Rhodium(I)‐Catalyzed Decarbonylative Spirocyclization through C?C Bond Cleavage of Benzocyclobutenones: An Efficient Approach to Functionalized Spirocycles

The rhodium‐catalyzed formation of all‐carbon spirocenters involves a decarbonylative coupling of trisubstituted cyclic olefins and benzocyclobutenones through C C activation. The metal–ligand combination [{Rh(CO)₂Cl}₂]/P(C₆F₅)₃ catalyzed this transformation most efficiently. A range of diverse spirocycles were synthesized in good to excellent yields and many sensitive functional groups were tolerated. A mechanistic study supports a hydrogen‐transfer process that occurs through a β‐H elimination/decarbonylation pathway.     

Ruthenium‐Catalyzed Cascade CH Functionalization of Phenylacetophenones

Three orthogonal cascade C? H functionalization processes are described, based on ruthenium‐catalyzed C? H alkenylation. 1‐Indanones, indeno indenes, and indeno furanones were accessed through cascade pathways by using arylacetophenones as substrates under conditions of catalytic [{Ru(p‐cymene)Cl₂}₂] and stoichiometric Cu(OAc)₂. Each transformation uses C? H functionalization methods to form C? C bonds sequentially, with the indeno furanone synthesis featuring a C? O bond formation as the terminating step. This work demonstrates the power of ruthenium‐catalyzed alkenylation as a platform reaction to develop more complex transformations, with multiple C? H functionalization steps taking place in a single operation to access novel carbocyclic structures.     

Palladium‐Catalyzed Oxidative C≡C Triple Bond Cleavage of 2‐Alkynyl Carbonyl Compounds Toward 1,2‐Dicarbonyl Compounds†

A new, general palladium‐catalyzed oxidative strategy for the cleavage of the C≡C triple bond is presented. By employing PdCl₂, CuBr₂, TEMPO and air as the catalytic system and H₂O as the carbonyl oxygen atom source, a wide range of 2‐alkynyl carbonyl compounds, including 1,3‐disubstituted prop‐2‐yn‐1‐ones, propiolamides and propiolates, lost an alkynyl carbon to access various 1,2‐dicarbonyl compounds, e.g., 1,2‐diones, 2‐keto amides and 2‐keto esters, through Wacker oxidation, intramolecular cyclization and C—C bond cleavage cascades.     

Ruthenium Catalyzed C−H Acylmethylation of N‐Arylphthalazine‐1,4‐diones with α‐Carbonyl Sulfoxonium Ylides: Highway to Diversely Functionalized Phthalazino‐fused Cinnolines

A direct ortho‐Csp²‐H acylmethylation of 2‐aryl‐2,3‐dihydrophthalazine‐1,4‐diones with α‐carbonyl sulfoxonium ylides is achieved through a Ru^II‐catalyzed C?H bond activation process. The protocol featured high functional group tolerance on the two substrates, including aryl‐, heteroaryl‐, and alkyl‐substituted α‐carbonyl sulfoxonium ylides. Thereafter, 2‐(ortho‐acylmethylaryl)‐2,3‐dihydrophthalazine‐1,4‐diones were used as potential starting materials for the expeditious synthesis of 6‐arylphthalazino[2,3‐a]cinnoline‐8,13‐diones and 5‐acyl‐5,6‐dihydrophthalazino[2,3‐a]cinnoline‐8,13‐diones under Lawesson's reagent and BF₃?OEt₂ mediated conditions, respectively. Of these, the BF₃?OEt₂‐mediated cyclization proceeded in DMSO as a solvent and a methylene source via dual C?C and C?N bond formations.     

