Palladium-catalyzed electrophilic allylation reactions via bis(allyl)palladium complexes and related intermediates

The synthetic scope of the allyl-palladium chemistry can be extended to involve electrophilic reagents. The greatest challenge in these reactions is the catalytic generation of an allyl-palladium intermediate incorporating a nucleophilic allyl moiety. A vast majority of the published reactions that involve palladium-catalyzed allylation of electrophiles proceed via bis(allyl)palladium intermediates. The eta(1)-moiety of the bis(allyl)palladium intermediates reacts with electrophiles, including aldehydes, imines, or Michael acceptors. Recently, catalytic electrophilic allylations via mono-allylpalladium complexes were also presented by employment of so-called "pincer complex" catalysts.     

Palladium-pincer complex catalyzed C-C coupling of allyl nitriles with tosyl imines via regioselective allylic C-H bond functionalization

A mechanistically new palladium-pincer complex catalyzed allylation of sulfonimines is presented. This reaction involves C-H bond functionalization of allyl nitriles under mild conditions. The reaction proceeds with a high regioselectivity, without allyl rearrangement of the product. Modeling studies indicate that the carbon-carbon bond formation process proceeds via (eta (1)-allyl)palladium pincer complex intermediates.     

Direct synthesis of B-allyl and B-allenyldiisopinocampheylborane reagents using allyl or propargyl halides and indium metal under Barbier-type conditions

We report the first one-pot process for the asymmetric addition of allyl, methallyl, and propargyl groups to aldehydes and ketones using B-chlorodiisopinocampheylborane ((d)DIP-Cl) and indium metal. Under Barbier-type conditions, indium metal was used to generate allyl- and allenylindium intermediates, and subsequent reaction with (d)DIP-Cl successfully promoted the transfer of these groups to boron forming the corresponding chiral borane reagents. The newly formed borane reagents were reacted with aldehydes and ketones to produce the corresponding alcohol products in high yields and up to excellent enantioselectivity (98% ee). This method produced excellent enantioenriched secondary homoallylic alcohols from the allylation and methallylation of benzaldehyde. Using this method, the methallylation and cinnamylation of ketones afforded the highest enantioselectivities, while the propargylation of both aldehydes and ketones provided low enantiomeric excesses. In addition, this procedure provided the first synthesis of B-allenyldiisopinocampheylborane, which was characterized by (1)H and (11)B NMR spectroscopy. This is the first example of the direct synthesis of allylboranes that contained substitutions from the corresponding allyl bromide and indium, thereby expanding the utility of the DIP-Cl reagent. Hence, a general and straightforward route to these chiral organoborane reagents in one-pot has been developed along with the asymmetric Barbier-type allylation and propargylation of aldehyde and ketone substrates using these chiral organoborane reagents in subsequent coupling reactions.     

Symmetrical and unsymmetrical pincer complexes with group 10 metals: synthesis via aryl C-H activation and some catalytic applications

Aryl-based pincer metal complexes with anionic terdentate ligands have been widely applied in organic synthesis, organometallic catalysis and other related areas. Synthetically, the most simple and convenient method for the construction of these complexes is the direct metal-induced C(aryl)-H bond activation, which can be fulfilled by choosing the appropriate functional donor groups in the two side arms of the aryl-based pincer preligands. In this perspective, we wish to summarize some results achieved by our group in this context. Successful examples include symmetrical chiral bis(imidazoline) NCN pincer complexes with Ni(II), Pd(II) and Pt(II), bis(phosphinite) and bis(phosphoramidite) PCP pincer Pd(II) complexes, unsymmetrical (pyrazolyl)phosphinite, (amino)phosphinite and (imino)phosphinite PCN pincer Pd(II) complexes, chiral (imidazolinyl)phosphinite and (imidazolinyl)phosphoramidite PCN pincer complexes with Ni(II) and Pd(II) as well as unsymmetrical (oxazolinyl)amine and (oxazolinyl)pyrazole NCN' pincer Pd(II) complexes. Among them, the P-donor containing complexes are efficiently synthesized by the "one-pot phosphorylation/metalation" method. The obtained symmetrical and unsymmetrical pincer complexes have been used as catalysts in Suzuki-Miyaura reaction (Pd), asymmetric Friedel-Crafts alkylation of indole with trans-β-nitrostyrene (Pt) as well as in asymmetric allylation of aldehyde and sulfonimine (Pd). In the Suzuki couplings conducted at 40-50 °C, some unsymmetrical Pd complexes exhibit much higher activity than the related symmetrical ones which can be attributed to their faster release of active Pd(0) species resulting from the hemilabile coordination of the ligands. Literature results on the synthesis of some related pincer complexes as well as their activities in the above catalytic reactions are also presented.     

