Gold(I)‐Catalyzed 1,4‐ and/or 1,5‐Heteroaryl Migration Reactions through Regiocontrolled Cyclizations

Gold(I)‐catalyzed regioselective cycloisomerizations of furan‐ynes have been described. The reaction provides a concise access to stereodefined trisubstituted alkenes by endo cyclization with concomitant 1,5‐migration of the furanyl group in the presence of unactivated 3 Å molecular sieves. In the absence of molecular sieves, indene products are generated by exo cyclization, followed by 1,4‐furanyl migration/cyclization. The scope for 1,5‐migrations can be extended to other heterocycles, such as benzofurans, thiophenes, and pyrroles.     

Synthesis of Highly Substituted 3‐Formylfurans by a Gold(I)‐Catalyzed Oxidation/1,2‐Alkynyl Migration/Cyclization Cascade

3‐Formylfuran derivatives are core structures of a variety of bioactive natural products. However, procedures for their preparation are still rare and generally inefficient in terms of atom economy: These methods require multiple steps or harsh reaction conditions and show selectivity problems. An efficient gold(I)‐catalyzed cascade reaction that leads to 3‐formylfurans from easily accessible starting materials is now described. A wide variety of 3‐formylfurans were obtained from the corresponding symmetric and unsymmetric 1,4‐diyn‐3‐ols in the presence of an N‐oxide in good to excellent yields. Isotope‐labeling experiments as well as DFT calculations support a mechanism in which, after an initial oxygen transfer, a 1,2‐alkynyl migration is favored over a hydride shift; a cyclization ensues to afford the desired functionalized furan core.     

Radical Cyclization/ipso‐1,4‐Aryl Migration Cascade: Asymmetric Synthesis of 3,3‐Difluoro‐2‐propanoylbicyclo[3.3.0]octanes

A novel method for the asymmetric synthesis of 3,3‐difluoro‐2‐propanoylbicyclo‐[3.3.0]octanes involves an unprecedented intramolecular radical cyclization/ipso‐1,4‐aryl migration cascade.     

Tandem Double‐Michael‐Addition/Cyclization/Acyl Migration of 1,4‐Dien‐3‐ones and Ethyl Isocyanoacetate: Stereoselective Synthesis of Pyrrolizidines

Up to four adjacent stereocenters can be formed stereoselectively in the construction of a pyrrolizidine unit through a novel organocatalytic reaction that involves treatment of various dienones with ethyl isocyanoacetate (see scheme; DBU=1,8‐diazabicyclo[5.4.0]undec‐7‐ene). Mechanisms for this atom‐economic, one‐pot synthesis have been proposed.

     

O2‐Mediated Oxidation of Aminoboranes through 1,2‐N Migration

In analogy to the classical reaction of C?B bonds with peroxides, the first oxidative functionalization of aminoboranes through a 1,2‐N migration was realized. Readily available aliphatic nitro compounds are thereby transformed into N‐ and O‐functionalized hydroxylamines in a single synthetic operation. Addition of hazardous peroxides is avoided. Instead, the insertion of O₂, as the terminal oxidant, into Zn?C bonds provides the necessary peroxides. The required zinc organyls, in turn, are formed through a boron‐to‐zinc exchange, from an organoboronic ester byproduct of the nitro‐to‐aminoborane transformation.     

Regioselective Synthesis of β‐Aryl‐ and β‐Amino‐Substituted Aliphatic Esters by Rhodium‐Catalyzed Tandem Double‐Bond Migration/Conjugate Addition

Rhodium–phosphite catalysts were found to effectively mediate double‐bond migrations within unsaturated esters. Once the double‐bond is in conjugation with the carboxylate group, they also catalyze the Michael addition of carbon and nitrogen nucleophiles. In the presence of these catalysts, unsaturated carboxylates enter a dynamic equilibrium of positional and geometrical double‐bond isomers. The conjugated species are continuously removed through 1,4‐additions with formation of β‐amino esters or β‐arylated products, depending on the nucleophile employed. The applicability of both protocols to a range of substrates, such as fatty esters of different chain lengths and double‐bond positions, and several nucleophiles including arylborates and primary and secondary amines, is demonstrated.     