Stereodivergent Synthesis of Arylcyclopropylamines by Sequential CH Borylation and Suzuki–Miyaura Coupling

A step‐economical and stereodivergent synthesis of privileged 2‐arylcyclopropylamines (ACPAs) through a C(sp³)? H borylation and Suzuki–Miyaura coupling sequence has been developed. The iridium‐catalyzed C? H borylation of N‐cyclopropylpivalamide proceeds with cis selectivity. The subsequent B‐cyclopropyl Suzuki–Miyaura coupling catalyzed by [PdCl₂(dppf)]/Ag₂O proceeds with retention of configuration at the carbon center bearing the Bpin group, while epimerization at the nitrogen‐bound carbon atoms of both the starting materials and products is observed under the reaction conditions. This epimerization is, however, suppressed in the presence of O₂. The present new ACPA synthesis results in not only a significant reduction in the steps required for making ACPA derivatives, but also the ability to access either isomer (cis or trans) by simply changing the atmosphere (N₂ or O₂) in the coupling stage.     

Ruthenium‐Catalyzed Cascade C?H Functionalization of Phenylacetophenones

Three orthogonal cascade C H functionalization processes are described, based on ruthenium‐catalyzed C H alkenylation. 1‐Indanones, indeno indenes, and indeno furanones were accessed through cascade pathways by using arylacetophenones as substrates under conditions of catalytic [{Ru(p‐cymene)Cl₂}₂] and stoichiometric Cu(OAc)₂. Each transformation uses C H functionalization methods to form C C bonds sequentially, with the indeno furanone synthesis featuring a C O bond formation as the terminating step. This work demonstrates the power of ruthenium‐catalyzed alkenylation as a platform reaction to develop more complex transformations, with multiple C H functionalization steps taking place in a single operation to access novel carbocyclic structures.     

Synthesis of Silaphenalenes by Ruthenium‐Catalyzed Annulation between 1‐Naphthylsilanes and Internal Alkynes through CH Bond Cleavage

Ruthenium‐catalyzed annulation of 1‐naphthylsilanes with internal alkynes afforded silaphenalenes through cleavage of the C?H bond at the 8‐position of the naphthalene. [RuH₂(CO){P(p‐FC₆H₄)₃}₃] efficiently catalyzed the reaction. The use of 1‐naphthyldiphenylsilane as a substrate resulted in a better yield of the annulation product compared to the use of silanes with alkyl groups on the silicon atom. Internal alkynes with both aryl and alkyl groups were tolerated in this reaction.     

Short Syntheses of 4‐Deoxycarbazomycin B,Sorazolon E,and (+)‐Sorazolon E2

Short syntheses of 4‐deoxycarbazomycin B and sorazolon E were established through the condensation of cyclohexanone and commercially available 4‐methoxy‐2,3‐dimethylaniline, followed by Pd^II‐catalyzed dehydrogenative aromatization/intramolecular C−C bond coupling and deprotection. A chiral dinuclear vanadium complex (R _a,S,S )‐ 6 mediated the enantioselective oxidative coupling of sorazolon E, affording (+)‐sorazolon E2 in good enantioselectivity.     

Microwave‐Accelerated Pd‐Catalyzed Desulfitative Direct C2‐Arylation of Free (NH)‐Indoles with Arylsulfinic Acids

The rapid and efficient direct C2‐arylation of free (NH)‐indoles with arylsulfinic acids proceeded through a microwave‐accelerated palladium‐catalyzed desulfitation reaction. By using PdCl₂ as a catalyst, silver acetate as an oxidant, and H₂SO₄ as an additive, arylsulfinic acids with both electron‐donating and electron‐withdrawing groups underwent desulfitative coupling with an array of free (NH)‐indoles, thereby selectively providing C2‐arylindoles in good yields.     

Palladium‐Catalyzed Multi‐Component Reactions of N‐Tosylhydrazones, 2‐Iodoanilines and CO2 towards 4‐Aryl‐2‐Quinolinones

A palladium‐catalyzed three‐component reaction between N‐tosylhydrazones, 2‐iodoanilines and atmospheric pressure CO₂ was developed whereby a tandem carbene migration insertion/lactamization strategy afforded 4‐aryl‐2‐quinolinones in moderate to good yields. Notably, a wide range of functional groups were tolerated in this procedure. This protocol features the simultaneous formation of four novel bonds; two C?C, one C=C and one C?N (amide), representing an efficient methodology for incorporation of CO₂ into heterocycles.     

