Palladium and Copper Cocatalyzed Intermolecular Cyclization Reaction: Synthesis of 5‐Aminopyrazole Derivatives

A novel and efficient palladium and copper co‐catalyzed intermolecular cyclization of acetonitriles with hydrazones has been developed for the synthesis of 5‐aminopyrazoles through C C and C N bond formation. The reaction has the advantages of easily available starting materials, simple manipulation and mild reaction conditions. The reaction involving various substituted acetonitriles and hydrazones proceeds smoothly and 5‐aminopyrazoles are synthesized in good yields. In contrast to the aliphatic and heteroaromatic substrates, the aromatic substrates tend to have a higher degree of reactivity.

     

Aryl λ3‐Iodane‐Mediated 6‐exo‐trig Cyclization to Synthesize Highly Substituted Chiral Morpholines

A mild and efficient transition metal‐free approach has been developed for the synthesis of highly substituted chiral morpholines from alkenols by amino acid‐derived iodine(III) reagents via a 6‐exo‐trig cyclization. The key features of this work include the formation of three chiral centers with a high diastereomeric ratio, broad functional group compatibility, and atom/time economic methodology.

     

Selective 5‐exo‐dig Cyclization of in Situ Synthesized N‐Boc‐2‐aminophenyl Ethoxyethynyl Carbenols: Synthesis of Multifunctional Indoles and Their Derivatives

A method to prepare 3‐substituted‐2‐formylindole derivatives from N‐Boc‐ortho‐aminoaryl ketones and ethoxyacetylene through a cascade of reactions in a single operation that included a nucleophile‐triggered 5‐exo‐dig cyclization and an acid‐mediated 1,3‐allyl alcohol isomerization (1,3‐AAI) is described. A variety of aryl, vinyl and alkynyl groups can be introduced at C‐3 of indole‐2‐carboxaldehyde while having a high functional group compatibility. The 3‐alkynyl adducts, which are highly valuable substrates for diversity‐oriented synthesis, can be further transformed to useful carboline and carbazole derivatives through novel pathways.

     

Synthesis of Fused Cyclopentenones through Palladium‐Catalyzed Cyclization of 2‐Iodoaryl Allenols

A versatile strategy for the synthesis of fused cyclopentenones, key structural motifs in biologically relevant compounds such as indenones and indole alkaloids, has been established successfully through regioselective palladium‐catalyzed cyclization of 2‐iodoaryl allenols.

     

Copper‐Catalyzed Activation of Dioxygen: Oxidative Cyclization of 2‐Arylindoles

A series of unusual six‐ring‐fused heterocycles containing indole and quinoline skeletons was successfully synthesized by a copper‐catalyzed reaction from 2‐arylated indoles. Two new bonds were regioselectively formed from C H and C H coupling. ¹⁸O‐Labelled experiments revealed that the dioxygen is not only the oxidant but also the reactant.     

Palladium‐Catalyzed Construction of Spirooxindoles by Arylative Cyclization of 3‐(γ,δ‐Disubstituted)allylidene‐2‐Oxindoles

The palladium‐catalyzed, one‐pot arylative cyclization of 3‐(γ,δ‐disubstituted)allylidene‐2‐oxindoles afforded spirodihydronaphthalene‐2‐oxindole frameworks via an oxidative Heck arylation (Fujiwara–Moritani reaction), an allylic palladium migration, and an aryl C H bond functionalization/arylation cascade of reactions. This is a first example of the palladium‐catalyzed oxidative arylation and an aryl C H bond functionalization/arylation cascade reaction which involves an electrophilic arylative quenching of a π‐allylpalladium intermediate and a regio‐controlled aryl C H bond activation assisted by a weak palladium‐arene interaction.

