Transition-metal catalyzed oxidative cross-coupling reactions to form C-C bonds involving organometallic reagents as nucleophiles

Transition-metal-catalyzed coupling reactions have become a versatile tool for chemical bond formation. From the variation of the coupling partners, coupling reactions can be classified into three models: traditional coupling, reductive coupling and oxidative coupling. The oxidative coupling, which is different from the traditional coupling, occurs between two nucleophiles. This critical review focuses on transition-metal-catalyzed oxidative coupling reactions involving organometallic reagents as nucleophiles. Since the scope of the oxidative coupling is highly diversified, this paper only reviews the oxidative coupling reactions concerning C-C bond formation, including the coupling between organometal reagents and hydrocarbons as well as coupling between two organometal reagents. Since terminal alkynes are normally activated by metal salts and in situ form the alkynyl metal reagents in coupling reactions, they are directly considered as organometal reagents in this review. Intramolecular oxidative couplings and oxidative cyclizations are not included in this critical review. Moreover, there are many examples of oxidative coupling leading to the formation of functional materials, such as the oxidative polymerization of thiophenes. Since several reviews in these areas have been published they are not included in this review either (99 references).     

Proline-catalysed asymmetric amination of alpha,alpha-disubstituted aldehydes: synthesis of configurationally stable enantioenriched alpha-aminoaldehydes

Proline-catalysed amination of alpha,alpha-disubstituted racemic aldehydes with azodicarboxylates proceeds smoothly to give configurationally stable scalemic aldehydes and oxazolidinones in up to 86% ee.     

All-carbon-substituted vinylsilane stable to TBAF: synthesis of allyldimethylvinylsilane and its Pd-catalyzed cross-coupling under mild conditions

[reaction: see text] Allyldimethylvinylsilanes 3 are easily synthesized by the reaction of silylallylmetals, generated from 1 by n-BuLi/t-BuOK, with carbonyl compounds in the absence or presence of metal halides. They can tolerate 2 equiv of TBAF in THF at room temperature for at least 6 h but can be easily activated in the presence of a palladium catalyst and TBAF to perform the cross-coupling reaction with aryl iodides at room temperature.     

Microwave assisted asymmetric Suzuki-Miyaura and Negishi cross-coupling reactions: synthesis of chiral binaphthalenes

Microwave assisted asymmetric Suzuki-Miyaura and Negishi enantioselective cross-coupling reactions are reported for the first time, and have been applied to the rapid synthesis of chiral sterically hindered binaphthalene derivatives in reasonable to excellent yields (65–96%) and fair to good enantioselectivities (43–70% ee).     

A new approach to carbon-carbon bond formation: development of aerobic Pd-catalyzed reductive coupling reactions of organometallic reagents and styrenes

Alkenes are attractive starting materials for organic synthesis and the development of new selective functionalization reactions is 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.     

An approach to an asymmetric synthesis of stemofoline

A stereoselective Mannich reaction between an (S)-tert-butylsulfinimine and methyl (S)-4-benzyloxy-3-methylbutanoate followed by treatment with acid and N-protection was used to prepare methyl (2R,3S)-2-[(S)-2-benzyloxy-1-methylethyl]-3-tert-butoxycarbonylamino-6-methylenedecanoate. This was taken through to methyl (4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-5-tert-butoxycarbonylamino-3,8-dioxododecanoate which on treatment with trifluoroacetic acid cyclised stereoselectively to give (1R,2S,4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-1-butyl-2-methoxycarbonyl-8-tert-butoxycarbonyl-3-oxo-8-azabicyclo[3.2.1]octane, a potential precursor of stemofoline. Reduction and N-deprotection of this ketone gave (1R,2S,3R,4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-1-butyl-2-methoxycarbonyl-8-azabicyclo[3.2.1]octan-3-ol the structure of which was confirmed by X-ray diffraction.     

