A general protocol for the palladium-catalyzed dearomative trimethylenemethane [3+2] cycloaddition reaction with simple nitroarene substrates is described. This methodology leads to the exclusive formation of the dearomatized alicyclic products without subsequent rearomatization. The reaction is tolerant toward a broad range of heterocyclic and benzenoid substrates. The use of chiral bisdiamidophosphite ligands enabled the development of an enantioselective variant of this transformation, representing one of the rare examples of an asymmetric catalytic dearomatization process.

A mild and general protocol for the carbonylative cross-coupling of sterically hindered orthodisubstituted aryl iodides is reported. Carbonylative Suzuki-Miyaura couplings of a variety of aryl boronic acids provide an array of substituted biaryl ketones in modest to excellent yield. A carbonylative Negishi coupling that utilizes alkynyl nucleophiles is also described.Aryl ketones and flavanoids are common scaffolds in many natural products and biologically active small molecules. 1 Many of these compounds possess substitution at both positions ortho to the ketone moiety. Chemists have most often turned to reactions in the synthome 2 that rely upon strongly acidic or basic conditions in order to install the carbonyl functional group. For example, the Friedel-Crafts acylation, 3a Fries rearrangement, 3b-d and additions of nucleophiles into a variety of acyl electrophiles, including N-methoxy-N-methyl amides, 3e have allowed access to ortho-disubstituted aryl ketones. However, obtaining sterically more encumbered ketones is notoriously difficult via the Friedel-Crafts acylation, 4 and the Fries rearrangement is limited to phenol derivatives.An alternative method for the construction of aryl ketones is the three component coupling of aryl halides, carbon nucleophiles, and carbon monoxide that was pioneered by Heck. 5 This process is one of the most efficient and direct routes to aryl ketones as it forms two carboncarbon bonds in a single operation, thereby alleviating the need to introduce the ketone function in a stepwise fashion. The carbonylative coupling has since been further developed to include a range of carbon nucleophiles, 6 including tin, 7 copper, 8 boron, 9 zinc, 10 aluminum, 11 magnesium, 12 and silicon. 13During the course of an ongoing synthetic project, we required a reliable method for preparing aryl ketones bearing two ortho substituents. While there are a plethora of methods for synthesizing simple aryl ketones via carbonylative cross-coupling, 5d to the best of our knowledge there is only one example of a carbonylative cross-coupling involving an orthodisubstituted aryl halide with a carbon nucleophile. 9b We discovered, however, that the direct application of this protocol to the problem with which we were confronted did not lead to the desired ortho-disubstituted aryl ketone. It was thus necessary to develop a new procedure that would enable efficient carbonylative cross-coupling of different ortho-disubstituted aryl halides with a variety of boronic acids and other nucleophilic partners. We now report the results of some of our findings. Toward developing a more general process for preparing hindered diaryl ketones, we examined the carbonylative cross-coupling of 2,6-dimethyliodobenzene (1) with phenylboronic acid under a variety of conditions (Table 1). In initial experiments we found that Cs 2 CO 3 and dioxane was the optimal base/solvent combination. Several common phosphine containing catalyst systems were next examined. 14 Use of Pd(PPh 3 ) 4 and PdCl 2 (dppf) as catalysts at ele...

We report the first total synthesis of the complex C-aryl glycoside isokidamycin, the epimer of the naturally-occurring pluramycin antibiotic kidamycin. The synthesis features a highly efficientDiels-Alder reaction between a substituted naphthyne and a glycosylatedfuran to form the anthracene core bearing a pendant angolosamine C-glycoside. The regiochemical outcome of the Diels-Alder reaction was controlled by employing a disposable silicon-tether to link the reactive napthyne and the glycosyl furan, rendering the cycloaddition intramolecular. The benzopyranone moietyof the aromatic nucleus was appended by cyclization of a functionalized vinylogous amide onto an advanced anthrol intermediate. The vancosamine amino glycoside was introduced by an O→C-glycoside rearrangement that produced the β-anomer. Subsequent refunctionalizations then led to isokidamycin.

An atom-economical method for the direct synthesis of [3.1.0]- and [4.1.0]-bicyclic frameworks via Ru-catalyzed redox bicycloisomerization of enynols is reported. The presented results highlight the unique reactivity profile of propargyl alcohols, which function as β-oxocarbene precursors, in the presence of a ruthenium(II) complex. Furthermore, a rare case of a formal vinylic C-H insertion reaction is described.

Leustroducsin B exhibits a large variety of biological activities and unique structural features. An efficient and highly convergent total synthesis of Leustroducsin B was achieved in 17 longest linear and 39 total steps by disconnecting the molecule into three fragments having similar levels of complexity. These pieces were connected via a highly efficient chelate-controlled addition of a vinyl zincate to an α-hydroxy ketone and a silicon-mediated cross-coupling. The stereochemistry of the central and western fragments was set catalytically in high yields and excellent de by a zinc-ProPhenol-catalyzed aldol reaction and a palladium-catalyzed asymmetric allylic alkylation.