Toward Efficient and Stereoselective Aromatic and Dearomative Cope Rearrangements: Experimental and Theoretical Investigations of α-Allyl-α'-Aromatic γ-Lactone Derivatives.

The aromatic Cope rearrangement is an elusive transformation that has been the subject of a limited number of investigations compared to those seemingly close analogues, namely the Cope and aromatic Claisen rearrangement. Herein we report our investigations inspired by moderate success observed in the course of pioneering works. By careful experimental and theoretical investigations, we demonstrate that key substitutions on 1,5-hexadiene scaffold allow fruitful transformations. Especially, efficient functionalisation of the heteroaromatic rings results from the aromatic Cope rearrangement, while highly stereoselective interrupted aromatic Cope rearrangements highlight the formation of chiral compounds through a dearomative process.

Rhazinilam-leuconolam family of natural products: a half century of total synthesis.

Covering: 1972 to 2021The rhazinilam family of natural products exhibits a main structure with a stereogenic quaternary carbon and a tetrahydroindolizine core imbedded within a 9-membered macrocycle, imposing axial chirality. This unique architecture combined with their taxol-like antimitotic activities have attracted various attention, especially from synthetic chemists, notably in the past decade. The present review describes the known total and formal syntheses of the members of the rhazinilam family (rhazinilam, rhazinal, leuconolam and kopsiyunnanines), according to the strategy developed.

Chiral Gold(III) Complexes: Synthesis, Structure, and Potential Applications.

Since the beginning of the 2000's, homogeneous gold catalysis has emerged as a powerful tool to promote the cyclization of unsaturated substrates with excellent regioselectivity allowing the synthesis of elaborated organic scaffolds. An important goal to achieve in gold catalysis is the possibility to induce enantioselective transformations by the assistance of chiral complexes. Unfortunately, the linear geometry of coordination for gold usually encountered in complexes at the +1 oxidation states renders this goal very challenging. In consequence, the interest toward the synthesis of chiral gold(III) complexes is steadily growing. Indeed, the square planar geometry of the gold(III) cation appears more suitable to promote chiral induction. Beside catalysis, gold(III) complexes have also shown promising potential in the field of pharmacology. Herein, syntheses and applications of well-defined gold(III) complexes reported over the last fifteen years are summarized.

When Gold Cations Meet Polyoxometalates.

Merging gold(I) cations with polyoxometalate anions results in various interclusters and complexes. Herein, the synthesis of these newly emerging gold(I)/polyoxometalate materials is reviewed. The applications of these promising hybrids in organic catalysis are also summarized and evaluated in terms of the advantages and limitations of the catalysts including efficiency, synergistic effects and recyclability.

Synthesis, Characterization and Catalytic Activity of NHC Gold(I) Polyoxometalate Complexes.

The new hybrid NHC gold(I) acetonitrile polyoxometalate complexes {[Au(IPr)(MeCN)+ ][H+ ]3 [SiW12 O404- ] (1), [Au(IPr)(MeCN)+ ][H+ ]2 [PMo12 O403- ] (2), [Au(IPr)(MeCN)+ ][H+ ]5 [P2 W18 O626- ] (3), [Au(IPr)(MeCN)+ ][H+ ]2 [PW12 O403- ] (4), [Au(IPr)(MeCN)+ ]3 [PMo12 O403- ] (5) and [Au(ItBu)(MeCN)+ ] [H+ ]2 [PMo12 O403- ] (6)} were readily synthesized in high yield and characterized by NMR and MS-ESI spectroscopy. In a preliminary catalytic study, their activity was assessed under heterogeneous conditions for the ene-yne rearrangement reaction and a cycloisomerization reaction. Additionally, their reactivity and recyclability were tested in the hydration of alkynes under homogeneous conditions.

Zeolite-Based Organic Synthesis (ZeoBOS) of Acortatarin A: First Total Synthesis Based on Native and Metal-Doped Zeolite-Catalyzed Steps.

Similarly to polymer-supported assisted synthesis (PSAS), organic synthesis could be envisaged being performed by using zeolites, native or metal-doped, as heterogeneous catalysts. To illustrate this unprecedented Zeolite-Based Organic Synthesis (ZeoBOS), the total synthesis of acortatarin A was achieved through a novel strategy and using five out of eleven synthetic steps catalyzed by H- or metal-doped zeolites as catalysts. Notably, the formation of an yne-pyrrole intermediate with a copper-doped zeolite and the spiroketalization of an alkyne diol with a silver-doped zeolite have been developed as key steps of the synthesis.

Metal Confinement through N-(9-Alkyl)fluorenyl-Substituted N-Heterocyclic Carbenes and Its Consequences in Gold-Catalysed Reactions Involving Enynes.