A Light/Ketone/Copper System for Carboxylation of Allylic C−H Bonds of Alkenes with CO2

A photo‐induced carboxylation reaction of allylic C?H bonds of simple alkenes with CO₂ is prompted by means of a ketone and a copper complex. The unique carboxylation reaction proceeds through a sequence of an endergonic photoreaction of ketones with alkenes forming homoallyl alcohol intermediates and a thermal copper‐catalyzed allyl transfer reaction from the homoallyl alcohols to CO₂ through C?C bond cleavage.     

Enantioselective Total Synthesis of (+)‐Plumisclerin A

The first and enantioselective total synthesis of (+)‐plumisclerin A, a novel unique complex cytotoxic marine diterpenoid, has been accomplished. Around the central cyclopentane anchorage, a sequential ring‐formation protocol was adopted to generate the characteristic tricycle[4.3.1.0^1,5]decane and trans‐fused dihyrdopyran moiety. Scalable enantioselective La^III‐catalyzed Michael reaction, palladium(0)‐catalyzed carbonylation and SmI₂‐mediated radical conjugate addition were successfully applied in the synthesis, affording multiple grams of the complex and rigid B/C/D‐ring system having six continuous stereogenic centers and two all‐carbon quaternary centers. The trans‐fused dihyrdopyran moiety with an exo side‐chain was furnished in final stage through sequential redox transformations from a lactone precursor, which overcome the largish steric strain of the dense multiring system. The reported total synthesis also confirms the absolute chemistries of natural (+)‐plumisclerin A.     

Ligand‐Promoted C(sp3)−H Olefination en Route to Multi‐functionalized Pyrazoles

A Pd‐catalyzed/N‐heterocycle‐directed C(sp³)?H olefination has been developed. The monoprotected amino acid ligand (MPAA) is found to significantly promote Pd‐catalyzed C(sp³)?H olefination for the first time. Cu(OAc)₂ instead of Ag⁺ salts are used as the terminal oxidant. This reaction provides a useful method for the synthesis of alkylated pyrazoles.     

Novel and Stereospecific Synthesis of (2S)‐3‐(2,4,5‐Trifluorophenyl)propane‐1,2‐diol from D‐Mannitol

A stereospecific synthesis of (2S)‐3‐(2,4,5‐trifluorophenyl)propane‐1,2‐diol from D ‐mannitol has been developed. The reaction of 2,3‐O‐isopropylidene‐D ‐glyceraldehyde with 2,4,5‐trifluorophenylmagnesium bromide gave [(4R)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl](2,4,5‐trifluorophenyl)methanol in 65% yield as a mixture of diastereoisomers (1 : 1). The Ph₃P catalyzed reaction of the latter with C₂Cl₆ followed by reduction with Pd/C‐catalyzed hydrogenation gave (2S)‐3‐(2,4,5‐trifluorophenyl)propane‐1,2‐diol with >99% ee and 65% yield.     

Copper(II)‐Catalyzed Synthesis of N‐Substituted‐3‐amino‐4‐cyano‐isoquinoline‐1(2H)‐ones by the Reaction of N‐Substituted‐2‐iodobenzamides with Malononitrile

A novel Cu(OAc)₂·H₂O catalyzed coupling reaction of N‐substituted‐2‐iodobenzamides with malononitrile to afford N‐substituted‐3‐amino‐4‐cyano‐isoquinoline‐1(2H)‐ones is described. The reaction proceeded in DMSO at 90°C for 5 h in nitrogen without external ligands.     

Regio‐ and Enantioselective Synthesis of N‐Allylindoles by Iridium‐Catalyzed Allylic Amination/Transition‐Metal‐Catalyzed Cyclization Reactions

Regio‐ and enantioselective synthesis of N‐allylindoles was realized through an iridium‐catalyzed asymmetric allylic amination reaction with 2‐alkynylanilines and subsequent transition‐metal‐catalyzed cyclization reactions. The highly enantioenriched allylic amines prepared from Ir‐catalysis were treated with catalytic amount of NaAuCl₄ ? 2 H₂O or PdCl₂ providing various substituted N‐allylindoles in excellent yields and enantioselectivities.     

