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)

Catalytic Intermolecular Hydroamination of Vinyl Ethers

This manuscript details the development of a palladium-catalyzed hydroamination of vinyl ethers. It is proposed that palladium catalyzes the hydroamination via Brønsted base catalysis, where palladium is protonated by the relatively acidic sulfonamide to generate a palladium hydride as well as the active anionic sulfonamide nucleophile. Thus, this process is distinct from known palladium-catalyzed hydroaminations of styrene derivatives that utilize less acidic amines

Regiospecific decarboxylative allylation of nitriles

Palladium-catalyzed decarboxylative α-allylation of nitriles readily occurs using Pd2(dba)3 and rac-BINAP. This catalyst mixture also allows the highly regiospecific α-allylation of nitriles in the presence of much more acidic α-protons. Thus, the reported method provides access to compounds that are not readily available via base-mediated allylation chemistries. Lastly, mechanistic investigations indicate that there is a competition between C- and N-allylation of an intermediate nitrile-stabilized anion and that N-allylation is followed by a rapid [3,3]-sigmatropic rearrangement

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 © 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 “deacylative allylation” 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 C–C 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

Lewis acid-catalyzed diastereoselective hydroarylation of benzylidene malonic esters

Herein we report that simple Lewis acids catalyze the hydroarylation of benzylidene malonates with phenols. Ultimately, 3,4-disubstituted dihydrocoumarins are obtained via a hydroarylation-lactonization sequence. Moreover, the dihydrocoumarins are formed with a high degree of diastereoselectivity favoring the trans stereoisomer

Mild Decarboxylative Allylation of Coumarins

Allyl esters of 3-carboxylcoumarins undergo facile decarboxylative coupling at just 25–50 °C. This represents the first extension of decarboxylative C–C bond-forming reactions to the coupling of aromatics with sp3-hybridized electrophiles. Finally, the same concept can be applied to the sp2–sp3 couplings of pyrones and flavones. Thus, a variety of biologically important heteroaromatics can be readily functionalized without the need for strong bases or stoichiometric organometallics that are typically required for more standard cross-coupling reactions

Decarboxylative Cyclizations and Cycloadditions of Palladium-polarized Aza-ortho-Xylylenes

Previously we have shown that palladium catalysts effect the decarboxylation of vinyl oxazinones to form zwitterionic π-allyl palladium intermediates (A, Scheme 1).1 Thus, vinyl oxazinones can be equated with zwitterionic synthons (B). In the absence of other electrophiles, the zwitterionic intermediate cyclizes to form vinyl azetidines with high diastereoselectivity. Moreover, in the presence of suitably electrophilic Michael acceptors,2 the intermediates undergo diastereoselective cycloadditions to generate highly substituted piperidine derivatives.3 The related vinyl benzoxazinones (3) undergo similar palladium-induced decarboxylation (Scheme 2).4 However, these substrates give rise to aza-ortho-xylylene synthons (C).5 The decarboxylation of vinyl benzoxazinones under conditions of palladium catalysis occurs at 25 °C and is thus significantly milder than thermal decarboxylation of benzoxazinones which typically requires temperatures near 200 °C.6 In addition, the aza-ortho-xylylene equivalents generated in the presence of palladium are more polarized than standard aza-ortho-xylylenes. Thus, while standard aza-ortho-xylylenes preferentially react with electron rich olefins, palladium-polarized aza-ortho-xylylenes (D) prefer to react with electron deficient olefins. Herein, we further describe the cyclization and cycloaddition chemistry of these unique intermediates

Synthesis of Chiral Nonracemic Tertiary α-Thio and α-Sulfonyl Acetic Esters via SN2 Reactions of Tertiary Mesylates

Syntheses of enantioenriched sulfides and sulfones via substitution of tertiary mesylate with thiolate nucleophile were achieved with modest to excellent success

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 π-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