The breitfussins are halogenated natural products whose structures were determined with the assistance of atomic-force microscopy. The site selectivity of N-bromosuccinimide-mediated bromination of a model breitfussin core was found to be strongly dependent on solvent selection; use of acetone led to oxazole bromination, and use of a pyridine-containing mixture led to pyrrole bromination. This tunable site-selective bromination was used in a protecting-group-free synthesis of breitfussin B that proceeded in 9.2% yield over 12 reactions and five chromatographic separations. A bromooxazole analogue of breitfussin A was also prepared by late-stage bromination but isomerized on silica gel to form breitfussin B. This isomerization appeared to proceed through a unimolecular pathway.

Applying a catalytic enantioselective aldehyde α-oxygenation condition to an enal substrate led to the discovery of the first α,β,γ-trifunctionalization cascade of enals. Under optimal conditions, a tryptophan-derived imidazolidinone catalyst in fluorinated aromatic solvents provided α,β,γ-trioxyaldehydes in up to 51% isolated yield (average of 80% yield per oxygenation step) and 85:15 er. Substitution at the δ position was tolerated, but not at the α, β, or γ positions. The reaction proceeded through initial TEMPO incorporation at the γ position, and rapid racemization of this intermediate, reversible conjugate addition of water, followed by TEMPO incorporation at the α position to set all three stereocenters with double dynamic kinetic resolution.

2,2,6,6-Tetramethylpiperidinyl-masked 1,2-diols exhibited stereochemistry-dependent hydroxyl proton chemical shifts: ca. 7 ppm for the syn diastereomer and ca. 2 ppm for the anti diastereomer. A computational search for low energy geometries revealed that the syn isomer favors a six-membered ring hydrogen bond to nitrogen and the anti isomer favors a five-membered ring hydrogen bond to oxygen. The computed low energy conformations were found to have a large difference in hydroxyl proton shielding that was reflected in the experimental chemical shift difference. This chemical shift difference was observed in a broad range of solvents, and thus may be useful as a stereochemical probe. The stereochemistry-dependent conformation and chemical shift signature appeared to be due to a syn pentane interaction between the gem-dimethyl groups on the 2,2,6,6-tetramethylpiperidinyl moiety.

Differentially protected 1,2-diols were synthesized by enantioselective aldehyde α-oxygenation followed by organomagnesium or -lithium addition. Contrary to a previous report, the resultant diols possess an anti configuration. Good selectivity was achieved regardless of the hybridization state of the nucleophile or the presence or absence of branching. This method was applied to short syntheses of all possible stereoisomers of two oxylipins from Dracontium loretense with incomplete stereochemical assignments. Spectroscopic comparisons between the synthetic and natural oxylipins led to unambiguous assignments.

The thermodynamic driving force from the release of a gaseous molecule drives a broad range of synthetic transformations. This review focuses on gas expulsion in key reactions within natural products total syntheses, selected from the past two decades. The highlighted examples survey transformations that generate sulfur dioxide, carbon dioxide, carbonyl sulfide, or nitrogen through polar, radical, pericyclic, photochemical, or organometallic mechanisms. Of particular interest are applications wherein the gas extrusion enables formation of a synthetically challenging motif, such as an unusually hindered or strained bond.

The thermodynamic driving force from the release of a gaseous molecule drives a broad range of synthetic transformations. This review focuses on gas expulsion in key reactions within natural products total syntheses, selected from the past two decades. The highlighted examples survey transformations that generate sulfur dioxide, carbon dioxide, carbonyl sulfide, or nitrogen through polar, radical, pericyclic, photochemical, or organometallic mechanisms. Of particular interest are applications wherein the gas extrusion enables formation of a synthetically challenging motif, such as an unusually hindered or strained bond.