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Palladium-catalyzed hydroalkylation of allylic amine derivatives by alkylzinc reagents is reported. This reductive cross-coupling reaction yields anti-Markovnikov products using a variety of allylic amine protecting groups. Preliminary mechanistic studies suggest that a reversible β-hydride elimination/hydride insertion process furnishes the primary Pd-alkyl intermediate, which then undergoes transmetalation followed by reductive elimination to form a new sp(3)-sp(3) carbon-carbon bond.

Simple, mild, and efficient conditions are reported for a Pd(0)-catalyzed Heck reaction that delivers high yields and selectivity for (E)-styrenyl products using electronically nonbiased olefin substrates bearing a range of useful functionality. Preliminary mechanistic studies demonstrate that the σ-donating DMA solvent is crucial for high selectivity. Further studies suggest that the catalyst distinguishes between β-hydrogens on the basis of their relative hydridic character, in contrast to previously reported Pd(II)-catalyzed oxidative reaction conditions.

A three-component coupling of vinyl triflates and boronic acids to alkenes catalyzed by palladium is reported. Using 1,3-dienes, selective 1,2-alkene difunction-alization is observed, whereas the use of terminal alkenes results in 1,1-alkene difunctionalization. The reaction outcome is attributed to the formation of stabilized, cationic Pd-π-allyl intermediates to regulate β-hydride elimination.

Allylic amines are selectively oxidized to methyl ketones in the presence of tBuOOH and the [2-(oxazolin-2-yl)quinoline]palladium catalyst.

The oxidative Heck reaction proceeds with high (E)-selectivity under mild conditions without the need of any bases or high temperatures.

High selectivity, that has steric origin, is observed for the 1,2-addition products and is shown to have a steric origin.

An overview of oxidative reactions promoted by N-heterocyclic carbene (NHC) metal complexes is presented. Rather than attempting to provide a comprehensive review, key systems and recent developments are laid out, with special attention given to mechanistic aspects. Specifically, O2 activation by metal carbene complexes is covered, followed by alcohol oxidation, Wacker-type reactions and oxidative cleavage of alkenes, and alkane as well as arene oxidations proceeding via C–H activation.

The mechanism of an enantioselective palladium-catalyzed alkene difunctionalization reaction has been investigated. Kinetic analysis provides evidence of turnover-limiting attack of a proposed quinone methide intermediate with MeOH and suggests that copper is involved in productive product formation, not just catalyst turnover. Through examination of substrate electronic effects, a Jaffe relationship was observed correlating rate to electronic perturbation at two positions of the substrate. Ligand effects were evaluated to provide evidence of rapid ligand exchange between palladium and copper as well as a correlation between ligand electronic nature and enantioselectivity.

The reaction is tolerant to a variety of functionalities and proceeds with complete retention of the optical purity, when a chiral substrate is applied [cf.

