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Palladium-catalyzed alkene difunctionalization reactions between alkenes bearing tethered aryl or alkenyl triflates and enolate nucleophiles are described. The transformations form two C–C bonds, a ring, and up to two stereocenters, while producing substituted cyclopentane derivatives that contain appended carbonyl functionality. Products are formed with up to >20:1 diastereoselectivity, and formation of sterically congested bonds between quaternary carbon atoms is feasible.

The Pd-catalyzed coupling of malonate nucleophiles with alkenes bearing tethered aryl or alkenyl triflates is described. These alkene difunctionalization reactions afford malonate-substituted cyclopentanes that contain fused aryl or cycloalkenyl rings. The transformations generate a five-membered ring, two C-C bonds, and provide products bearing up to three stereocenters with good chemical yield and generally high diastereoselectivity.

The asymmetric synthesis of six-membered cyclic sulfamides via palladium-catalyzed alkene carboamination reactions of N-homo­allylsulfamides with aryl halides is described. High levels of enantio­selectivity were obtained with a catalyst composed of Pd2dba3 and (S)-Siphos-PE.

Intermolecular alkene difunctionalization reactions between terminal alkenes bearing a pendant aryl or alkenyl triflate electrophile and exogenous alcohol or phenol nucleophiles are described. These transformations afford substituted indanyl or alkylidenecyclopentyl ethers in high yield with excellent diastereoselectivity. The transformations proceed through intermolecular capture of an intermediate [Pd(II)-alkene]+[OTf]− complex by the alcohol or phenol nucleophile.

The synthesis of substituted γ- and δ-lactams via palladium-catalyzed alkene carboamination reactions between aryl halides and alkenes bearing pendant amides is described. The substrates for these reactions are generated in 1–3 steps from commercially available materials, and products are obtained in good yield with up to >20:1 diastereoselectivity. The stereochemical outcome of the alkene addition is consistent with a mechanism involving anti-aminopalladation of the alkene.

Over the past few years our group has described a new type of alkene difunctionalization reaction in which aryl or alkenyl triflates bearing tethered alkenes are coupled with various nucleophiles to afford carbocyclic products. The products are formed in moderate to good chemical yield, with generally high levels of stereoselectivity. Our progress to date in this area, which includes reactions of amine, alcohol, enolate, and indole nucleophiles, is described in this review.

The synthesis of bicyclic ureas and sulfamides via palladium-catalyzed alkene carboamination reactions between aryl/alkenyl halides/triflates and alkenes bearing pendant cyclic sulfamides and ureas is described. The substrates for these reactions are generated in 3-5 steps from commercially available materials, and products are obtained in good yield with up to >20:1 diastereoselectivity. The stereochemical outcome of the sulfamide alkene addition is consistent with a mechanism involving anti-aminopalladation of the alkene, whereas the stereochemical outcome of the urea alkene addition is consistent with a syn-aminopalladation mechanism.

The Pd-catalyzed alkene carboheteroarylation of aryl and alkenyl triflate electrophiles bearing pendant alkenes with heteroaromatic nucleophiles affords substituted carbocycles with 3-indolyl or 3-pyrrolyl groups. The products are obtained in moderate to good yields, and the use of alkenyl triflate substrates produces products with high diastereoselectivities. The transformation is believed to proceed via a Friedel-Crafts-like reaction between the heteroaromatic nucleophile and an intermediate electrophilic palladium complex.

Modified reaction conditions that facilitate Pd-catalyzed alkene carboamination reactions of electron-deficient nitrogen nucleophiles are reported. Pent-4-enylamine derivatives bearing N-tosyl or N-trifluoroacetyl groups are coupled with aryl triflates to afford substituted pyrrolidines in good yield. These reactions proceed via a mechanism involving anti-aminopalladation of the alkene, which differs from previously reported analogous reactions of N-aryl and N-boc pentenylamines. The application of these conditions to a formal synthesis of (±)-aphanorphine is also described.

