Dialkylbiaryl phosphines are a valuable class of ligand for Pd-catalyzed amination reactions and have been applied in a range of contexts. This perspective attempts to aid the reader in the selection of the best choice of reaction conditions and ligand of this class for the most commonly encountered and practically important substrate combinations.

Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide

This review describes the gold-catalyzed reactions of specially activated alkynes, allenes, and alkenes. Such species are characterized by the presence of either electron-donating or electron-withdrawing groups as substituents of the carbon π-system. They are intrinsically polarized, and when compared to their nonspecially activated counterparts can therefore be involved in gold-catalyzed transformations featuring increased regio-, stereo-, and chemoselectivities. The chemistry of specially activated carbon π-systems under homogeneous gold catalysis is extremely rich and varied. The reactivity observed with nonspecially activated unsaturated systems can often be transposed to specially activated ones without loss of efficiency. However, specially activated carbon π-systems also exhibit specific reactivities that cannot be attained with regular substrates. In this family of carbon π-systems, ynamides and their analogs, along with alkynyl carbonyl derivatives, are the classes of substrates that have retained the most attention. This review provides an overview of the chemistry developed with all classes of specially activated carbon π-systems by discussing their general and specific reactivities, presenting and commenting on their gold-catalyzed transformations as well as their applications.

Gold-Catalyzed Reactions of Specially Activated Alkynes, Allenes, and Alkenes

cis-Delivery of H2 to the π-system of an unsaturated substrate is the canonical course of metal catalyzed hydrogenation reactions. The semireduction of internal alkynes with the aid of [Cp*Ru]-based catalysts violates this rule and affords E-alkenes by direct trans-hydrogenation. A pathway involving σ-complexes and metallacyclopropenes accounts for this unconventional outcome. Connected to this process is an even more striking reactivity mode, in which both H atoms of H2 are delivered to one and the same C atom. Such gem-hydrogenation of stable carbogenic compunds is a fundamentally new transformation that leads to the formation of discrete metal carbene complexes. Computational studies suggest that the trans- and the gem-pathway have similar barriers, but polar substituents in the vicinity of the reacting triple bond provide opportunities for imposing selectivity and control. Moreover, it is shown that catalytic trans-hydrogenation is by no means a singularity: rather, the underlying principle is also ma...

trans-Hydrogenation, gem-Hydrogenation, and trans-Hydrometalation of Alkynes: An Interim Report on an Unorthodox Reactivity Paradigm

2-Pyrones and 4-pyrones are common structural motif in bioactive natural products. Traditional methods for their synthesis, which try to emulate the biosynthetic pathway of cyclization of a 1,3,5-tricarbonyl precursor, are often harsh and therefore not particularly suitable for applications to polyfunctionalized and/or sensitive target compounds. -Acid catalysis, in contrast, proved much more adequate for a systematic exploration of the pyrone estate. To this end, alkynes are used as stable ketone surrogates, which can be activated under exceedingly mild conditions due to the pronounced carbophilicity of LAu+ (L = two electron donor ligand); intramolecular attack of a tethered ester carbonyl group onto the transient alkyne-gold complex then forges the pyrone ring in a fully regiocontrolled manner. This new methodology proved instrumental for the total synthesis of various natural products, including the very sensitive cyclophane neurymenolide A and an unnamed sibling thereof, the polyunsaturated C-glycosidic polyene derivative orevactaene, and the highly cytotoxic macrolide DMDA-pateamine A. The latter synthesis features an unorthodox sequence of a gold catalyzed pyrone formation followed by an iron catalyzed pyrone ring opening/cross coupling reaction. From the conceptual viewpoint, these cases studies are thought to be representative for the many inherent advantages that pi-acid catalysis can provide for contemporary heterocyclic chemistry.

Gold Catalysis for Heterocyclic Chemistry: A Representative Case Study on Pyrone Natural Products

This review article will consider the preparation and application of ynones in synthetic organic chemistry. Concerning the preparation of these bifunctional compounds, several methodologies startin...

Conjugated Ynones in Organic Synthesis.

3-Oxo-5-alkynoic acid esters, on treatment with a carbophilic catalyst, undergo 6-endo-dig cyclization reactions to furnish either 2-pyrones or 4-pyrones in high yields. The regiochemical course can be dialed in by the proper choice of the alcohol part of the ester and the π-acid. This transformation is compatible with a variety of acid-sensitive groups as witnessed by a number of exigent applications to the total synthesis of natural products, including pseudopyronine A, hispidine, phellinin A, the radininol family, neurymenolide, violapyrone, wailupemycin and an unnamed brominated 4-pyrone of marine origin. Although the reaction proceeds well in neutral medium, the rate is largely increased when HOAc is used as solvent or co-solvent, which is thought to favor the protodeauration of the reactive alkenyl-gold intermediates as the likely rate-determining step of the catalytic cycle. Such intermediates are prone to undergo diauration as an off-cycle event that sequesters the catalyst; this notion is consistent with literature data and supported by the isolation of the gem-diaurated complexes 12 and 15. Furthermore, silver catalysis allowed access to be gained to 2-alkoxypyridine and 2-alkoxyisoquinoline derivatives starting from readily available imidate precursors.

Gold- or Silver-Catalyzed Syntheses of Pyrones and Pyridine Derivatives: Mechanistic and Synthetic Aspects

Countless natural products of polyketide origin have an E-configured 2-methyl-but-2-en-1-ol substructure An unconventional entry into this important motif was developed as part of a concise total synthesis of 5,6-dihydrocineromycin B The choice of this particular target was inspired by a recent study, which suggested that the cineromycin family of antibiotics might have overlooked lead qualities, although our biodata do not necessarily support this view The new approach consists of a sequence of alkyne metathesis followed by a hydroxy-directed trans-hydrostannation and a largely unprecedented methyl-Stille coupling The excellent yield and remarkable selectivity with which the signature trisubstituted alkene site of the target was procured is noteworthy considering the rather poor outcome of a classical ring-closing metathesis reaction Moreover, the unorthodox ruthenium-catalyzed trans-hydrostannation is shown to be a versatile handle for diversity-oriented synthesis

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Selective Formation of a Trisubstituted Alkene Motif by trans-Hydrostannation/Stille Coupling: Application to the Total Synthesis and Late-Stage Modification of 5,6-Dihydrocineromycin B†

Orevactaene and epipyrone A were previously thought to comprise the same polyunsaturated tail but notably different C-glycosylated 4-hydroxy-2-pyrone head groups. Total synthesis now shows that the signature bicyclic framework assigned to orevactaene is a chimera; the compound is almost certainly identical with epipyrone A, whose previously unknown stereochemistry has also been established during this study. Key to success was the ready formation of the bicyclic core of putative orevactaene by a sequence of two alkyne cycloisomerization reactions using tungsten and gold catalysis. Equally important was the flexibility in the assembly process gained by the use of heterobimetallic polyunsaturated modules whose termini could be selectively and consecutively addressed in a practical one-pot cross-coupling sequence.

Johannes Preindl

Papers

Gold- or Silver-Catalyzed Syntheses of Pyrones and Pyridine Derivatives: Mechanistic and Synthetic Aspects

Selective Formation of a Trisubstituted Alkene Motif by trans-Hydrostannation/Stille Coupling: Application to the Total Synthesis and Late-Stage Modification of 5,6-Dihydrocineromycin B†

Polyunsaturated C-Glycosidic 4-Hydroxy-2-pyrone Derivatives: Total Synthesis Shows that Putative Orevactaene Is Likely Identical with Epipyrone A.