Catalytic asymmetric hydrogenation of N-iminopyridinium ylides: expedient approach to enantioenriched substituted piperidine derivatives

We have developed an efficient catalytic enantioselective hydrogenation of pyridine derivatives. Enhanced reactivity was possible by an optimization of the electronic properties of the catalyst through ligand modification. This methodology shows the particular reactivity of N-iminopyridinium ylides that provides access to substituted piperidines in good enantiomeric excesses.     

Highly convergent, stereospecific synthesis of 11-cis-retinoids by metal-catalyzed cross-coupling reactions of (Z)-1-alkenylmetals

A stereospecific synthesis of 11-cis-retinoids has as its key step the hitherto unexplored palladium-catalyzed cross-coupling of trans-trienyl electrophiles and (1Z,3E)-penta-1,3-dienyl boronates (a Suzuki-Miyaura reaction) or stannanes (a Stille reaction). This highly convergent approach constitutes the first application of cis-organometallic moieties to the synthesis of 11-cis-retinoids and represents a general, straightforward route to the visual chromophore.     

Pd-catalyzed carbocyclization-Negishi cross-coupling cascade: a novel approach to 1alpha,25-dihydroxyvitamin D3 and analogues

[reaction: see text] A mild palladium-catalyzed cascade has been used for the synthesis of the hormone 1alpha,25-dihydroxyvitamin D3 (calcitriol, 1a) and its analogues 1b and 1c. This one-pot process involves two consecutive transformations at room temperature: An initial palladium-catalyzed 6-exo-cyclocarbopalladation of vinyl triflates followed by a Negishi cross-coupling reaction with an alkenyl zinc. This novel strategy opens new possibilities for the preparation of a variety of new vitamin D analogues of therapeutic potential, particularly with modifications at the triene and/or ring-A.     

Nonsimple relationships between the P-chiral diamidophosphite and the arylphosphine moieties in Pd-catalyzed asymmetric reactions: combinatorial approach and P,P-bidentate phosphine-diamidophosphites

A small family of P,P^∗-bidentate C₁-symmetric ligands containing 1,3,2-diazaphospholidine rings with stereogenic phosphorus atoms has been prepared. Palladium catalytic systems with these phosphine-diamidophosphites afforded 95% and 63% ees in asymmetric allylic substitution and desymmetrization processes, respectively. The influence of the nature of both the phosphine and diamidophosphite moieties of these compounds on the enantioselectivity is discussed. The ‘mixed-ligand approach’ in Pd-catalyzed asymmetric allylation with participation of some new P^∗-monodentate diamidophosphites and PPh₃ is also considered.     

Pd-catalyzed amination as an alternative to nucleophilic aromatic substitution for the synthesis of N-alkyltacrines and analogues

A reliable Pd-catalyzed amination protocol is described for the synthesis of N-alkyltacrines and analogs. The Josiphos ligand CyPFtBu was found to provide optimum yields: 16 examples are given. Compared to the typical high-temperature nucleophilic aromatic substitution (NAS) routes, Pd-catalyzed aminations proceed at significantly lower reaction temperatures, and enable the synthesis of otherwise inaccessible products.     

Enantiopure fluorous amino-derivatives: synthesis and some applications in asymmetric organometallic catalysis

The preparation of (2R,3R)-1,4-bis[(1H,1H,2H,2H,3H,3H-perfluoroundecyl)oxy]butane-2,3-diol 5 from (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol is described. This fluorous diol 5 can be easily converted to the corresponding fluorous enantiopure diamine 8 and amino alcohol 12. While diamine 8 afforded fluorous diimine 9, amino alcohol 12 is the precursor of imino alcohol 13 and amino alcohol 14. Enantioselectivities of up to 31% were obtained in the reduction of acetophenone using iridium or ruthenium complexes associated with these compounds.     