A series of gold(I) and gold(III) complexes containing bulky bis-N,N'-(9-alkylfluorenyl) heterocyclic carbene (R F-NHC) ligands have been prepared in high yields from appropriate imidazolinium, imidazolium and benzimidazolium salts. In all complexes, the carbene ligand provides high steric protection of the Au-X bond trans to the carbenic C atom. Irrespective of the metal oxidation state, the complexes showed high efficiency in a tandem 3,3-rearrangement/Nazarov reaction of an enynyl acetate. One of the AuIII complexes, [AuCl3 (R F-NHC)], was further found to be suitable for the efficient cyclisation of a propargylcarboxamide. Furthermore, unlike related NHC-gold(I) complexes based on conventional bulky N-heterocyclic carbenes (notably, 1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr), 1,3-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) and 1,3-(bis-tert-butyl)imidazol-2-ylidene (ItBu)), the studied [AuI Cl(R F-NHC)] complexes catalysed the conversion of a 1,6-enyne in the presence of indole into a single product; this arises from the embracing character of the ligand, which prevents indole addition on one of the catalytic intermediates. A structure/selectivity relationship was established for all carbenes tested that took into account percent buried volumes and topographic steric maps. The results illustrate the high potential of confining NHCs in organic synthesis.

Silver & gold-catalyzed routes to furans and benzofurans.

Silver and gold have become incredibly versatile and mild catalysts for numerous transformations, especially in heterocycle synthesis. For the most prominent of them, i.e. furans, silver and gold, with their unique reactivity and mildness, allow numerous possible routes to highly substituted and/or functionalized furans from a large variety of starting materials. Silver and gold catalysis provide thus the most flexible way to this important family of compounds. The present review describes these silver and gold-catalyzed routes, with some emphasis on mechanistic aspects, and proposes a comparison of both the silver and the gold-catalyzed syntheses of furans.

Gold(I)-Catalyzed N-Desulfonylative Amination versus N-to-O 1,5-Sulfonyl Migration: A Versatile Approach to 1-Azabicycloalkanes.

Valuable 1-azabicycloalkane derivatives have been synthesized through a novel gold(I)-catalyzed desulfonylative cyclization strategy. An ammoniumation reaction of ynones substituted at the 1-position with an N-sulfonyl azacycle took place in the presence of a gold cation by intramolecular cyclization of the disubstituted sulfonamide moiety onto the triple bond. Depending on the size of the heterocyclic ring and substitution of the substrates, two unprecedented forms of nucleophilic attack on the sulfonyl group were exploited, that is, a N-desulfonylation in the presence of an external protic O nucleophile (37-87 %, 10 examples) and a unique N-to-O 1,5-sulfonyl migration (60-98 %, 9 examples).

Inorganic-organic heteropolyacid-gold(I) hybrids: structures and catalytic applications.

Gold(I)-polyoxometalate hybrid complexes 1-4 ([PPh3AuMeCN]xH4-x SiW12O40, x=1-4) were synthesized and characterized. The structure of the primary gold(I)-polyoxometalate 1 (x=1) was fully ascertained by XRD, FTIR, (31)P and (29)Si magic-angle spinning (MAS) NMR, mass spectroscopy, and SEM-energy dispersive X-ray spectroscopy (EDX) techniques. Moreover, this complex exhibited better catalytic activity and selectivity compared with standard, homogeneous, gold catalysts in the new rearrangement of propargylic gem-diesters.

Gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones.

Various γ-acyloxyalkynyl ketones were efficiently converted into highly substituted furans with 2.5 mol % of triflimide (triphenylphosphine)gold(I) as a catalyst in dichloroethane at 70 °C.

Silver(I)-catalyzed deprotection of p-methoxybenzyl ethers: a mild and chemoselective method.

The p-methoxybenzyl protecting group (PMB) on various alcohols and an acid was efficiently and selectively cleaved by the action of a catalytic amount of silver(I) hexafluoroantimonate combined with 0.5 equiv of 1,3,5-trimethoxybenzene in dichloromethane at 40 °C.

Coinage metals-catalyzed cascade reactions of aryl alkynylaziridines: silver(I)-single vs gold(I)-double cyclizations.