The Pd-catalyzed coupling of γ-hydroxyalkenes with aryl bromides affords enantiomerically enriched 2-(arylmethyl)tetrahydrofuran derivatives in good yield and up to 96:4 e.r. This transformation was achieved through the development of a new TADDOL/2-arylcyclohexanol-derived chiral phosphite ligand. The transformations are effective with an array of different aryl bromides, and can be used for the preparation of products bearing quaternary stereocenters.

Treatment of N-(arylmethyl)-N-aryl glycine methyl ester derivatives with Bu2BOTf and iPr2NEt effects an aza-[1,2]-Wittig rearrangement that provides N-aryl phenylalanine methyl esters in good yields. Analogous substrates bearing N-carbonyl groups are converted to 1,4,2-oxazaborole derivatives under similar conditions.

A catalyst composed of Pd2(dba)3 and (S)-Siphos-PE provides excellent results in Pd-catalyzed alkene carboamination reactions between aniline derivatives bearing pendant alkenes and aryl or alkenyl halides. These transformations generate tetrahydroquinolines and tetrahydroquinoxalines that contain quaternary carbon stereocenters with high levels of asymmetric induction. In addition this catalyst also effects the asymmetric synthesis of tetrahydroisoquinolines via related transformations of 2-allylbenzylamines. In contrast to most other approaches to the asymmetric synthesis of these compounds, which frequently involve functional group interconversion or a single C–C or C–N bond-forming event, the carboamination reactions generate both a C–N bond, a C–C bond, and a stereocenter.

A new approach to the synthesis of substituted 5-membered cyclic guanidines is described. Palladium-catalyzed alkene carboamination reactions between acyclic N-allyl guanidines and aryl or alkenyl halides provide these products in good yield. This method allows access to a number of different cyclic guanidine derivatives in only two steps from readily available allylic amines.

A new Pd-catalyzed alkene carboalkoxylation strategy for the preparation of 2,3-dihydrobenzofurans is described. This method effects the coupling of readily available 2-allylphenol derivatives with aryl triflates to generate a wide range of functionalized 2,3-dihydrobenzofurans in good yields and diastereoselectivities (up to >20:1). Use of newly developed reaction conditions that promote anti-heteropalladation of the alkene is essential in order to generate products in high yield.

The synthesis of cyclic sulfamides by enantioselective Pd-catalyzed alkene carboamination reactions between N-allylsulfamides and aryl or alkenyl bromides is described. High levels of asymmetric induction (up to 95:5 e.r.) are achieved using a catalyst composed of [Pd2 (dba)3 ] and (S)-Siphos-PE. Deuterium-labelling studies indicate the reactions proceed through syn-aminopalladation of the alkene and suggest that the control of syn- versus anti-aminopalladation pathways is important for asymmetric induction.

The synthesis of cyclic sulfamides by enantioselective Pd-catalyzed alkene carboamination reactions between N-allylsulfamides and aryl or alkenyl bromides is described. High levels of asymmetric induction (up to 95:5 e.r.) are achieved using a catalyst composed of [Pd2 (dba)3 ] and (S)-Siphos-PE. Deuterium-labelling studies indicate the reactions proceed through syn-aminopalladation of the alkene and suggest that the control of syn- versus anti-aminopalladation pathways is important for asymmetric induction.

The Pd-catalyzed coupling of γ-hydroxyalkenes with aryl bromides affords enantiomerically enriched 2-(arylmethyl)tetrahydrofuran derivatives in good yield and up to 96:4 e.r. This transformation was achieved through the development of a new TADDOL/2-arylcyclohexanol-derived chiral phosphite ligand. The transformations are effective with an array of different aryl bromides, and can be used for the preparation of products bearing quaternary stereocenters.

Positive water effect: A catalyst composed of [Pd(2)(dba)(3)] (dba=dibenzylideneacetone) and (S)-Siphos-PE is effective for the enantioselective coupling of N-allyl ureas with aryl bromides to afford 4-substituted imidazolidin-2-ones. Added water leads to significantly improved enantioselectivities with electron-poor aryl halide substrates. It is suggested that the C-C bond-forming reductive elimination is the enantiodetermining step in these reactions.