Synthesis of Highly Substituted N‐(Furan‐3‐ylmethylene)benzenesulfonamides by a Gold(I)‐Catalyzed Oxidation/1,2‐Alkynyl Migration/Cyclization Cascade

A variety of N‐(furan‐3‐ylmethylene)benzenesulfonamides were obtained by a gold(I)‐catalyzed cascade reaction from easily accessible starting materials. The reaction pathway involves a rarely observed 1,2‐alkynyl migration onto a gold carbenoid. This observation further enriches gold carbenoid chemistry with regard to group migration.     

Silver(I)‐Catalyzed Tandem 1,3‐Acyloxy Migration/Mannich‐type Addition/Elimination of the Sulfonyl Group of N‐Sulfonylhydrazone‐propargylic Esters to 5,6‐Dihydropyridazin‐4‐one Derivatives

The addition of nucleophiles to C?N bonds offers a highly efficient synthetic strategy for accessing nitrogen‐containing molecules. 1 Among the well‐developed addition reactions, such as the highly efficient Mannich reaction, various C? H bond‐activated compounds including carboxylic acid derivatives, nitroalkanes, and terminal alkynes have been applied as nucleophiles to achieve different classes of amines. 2 However, employing new nucleophiles without activated C? H bonds, such as internal alkynes and allenic esters are limited when using metal catalysts. 3 Herein, we wish to report a new addition of allenic esters to C?N bonds initiated by a silver‐catalyzed 1,3‐migration of propargylic esters.     

Studies on [PtCl2]‐ or [AuCl]‐Catalyzed Cyclization of 1‐(Indol‐2‐yl)‐2,3‐Allenols: The Effects of Water/Steric Hindrance and 1,2‐Migration Selectivity

The [PtCl₂]‐ or [AuCl]‐catalyzed reaction of 1‐(indol‐2‐yl)‐2,3‐allenols occurred smoothly at room temperature to afford a series of poly‐substituted carbazoles efficiently. Compared with the [PtCl₂]‐catalyzed process, the [AuCl]‐catalyzed reaction represents a significant advance in terms of the scope and the selectivity. Selective 1,2‐alkyl or aryl migration of the gold carbene intermediate was observed: compared with the methyl group, the isopropyl, cyclopropyl, cyclobutyl, and cyclohexyl groups migrate exclusively; the cyclopropyl group shifts selectively over the ethyl group; the 1,2‐migration of a non‐methyl linear alkyl is faster than methyl group; the phenyl group migrates exclusively over methyl or ethyl group. DFT calculations show that water makes the elimination of H₂O facile requiring a much lower energy and validates the migratory preferences of different alkyl or phenyl groups observed.     

Highly Stereoselective Synthesis of 1,3‐Dienes through an Aryl to Vinyl 1,4‐Palladium Migration/Heck Sequence

An efficient aryl to vinyl 1,4‐palladium migration/Heck sequence was developed for the stereoselective synthesis of 1,3‐dienes. High stereoselectivity was observed not only for 1,3‐dienes bearing two similar aryl groups at terminal positions, but also for those with configurations shown to be unfavorable with previous methods.     

Palladium‐Catalyzed Asymmetric Synthesis of Silicon‐Stereogenic 5,10‐Dihydrophenazasilines via Enantioselective 1,5‐Palladium Migration

A palladium‐catalyzed asymmetric synthesis of silicon‐stereogenic 5,10‐dihydrophenazasilines was developed that proceeds via an unprecedented enantioselective 1,5‐palladium migration. High enantioselectivity was achieved by employing 4,4′‐bis(trimethylsilyl) (R )‐Binap as the chiral ligand, and a series of mechanistic investigations were carried out to probe the catalytic cycle of this process.     