The Tsuji-Wacker oxidation provides access to methyl ketones from terminal olefins and is commonly utilized in complex molecule synthesis.[1] However, this reaction is under substrate control, which can lead to a mixture of aldehyde and ketone products, especially when the alkene bears a proximal heteroatom.[2,3] An excellent example of exploiting this was recently reported by Feringa and co-workers wherein allylic phthalimides provided high selectivity (> 95:5) for anti-Markovnikov oxidation of olefins to β-amino aldehydes (Scheme 1a).[4] In contrast, an example of an o-nosyl-protected allylic amine yields mainly methyl ketone product.[4] The proposed difference in selectivity between these two protecting groups is that the Lewis basic phthalimide can chelate with Pd-directing anti-Markovnikov oxidation, while the o-nosyl group is a relatively poor directing group. An underlying problem is the difficulty in predicting which protecting groups and which of the numerous possible variants of the Tsuji-Wacker oxidation will lead to the desired product for a given substrate. Scheme 1 a) Allylic phthalimides give high aldehyde selectivity under Tsuji–Wacker conditions, as reported by Feringa and co-workers.[4] b) Proposed intermediate in [Pd(Quinox)]–TBHP catalyst system. c) [Pd(Quinox)]–TBHP represents a catalyst-controlled ... A goal of our research program is to use ligands on PdII to control oxidative processes.[5] In this regard, we recently reported a tert-butylhydroperoxide (TBHP) mediated Wacker-type oxidation, which was shown to be highly selective for the methyl ketone product in the oxidation of terminal olefins, including protected allylic alcohols.[6] The system was designed to overcome substrate control by using a bidentate ligand (Quinox) along with TBHP (Scheme 1b). It is believed that TBHP undergoes a syn-oxypalladation mechanism, which would preclude the interaction of the group adjacent to the olefin with the Pd center (Scheme 1c).[7] Therefore, using the Pd(Quinox)–TBHP catalyst system under modestly modified reaction conditions, the phthalimide substrate used by Feringa and co-workers (1) gives high ketone selectivity in excellent yield, overcoming the inherent substrate control (Table 1, entry 1). The crude reaction mixture was analyzed by 1H NMR spectroscopy and gas chromatography (GC), which revealed the ketone was favored in a 96:4 ratio. This highlights our TBHP-mediated oxidation as a complimentary method to access α-amino ketones, which are highly versatile building blocks for targeted synthesis. Table 1 Oxidation of allylic phthalimides and comparison to results under Tsuji-Wacker conditions. Using our conditions, we initially evaluated some additional allylic and homoallylic phthalimide substrates and compared the results to the Tsuji–Wacker oxidation (Table 1). In all cases, the TBHP-mediated system provided the methyl ketone product with high selectivity (Table 1, entry 3). Interestingly, under Tsuji–Wacker conditions using 40 mol% PdCl2, allyl phthalimide (Table 1, entry 4) gave a mixture of ketone and aldehyde in a 40:60 ratio. This is further support for substrate control under Tsuji–Wacker conditions, as the selectivity is diminished in a substrate which does not have assistance from a Thorpe–Ingold effect. The homoallylic phthalimide is oxidized rapidly to the methyl ketone using 5 mol% [Pd(Quinox)] in high yield (Table 1, entry 5). The Tsuji–Wacker conditions also provide the ketone, albeit in an 85:15 ratio, where a substantially higher loading of Pd (30 mol%) and extended reaction times are required (Table 1, entry 6). As a result of the successful oxidation of phthalimide substrates, the scope of the protecting group on the allylic amine was evaluated. Due to ease of synthesis, a number of protected allyl amine substrates were subjected to oxidation. Substrates singly protected with either benzyl carbamate (Cbz) or tert-butyl carbamate (Boc) were oxidized to the methyl ketone products in good yields (Table 2, entries 1 and 2), and substrates with two protecting groups on the nitrogen provided the ketone products in excellent yields (Table 2, entries 3 and 5). To emphasize the selectivity of the [Pd-(Quinox)]-TBHP system, the N-Cbz-N-Boc allyl amine was evaluated under Tsuji–Wacker conditions. Using 20 mol% of PdCl2 and extended reaction times, nearly full conversion (6% recovered starting material) was observed to provide a 57:43 mixture of ketone to aldehyde products. Table 2 Scope of protecting groups. Allylic carbamates with additional substitution at the allylic position were prepared to investigate whether this would affect ketone