     

Improved conversion of 6‐endo‐tosyloxybicyclo[2.2.2]octan‐2‐ones into 6‐exo‐acetoxy and 6‐exo‐benzoyloxybicyclo[2.2.2]octan‐2‐ones

The reaction conditions for the conversion of 6‐endo‐tosyloxybicyclo[2.2.2]octan‐2‐one ( 7b ) into 6‐exo‐acetoxy ( 8b ) and 6‐exo‐benzoyloxybicyclo[2.2.2]octan‐2‐one ( 8a ), respectively, were improved. Thus known 6‐endo‐tosyloxy‐bicyclo[2.2.2]octan‐2‐ones (+)‐(1RS,6SR,8SR,11RS)‐11‐[(4‐toluenesulfonyl)oxy]tricyclo[6.2.2.0^1,6]dodecan‐9‐one ( 1a ), 13‐methyl‐15‐oxo‐9β,13b‐ethano‐9β‐podocarpan‐12β‐yl‐4‐toluenesulfonate ( 3a ), and methyl (13R)‐16‐oxo‐13‐[(4‐tolylsulfonyl)oxy]‐17‐noratisan‐18‐oate ( 5 ), were converted,in comparable yields, as previously recorded, but much shorter times, into (+)‐(1RS,6SR,8SR,11SR)‐11‐(benzoyloxy) tricyclo[6.2.2.0^1,6]dodecan‐9‐one ( 2 ), 13‐methyl‐15‐oxo‐9β,13β‐ethano‐9β‐podocarpan‐12α‐yl benzoate ( 4 ), and methyl (13S)‐13‐(benzoyloxy)‐16‐oxo‐17‐noratisan‐18‐oate ( 6 ), respectively.     

Chlorinative Cyclization of 1,6‐Enynes by Enantioselective Palladium(II)/Palladium(IV) Catalysis

A novel asymmetric catalysis via a palladium(II)/palladium(IV) cycle has been developed by utilizing a chiral spiro bis(isoxazoline) ligand (SPRIX). Intramolecular chlorinative cyclization of 1,6‐enynes catalyzed by a palladium‐SPRIX complex proceeded enantioselectively to afford α‐methylene‐γ‐lactone derivatives.     

Palladium‐Catalyzed Tandem‐Cyclization of Functionalized Ynamides: An Approach to Benzosultams

A palladium‐catalyzed tandem‐cyclization of functionalized ynamides to afford a wide range of hetero‐substituted benzosultams (1,2‐benzothiazine 1,1‐dioxides) has been achieved. Medicinally useful compounds like nortriptyline and eugenol could also be used as nucleophiles. Base has a significant effect in the cyclization process, depending on the nucleophile source used. DFT studies suggest that the reaction involves a [Pd(II)]–[Pd(0)]–[Pd(II)] cycle. Structures of key products were proven by X‐ray crystallography.

     

Development of a New Spiro‐BOX Ligand and Its Application in Highly Enantioselective Palladium‐Catalyzed Cyclization of 2‐Iodoanilines with Allenes

In this communication, we report the synthesis of a new chiral spiro‐bisoxazoline ligand, i.e., β‐naphthylmethyl‐substituted spiro‐BOX [(R_a,S,S)‐ L7 ] and have successfully applied it to the palladium‐catalyzed enantioselective cyclization reaction of simple allenes with o‐aminoiodobenzenes, affording highly optically active 3‐alkylideneindolines in good yields with excellent enantiomeric excesses.     

Silver Triflate‐Catalyzed Cyclization of 2‐Amino‐6‐propargyl‐ amineazines Leading to Iminoimidazoazines

We report here that the silver triflate‐catalyzed cyclization of 2‐amino‐6‐propargylamineazines affords new and highly functionalized iminoimidazoazines. We have investigated the scope and limitations of the present methodology, and some aspects of the reactivity of the resulting iminoimidazopyridines have been explored, and a DFT‐based mechanistic analysis of the silver triflate‐catalyzed cyclization has been undertaken.

     

Cyclization of 1,4‐Phenylenediacrylic Acid with Thionyl Chloride and Subsequent Suzuki–Miyaura Reactions Revisited. The Products are Benzo[1,2‐b;5,6‐b′]dithiophenes and not Benzo[1,2‐b;4,5‐b′]dithiophenes