The synthesis of tropane derivatives via intramolecular Pd-catalyzed alkene difunctionalization reactions is described. Enantiopure N-aryl-γ-aminoalkenes bearing an aryl or alkenyl halide adjacent to the amino group were converted to benzo- or cycloalkenyl-fused tropane products in good yield and with no loss of enantiopurity.

Palladium-catalyzed carboamination reactions between aryl bromides and 4-(but-3-enyl)-substituted oxazolidin-2-ones are described. These transformations afford bicyclic oxazolidin-2-one derivatives that can be converted to trans-2,5-disubstituted pyrrolidines in one step. The starting materials are easily prepared from amino acid precursors, and products that contain up to three stereocenters are generated with >20:1 dr.

A four-step synthesis of cis-3,5-disubstituted morpholines from enantiomerically pure amino alcohols is described. The key step in the synthesis is a Pd-catalyzed carboamination reaction between a substituted ethanolamine derivative and an aryl or alkenyl bromide. The morpholine products are generated as single stereoisomers in moderate to good yield. This strategy also provides access to fused bicyclic morpholines as well as 2,3- and 2,5-disubstituted products.

The development of palladium-catalyzed carboetherification andcarboamination reactions between aryl or alkenyl halides and alkenesbearing pendant heteroatoms is described. These transformationseffect the stereoselective construction of useful heterocycles,such as tetrahydrofurans, pyrrolidines, imidazolidin-2-ones, isoxazolidines,and piperazines. The scope, limitations, and applications of thesereactions are presented, and current stereochemical models are described.The mechanism of the product formation, which involves an unusualintramolecular SYN-insertion of an alkene intoa palladium-heteroatom bond, is also discussed in detail. 1 Introduction 2 Palladium-Catalyzed Synthesis of Tetrahydrofurans from γ-Hydroxyalkenesand Aryl or Alkenyl Halides 2.1 Mechanism of the Tetrahydrofuran Formation 3 Palladium-Catalyzed Synthesis of Pyrrolidines from γ-Aminoalkenesand Aryl or Alkenyl Halides 3.1 Tandem Palladium-Catalyzed N-Arylation-CarboaminationReactions of Primary Amines 3.2 Palladium-Catalyzed Carboamination Reactions of N-Protected γ-Aminoalkenes 3.3 Mechanism of the Palladium-Catalyzed Carboamination Reactions:Surprises and Utility 3.4 Application of the Palladium-Catalyzed Carboamination of N-Protected γ-Aminoalkenesto the Stereoselective Synthesis of (+)-Preussin and ItsAnalogues 4 Synthesis of Imidazolidin-2-ones via Palladium-Catalyzed CarboaminationReactions 5 Synthesis of Isoxazolidines via Palladium-Catalyzed CarboetherificationReactions 6 Synthesis of Piperazines via Palladium-Catalyzed CarboaminationReactions 7 Summary and Future Outlook

A method for the synthesis of imidazolidin-2-ones from N-allylureas and aryl or alkenyl bromides via Pd-catalyzed carboamination reactions is described. The N-allylurea precursors are prepared in one step from readily available allylic amines and isocyanates, and the Pd-catalyzed reactions effect the formation of a C-C bond, a C-N bond, and up to two stereocenters in a single step. Good diastereoselectivities are obtained for the conversion of substrates bearing allylic substituents to 4,5-disubstituted imidazolidin-2-ones, and excellent selectivity for the generation of products resulting from syn-addition across the alkene is observed when substrates derived from cyclic alkenes or E-1,2-disubstituted alkenes are employed. A brief discussion of reaction mechanism and product stereochemistry is presented.

[reaction: see text] The palladium-catalyzed carboamination of N-protected gamma-aminoalkenes with aryl bromides and triflates has been achieved under new, mild reaction conditions using the weak base Cs(2)CO(3) in dioxane solvent. These reactions tolerate a wide variety of functional groups, including enolizable ketones, nitro groups, methyl esters, and acetates, which are not compatible with previously described conditions.

Modified reaction conditions that facilitate Pd-catalyzed alkene carboamination reactions of electron-deficient nitrogen nucleophiles are reported. Pent-4-enylamine derivatives bearing N-tosyl or N-trifluoroacetyl groups are coupled with aryl triflates to afford substituted pyrrolidines in good yield. These reactions proceed via a mechanism involving anti-aminopalladation of the alkene, which differs from previously reported analogous reactions of N-aryl and N-boc pentenylamines. The application of these conditions to a formal synthesis of (±)-aphanorphine is also described.