Ring-closure reactions through intramolecular substitution of thiophenoxide by oxygen and nitrogen nucleophiles: simple stereospecific synthesis of 4,5-dihydroisoxazoles and 4,5-dihydropyrazoles

A new and simple method for the stereospecific synthesis of 3,5-disubstituted-4,5-dihydro-isoxazoles (chiral isoxazolines) from readily available oximes of chiral Michael adducts of thiophenol to chalcones is reported. An analogous reaction with the N-arylhydrazones of the Michael adduct gave nonracemic 1-(aryl)-3,5-diphenyl-4,5-dihydro-1H-pyrazoles (chiral pyrazolines), but these products are configurationally unstable. The key step of the synthesis is the ring-closure reaction, which occurs by a stereospecific intramoleculer nucleophilic substitution of thiophenoxide.     

Synthesis of novel bidentate P-chiral diaminophosphine oxide preligands: application to Pd-catalyzed asymmetric allylic substitution reactions

We developed a novel (S)-L-phenylalanine derived-bidentate chiral diaminophosphine oxide (DIAPHOX) preligand (S,S(P))-9b, which was successfully applied to Pd-catalyzed asymmetric allylic alkylation and amination. Using the Pd-(S,S(P))-9b catalyst system, asymmetric allylic alkylation and amination proceeded very smoothly, affording the corresponding products in excellent yield with high enantiomeric excess. It is noteworthy that both enantiomers were accessible with high enantiomeric purity using the structurally related DIAPHOX preligands (S,S(P))-9b and a monodentate chiral diaminophosphine oxide preligand (S,R(P))-10a, both of which can be prepared from a single chiral source, (S)-L-phenylalanine.     

Asymmetric synthesis of oxygen heterocycles via Pd-catalyzed dynamic kinetic asymmetric transformations: application to nucleosides

Racemic butadiene and isoprene monoepoxide react with unsaturated alcohols in the presence of a chiral palladium catalyst and a boron co-catalyst to give 3-alkoxy-4-hydroxy-1-butene and 3-alkoxy-4-hydroxy-3-methyl-1-butene, respectively, with excellent regio- and enantioselectivity in a dynamic kinetic asymmetric transformation whereby both enantiomers of the starting epoxides provide the same enantiomeric product. In the case of 2-phenylbutadiene monoepoxide, easily available from phenacyl chloride and vinylmagnesium bromide, the reaction proceeds by kinetic resolution. A model to rationalize the result is presented. The bis-olefin products are ideal substrates for the Ru catalyzed ring closing metathesis. In this way, five-, six-, and seven-membered oxygen heterocycles are readily available enantiomerically pure. The value of this very simple two step process is demonstrated by the use of the five-membered ring heterocycles to form unnatural and unusual nucleosides that cannot be easily accessed by other means. The sequence involves a Ru catalyzed isomerization of the initial 2,5-dihydrofuran to a 2,3-dihydrofuran followed by a selenium promoted addition of a pyrimidine or purine base. One advantage of this strategy is the easy access to either enantiomeric series, both of which have important biological applications.     

Pd-catalyzed carbonylative cross-coupling reactions by triorganoindiums: highly efficient transfer of organic groups attached to indium under atmospheric pressure

[reaction: see text] A highly atom-efficient synthetic method of unsymmetrical ketones was developed by using trialkyl- and triarylindiums, which could be employed as effective cross-coupling partners in Pd-catalyzed carbonylative cross-coupling reactions with a variety of organic electrophiles. The present method produced unsymmetrical ketones and 1,4-diacylbenzenes in good yields with highly efficient transfer of almost all the organic groups attached to the indium under atmospheric pressure of CO gas in THF at 66 degrees C.     

Vinyl ketones to allenes: preparation of 1,3-dien-2-yl triflates and their application in Pd-catalyzed reactions with soft nucleophiles

[chemical reaction: see text]. A general route of converting alkenyl ketones to functionalized allenes was developed. Substituted 1,3-dien-2-yl triflates, which were prepared from the alkenyl ketones via silyl dienol ethers, were excellent substrates for the palladium-catalyzed reaction with soft nucleophiles giving the multisubstituted allenes in high yields. Comparison between the dienyl triflates and analogous bromodienes in the Pd-catalyzed reaction was studied as well.