Pincer complex-catalyzed allylation of aldehyde and imine substrates via nucleophilic eta1-allyl palladium intermediates

Electrophilic allylic substitution of allylstannanes with aldehyde and imine substrates could be achieved by employment of palladium pincer complex catalysts. It was found that the catalytic activity of the pincer complexes is highly dependent on the ligand effects. The best results were obtained by employment of PCP pincer complexes with weakly coordinating counterions. In contrast to previous applications for electrophilic allylic substitutions via bisallylpalladium complexes, the presented reactions involve monoallylpalladium intermediates. Thus, employment of pincer complex catalysts extends the synthetic scope of the palladium-catalyzed allylic substitution reactions. Moreover, use of these catalysts eliminates the side reactions occurring in transformations via bisallylpalladium intermediates. The key intermediate of the electrophilic substitution reaction was observed by (1)H NMR spectroscopy. This intermediate was characterized as an eta(1)-allyl-coordinated pincer complex. Density functional theory (DFT) modeling shows that the electrophilic attack can be accomplished with a low activation barrier at the gamma-position of the eta(1)-allyl moiety. According to the DFT calculations, this reaction takes place via a six-membered cyclic transition-state (TS) structure, in which the tridentate coordination state of the pincer ligand is preserved. The stereoselectivity of the reaction could be explained on the basis of the six-membered cyclic TS model.     

Stereocontrolled palladium-catalysed umpolung allylation of aldehydes with allyl acetates

In the present work the stereocontrolled palladium-catalysed umpolung allylation of aldehydes is described. Allyl acetates are in situ transformed into the corresponding allyl boronates, which directly react with aldehydes. The question of stereocontrol is raised by employing (a) chiral boronating agents (reagent control) and by (b) utilising chiral aldehydes (substrate control). These studies reveal that the approach based on substrate control is superior to the former one with respect to yields and stereoselectivity. Remarkably, this umpolung protocol often yields the 4,5-syn products in high selectivity, which is unprecedented for direct crotylations.     

Scope of the allylation reaction with [RuCp(PP)]+ catalysts: changing the nucleophile or allylic alcohol

The scope of the dehydrative allylation reaction using allyl alcohol as allyl donor with [RuCp(PP)]⁺ complexes as catalysts is explored. Aliphatic alcohols are successfully allylated with allyl alcohol or diallyl ether, obtaining high selectivity for the alkyl allyl ether. The reactivity of aliphatic alcohols is in the order of primary > secondary ? tertiary. The tertiary alcohol 1‐adamantanol reacts extremely slowly in the absence of strong acid, but when HOTs is added, reasonable yields of 1‐adamantyl allyl ether are obtained. The alkyl allyl ether is found to be the thermodynamically favored product over diallyl ether. Apart from alcohols, thiols and indole are also efficiently allylated, while aniline acts as a catalyst inhibitor. Allylation reactions with various substituted allylic alcohols give products with retention of the substitution pattern. It is proposed that a Ru(IV) σ‐allyl species plays a key role in the mechanism of these allylation reactions. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis, structure and catalytic properties of CNN pincer palladium(II) and ruthenium(II) complexes with N-substituted-2-aminomethyl-6-phenylpyridines

