thereby allowing regioselective substitutions at either the α- or γ-allenic position. A specific synthetic application of the novel α-substituted allenamides in intramolecular Pauson−Khand-type cycloadditions is also described here.

A 20-step total synthesis of (±)-arisugacin A with an overall yield of 2.1% is described here in detail. This synthesis features a formal [3+3] cycloaddition reaction of α,β-unsaturated iminium salts with 6-aryl-4-hydroxy-2-pyrones through a highly stereoselective 6π-electron electrocyclic ring-closure of 1-oxatriene. A strategic dihydroxylation–deoxygenation protocol leading to the desired angular C12a–OH was developed to serve as a critical step in leading to the final total syntheses of arisugacin A. This synthetic endeavor also led to an interesting and unexpected retro-aldol–aldol sequence in the AB-ring.