Synthesis of β-homophenylalanine derivatives by Negishi cross-coupling reactions

Three approaches to the synthesis of β²-homophenylalanine derivatives using Negishi cross-coupling reaction are reported. In the first two approaches, two protected α-iodomethyl-β-amino esters are each converted into the corresponding organozinc iodides, which then undergo Pd-catalysed cross-coupling with aromatic halides to give β²-homophenylalanine derivatives, and the X-ray crystal structure of one product is reported. Alternatively, Negishi cross-coupling of the zinc reagent derived from N-benzyl 3-iodomethyl azetidin-2-one and aryl halides gave 3-benzylazetidin-2-ones, masked β²-homophenylalanine derivatives. The X-ray crystal structure of 1-benzyl-3-[(p-toluenesulfonyloxy)-methyl]-azetidin-2-one confirms the structural assignment.     

Synthesis of α-aryl-diazophosphonates via palladium-catalyzed cross-coupling of aryl iodides with diethyl diazomethylphosphonate

An efficient procedure for the Pd-catalyzed arylation of diethyl α-diazomethylphosphonate with aryl iodides is described. It can serve as a pathway for the generation of arylated diazophosphonates, which are typically difficult to access. The significance of this methodology was demonstrated via further synthetic transformations of newly synthesized diazo compounds in cyclopropanation, epoxidation, N–H and O–H insertion reactions.     

Synthesis of α,ω-dichloropermethyloligosilanes by reactions of polydimethylsilane with metal chlorides

The reactions of high-molecular-weight polydimethylsilane with metal chlorides in variable oxidation states at high temperature in the absence of a solvent afford mixtures of ,-dichloropermethyloligosilanes Cl(Me₂Si) _m Cl (m= 2—9). The influence of the reaction conditions (temperature, reaction time, and the reagent ratio) on the composition and yields of the reaction products was examined.     

Synthesis of novel α-acyloxycarboxamides containing vinylbis(silanes) through three-component Passerini reactions

A three-component efficient procedure is described for the synthesis of novel α-acyloxycarboxamides containing bis(trimethylsilyl)ethenyl group from 4-[2,2-bis(trimethylsilyl)ethenyl]benzaldehyde, aromatic carboxylic acids and isocyanides, via the Passerini reaction. This reaction proceeds smoothly and cleanly under mild conditions in H₂O and [bmim]BF₄ at room temperature and led to products in good yields. The silylated aldehyde was obtained via Peterson olefination reaction of terephthalaldehyde with tris(trimethylsilyl)methyllithium in THF at 0 °C.     

Synthesis of α-arylalkylferrocenes through cesium fluoride-promoted coupling of arylboronic acids with N-tosylhydrazones

A cesium fluoride-promoted reductive coupling reaction of acylferrocene tosylhydrazones with arylboronic acids has been developed, producing highly substituted α-arylalkylferrocenes in moderate to excellent yields. The reaction employs anionic fluorine to facilitate the cleavage of C–B bond. The developed methodology demonstrates a wide substrate scope and high functional groups tolerance. Moreover, the α-arylalkylferrocenes compounds were also obtained on a multi-gram scale.     

Negishi cross-coupling reactions of α-amino acid-derived organozinc reagents and aromatic bromides

The Negishi cross-coupling reaction of organozinc iodides derived from α-amino acids with aromatic bromides to give substituted phenylalanine derivatives is described, using either Pd(OAc)₂ or Pd₂(dba)₃ in combination with P(o-Tol)₃ as catalyst in DMF at 50 °C. Similar results are obtained using Pd[P^tBu₃]₂ as catalyst. The difference in reactivity displayed between aryl iodides and bromides (ArI>ArBr) has been utilised in a short synthesis of an unsymmetrical, orthogonally protected para-phenylene bis-alanine derivative.     

Synthesis of indoles through Rh(III)-catalyzed C–H cross-coupling with allyl carbonates

A practical Rh-catalyzed reaction was developed to achieve 2-alkyl-substituted indole synthesis. The reaction can tolerate a variety of synthetically important functional groups. The indole products can also be transformed into other important skeletons. Two bioactive compounds, that is indomethacin and pravadoline were prepared using the new method.     

Synthesis and reactions of α-fluoro-α-amino amides

N-((S)-1-Phenylethyl)halofluoroethanamides have been investigated as precursors to N-protected α-fluoro-α-amino amides by nucleophilic displacement of halide with nitrogen nucleophiles such as potassium phthalimide, sodium succinimide, sodium glutarimide, trimethylamine and sodium azide. With single diastereoisomers of the iodofluoroethanamide, clean inversion of configuration occurs at room temperature, but subsequent epimerisation may occur as a result of the liberated iodide. The α-fluoro-α-amino amides made underwent a wide variety of reactions depending on conditions, but in many cases the carbon-fluorine bond was compromised. However, reacting trimethylamine and N-((S)-1-phenylethyl)iodofluoroethanamide gave the corresponding α-fluorobetaine amide, and subsequent acidic hydrolysis led to α-fluorobetaine as the first example of an ‘unprotected’ α-fluoroamino acid.     