Gold‐Catalyzed 1,2‐/1,2‐Bis‐acetoxy Migration of 1,4‐Bis‐propargyl Acetates: A Mechanistic Study

The late transition metal catalyzed rearrangement of propargyl acetates offers an interesting platform for the development of synthetically useful transformations. We have recently shown that gold complexes can catalyze a highly selective tandem 1,2‐/1,2‐bis‐acetoxy migration in 1,4‐bis‐propargyl acetates to form 2,3‐bis‐acetoxy‐1,3‐dienes. In this way, (1Z,3Z)‐ or (1Z,3E)‐ and (1E,3Z)‐1,3‐dienes could be obtained in a stereocontrolled manner depending on the electronic and steric features of the ancillary ligand bound to gold and the substituents at the propargylic positions. In this work, we report an experimental study on the scope of this transformation, plus a detailed theoretical examination of the reaction mechanism, which has revealed the key features responsible for the reaction stereoselectivity. Synthetic applications towards the one‐pot synthesis of quinoxaline heterocycles and tandem Diels–Alder processes have also been devised.     

Alkene 1,2‐Difunctionalization by Radical Alkenyl Migration

Transition‐metal‐free radical α‐perfluoroalkylation with the accompanying vicinal β‐alkenylation of unactivated alkenes is presented. These radical cascades proceed by means of 1,4‐ or 1,5‐alkenyl migration by electron catalysis on readily accessed allylic alcohols. The reactions comprise a regioselective perfluoroalkyl radical addition with subsequent alkenyl migration and concomitant deprotonation to generate a ketyl radical anion that sustains the chain as a single‐electron‐transfer reducing reagent.     

Gold(I)‐Catalyzed Regiodivergent Rearrangements: 1,2‐ and 1,2′‐Alkyl Migration in Skipped Alkynyl Ketones

A series of 2‐alkynyl carbonyl compounds that contain a cyclopentene ring or a heterocycle can be transformed into various fused dihydrobenzofurans and tetrahydrofuro[2,3‐c]pyridines by means of a 1,2‐alkyl migration process. Both of these reactions proceed with excellent regioselectivity and stereospecificity when using a cationic gold(I) catalyst. Treatment of 4‐styrylcyclopent‐1‐enecarboxylates under different conditions affords a range of highly functionalized dihydrobenzofurans and dihydroisobenzofurans. A divergence in product selectivity, which depends on the anion of the silver salts used, was observed. Interestingly, ring‐fused tetrahydroquinolines undergo only 1,2′‐alkyl migration reaction by means of a C? C cleavage/cyclization sequence to provide tetrahydroazepine derivatives. Mechanistic studies suggest that the gold complexes catalyze 1,2‐alkyl migration reactions through a concerted reaction pathway and 1,2′‐alkyl migration reactions through a stepwise reaction pathway.     

Synthesis and antibacterial activity of 2‐alkylcarbamato/trichloromethyl/chloroethoxy/aryloxy‐1,2,3,4‐tetrahydro‐1,3,2‐benzodiazaphosphorine 2‐oxides

Several 2‐trichloromethyl/2‐chloro‐ethoxy/2‐aryloxy‐1,2,3,4‐tetrahydro‐1,3,2‐benzodiaza‐phosphorine 2‐oxides ( 4a–d ), and 2‐alkyl/alkenyl/alkynylcarbamato 2‐oxides ( 7a‐f ) have been synthesized from reactions of equimolar quantities of 2‐aminobenzylamine ( 2 ) with various aryl or alkyl phosphorodichloridates ( 3b–d ), trichloromethylphosphonic dichloride ( 3a ) and dichlorophosphinyl carbamates ( 6a–f ) at 40–50°C in dry toluene in the presence of triethylamine. IR, ¹H, ¹³C, ³¹P NMR and mass spectral analyses were collected and analyzed and supported all structures. The title compounds were screened for antibacterial activity against Bacillus subtilis and Escherichia coli. Several of the agents exhibited significant activity in the assays. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:323–328, 2000