selectivity. While a degradation in selectivity is observed with the Cbz-protected substrate (Table 2, entry 6), the ketone is still favored in a synthetically useful ratio. High ketone selectivity is regained with the doubly and orthogonally protected substrate (Table 2, entry 7). Somewhat surprisingly, the labile trichloracetamide (TAc) protecting group remained intact and provided only the ketone product; however, some starting material was recovered from the reaction mixture (Table 2, entry 8). Allylic sulfonamides were oxidized cleanly and with short reaction times in high yields (Table 2, entries 9 and 10). Highlighting the utility to prepare optically active α-amino ketones, an enantiomerically enriched substrate 4 (>99% ee) derived from L-serine[8] was oxidized to give the methyl ketone product 5 in high selectivity and good yield, and with no erosion of enantiomeric excess (Scheme 2). The same substrate was evaluated under Tsuji–Wacker conditions. Again, high loadings of PdCl2 and extended reaction times were required to achieve 56% yield (32% recovered starting material) of an inseparable mixture of 5 and 6 in a 60:40 ratio.[9] Scheme 2 a) Examination of the retention of enantiomeric excess and b) comparison to the Tsuji–Wacker oxidation. When N-methyl-N-benzoyl allyl amine 7a was subjected to the reaction conditions an inseparable mixture of the formal deallylation product 10a, in addition to ketone 8a, and aldehyde 9a was observed (Scheme 3). It is not evident whether the deallylation is a result of Pd–allyl chemistry or an E1CB elimination from the aldehyde. An electrophilic palladium species has been reported to catalytically deallylate the same substrate;[10] however, the aldehyde 9a was observed to decompose to 10a on silica and during gas chromatography. Regardless of the mechanism, it is likely that the poor outcome of this reaction is due to coordination of the electron-rich benzoyl group to the palladium center. Qualitative examination of electronically disparate benzoyl groups supports this hypothesis as 4-Cl benzoyl 7b provided a greater ratio of ketone 8b to a mixture of 9b and 10b. Conversely, a more electron-rich substrate, 4-OMe benzoyl 7c, led to less 8c than 9c and 10c.[11] Scheme 3 N-Methyl benzoyl protected allylic amines proved to be a limitation and a mechanistic tool. To further emphasize the utility of the α-amino ketones produced using this method, the corresponding β-amino alcohols with either a 1,2-syn or 1,2-anti relationship were accessed. By using LiAl(tBuO)3H to reduce the Cbz-protected α-amino ketone 11, the chelation-controlled reduction product 12 (anti) was obtained with excellent diastereoselectivity (Scheme 4a).[12] With the addition of a Boc group and use of NaBH4, 13 was reduced predominately to the Felkin–Anh product, which undergoes a concomitant cyclization on the benzyl carbamate to give 14 (syn) (Scheme 4b). Scheme 4 Diastereoselective reductions to provide both a) anti and b) syn β-amino alcohols. Finally, we would like to report an improved one-pot synthesis of the Quinox ligand, which utilizes the commercially available HCl salt of 2-chloroethylamine (Scheme 5). Following the standard amide coupling procedure, the solvent is switched to methanol and addition of KOH promotes the cyclization to the oxazoline ring. The [Pd(Quinox)Cl2] complex can then be prepared quantitatively by stirring Quinox with [Pd(CH3CN)2Cl2].[13] Scheme 5 Improved one-pot synthesis of the Quinox ligand. In conclusion, we have reported the [Pd(Quinox)]–TBHP catalyst system as providing a catalyst-controlled oxidation of protected allylic amines. The methyl ketone is provided with high selectivity and good to excellent yields for substrates, which either provide substrate-controlled anti-Markovnikov oxidation or incomplete oxidation under Tsuji–Wacker conditions. This is further support for the mechanistic hypothesis that coordination sites on PdII are blocked with a bidentate ligand and an oxidant, which promotes syn-oxypalladation of the substrate. Enantiomerically pure substrates do not undergo racemization under the reaction conditions. This provides facile access to the α-amino ketone synthon, which can be diastereoselectively reduced to give a syn or anti β-amino alcohol by proper selection of reducing conditions and protecting groups. Finally, a one-pot synthesis of the Quinox ligand was reported, which makes this chemistry more accessible for use in targeted synthesis. Future work is ongoing to further extend the applications of this catalyst system and to gain a more precise understanding of the factors resulting in catalyst control.