Treatment of N-(arylmethyl)-N-aryl glycine methyl ester derivatives with Bu2BOTf and iPr2NEt effects an aza-[1,2]-Wittig rearrangement that provides N-aryl phenylalanine methyl esters in good yields. Analogous substrates bearing N-carbonyl groups are converted to 1,4,2-oxazaborole derivatives under similar conditions.

New strategy for the construction of 2-aminoimidazoles via the Pd-catalyzed alkyne carboamination of tosyl-protected N-propargyl guanidines and aryl triflates is reported.

A palladium-catalyzed carboamination reaction of γ-N-arylamino alkenes with vinyl bromides that affords N-aryl-2-allyl pyrrolidines is described. These reactions proceed with high diastereoselectivity for the formation of trans-2,3- and cis-2,5-disubstituted pyrrolidines. Conditions for a tandem N-arylation/carboamination sequence that leads to the formation of an N-aryl-2-allyl pyrrolidine or indoline via the coupling of a primary γ-amino alkene, an aryl bromide, and a vinyl bromide are also reported. The mechanism of the carboamination reactions and the origin of unexpected products that formally derive from rearrangement of the vinyl bromide are discussed.

The stereoselective synthesis of N-acyl- and N-Boc-protected pyrrolidines via Pd-catalyzed reactions of γ-(N-acylamino) alkenes and γ-(N-Boc-amino) alkenes with aryl bromides is described. These reactions effect formation of two bonds in a single operation and proceed with generally high levels of diastereoselectivity. In contrast to previously described reactions of γ-(N-arylamino) alkenes, these transformations proceed in high yield and high regioselectivity with both electron-rich and electron-deficient aryl bromides as well as vinyl bromide substrates.

Cyclic sulfamides are obtained by Pd-catalyzed coupling of N-allylsulfamides with aryl and alkenyl triflates.

A new annulation strategy for the synthesis of trans-bicyclic sulfamides is described. The Pd-catalyzed alkene carboamination reactions of 2-allyl and cis-2,5-diallyl pyrrolidinyl sulfamides with aryl and alkenyl triflates afford the fused bicyclic compounds in good yields and with good diastereoselectivity (up to 13:1 dr). Importantly, by employing reaction conditions that favor an anti-aminopalladation mechanism, the relative stereochemistry between the C3 and C4a stereocenters of the products is reversed relative to related Pd-catalyzed carboamination reactions that proceed via syn-aminopalladation.

The Pd-catalyzed coupling of N-allylsulfamides with aryl and alkenyl triflates to afford cyclic sulfamide products is described. In contrast to other known Pd-catalyzed alkene carboamination reactions, these transformations may be selectively induced to occur by way of either anti- or syn-aminopalladation mechanistic pathways by modifying the catalyst structure and reaction conditions.

The enantioselective synthesis of 2-(arylmethyl)- and 2-(alkenylmethyl)pyrrolidine derivatives via Pd-catalyzed alkene carboamination reactions is described. These transformations generate enantiomerically enriched products with up to 94% ee from readily available alkenyl or aryl bromides and N-boc-pent-4-enylamines. The application of this method to a concise asymmetric synthesis of (−)-tylophorine is also discussed.

Mixtures of Pd(2)(dba)(3) or Pd(OAc)(2) and BINAP catalyze the cross-coupling of amines with a variety of aryl bromides. Primary amines are arylated in high yield, and certain classes of secondary amines are also effectively transformed. The process tolerates the presence of several functional groups including methyl and ethyl esters, enolizable ketones, and nitro groups provided that cesium carbonate is employed as the base. Most reactions proceed to completion with 0.5-1.0 mol % of the palladium catalyst; in some cases, catalyst levels as low as 0.05 mol % Pd may be employed. Reactions are considerably faster if Pd(OAc)(2) is employed as the precatalyst, and the order in which reagents are added to the reaction has a substantial effect on reaction rate. It is likely that the catalytic process proceeds via bis(phosphine)palladium complexes as intermediates. These complexes are less prone to undergo undesirable side reactions which lead to diminished yields or catalyst deactivation than complexes of the corresponding monodentate triarylphosphines.