The reaction of 1,4‐phenylenediacrylic acid with thionyl chloride was reinvestigated. In earlier reports [Liebigs Ann. Chem. 1980 , 1172; Heterocycles 1995 , 41, 2691; Adv. Synth. Catal. 2009 , 351, 2683] it was claimed that 3,7‐dichlorobenzo[1,2‐b;4,5‐b′]dithiophenes were formed in these reactions. Herein, we provide unambiguous evidence that the assignment of these structures is wrong and that, in contrast, 3,6‐dichlorobenzo[1,2‐b;5,6‐b′]dithiophenes are formed. As a consequence, the structures of these parent molecules and of numerous aryl‐substituted derivatives prepared by Pd‐catalyzed cross‐coupling reactions have to be revised. As many of these dithiophenes were reported to show interesting optical, thermal and electronic properties, the theoretical explanations for these properties have to be reconsidered in the light of the corrected structures reported herein. Our structural assignments are based on X‐ray crystal structure analyses of the parent molecules and on NMR spectroscopic studies of the first unsymmetrical derivatives. Besides, mechanistic investigations based on quantum chemical calculations have been carried out which support the formation of the 3,6‐dichlorobenzo[1,2‐b;5,6‐b′]dithiophene isomers.     

Chemoselectivity in the Pd‐Catalyzed Cyclization of 1,6‐Enynes and Proof of the Relative Configuration of the New Stereogenic Centers

The dimerization of dienyne 6 with a palladole catalyst readily provides the bicyclic enyne rac‐ 7 . A second cyclization of the 1,6‐enyne substructure in rac‐ 7 works best with a hydropalladation catalyst and delivers rac‐ 8 . Diels‐Alder reactions of the latter finally lead to a crystalline product rac‐ 12 . A crystal structure analysis of rac‐ 12 allowed the determination of the relative configuration of all stereogenic centers formed in the dimerization of 6 .     

Synthesis of β‐Lactams by 4‐exo‐tet Cyclization Process Induced by Electrogenerated Cyanomethyl Anion,Part 2:[1] Stereochemical Implications

An efficient electrochemically induced synthesis of chiral cis β‐lactams has been described, via deprotonation of chiral amides containing an acidic methylene group and a bromine atom as leaving group and bearing a chiral auxiliary or amine function. The electrogenerated base – cyanomethyl anion – is easily obtained by galvanostatic reduction of acetonitrile‐tetraethylammonium hexafluorophosphate solutions under very mild conditions. The yields are high and the cis‐diastereoselection complete. The use of starting chiral amides has allowed in many cases the preparation of the most abundant isomer in a pure form.     

Silver‐Catalyzed One‐Pot Cyclization Reaction of Electron‐ Deficient Alkynes and 2‐Yn‐1‐ols: An Efficient Domino Process to Polysubstituted Furans

Transition metal‐catalyzed domino reactions have been used as powerful tools for the preparation of polysubstituted furans in a one‐pot manner. In this paper, an efficient synthetic method was developed for the construction of tri‐ or tetrasubstituted furans from electron‐deficient alkynes and 2‐yn‐1‐ols by a silver‐catalyzed domino reaction. It is especially noteworthy that a 2,3,5‐trisubstituted 4‐ynyl‐furan was formally obtained in an extremely direct manner without tedious stepwise synthesis. In addition, regio‐isomeric furans were observed when substituted aryl alkynyl ketones were employed. This methodology represents a highly efficient synthetic route to electron‐deficient furans for which catalytic approaches are scarce. The reaction proceeds efficiently under mild conditions with commercially available catalysts and materials.     

Palladium Nanoparticles in Water: A Reusable Catalytic System for the Cycloetherification or Benzannulation of α‐Allenols

A convenient ligand‐free catalytic system has been developed for the chemoselective cyclization reaction of various α‐allenol derivatives by palladium nanoparticles (PdNPs) in an aqueous reaction medium.

     

Palladium‐Catalyzed Cyclization of Enediynes to Benzopyranones

Treatment of methyl 2‐[6‐substituted‐3(Z)‐hexen‐1,5‐diynyl]benzoates ( 1 ) with five mol% of palladium chloride and three equivalents of cupric chloride in refluxing acetonitrile gave dibenzo[b,d]pyran‐6‐ones ( 2 ) in modest to good yields.     

Gold(III) Chloride‐Catalyzed 6‐endo‐trig Oxa‐Michael Addition Reactions for Diastereoselective Synthesis of Fused Tetrahydropyranones

Alkynones were treated with boron trifluoride diethyl etherate to generate β‐iodoallenolates, which underwent intramolecular aldol reactions to produce cycloalkenyl alcohols. Diastereoselective oxa‐Michael ring closure could then be induced by treatment with a catalytic amount of gold(III) chloride, affording highly functionalized tetrahydropyranone‐containing ring systems.