N-substituted-2-aminomethyl-6-phenylpyridines 2a-c have been easily prepared from commercially available 6-bromo-2-picolinaldehyde in two steps. Reaction of 2a-c with PdCl(2) in toluene in the presence of triethylamine gave the CNN pincer Pd(II) complexes 3a-c in 18-28% yields. The CNN pincer Ru(II) complex 5 containing a Ru-NHR functionality could be obtained in a 71% yield by treatment of 2c with a Ru(II) precursor instead of PdCl(2). Additionally, the related CNN pincer Ru(II) complex 7 containing a Ru-NH(2) functionality has been synthesized by the reaction of 2-aminomethyl-6-phenylpyridine with the same Ru(II) precursor in a 68% yield. All the new compounds were characterized by elemental analysis (MS for ligands), (1)H, (13)C NMR, (31)P{(1)H} NMR (for Ru complexes) and IR spectra. Molecular structures of Pd complex 3c as well as Ru complexes 5 and 7 have been determined by X-ray single-crystal diffraction. The obtained Pd complexes 3a-c were effective catalysts for the allylation of aldehydes as well as for three-component allylation of aldehydes, arylamines and allyltributyltin and their activity was found to be much higher than a related NCN Pd(II) pincer in the allylation of aldehyde. On the other hand, the two new CNN pincer Ru(II) complexes 5 and 7 displayed excellent catalytic activity in the transfer hydrogenation of ketones in refluxing 2-propanol with the latter being much more active. The final TOF values were up to 4510 h(-1) with 0.01 mol% of 5 and 220,800 h(-1) with 0.005 mol% of 7, respectively.     

Structurally simple pyridine N-oxides as efficient organocatalysts for the enantioselective allylation of aromatic aldehydes

A series of structurally simple pyridine N-oxides have readily been assembled from inexpensive amino acids and tested as organocatalysts in the allylation of aldehydes with allyl(trichloro)silane to afford homoallylic alcohols. (S)-proline-based catalysts afforded the products derived from aromatic aldehydes in fair to good yields and in up to 84% enantiomeric excess (ee). The allylation of heteroaromatic, unsaturated, and aliphatic aldehydes was less satisfactory. By running the reaction in the presence of achiral and chiral additives and structurally different catalysts, we collected some insights into the relationship between the stereochemical outcome and the catalyst's structural features. Even if the ee's obtained are inferior to the best values observed with other catalysts, this work concurs to show that structurally simple pyridine N-oxides can also promote the allylation reaction with satisfactory stereocontrol.     

Catalytic performance of symmetrical and unsymmetrical sulfur-containing pincer complexes: synthesis and tandem catalytic activity of the first PCS-pincer palladium complex

The synthesis and catalytic applications of a new aryl-based unsymmetrical PCS-pincer complex are reported. Preparation of the robust air- and moisture-stable PCS-pincer palladium complex 5[X] started from the symmetrical alpha,alpha'-dibromo-meta-xylene and involved the selective substitution of one bromide by PPh(2)(BH(3)), followed by substitution of the second bromide by SPh and subsequent introduction of the palladium. The new PCS complexes (5[X]) were employed as catalysts in two important organic transformations. Firstly, complex 5[Cl] displays high catalytic activity in aldol reactions but enters the catalytic cycle as a precatalyst. Secondly, complex 5[BF(4)] displays tandem catalytic activity in the coupling of allyl chlorides with aldehydes and imines in the presence of hexamethylditin. In these tandem catalytic reactions the first process is the conversion of allyl chlorides into trimethylallyltin (and trimethyltin chloride) with Sn(2)Me(6), which is followed by catalytic allylation of aldehyde and sulfonimine substrates. In addition, we present a new catalytic process for the one-pot allylation of 4-nitrobenzaldehyde with vinyloxirane. The catalytic performance of the novel PCS-pincer palladium complex was compared to those of its symmetrical PCP- and SCS-pincer complex analogues. It was concluded that the unsymmetrical PCS complex advantageously unifies the attractive catalytic features of the corresponding symmetrical pincer complexes including both (pi-) electron-withdrawing (such as phosphorus) or (sigma-) electron-donating (such as sulfur and nitrogen) heteroatoms. Thus, in the aldol reaction the PCS-pincer palladium complex 5[X] provides a high turnover frequency, while in the tandem process both reactions are catalysed with sufficiently high activity.     