Mixtures of palladium acetate and o-(di-tert-butylphosphino)biphenyl (4) catalyze the room-temperature Suzuki coupling of aryl bromides and aryl chlorides with 0.5−1.0 mol % Pd. Use of o-(dicyclohexylphosphino)biphenyl (2) allows Suzuki couplings to be carried out at low catalyst loadings (0.000001−0.02 mol % Pd). The process tolerates a broad range of functional groups and substrate combinations including the use of sterically hindered substrates. This is the most active catalyst system in terms of reaction temperature, turnover number, and steric tolerance which has been reported to date.

A unique combination of steric and electronic properties appears to determine the effectiveness of phosphanyl-substituted biphenyls as ligands in palladium-catalyzed aminations and Suzuki coupling of aryl chlorides at room temperature [Eq. (1)]. The oxidative addition step is greatly accelerated, and transmetalation (or Pd-N bond formation) and reductive elimination processes are facilitated. Use of these ligands allows for Suzuki coupling at very low catalyst loadings (as little as 10(-6) mol % Pd). R"=cyclohexyl, tert-butyl.

A general method for the palladium-catalyzed formation of diaryl ethers is described. Electron-rich, bulky aryldialkylphosphine ligands, in which the two alkyl groups are either tert-butyl or 1-adamantyl, are the key to the success of the transformation. A wide range of electron-deficient, electronically neutral and electron-rich aryl bromides, chlorides, and triflates can be combined with a variety of phenols with the use of sodium hydride or potassium phosphate as base in toluene at 100 °C. The bulky yet basic nature of the phosphine ligand is thought to be responsible for increasing the rate of reductive elimination of the diaryl ether from palladium.