Rhodium‐Complex‐Catalyzed Hydroformylation of Olefins with CO2 and Hydrosilane

A rhodium‐catalyzed one‐pot hydroformylation of olefins with CO₂ , hydrosilane, and H₂ has been developed that affords the aldehydes in good chemoselectivities at low catalyst loading. Mechanistic studies indicate that the transformation is likely to proceed through a tandem sequence of poly(methylhydrosiloxane) (PMHS) mediated CO₂ reduction to CO and a conventional rhodium‐catalyzed hydroformylation with CO/H₂. The hydrosilylane‐mediated reduction of CO₂ in preference to aldehydes was found to be crucial for the selective formation of aldehydes under the reaction conditions.     

Energy Transfer and Concentration‐Dependent Conformational Modulation: A Porphyrin‐Containing [3]Rotaxane

A zinc porphyrin‐containing [3]rotaxane A was synthesized through a copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) reaction. Energy donors and acceptor porphyrin were introduced to dibenzo[24]crown‐8 (DB24C8) and dibenzyl ammonium (DBA) units of [3]rotaxane A to understand the intramolecular energy transfer process. Investigations of the photophysical properties of [3]rotaxane A demonstrated that the intramolecular efficient energy transfer readily occurred from the donors on the wheels to the porphyrin center on the axis. The fluorescence of energy donors in the region of 400 to 450 nm was efficiently absorbed by the porphyrin acceptor under irradiation at 345 nm, and finally a red light emission at about 600 nm was achieved. Further investigation indicated that the conformation of [3]rotaxane A was self‐modulated by changing its concentration in CH₂Cl₂. The triazole groups on the wheel coordinated or uncoordinated to Zn²⁺ through intramolecular self‐coordination with the change in the concentration of [3]rotaxane A in CH₂Cl₂. Therefore, this conformational change was reversible in a non‐coordinating solvent such as CH₂Cl₂ but inhibited in a coordinating solvent such as THF. Such interesting behaviors were rarely observed in porphyrin derivatives. This self‐modulation feature opens up the possibility of controlling molecular conformation by varying concentration.     

Total Syntheses of (+)‐Polygalolide A and (+)‐Polygalolide B: Elucidation of the Absolute Stereochemistry and Biogenetic Implications

The total syntheses of (+)‐polygalolide A and (+)‐polygalolide B have been completed by using a carbonyl ylide cycloaddition strategy. Three of the four stereocenters, including two consecutive tetrasubstituted carbon atoms at C2 and C8, were incorporated through internal asymmetric induction from the stereocenter at C7 by a [Rh₂(OAc)₄]‐catalyzed carbonyl ylide formation/intramolecular 1,3‐dipolar cycloaddition sequence. The arylmethylidene moiety of these natural products was successfully installed by a Mukaiyama aldol‐type reaction of a silyl enol ether with a dimethyl acetal, followed by elimination under basic conditions. We have also developed an alternative approach to the carbonyl ylide precursor based on a hetero‐Michael reaction. This approach requires 18 steps, and the natural products were obtained in 9.8 and 9.3 % overall yields. Comparison of specific rotations of the synthetic materials and natural products suggests that polygalolides are biosynthesized in nearly racemic forms through a [5+2] cycloaddition between a fructose‐derived oxypyrylium zwitterion with an isoprene derivative.     

Cobalt‐Catalyzed,Aminoquinoline‐Directed C(sp2)H Bond Alkenylation by Alkynes

A method for cobalt‐catalyzed, aminoquinoline‐ and picolinamide‐directed C(sp²)? H bond alkenylation by alkynes was developed. The method shows excellent functional‐group tolerance and both internal and terminal alkynes are competent substrates for the coupling. The reaction employs a Co(OAc)₂?4 H₂O catalyst, Mn(OAc)₂ co‐catalyst, and oxygen (from air) as a terminal oxidant.