Several N-protected indoles are employed as nucleophiles in the difunctionalization reaction of ω-hydroxyalkenyl-substituted phenols.

Department of Chemistry, Washington State UniVersityP.O. Box 644630, Pullman, Washington 99164-4630NeXstar Pharmaceuticals, 2860 Wilderness PlaceBoulder, Colorado 80301ReceiVed March 5, 1998Many of the most useful methods for the assembly of cyclicorganic molecules involve transition-metal-catalyzed cycloaddi-tion. Because aromatic rings are central to many biological,pharmaceutical, and polymer molecules, alkyne cyclotrimerizationis an important methodology. Vollhardt was first to realize thepotential of cobalt-catalyzed cyclotrimerization in organic syn-thesis.

An unconventional route for the formation of sp3−sp3 C−C bonds from various styrenes and an organozinc reagent in a formal alkene hydroalkylation process is detailed. Mechanistically, this process ...

A sequential intramolecular−intermolecular enantioselective alkene difunctionalization reaction has been developed which is thought to proceed through Pd-catalyzed quinone methide formation. The synthesis of new chiral heterocyclic compounds with adjacent chiral centers is achieved in enantiomeric ratios up to 99:1 and diastereomeric ratios up to 10:1.

The bridged bis(ferrocenyl) monomer ((N5-C5H4CHO)Fe(n5-C5H4))2SiMe2 (1) was prepared in two steps from (n5-C5H4SnBu3)2Fe. The bis(cyanoacetate) monomers, CNCH2CO2(CH2)nO2CCH2CN (2) where n = 4, 6, and 8 where prepared in high yield by reacting ethyl cyanoacetate with the appropriate diol in the presence of Ti(OC4H9)4. Knoevenagel polycondensation [K2CO3, THF, 40 deg C] of 1 and 2 afforded a new class of organometallic accordion copolymers. Average molecular weights for the accordion copolymers ranged from 9,100 to 26,600 with polydispersities of approximately 2.1. The Knoevenagel polycondensation reaction appeared to produce a mixture of E- and Z-isomers (9/1, respectively); however, isomerically enriched polymer (i.e. 98% E-isomer) was obtained through selective precipitation.

A sequential intramolecular−intermolecular enantioselective alkene difunctionalization reaction has been developed which is thought to proceed through Pd-catalyzed quinone methide formation. The synthesis of new chiral heterocyclic compounds with adjacent chiral centers is achieved in enantiomeric ratios up to 99:1 and diastereomeric ratios up to 10:1.

Alkenes are attractive starting materials for organic synthesis and the development of new selective functionalization reactions are desired. Previously, our laboratory discovered a unique Pd-catalyzed hydroalkoxylation reaction of styrenes containing a phenol. Based upon deuterium labeling experiments, a mechanism involving an aerobic alcohol oxidation coupled to alkene functionalization was proposed. These results inspired the development of a new Pd-catalyzed reductive coupling reaction of alkenes and organometallic reagents that generates a new carbon-carbon bond. Optimization of the conditions for the coupling of both organostannanes and organoboronic esters is described and the initial scope of the transformation is presented. Additionally, several mechanistic experiments are outlined and support the rationale for the development of the reaction based upon coupling alcohol oxidation to alkene functionalization.

During the past 10 years there have been significant advances in PdII-catalyzed oxidation reactions where the use of ligands has led to the development of catalytic systems capable of achieving high turnover numbers, which employ molecular oxygen as the sole stoichiometric oxidant. This Feature article will highlight some of the recent developments in direct molecular oxygen-coupled PdII-catalyzed oxidation reactions with an emphasis on enhanced catalytic systems and new reactions. Additionally, limitations of current catalytic systems, such as ligand oxidation, are presented and their implications for the development of new reactions are discussed.

We report the use of Taft steric parameters to correlate the substituent size of a ligand with the enantiomeric ratio of a reaction. Linear free energy relationships can be constructed by plotting the log of enantiomeric ratio (er) versus the steric parameters reported by Taft and modified by Charton. Successful correlations were found for aldehyde and ketone allylation under NHK conditions using modular oxazoline ligands developed in our laboratory. Using these correlations, ligands were designed and evaluated for carbonyl allylation reactions. A break in the Charton plot results and is attributed to a global structural change in the catalyst. Additionally, several previously reported enantioselective reactions are analyzed resulting in excellent correlations for both catalysts and substrates. Finally, limitations and issues are presented with illustrative examples.

Utilizing the rapidly synthesized Quinox ligand and commercially available aqueous TBHP, a Wacker-type oxidation has been developed, which efficiently converts the traditionally challenging substrate class of protected allylic alcohols to the corresponding acyloin products. Additionally, the catalytic system is general for several other substrate classes, converting terminal olefins to methyl ketones, with short reaction times. The system is scalable (20 mmol) and can be performed with a reduced catalyst loading of 1 mol%. Enantioenriched substrates undergo oxidation with complete retention of enantiomeric excess.

This paper describes the synthesis of three classes of amine functionalized oxazolines that have been successfully used in asymmetric catalysis in our laboratory. Failed synthetic routes and significantly improved procedures are discussed including the synthesis of ligands for Nozaki–Hiyama–Kishi (NHK) carbonyl allylation reactions that do not require chromatography for purification.

A cationic palladium complex catalyzes the title transformations, which are thought to proceed via a pi-allyl or pi-benzyl intermediate. The regioselectivity of the reaction (1,2- or 1,1-difunctionalization) depends on the type of terminal double bond (conjugated or nonconjugated) in the substrate (see scheme) and appears to be controlled by the relative rates of beta-hydride elimination and transmetalation. DMA=dimethylacetamide, Tf=triflyl.

Alkene difunctionalization, the addition of two functional groups across a double bond, exemplifies a class of reactions with significant synthetic potential. This emerging area examines recent developments of palladium-catalyzed difunctionalization reactions, with a focus on mechanistic strategies that allow for functionalization of a common palladium alkyl intermediate.

