Tandem Isomerization Research Articles

Synthesis of α-Quaternary Aldehydes via a Dual Ni/Rh-Catalyzed Tandem Isomerization–Propargylation Reaction

Synthesis of α-Quaternary Aldehydes via a Dual Ni/Rh-Catalyzed Tandem Isomerization–Propargylation Reaction

Biosynthesis of Polycyclic Natural Products from Conjugated Polyenes via Tandem Isomerization and Pericyclic Reactions.

We report biosynthetic pathways that can synthesize and transform conjugated octaenes and nonaenes to complex natural products. The biosynthesis of (-)-PF1018 involves an enzyme PfB that can control the regio-, stereo-, and periselectivity of multiple reactions starting from a conjugated octaene. Using PfB as a lead, we discovered a homologous enzyme, BruB, that facilitates diene isomerization, tandem 8π-6π-electrocyclization, and a 1,2-divinylcyclobutane Cope rearrangement to generate a new-to-nature compound.

Nickel-catalyzed tandem isomerization/anti-Markovnikov hydroarylation of unactivated internal alkenes with heteroarenes

A tandem isomerization/anti-Markovnikov hydroarylation of unactivated internal alkenes with heteroarenes was realized in a highly linear regioselective fashion using a catalytic system containing an NHC-based heteroleptic Ni(ii) complex and a base.

Correction: Nickel-catalyzed tandem isomerization/anti-Markovnikov hydroarylation of unactivated internal alkenes with heteroarenes

Correction for ‘Nickel-catalyzed tandem isomerization/anti-Markovnikov hydroarylation of unactivated internal alkenes with heteroarenes’ by Sajid Imran et al., Org. Chem. Front., 2023, https://doi.org/10.1039/d2qo01905a.

Pd/Rh Dual Catalysis: Tandem Isomerization–Allylation to Access α-Quaternary Carbonyl Compounds

A dual metal approach enables the use of unsymmetrical diallyl carbonates as viable enolate precursors for allylic alkylation reactions, allowing facile access to various α-quaternary allylated aldehydes and ketones. This methodology features a regioselective Pd-catalyzed decarboxylative oxidative addition, forming an electrophilic Pd π-allyl species and releasing an allylic alkoxide, which undergoes a Rh-catalyzed isomerization to an enolate in situ. Recombination of the Pd π-allyl species and Rh-enolate nucleophile then affords the α-quaternary carbonyl compound.

Asymmetric Total Synthesis of (2E)-Macrolactin 3

AbstractAsymmetric total synthesis of (2E)-macrolactin 3 has been accomplished in a highly convergent manner utilizing our earlier developed tandem isomerization followed by C–O and C–C bond-forming reaction, Sharpless asymmetric dihydroxylation, and a late-stage intramolecular Heck coupling reaction. Comparison of the NMR spectra of the coupled product and thorough analysis of the 2D NMR data of the final compound led to the conclusion that the Z-double bond at C2 was isomerized during the coupling reaction.

New trifluoromethylated sesquiterpenoids: synthesis, rearrangement, and biological activity

The tandem isomerization and trifluoromethylation reactions are a simple, convenient, and atom-economical strategy for the synthesis of various products in high yields from simple substrates.

Palladium-Mediated Tandem Isomerization-Methylenation of Allyl Alcohols: One-Pot Synthesis of 1,5-Diketones.

A novel methodology for the synthesis of 1,5-diketones through a one-pot isomerization-methylenation of a variety of allylic alcohols has been established for the first time. This methodology utilizes commercially available palladium acetate and easily accessible BINOL phosphoric acid. Both isomerization of allylic alcohol and oxidation of methanol occurred through a single catalyst. The practical utility of the methodology has been shown by synthesizing substituted pyridines via sequential addition. Mechanistic investigation reveals the isomerization of allylic alcohols to the corresponding ketone, which ultimately undergoes methylenation, leading to 1,5-diketones, having H2 and H2O as the only byproduct.

BF3·OEt2-Catalyzed Unexpected Stereoselective Formation of 2,4-trans-Diallyl-2-methyl-6-aryltetrahydro-2H-pyrans with Quaternary Stereocenters.

The present manuscript describes a convenient, mild, and highly stereoselective method for the allylation of δ-hydroxy-α,β-unsaturated ketones having a benzylic hydroxyl group at the δ-position using allyltrimethylsilane mediated by BF3·OEt2, leading to 2,4-diallyl-2-methyl-6-aryltetrahydro-2H-pyran ring systems with quaternary carbon stereogenic centers. This represents the first example of a tandem isomerization followed by one C-O and two C-C bond-forming reactions in one pot. The isolation of TMS-protected lactol as an intermediate from the reaction strongly supports the proposed mechanistic pathway.