Alkynylaziridines carrying an aryl group could be efficiently converted into aminoallenylidene isochromans, isoquinolines, or tetrahydronaphtalenes with silver(I) salts and into 1-azaspiro[4.5]decane derivatives with gold(I) complexes. Mechanistic investigations revealed that both Ag- and Au-catalyzed reactions involved a Friedel-Crafts type intramolecular reaction leading to an allene and that Au also rapidly promoted a second intramolecular cyclization of the aminoallene intermediate to the corresponding spiro derivative. Stereochemical investigations suggested an anti-SN(2)'-type pathway for the first cyclization leading to a stereodefined allene, which could then be cyclized to the corresponding stereodefined spiro product. These results highlight the duality between oxo- or azaphilicity and alkynophilicity of Ag and Au as well as their complementarity in terms of reactivity.

A gold(i)-catalysed approach towards harmalidine an elusive alkaloid from Peganum harmala.

Upon gold catalysis, the 2,3-dihydropyrrolo[1,2-a]indole motif, encountered in few but interesting bioactive natural products, was efficiently obtained from N-aryl 2-alkynylazetidine derivatives. In an attempt to apply this methodology to the synthesis of harmalidine, isolated from the seeds of Peganum harmala, advanced amino 2,3-hydropyrrolo[1,2-a]indol(one) derivatives were readily obtained in only 11 steps from but-3-yn-1-ol. While the reported structure of harmalidine could not be reached from these intermediates, a surprising 12-membered diimino dimer was isolated. Extensive comparison of the reported harmalidine NMR data to the experimental and calculated data of our synthetic molecules, harmaline or the synthetised N-methylharmaline show discrepancies with the proposed natural product structure.

trans-Dichlorobis(XPhos)palladium(II) Precatalyst for Suzuki-Miyaura Cross-Coupling Reactions of Aryl/Vinyl Sulfonates/Halides: Scope, Mechanistic Study, and Synthetic Applications.

Suzuki-Miyaura cross-coupling reactions of aryl/vinyl sulfonates/halides with various boron species were performed using an easily available trans-dichlorobis(XPhos)palladium(II) precatalyst. Under microwave assistance, more than 30 coupling products were obtained with yields ranging from 23 to 99%, including the synthesis of two bioactive compounds, dubamine and tamoxifen. A mechanistic investigation of the Suzuki-Miyaura reaction was conducted notably by nuclear magnetic resonance (NMR) and high-resolution mass spectroscopy, revealing the nature of the active Pd0 species and of the reducing entity.

Mechanistic studies and improvement of coinage metal-catalyzed transformation of alkynyloxiranes to furans: an alcohol addition-cyclization-elimination cascade.

In the presence of alcohol Ag or Au salts or complexes catalyze the conversion of alkynyloxiranes to substituted furans. Both catalysts are effective, and a large furan diversity can be obtained in high yield with one or the other catalyst. Mechanistic studies revealed that a cascade pathway and not the sometimes reported direct intramolecular nucleophilic addition of oxirane oxygen atom to intermediate acetylene-metal pi-complex occurs. Under the defined conditions, the intermediate formation of epoxide opening products has been identified. Depending on the catalyst, one or both of the latter cyclized to dihydrofurans, and further elimination of the alcohol led to the corresponding furans. These results highlight the duality between oxophilicity and alkynophilicity of Ag or Au salts.

Silver(I)-catalyzed cascade: direct access to furans from alkynyloxiranes.

Functionalized furans are conveniently formed by a new silver(I)-catalyzed reaction of alk-1-ynyl oxiranes in the presence of p-toluenesulfonic acid and methanol. Evidence supported a cascade mechanism.

Benzosultam Synthesis by Gold(I)-Catalyzed Ammonium Formation/Nucleophilic Substitution.

The synthesis of benzosultams has been achieved through a gold(I)-catalyzed ammonium formation strategy. Starting from easily available N-(2-alkynyl)phenylsulfonyl azetidine derivatives, a cyclization reaction generated a spiroammonium gold intermediate that was ring-opened by nucleophilic alcohol or indole. This new methodology is compatible with the large variation in the substrates and nucleophiles and allowed the formation of benzosultams in high yield (18-98%, 20 examples). This strategy also allowed the preparation of benzosultam analogs via iododeauration and subsequent cross-coupling reactions.

Total Synthesis of Rhazinilam through Gold-Catalyzed Cycloisomerization-Sulfonyl Migration and Palladium-Catalyzed Suzuki-Miyaura Coupling of Pyrrolyl Sulfonates.

We report the first general conditions for the challenging Suzuki-Miyaura reaction with pyrrole-related sulfonate coupling partners (24 examples, 60-97%). Bis(dichloro)bis(2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl)palladium(II) precatalyst ensures the high efficiency of the reaction. The total synthesis of rhazinilam, a monoterpenoid indole alkaloid, highlights such cross-coupling as well as the simple preparation of pyrrolyl sulfonates by N-to-O 1,5-sulfonyl migration catalyzed by gold(I) (15 examples, 54-93%).