The Suzuki reaction, which couples an organohalide and an organoboron compound,[1] is an attractive cross-coupling reaction for use in the synthesis of natural products[2] and pharmaceuticals.[3] This utility is mainly because of the excellent functional group compatibility, ease of preparation of boronic acid derivatives, and the low toxicity of the boron byproducts.[2] The mechanistic details have been widely investigated and the reaction is thought to proceed through oxidative addition of the organohalide (R–X) to Pd0 to form R–PdII–X and then transmetalation of the organoborane (R1– B(OR)2).[1] The resulting R–PdII–R1 intermediate undergoes reductive elimination to form the product. An exogenous base is required to activate the boronic acid derivative for transmetalation, which is proposed to occur through a four-centered transition state (intermediate C, Scheme 1a).[4]

A hydrochlorination reaction of styrenes catalyzed by Pd(II) in combination with Cu(II) was developed, which was followed by an in situ conversion of electron-rich products to an ether in the presence of an alcohol. Mechanistic experiments indicate that olefin functionalization is coupled to an alcohol oxidation, wherein a Pd hydride formed in the β-hydride elimination step of the alcohol oxidation was incorporated into the product.

A direct O2-coupled Pd(II)-catalyzed enantioselective dialkoxylation of 2-propenylphenols has been developed by utilizing chiral quinoline oxazoline ligands. A detrimental effect of added copper salts on enantioselectivity was observed which is attributed to the displacement of the chiral ligand off of Pd(II).

By systematically evaluating ligand diastereomers using a modular oxazoline template, a new ligand has been identified leading to the discovery of the first example of a chromium-catalyzed enantioselective allylation of ketones using allylic bromides.

Wacker oxidations, the conversion of terminal olefins to methyl ketones with Pd(II) catalysts, have seen widespread use in synthetic applications. Standard synthetic Wacker conditions use catalytic PdCl2 with stoichiometric CuCl under an aerobic atmosphere in a mixed-solvent system of N,N-dimethylformamide and H2O. Though much attention has been directed toward elucidating the rate-determining step and the mechanism of nucleopalladation, the assumption that Cu does not participate in this portion of the catalytic cycle has recently been called into question based on an isolated Pd/Cu bimetallic species and the influence of Cu on product selectivity. Fortunately, recent advancements have been made toward the elimination of Cu additives, thereby alleviating these issues. Success in this area has come from the application of information gained in studying other direct-O2-coupled Pd(II) oxidation systems, including ligand modulation, something which could not be achieved in the presence of Cu. The developments in peroxide-mediated and direct-O2-coupled Wacker oxidations are highlighted herein.

The discovery of a direct O2-coupled Wacker oxidation with use of balloon pressure of O2 and low catalyst loading is described. Use of (-)-sparteine as a ligand on Pd prevents olefin isomerization and leads to selective formation of methyl ketones from terminal olefins in good yields. Oxidation of enantiomerically enriched substrates is reported with no observed racemization.

Recently there has been an increased interest in the development of small molecule electrooxidation catalysts such as (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), for use in the anodic compartment of a biofuel cell. Some TEMPO derivatives are capable of electrochemically oxidizing short chain alcohols and various sugars to the corresponding aldehydes and carboxylic acids under physiological aqueous conditions. However, building libraries of such a catalyst is difficult due to the limited number of commercially available TEMPO derivatives and the lack of modular synthetic pathways to more complicated TEMPO structures. A promising alternative to the physical preparation of such libraries is the use of computational modeling to allow for in silico catalytic screening of a much wider range of TEMPO compounds. We have developed a computational model based on simple geometry optimization and population analysis to probe the catalytic activity and oxidation potential of TEMPO-derived species. Redox potentials were calculated from the free energy cycle of TEMPO oxidation while the relative catalytic activity was modeled using multidimensional analysis involving the computed pKas of various protonation states of the hydroxylamine form of TEMPO along with the corresponding redox potentials. We will also discuss how analysis of the atomic polar tensor (APT) charge of TEMPO can provide insight into the factors that affect its redox potential.