Isoxazolidines are frequently used as intermediates in the synthesis of complex molecules,[1] and are found in several interesting biologically active compounds.[2] In addition, the isoxazolidine N-O bond can be easily cleaved under reducing conditions to afford 1,3-amino alcohols, which are also of synthetic utility.[3] The most commonly employed method for the construction of isoxazolidines involves 1,3-dipolar cycloaddition reactions between nitrones and alkenes,[4] which generates the O1-C5 bond and the C3-C4 bond in one step [Eq. (1)]. Although these transformations are very useful, many intermolecular cycloadditions of unactivated alkenes generate mixtures of regioisomers.[4] Moreover, the major stereoisomers typically result from endo-addition on the less hindered face of the alkene, and the selective preparation of stereoisomers resulting from exo-addition and/or addition to the more substituted alkene face cannot be achieved in a straightforward manner.[4] In this communication, we describe a new approach to the construction of substituted isoxazolidines that involves palladium-catalyzed carboetherification reactions of N-butenyl hydroxylamine derivatives with aryl bromides [Eq. (2)]. This method represents a new strategy for construction of the isoxazolidine ring, in which the O1-C5 bond and a C5′-Ar bond are formed in one step.[5] These transformations also provide access to isoxazolidine stereoisomers that cannot be generated with currently available methods. The reactions appear to proceed via intramolecular alkene insertion into previously unprecedented palladium alkoxyamine intermediates, which may be of utility in other Pd-catalyzed carbon-heteroatom bond-forming processes. (1) (2) In preliminary experiments, we examined Pd-catalyzed reactions of N-butenyl hydroxylamines 1-3 with 4-bromobiphenyl using conditions that were employed in our prior studies on Pd-catalyzed carboetherification reactions of γ-hydroxyalkenes.[6-8] As shown below (Table 1), attempts to cyclize unprotected hydroxylamine substrate 1 or N-boc-protected derivative 2 were unsuccessful.[9] However, we were gratified to find that treatment of N-benzyl-protected substrate 3 with 4-bromobiphenyl and NaOtBu in the presence of catalytic amounts of Pd(OAc)2 and DPE-Phos[10] afforded the desired product 4 in 80% isolated yield. Table 1 Carboetherification of N-butenyl hydroxylamines[a] With viable reaction conditions and a suitable nitrogen protecting group identified, we examined Pd-catalyzed carboetherification reactions between several different substituted hydroxylamines and a number of aryl bromides. As shown in Table 2, this method is effective with electron-rich (entry 10), electron-neutral (entries 4, 7, 8, and 12), electron-poor (entries 1, 2, 11, and 13), o-substituted (entry 8), and heterocyclic (entries 3, 5, 6, and 9) aryl bromides. In addition to the N-benzyl protected derivatives described above, hydroxylamine substrates bearing N-methyl or N-tert-butyl groups also undergo cyclization in good yield. Table 2 Pd-catalyzed synthesis of substituted isoxazolidines[a] The carboetherification reactions are also effective with substrates bearing substituents along the tether between the hydroxylamine moiety and the alkene. Transformations of these substrates provide access to disubstituted isoxazolidines with moderate to excellent stereocontrol. Importantly, in many cases these cyclizations provide a means to generate isoxazolidines that could not be prepared using 1,3-dipolar cycloaddition methods. For example, Pd-catalyzed reactions of 10 with 4-bromobiphenyl or 3-bromobenzotrifluoride provide 22 and 23 in 78% and 69% isolated yields, with >20:1 diastereoselectivity and regioselectivity (Table 2, entries 12-13). In contrast, a 1,3-dipolar cycloaddition reaction between a nitrone and a 3-arylcyclopentene would be expected to occur on the less hindered face of the alkene to afford a different stereoisomer, and would likely generate mixtures of regioisomers.[4] In addition, reactions of 8 with aryl bromides proceed in 82-85% yield and 10:1 dr to afford the 2R*,3aS*-hexahydropyrrolo[1,2b]isoxazole isomers 18-19 (entries 8-9). However, dipolar cycloadditions between 3,4-dihydropyrrole-1-oxide and allylbenzene derivatives instead generate stereoisomeric 2S*,3aS*-hexahydropyrrolo[1,2b]isoxazoles.[11] The hydroxylamine carboetherifications can also be used to prepare trans-4,5-disubstitued isoxazolidines 12-14 and cis-3,5-disubstituted isoxazolidines 15-17 in good yield with 3-5:1 diastereoselectivity. A plausible mechanism for the isoxazolidine-forming reactions is shown in Scheme 1. These transformations appear to be mechanistically related to Pd-catalyzed carboetherification reactions of γ-hydroxy alkenes with aryl bromides,[6] and are likely initiated by oxidative addition of the aryl bromide to Pd(0) to afford 24. The LnPd(Ar)(Br) complex can then be transformed to intermediate 25 via reaction with the hydroxylamine substrate and NaOtBu. Intramolecular syn-oxypalladation[6,12] of the tethered alkene moiety of 25 would generate 26, which can undergo C-C bond-forming reductive elimination[13] to afford the observed isoxazolidine products. The conversion of 10 to syn-addition products 22 and 23 is consistent with this hypothesis. Moreover, this model also accounts for the observed stereochemistry of 12-21, as the syn-oxypalladation likely occurs from an organized cyclic transition state in which nonbonding interactions are minimized by pseudoequatorial orientation of the substrate R1 and R2 groups. This transition state arrangement would provide cis-3,5-disubstituted products (R2 = H) and trans-4,5-disubstituted compounds (R1 = H). Although palladium(aryl)alkoxides have been shown to be important intermediates in a number of catalytic processes,[6,14-15] the analogous complexes derived from hydroxylamines (e.g. 25) are unknown. The reactions described in this paper represent the first examples of catalytic transformations involving Pd(Ar)(ONRR’) species. These previously unknown intermediates will likely find additional applications in other metal-catalyzed carbon-heteroatom bond-forming reactions.[15] In conclusion, we have developed a new stereoselective method for the construction of substituted isoxazolidines via Pd-catalyzed carboetherification reactions of unsaturated hydroxylamine substrates. In many cases the stereochemical outcome of these transformations is complementary to nitrone cycloadditions, and this method provides a new strategic disconnection that can be used for retrosynthetic analysis of substituted isoxazolidines.

