66 research outputs found
Rapid decarboxylative allylation of nitroalkanes
Allyl nitroacetates undergo decarboxylative allylation to provide tertiary nitroalkanes in high yield. Moreover, the transformations are complete within several minutes under ambient conditions. High yields result because O-allylation of the intermediate nitronates, which is typically problematic, is reversible under conditions of the decarboxylative allylation process. Lastly, the preparation of substrate allyl nitroacetates by tandem Knoevenagel/Diels-Alder sequences allows the facile synthesis of relatively complex substrates that undergo diastereoselective decarboxylative allylation
Deacylative allylation of nitroalkanes: unsymmetric bisallylation via 3-component coupling
Use it and lose it! Allylic alcohols were used directly for the synthesis of diallylated nitroalkanes in a three-component coupling based on the strategy of deacylative allylation for the in situ generation of a nucleophile and an allyl electrophile (see scheme)
Deacylative allylation: allylic alkylation via retro-Claisen activation
This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of the American Chemical Society, copyright Ā© American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ja205717f.A new method for allylic alkylation of a variety of relatively non-stabilized carbon nucleophiles is described herein. In this process of ādeacylative allylationā the coupling partners, an allylic alcohol and a ketone pronucleophile, undergo in situ retro-Claisen activation to generate an allylic acetate and a carbanion. In the presence of palladium, these reactive intermediates undergo catalytic coupling to form a new CāC bond. In comparision to unimolecular decarboxylative allylation, a commonly utilized method for allylation of carbon anions, deacylative allylation is an intermolecular process. Moreover, deacylative allylation allows the direct coupling of readily available allylic alcohols. Lastly, the full utility of deacylative allylation is demonstrated by the rapid construction of a variety 1,6-heptadienes via 3-component couplings
Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles
The palladium-catalyzed nucleophilic substitution of (coumarinyl)methyl acetates is described. The reaction proceeds though a palladium Ļ-benzyl-like complex and allows for many different types of C-, N-, and S-nucleophiles to be regioselectively added to the biologically active coumarin motif. This new method was utilized to prepare a 128-membered library of aminated coumarins for biological screening.We thank the National Institutes of Health KU Chemical Methodologies and Library Development Center of Excellence (P50 GM069663) for funding. We are indebted to Dr. Conrad Santini and Ben Neuenswander for help in library production and purification
Transition Metal-Catalyzed Decarboxylative Allylation and Benzylation Reactions
This document is the Accepted Manuscript version of a Published Work that appeared in final form in
Chemical Reviews, copyright Ā© American Chemical Society after peer review and technical editing by the publisher.
To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/cr1002744A review. Transition metal catalyzed decarboxylative allylations, benzylations, and interceptive allylations are reviewed
Stereospecific decarboylative allylation of sulfones
This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of the American Chemical Society, copyright Ā© American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ja104196x.Allyl sulfonyl acetic esters undergo highly stereospecific, palladium-catalyzed decarboxylative allylation. The reaction allows the stereospecific formation of tertiary homoallylic sulfones in high yield. In contrast to related reactions that proceed at -100 Ā°C and require highly basic preformed organometallics, the decarboxylative coupling described herein occurs under mild non-basic conditions and requires no stoichiometric additives. Allylation of the intermediate Ī±-sulfonyl anion is more rapid than racemization, leading to a highly enantiospecific process. DFT calculations indicate that the barrier for racemization is 9.9 kcal/mol and thus the barrier of allylation must be <9.9 kcal/mol
Development of Asymmetic Deacylative Allylation
Herein we present the development of asymmetric deacylative allylation of ketone enolates. The reaction directly couples readily available ketone pronucleophiles with allylic alcohols using facile retro-Claisen cleavage to form reactive intermediates in situ. The simplicity and robustness of the reaction conditions is demonstrated by the preparation of > 6 grams of an allylated tetralone from commercially available materials. Furthermore, use of non-racemic PHOX ligands allows intermolecular formation of quaternary stereocenters directly from allylic alcohols
Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed CāH Bond Activation
Nitrogen heterocycles are present in many compounds of enormous practical importance, ranging from pharmaceutical agents and biological probes to electroactive materials. Direct functionalization of nitrogen heterocycles through CāH bond activation constitutes a powerful means of regioselectively introducing a variety of substituents with diverse functional groups onto the heterocycle scaffold. Working together, our two groups have developed a family of Rh-catalyzed heterocycle alkylation and arylation reactions that are notable for their high level of functional-group compatibility. This Account describes our work in this area, emphasizing the relevant mechanistic insights that enabled synthetic advances and distinguished the resulting transformations from other methods.
We initially discovered an intramolecular Rh-catalyzed C-2 alkylation of azoles by alkenyl groups. That reaction provided access to a number of di-, tri-, and tetracyclic azole derivatives. We then developed conditions that exploited microwave heating to expedite these reactions. While investigating the mechanism of this transformation, we discovered that a novel substrate-derived RhāN-heterocyclic carbene (NHC) complex was involved as an intermediate. We then synthesized analogous RhāNHC complexes directly by treating precursors to the intermediate [RhCl(PCy3)2] with N-methylbenzimidazole, 3-methyl-3,4-dihydroquinazoline, and 1-methyl-1,4-benzodiazepine-2-one.
Extensive kinetic analysis and DFT calculations supported a mechanism for carbene formation in which the catalytically active RhCl(PCy3)2 fragment coordinates to the heterocycle before intramolecular activation of the CāH bond occurs. The resulting RhāH intermediate ultimately tautomerizes to the observed carbene complex. With this mechanistic information and the discovery that acid cocatalysts accelerate the alkylation, we developed conditions that efficiently and intermolecularly alkylate a variety of heterocycles, including azoles, azolines, dihydroquinazolines, pyridines, and quinolines, with a wide range of functionalized olefins. We demonstrated the utility of this methodology in the synthesis of natural products, drug candidates, and other biologically active molecules.
In addition, we developed conditions to directly arylate these heterocycles with aryl halides. Our initial conditions that used PCy3 as a ligand were successful only for aryl iodides. However, efforts designed to avoid catalyst decomposition led to the development of ligands based on 9-phosphabicyclo[4.2.1]nonane (phoban) that also facilitated the coupling of aryl bromides. We then replicated the unique coordination environment, stability, and catalytic activity of this complex using the much simpler tetrahydrophosphepine ligands and developed conditions that coupled aryl bromides bearing diverse functional groups without the use of a glovebox or purified reagents. With further mechanistic inquiry, we anticipate that researchers will better understand the details of the aforementioned Rh-catalyzed CāH bond functionalization reactions, resulting in the design of more efficient and robust catalysts, expanded substrate scope, and new transformations
Synthesis of Spirooxindoles via the <i>tert</i>-Amino Effect
A new
method is developed
for the synthesis of spirooxindoles from amines and isatins via CāH
functionalization. The reaction leverages the <i>tert</i>-amino effect to form an enolateāiminium intermediate via
[1,5]-hydride shift followed by cyclization. Interestingly the hydride
migrates to the N atom of a Cī»N, which is atypical for hydride
additions to imines
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