Concise Total Synthesis of Curvulone B

AbstractA concise and convergent stereoselective synthesis of curvulone B is described. The synthesis utilized a tandem isomerization followed by C–O and C–C bond-forming reactions following Mukaiyama-type aldol conditions for the construction of the trans-2,6-disubstituted dihydropyran ring system as the key steps. Other important features of this synthesis are a cross-metathesis, epimerization, and Friedel–Crafts acylation.

Lewis acid-catalyzed asymmetric reactions of \u03b2,\u03b3-unsaturated 2-acyl imidazoles

The investigation of diverse reactivity of β,γ-unsaturated carbonyl compounds is of great value in asymmetric catalytic synthesis. Numerous enantioselective transformations have been well developed with β,γ-unsaturated carbonyl compounds as nucleophiles, however, few example were realized by utilizing them as not only nucleophiles but also electrophiles under a same catalytic system. Here we report a regioselective catalytic asymmetric tandem isomerization/α-Michael addition of β,γ-unsaturated 2-acyl imidazoles in the presence of chiral N,N′-dioxide metal complexes, delivering a broad range of optically pure 1,5-dicarbonyl compounds with two vicinal tertiary carbon stereocenters in up to >99% ee under mild conditions. Meanwhile, stereodivergent synthesis is disclosed to yield all four stereoisomers of products. Control experiments suggest an isomerization process involved in the reaction and give an insight into the role of NEt3. In addition, Mannich reaction and sulfur-Michael addition of β,γ-unsaturated 2-acyl imidazoles proceed smoothly as well under the same catalytic system.

General Asymmetric Synthetic Strategy for the α‐Alkylated 2,5,6‐Trisubstituted Pyran of Indanomycin and Related Natural Products

A general synthetic strategy for convergent asymmetric synthesis of C1–C10 fragment of tetraene‐containing natural product indanomycin was achieved starting from 2‐(benzyloxy)acetaldehyde which in turn was obtained from very inexpensive material cis‐1,4‐butene‐diol. Key steps include Evans' aldol reaction, HWE olefination, iodine‐catalyzed tandem isomerization followed by C–O and C–C bond formation similar to our earlier report in constructing the trans‐2,6‐disubstituted dihydropyran ring and Evans' asymmetric alkylation.

Rhodium-Catalyzed Tandem Isomerization–Allylation: From Diallyl Carbonates to α-Quaternary Aldehydes

We report a Rh-catalyzed tandem isomerization–allylation sequence for the generation of α-quaternary aldehydes, starting from unsymmetrical diallyl carbonates. This reaction features a highly selec...

Bismuth(III)‐Triflate‐Catalyzed Highly Diastereoselective Synthesis of Substituted Tetrahydrothiophene via Tandem Isomerization, Michael and Aldol Reactions

AbstractBismuth(III)trifluoromethanesulfonate (Bi(OTf)3) catalyzes the reaction of β,γ‐unsaturated ketone and 1,4‐dithiane‐2,5‐diol to afford highly substituted tetrahydrothiophenes via sequential rearrangement, Michael and aldol reactions in good yields. The reaction is highly diastereoselective. Bi(OTf)3 acts as a catalyst for all three reactions.

Hydride–Rhodium(III)-N-Heterocyclic Carbene Catalyst for Tandem Alkylation/Alkenylation via C–H Activation

The unsaturated hydride complex RhClH{κ2-N,C-(C11H8N)}(IPr) {IPr = 1,3-bis-(2,6-diisopropylphenyl)imidazolin-2-carbene} (2) has been prepared via C–H activation of 2-phenylpyridine and fully characterized by spectroscopic methods and X-ray diffraction analysis. Complex 2 efficiently catalyzes the isomerization of terminal and internal olefins under mild conditions to give preferentially the E regioisomers. Complex 2 also catalyzes the hydroarylation of terminal olefins with 2-phenylpyridine to yield selectively mono-ortho-alkylated derivatives. Tandem isomerization–alkylation processes were observed for internal olefins. In contrast to olefins, double alkenylation is operative for internal alkynes. The marked complementary reactivity of olefins and alkynes allows for a tandem alkylation/alkenylation of 2-phenylpyridine to yield substituted styrenes. These heterobiaryl compounds exhibit axial chirality. The rotational barrier has been experimentally calculated and corroborated by density functional theory ...

Cooperative Use of Brønsted Acids and Metal Catalysts in Tandem Isomerization Reactions of Olefins

AbstractDual catalysis constitutes a growing field of the organic synthesis. It is a useful methodology, which allows for a discovery of new and more efficient transformations. This concept article describes tandem reactions, which comprise of an isomerization of the double bond and following transformation, whereby a combination of a homogeneous metal catalyst and Brønsted acid is used. The aim is to highlight the versatility of this catalyst combination.

