Synthesis of disubstituted dithioethers: tert-butoxide promoted elimination/ring opening of 1,3-dithianes followed by palladium-catalyzed C-S bond formation.

We report the tandem base-promoted elimination/ring-opening of 2-benzyl-1,3-dithianes with subsequent cross coupling of the pendent thiol with a range of aryl bromides. A simple Pd(OAc)2/Xantphos catalyst system affects this new reaction and is compatible with a wide range of functional groups, including heteroaromatic coupling partners. The transformation proceeds in good to excellent yields (69-99%) and exhibits strong stereoselectivity, forming the E-alkene as the major diastereomer. This new methodology provides access to nonsymmetric propylene styryl/aryl dithioethers, a previously undisclosed motif.

Reversed-polarity synthesis of diaryl ketones via palladium-catalyzed cross-coupling of acylsilanes.

Acylsilanes serve as acyl anion equivalents in a palladium-catalyzed cross-coupling reaction with aryl bromides to give unsymmetrical diaryl ketones. Water plays a unique and crucial activating role in these reactions. High-throughput experimentation techniques provided successful reaction conditions initially involving phosphites as ligands. Ultimately, 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane was identified as giving a longer-lived catalyst with higher turnover numbers. Its use, in conjunction with a palladacycle precatalyst, led to optimal reaction rates and yields. Scope and limitations of this novel method are presented along with initial mechanistic insight.

Probing "microwave effects" using Raman spectroscopy.

The use of in situ Raman spectroscopy is reported as a tool for probing the effects of microwave irradiation on molecules. Our results show no evidence for localized superheating, an often-cited specific microwave effect. While the microwave energy may interact with the polar molecules more so than with non-polar ones, the conversion of electromagnetic energy into kinetic energy is slower than conversion of kinetic energy into thermal energy. As a result, more polar molecules are not at a temperature greater than that of the bulk.

Use of Raman spectroscopy as an in situ tool to obtain kinetic data for organic transformations.

Raman spectroscopy has been used as an in situ tool to obtain kinetic data for an organic transformation. The model reaction studied was the synthesis of 3-acetylcoumarin from the condensation between salicylaldehyde and ethyl acetoacetate with piperidine as a catalyst. The study shows that precise kinetic data can be obtained quickly and reproducibly, allowing for the facile determination of both overall reaction order and reaction order with respect to each component of the reaction. Additionally, Arrhenius parameters such as activation energy for a reaction can be readily obtained. In conjunction with computational modeling, this data-rich analysis technique also allows for in-depth probing of mechanistic aspects of reactions. Microwave heating proves to be an ideal tool for aiding in kinetic studies. It offers reproducible noncontact heating as well as precise temperature monitoring and data recording.

Palladium-Catalyzed Synthesis of Aryl Vinyl Sulfides via 1,3-Oxathiolanes As Vinyl Sulfide Surrogates.

A nontraditional approach to synthesizing aryl vinyl sulfides is described. 2,2-Diphenyl-1,3-oxathiolane slowly liberates a vinyl sulfide anion under basic conditions. Using a Pd/Xantphos catalyst system to activate a wide range of aryl bromides, this transient sulfide species can be effectively trapped and fed into a traditional Pd0/PdII catalytic cycle. Scope and limitations of the methodology are presented along with significant discussion of a competitive C-S bond activation by this catalyst system.

Palladium-catalyzed cross-coupling of 2-aryl-1,3-dithianes.

Palladium-catalyzed cross-coupling of aryl bromides with 2-aryl-1,3-dithianes is described. This methodology takes advantage of the relatively acidic benzylic proton of the dithiane, allowing it to act as a competent, polarity-reversed transmetalation reagent. This unique approach affords the ability to employ an orthogonal deprotection strategy, and practical routes to both diaryl ketones and diarylmethanes are illustrated. Cross-coupling of a range of aryl dithianes with aryl bromides, including scope and current limitations, is presented.

Pd-catalyzed aldehyde to ester conversion: a hydrogen transfer approach.

Aliphatic and aromatic aldehydes are successfully converted into their corresponding esters using Pd(OAc)(2) and XPhos. This approach utilizes a hydrogen transfer protocol: concomitant reduction of acetone to isopropanol provides an inexpensive and sustainable approach that mitigates the need for other oxidants.

Palladium-catalyzed synthesis of diarylmethanes: exploitation of carbanionic leaving groups.

A novel route to the synthesis of diarylmethanes via a Pd-catalyzed alpha-arylation of benzyl ketones is reported. By harnessing the inherent reactivity of enolates, it is possible to circumvent the need for a transmetalating reagent such as boron for the coupling. Additionally, the two phenyl rings of the intermediate are exploited to stabilize the high-energy carbanionic leaving group in a straightforward synthesis.

Testing the validity of microwave-interfaced, in situ Raman spectroscopy as a tool for kinetic studies.

Raman spectroscopy in conjunction with microwave heating is a convenient and robust tool for monitoring organic reactions from a qualitative perspective. Its validity as a method for obtaining quantitative data is shown. Activation enthalpies for the synthesis of a range of substituted chalcones are determined and the results compared with well-established previous data and reactivity trends for this aldol condensation. The methodology is used for obtaining previously unreported pK(a) data for substituted acetophenones.

Use of Raman spectroscopy as a tool for in situ monitoring of microwave-promoted reactions.

The progress of microwave-promoted reactions can be monitored by interfacing a Raman spectrometer with a scientific microwave unit. The apparatus is assembled from commercially available components. It is used in this protocol to follow the base-catalyzed reaction of salicylaldehyde with ethylacetoacetate to yield 3-acetylcoumarin. It is possible to watch the reaction spectroscopically in real time, determine when it reaches completion and thus use it as a tool for rapid reaction optimization.

Microwave-promoted insertion of Group 10 metals into free base porphyrins and chlorins: scope and limitations.

The scope and limitations of microwave heating as a tool for insertion of Group 10 metals into meso-tetraphenyl-porphyrin, -porpholactone, and -2,3-dihydroxychlorin derivatives are discussed. In some cases it is possible to reduce reaction times dramatically while obtaining good yields of the metallated products while in others new issues arise relating to the metal salt used as well as acceleration not only of the metallation reaction but also of byproduct formation.