A new Pd-catalyzed reaction for the stereoselective synthesis of cyclopentane-fused benzocyclobutenes is described. These transformations likely proceed via carbamate-directed carbopalladation followed by intramolecular C-H activation of an alkylpalladium intermediate. The mechanistic relationship between these transformations and Pd-catalyzed reactions of gamma-(n-Boc-amino)alkenes with aryl bromides that afford pyrrolidines is discussed. Differences in reactivity between Pd-amino and Pd-amido complexes appear to play a key role in the outcome of these transformations.

Aryl bromides are coupled with amines in the presence of a palladium catalyst and a stoichiometric amount of cesium carbonate. Using these conditions base-sensitive functional groups, which were incompatible with our previously reported catalytic-amination reaction conditions, are well tolerated. © 1997 Elsevier Science Ltd.

Commercially available benzophenone imine serves as a convenient ammonia equivalent in the palladium-catalyzed amination of aryl halides and triflates. The benzophenone imine adducts can be cleaved directly to the corresponding primary anilines by catalytic hydrogenation or treatment with hydroxylamine hydrochloride or a catalytic amount of HCl in wet THF. © 1997 Elsevier Science Ltd.

Aryl chlorides are converted to aniline derivatives using catalytic amounts of Ni(COD)2 (COD = 1,5-cyclooctadiene) and DPPF (DPPF = 1,1‘-bis(diphenylphosphino)ferrocene) or 1,10-phenanthroline in the presence of sodium tert-butoxide. This procedure has a broad substrate scope: electron-rich or electron-poor aryl chlorides, as well as chloropyridine derivatives, can be combined with primary and secondary amines to give the desired aryl amine products in moderate to excellent yields. Additionally, a procedure which utilizes the air-stable precatalysts (DPPF)NiCl2 or (1,10-phenanthroline)NiCl2 is also described.

The conversion of aryl triflates to the corresponding aniline derivatives was accomplished in moderate to good yield using a catalyst consisting of the combination of palladium acetate (2 mol %) and either BINAP or Tol-BINAP. In contrast to the corresponding palladium-catalyzed amination of aryl bromides and iodides, electronically neutral aryl triflates gave higher yields of arylamines than did electron deficient aryl triflates, presumably due to the increased rate of base-promoted triflate cleavage in electron deficient substrates.

Substrate electron effects and additives greatly affect the levels of asymmetric induction in the reactions of N-allyl urea substrates with aryl bromides.

Upon treatment with a palladium catalyst and a suitable base, aromatic halides undergo intramolecular substitution to form five, six, and seven-membered rings. In a similar fashion aryl halides with pendant amides or sulfonamides are cyclized to form five and six-membered rings.

This short review describes new developments in Pd-catalyzed aminoarylation reactions between aryl halides and alkenes bearing pendant nitrogen nucleophiles. These transformations provide a novel and powerful method for accessing numerous 3-, 5-, 6-, and 7-membered nitrogen heterocycles.

A new method for the construction of 2-substituted and 2,2-disubstituted chromans viaPd-catalyzed carboetherification reactions between aryl/alkenyl halides and 2-(but-3-en-1-yl)phenols is described. These reactions effect formation of a C–O bond and a C–C bond to afford the chroman products in good yield, and also provide stereoselective access to tricyclic chroman derivatives.

A new method for the construction of 2-substituted and 2,2-disubstituted chromans via Pd-catalyzed carboetherification reactions between aryl/alkenyl halides and 2-(but-3-en-1-yl)phenols is described. These reactions effect formation of a C-O bond and a C-C bond to afford the chroman products in good yield, and also provide stereoselective access to tricyclic chroman derivatives.

A new method for the stereoselective synthesis of tetrahydropyrroloindoles and hexahydropyrroloquinolines of general structure 8 is described. These products are formed through cascade Pd-catalyzed coupling reactions between aryl chlorides and unsaturated amine substrates 5. A single catalyst effects an intramolecular N-arylation reaction followed by an intermolecular alkene carboamination reaction to generate two rings, three bonds, and one stereocenter with good chemoselectivity, diastereoselectivity, and chemical yield.