Tuning ligand structure in chiral bis(phosphite) and mixed phosphite-phosphinite PCP-palladium pincer complexes

A range of chiral resorcinol bis(phosphite) and phosphite-phosphinite ligands were produced and their propensity to form palladium PCP-pincer complexes examined. The ease of base-assisted C-H palladation of the ligands falls in the order bis(phosphinite) > phosphite-phosphinite > bis(phosphite). The catalytic activity of the complexes in the asymmetric allylation of benzaldehyde with allyl tributyltin was examined and it was found that, contrary to expectations, ligands with 3,3'-disubstituted BINOL residues show poorer activity and stereoselectivity than unsubstituted BINOL analogues. In addition the order of activity of the pincer complexes was established as bis(phosphite) > phosphite-phosphinite > bis(phosphinite). Crystal structures of representative examples of a 3,3'-disubstituted BINOL, mono- and bis(phosphite) ligands based on 2,4-di-tert-butyl resorcinol and Pd complexes of two of the chiral complexes are presented.     

Enantiomeric separation of glycidyl tosylate by CE: Application to the study of catalytic asymmetric epoxidation of allyl alcohol

A CE method using CDs as chiral selectors was developed and validated to achieve the separation of glycidyl tosylate enantiomers originated by in situ derivatization of glycidol enantiomers obtained in asymmetric epoxidation of allyl alcohol with chiral titanium‐tartrate complexes as catalysts. The effects of the nature, pH and concentration of the buffer, the nature and concentration of chiral selector, the addition of SDS, methanol, ethanol or 2‐propanol, the capillary temperature, the effective capillary length and the applied voltage on the chiral resolution of glycidyl tosylate enantiomers were investigated. The best separation conditions were achieved using a Tris‐borate buffer mixture (50 and 25 mM, respectively) at pH=9.3 with a dual CD system consisting of 2.5% succinyl‐β‐CD and 1.0% β‐CD w/v at 15°C. A baseline separation (resolution～2.0) of the glycidyl tosylate enantiomers was obtained in a relatively short time (less than 12 min). Satisfactory results were obtained in terms of linearity (r>0.99) and intermediate precision (RSD below 8.5%). The LOD and LOQ were 3.0 and 10.0 mg/L, respectively, and the recoveries ranged from 99.8 to 108.8%. Finally, the method was applied to the determination of the enantiomeric excess and the yield obtained in the asymmetric epoxidation of allyl alcohol employing chiral titanium‐tartrate complexes as catalysts after an in situ derivatization of glycidol enantiomers to glycidyl tosylate.     

Intramolecular allyl transfer reaction from allyl ether to aldehyde groups: experimental and theoretical studies

The intramolecular transfer of the allyl group of functionalized allyl aryl ethers to an aldehyde group in the presence of Ni0 complexes was studied from chemical, electrochemical and theoretical points of view. The chemical reaction involves the addition of Ni0 to the allyl ether followed by stoichiometric allylation. The electrochemical process is catalytic in nickel and involves the reduction of intermediate eta3-allylnickel(II) complexes.     

Catalytic asymmetric allylation of aldehydes and related reactions with bis(((S)-binaphthoxy)(isopropoxy)titanium) oxide as a mu-oxo-type chiral Lewis acid

A new, chiral bis-Ti(IV) oxide of type 3 has been designed and can be utilized for strong activation of aldehyde carbonyls, thereby allowing a new catalytic enantioselective allylation of aldehydes with allyltributyltin. The chiral bis-Ti(IV) catalyst (S,S)-3 can be readily prepared either by treatment of bis(triisopropoxy)titanium oxide with (S)-BINOL or by treatment of ((S)-binaphthoxy)isopropoxytitanium chloride with silver(I) oxide. Treatment of hydrocinnamaldehyde with allyltributyltin under the influence of chiral bis-Ti(IV) oxide (S,S)-3 generated in situ (10 mol %) in CH(2)Cl(2) afforded an allylation product in 84 % yield and with 99 % ee. This asymmetric allylation with non-racemic bis-Ti(IV) oxide 3 and partially resolved (S)-BINOL shows a positive nonlinear effect in correlation of the enantiopurity of the allylation product with the ee of the (S)-BINOL. Chiral bis-Ti(IV) oxide (S,S)-3 can also be utilized for related reactions such as asymmetric methallylation and propargylation of aldehydes with high enantioselectivity. This asymmetric approach provides a very useful way of obtaining high reactivity and selectivity through the simple introduction of the M-O-M unit into the design of chiral Lewis acid catalysts.     