Total Synthesis of Cryptorigidifoliol K: Confirmation of Structure and Absolute Configuration

AbstractTotal synthesis of the revised cryptorigidifoliol K and 2′‐epi‐cryptorigidifoliol K was accomplished. Salient features of the synthesis involve tandem isomerization followed by C−O and C−C bond forming reaction, iodolactonization and Nozaki‐Hiyama‐Kishi reaction. The synthesis allowed for confirmation of the structure as well as the elucidation of the unassigned stereocenter present in the side chain of the revised structure by correlating the spectral and analytical data of the synthetic cryptorigidifoliol K and 2′‐epi‐cryptorigidifoliol K with the natural product data, which was found to be 1S,5R,7S,2′R,3′E.

Transition-metal complex-catalyzed alkane functionalization

The selective conversion of simple alkane feedstocks to high-value organic compounds constitutes one of major challenges in organic synthesis. There are three general catalytic methods for alkane functionalizations: reactions via radical intermediates and through carbene/nitrene insertion pathways typically occur preferentially at the secondary and tertiary C−H bonds, whereas transition metal-mediated C−H bond activation holds promise for the functionalization of primary C−H bonds. From a practical point of view, the installation of a functional group at the terminal position of alkanes is of particular attractive for large-scale synthesis of specialty or commodity chemicals. This review focuses on the area of molecular transition-metal-catalyzed alkane transformations through catalytic alkane dehydrogenation. In the first section, the development of iridium pincer and related complexes for alkane dehydrogenation is summarized. Among various catalysts, the PCP type Ir pincer complexes have proven to be most active toward transfer dehydrogenation of alkanes. α-Olefins are the kinetic products at the early stage of the dehydrogenation process, but they can be rapidly isomerized to internal alkenes. Recently, other non-phosphorus-ligated Ir and non-Ir metal dehydrogenation catalysts have also been developed, but they are generally less efficient than the PCP Ir catalysts. The second section first describes two dehydrogenation-based alkane transformations without the incorporation of heteroatom-containing functionality. The dehydroaromatization reaction involves multiple steps of dehydrogenation of linear alkanes to form conjugate trienes, which undergo electrocyclization and another step of dehydrogenation to generate aromatic products. The alkane-alkene coupling reaction employs an Ir pincer catalyst for dehydrogenation and a tantalum catalyst for alkene/alkene coupling, thus providing a method for upgrading light alkanes to higher alkanes that may be suitable to transportation fuel. Following that, the selective installation of functional groups at the terminal positions of alkanes through a dehydrogenation-alkene isomerization-hydrofunctionalization strategy using a dual catalyst system is described. Several combinations between a PSCOP Ir pincer dehydrogenation catalyst and molecular Fe or Rh catalysts for tandem isomerization and hydrofunctionalization of terminal alkenes have been developed for terminal selective alkane silylation, borylation, carbonylation, and aminomethylation. The third section covers alkane metathesis and its application to polyethylene (PE) degradation. The alkane metathesis reaction described here consists of two catalysts, one Ir dehydrogenation catalyst and one olefin metathesis catalyst. The metathesis process can find potential application in upgrading low carbon number n -alkanes to higher-molecular-weight fuel alkanes. A cross-alkane metathesis strategy has been developed for PE degradation. Using excess of low-value light alkanes as the reagent/solvent, PE with molecular weight up to 1.7 million undergoes multiple times of cross-alkane metathesis at 175℃ to produce liquid fuels or high-quality waxes. The catalysts can tolerate the commercial HDPE, LDPE and LLDPE, and enable the efficient degradation of postconsumer PE plastic wastes. Finally, the review discusses the limitations of the known catalytic approaches and future opportunities in this field. Catalyst development will be the central theme of research, and insights into the factors controlling the activity and selectivity gained in mechanistic studies will guide the design of more efficient dehydrogenation catalysts. The cooperative catalysis involving enantioselective catalysts will provide a protocol for synthesis of valuable fine chemicals from simple saturated hydrocarbons. Lastly, we should not overlook the potential of cooperation between photo- or electro-catalysis and transition-metal catalysis, which may allow the exploitation of alkane feedstocks more cleanly and efficiently.

Controlled Tandem Isomerization of o-Lith-iated Aryl Benzyl Ethers in Continuous Flow

Controlled Tandem Isomerization of o-Lith-iated Aryl Benzyl Ethers in Continuous Flow

Rhodium-Biphephos-Catalyzed Tandem Isomerization–Hydroformylation of Oleonitrile

Tandem isomerization–hydroformylation of oleonitrile (an 18-carbon nitrile with a remote internal (9-)C=C bond) has been studied using Rh-bisphosphite catalyst systems, targeting formation of the linear aldehyde. The best compromise between regioselectivity (l/b = 58:42) and chemoselectivity (60%) was obtained at 120 °C and 10 bar CO/H2 (1:1) with a catalyst based on Biphephos at a 0.5 mol % catalyst load and a low ligand excess (2 equiv. versus Rh). These values stand among the better reported ones for the tandem isomerization–hydroformylation of long chain olefins with a single-component catalyst system.