There has been a significant interest lately in the complete oxidation of biofuels to CO2. The use of multiple biocatalysts allows for deeper biofuel oxidation and thus maximizes the energy density that can be extracted per molecule of biofuel. However, there are still many biofuels for which a suitable biocatalyst is not known. We have recently taken an alternative approach to combine the high catalytic activity of enzymatic biocatalysts with the promiscuous nature of small molecule organic catalysts. We demonstrate the complete electrochemical oxidation of the biofuel glycerol to CO2 using a hybrid enzymatic and small-molecule catalytic system. Combining an enzyme, oxalate oxidase, and an organic oxidation catalyst, 4-amino-TEMPO, we are able to electrochemically oxidize glycerol at a carbon electrode, while collecting as many as 16 e-s per molecule of fuel. Additionally, we investigate the anomalous electrocatalytic properties that allow 4-amino-TEMPO to be active under the acidic conditions required for oxalate oxidase to function.

The discovery of a direct O2-coupled Wacker oxidation with use of balloon pressure of O2 and low catalyst loading is described. Use of (-)-sparteine as a ligand on Pd prevents olefin isomerization and leads to selective formation of methyl ketones from terminal olefins in good yields. Oxidation of enantiomerically enriched substrates is reported with no observed racemization.

The discovery and investigation of ligand-modulated Pd-catalyzed aerobic alcohol oxidations is documented. The project has evolved from a simple empirical discovery that (-)-sparteine, in combination with Pd(II) salts, facilitates the aerobic oxidative kinetic resolution of secondary alcohols to an in-depth physical organic investigation that has provided key insights into how new, more effective catalysts can be designed. Mechanistic investigations, the substrate scope for the catalysts developed, and implications to oxidation catalysis are discussed.

We report a Pd(II)-catalyzed aerobic dialkoxylation of styrene derivatives that requires an o-phenol. Initial scope and preliminary mechanistic studies are presented in which the o-phenol is proposed to facilitate the formation of a quinone methide intermediate.

[reaction: see text] Pd[(-)-sparteine]Cl(2) catalyzes the formation of dialkyl acetals from styrene derivatives with Markovnikov regioselectivity. The substrate scope of this reaction has been investigated, and initial mechanistic studies indicate that the reaction proceeds through an enol ether intermediate and a Pd-hydride.

A kinetic investigation into the origin of enantioselectivity for the Pd[(-)-sparteine]Cl(2)-catalyzed aerobic oxidative kinetic resolution (OKR) is reported. A mechanism to account for a newly discovered chloride dissociation from Pd[(-)-sparteine]Cl(2) prior to alcohol binding is proposed. The mechanism includes (1) chloride dissociation from Pd[(-)-sparteine]Cl(2) to form cationic Pd(-)-sparteine]Cl, (2) alcohol binding, (3) deprotonation of Pd-bound alcohol to form a Pd-alkoxide, and (4) beta-hydride elimination of Pd-alkoxide to form ketone product and a Pd-hydride. Utilizing the addition of (-)-sparteine HCl to control the [Cl(-)] and [H(+)] and the resulting derived rate law, the key microscopic kinetic and thermodynamic constants were extracted for each enantiomer of sec-phenethyl alcohol. These constants allow for the successful simulation of the oxidation rate in the presence of exogenous (-)-sparteine HCl. A rate law for oxidation of the racemic alcohol was derived that allows for the successful prediction of the experimentally measured k(rel) values when using the extracted constants. Besides a factor of 10 difference between the relative rates of beta-hydride elimination for the enantiomers, the main enhancement in enantiodetermination results from a concentration effect of (-)-sparteine HCl and the relative rates of reprotonation of the diastereomeric Pd-alkoxides.

[reaction: see text] Three catalysts for aerobic oxidation of alcohols are discussed and the effectiveness of each is evaluated for allylic, benzylic, aliphatic, and functionalized alcohols. Additionally, chiral nonracemic substrates as well as chemoselective and diastereoselective oxidations are investigated. In this study, the most convenient system for the Pd-catalyzed aerobic oxidation of alcohols is Pd(OAc)(2) in combination with triethylamine. This system functions effectively for the majority of alcohols tested and uses mild conditions (3 to 5 mol % of catalyst, room temperature). Pd(IiPr)(OAc)(2)(H(2)O) (1) also successfully oxidizes the majority of alcohols evaluated. This system has the advantage of significantly lowering catalyst loadings but requires higher temperatures (0.1 to 1 mol % of catalyst, 60 degrees C). A new catalyst is also disclosed, Pd(IiPr)(OPiv)(2) (2). This catalyst operates under very mild conditions (1 mol %, room temperature, and air as the O(2) source) but with a more limited substrate scope.