Selectivity in reactions of allyl diazoacetates as a function of catalyst and ring size from gamma-lactones to macrocyclic lactones

Catalytic reactions of diazoacetates tethered through zero, one, two, and three ethylene glycol units to an allyl group have been investigated for chemoselectivity, diastereoselectivity, and enantioselectivity. Results from cyclopropanation, carbon-hydrogen insertion, and oxonium ylide generation are compared from reactions of achiral and chiral catalysts of copper(I) and dirhodium(II) carboxylates and carboxamidates. Relative to results from intermolecular reactions of ethyl diazoacetate with allyl ethyl ether, intermolecular reactions show a diversity of selectivities including preference for the opposite configurational arrangement from the one preferred in corresponding intermolecular cyclopropanation reactions. Enantioselectivities for cyclopropanation are dependent on the catalyst ligands in a manner that reflects divergent trajectories of the carbon-carbon double bond to the reacting carbene center. Enantioselectivity increases as a function of ring size with chiral copper catalysts, but the reverse occurs with chiral dirhodium(II) carboxamidates. Mechanistic implications, including those related to the conformation of the reacting metal carbene, offer a new dimension to understanding of enantioselectivity in catalytic asymmetric cyclopropanation reactions.     

Enantioselective allylation of aldehydes with chiral allyl organolanthanide reagents

The first example of enantioselective allylation of aldehydes with chiral allyl organolan-thanide reagents has been achieved in high chemical yield and moderate optical purity (up to 54% e.e.).     

Iridium‐Catalyzed Allylic Substitutions with Cyclometalated Phosphoramidite Complexes Bearing a Dibenzocyclooctatetraene Ligand: Preparation of (π‐Allyl)Ir Complexes and Computational and NMR Spectroscopic Studies

(π‐Allyl)Ir complexes derived from dibenzocyclooctatetraene and phosphoramidites by cyclometalation are effective catalysts for allylic substitution reactions of linear monosubstituted allylic carbonates. These catalysts provide exceptionally high degrees of regioselectivity and allow the reactions to be run under aerobic conditions. A series of (π‐allyl)Ir complexes were prepared and characterized by X‐ray crystal structure analyses. An allylic amination with aniline displayed different resting states depending on the presence of a strong base. DFT calculations were carried out on the mechanistic aspects of these reactions. The results suggest that for the (π‐allyl)Ir complexes, the formation and reactions with nucleophiles proceed with comparable rates.     

Chiral palladium bis(phosphite)PCP-pincer complexes via ligand C-H activation

The synthesis of a range of chiral palladium bis(phosphite) pincer complexes has been achieved via C-H activation of the parent ligands and one of the complexes formed shows good activity in the catalytic allylation of aldehydes.     

Stereoselective Pincer-complex catalyzed C-H functionalization of benzyl nitriles under mild conditions. An efficient route to beta-aminonitriles

An efficient palladium pincer-complex catalyzed reaction has been developed for alpha-C-H bond functionalization of benzyl nitriles. The studied coupling reaction with sulfonylimines affords beta-aminonitriles with usually high levels of stereoselectivity. The stereoselectivity of the process is highly dependent on the electronic effects of the ortho substituents of the benzyl moiety. Promising levels of enantiomeric excess are obtained using chiral pincer complexes as catalysts.     

Indium-mediated allylation of aldehydes, ketones and sulfonimines with 2-(alkoxy)allyl bromides

2-(Alkoxy)propenyl bromides are readily prepared from 1,3-dibromo-2-propanol in a two-step sequence involving hydroxyl protection and sodium hydride-induced dehydrobromination. Indium-mediated allylation of aldehydes, ketones, and sulfonimines with 2-(alkoxy)propenyl bromides furnishes the corresponding homoallylic alcohols and sulfonamines in good yields. The products can be easily transformed into β-hydroxy ketones and esters, as well as substituted dihydropyrans, and protected β-amino acids. Chiral 2-(alkoxy)propenyl halides, derived from (−)-menthol and d-glucal, furnish diastereomerically enriched products.