Synthesis of α, ω-dihydroxymethylphenylsiloxanes and their reactions with silicon tetrachloride and tetrabutoxytitanium

Russian Chemical Bulletin -     

Synthesis of chiral ferrocenylazines. Negishi cross-coupling or S N H reactions?

Preparation of new hetaryl-containing planar chiral ferrocene by a nucleophilic substitution of hydrogen in azines was performed using a lithium derivative of (S)-ferrocenyl-p-tolylsulfoxide as s nucleophilic reagent     

Suzuki-Miyaura cross-coupling of α-phosphoryloxy enol ethers with arylboronic acids

The Suzuki-Miyaura cross-coupling reaction of cyclic ketene acetal phosphates with arylboronic acids was found to be a convenient and highly efficient method for the construction of aryl vinyl ethers. A wide variety of differentially substituted electron-poor and electron-rich arylboronic acids smoothly underwent the coupling process to provide the desired dihydropyrans in moderate to excellent yields.     

Palladium-catalyzed cross-coupling of sterically demanding boronic acids with α-bromocarbonyl compounds

A catalyst system generated in situ from Pd(dba)(2) and tri(o-tolyl)phosphine mediates the coupling of arylboronic acids with alkyl α-bromoacetates under formation of arylacetic acid esters at unprecedented low loadings. The new protocol, which involves potassium fluoride as the base and catalytic amounts of benzyltriethylammonium bromide as a phase transfer catalyst, is uniquely effective for the synthesis of sterically demanding arylacetic acid derivatives.     

Direct palladium/copper oxidative cross-coupling of α-methylstyrene with acrylates

Fully palladium/copper catalytic oxidative cross-coupling of acrylates with α-methylstyrene was performed in a DMSO/AcOH (1:1) mixture at 60 °C in the air. This improves previous procedures which employed stoichiometric amounts of copper and oxygen. Thus various acrylates were effectively coupled to α-methylstyrene giving the expected compounds in moderate to good yields (44%–65%) as a mixture of E and Z isomers.     

Synthesis of arylglycine and mandelic acid derivatives through carboxylations of α-amido and α-acetoxy stannanes with carbon dioxide

Incorporation reactions of carbon dioxide (CO(2)) with N-Boc-α-amido and α-acetoxy stannanes were developed using CsF as a mild tin activator. Monoprotected α-amido stannanes could be used, and the corresponding arylglycine derivatives were obtained in moderate-to-high yields under 1 MPa (10 atm) of CO(2) pressure. α-Acetoxy stannanes also underwent carboxylation to afford mandelic acid derivatives in excellent yields under ambient CO(2) pressure. Both transformations enabled the synthesis of α-tertiary and α-quaternary carboxylic acid derivatives. In addition, the chirality of (S)-N-tert-butylsulfonyl-α-amido stannanes was transferred with up to 90% inversion of configuration at 100 °C.     

Titanium-mediated reductive cross-coupling reactions of imines with nitriles: an efficient route for the synthesis of α-aminoketones or 1,2-diketones

The reaction of imines with low-valent titanium species, generated in situ by using Ti(OⁱPr)₄/2 c-C₅H₉MgCl reagent, affords titanium–imine complex, which can couple with nitriles to provide 2,5-diazatitanacyclopentenes. α-Aminoketones are obtained in good yields by quenching the corresponding 2,5-diazatitanacyclopentenes with aqueous HCl solution. However, when the reaction is first quenched with MeOH in air followed by addition of aqueous HCl solution, 1,2-diketones are formed in good to high yields.     

Radical-clock α-halo-esters as mechanistic probes for bisphosphine iron-catalyzed cross-coupling reactions

The mechanism of chiral bisphosphine iron-catalyzed C(sp²)-C(sp³) cross-coupling reactions has been studied via the synthesis of novel radical-clock α-halo-esters and quantum mechanical calculations. These results provide insights into the role of the substrate (halogen and substituents) in competing in-cage and out-of-cage arylation pathways and provide a basis for the future rational design of novel tandem cyclization-arylation reactions using bisphosphine-iron as catalysts.     

Copper-catalyzed chemoselective cross-coupling reaction of thioamides and α-diazocarbonyl compounds: Synthesis of enaminones

The development of operationally simple and cost-effective methods for CC bond formation reactions are highly important in pharmaceutical, agrochemical and material research. In this article we describe the first copper-catalyzed cross-coupling reaction of thioamides with acceptor/acceptor-substituted and acceptor-only substituted α-diazocarbonyl compounds to yield enaminones. The reaction shows broad substrate scope in terms of thioamides and diazocarbonyl compounds. Primary, secondary and tertiary thioamides all give enanminones when reacted with α-diazodiesters, α-diazoketoesters, α-diazodiketones, α-diazoketoamides, α-diazoesteramides, α-diazoketosulfones and α-diazomonoketones.     

Synthesis of 3-acylated indoles through iron-catalyzed oxidative coupling of indoles with α-amino carbonyl compounds

A novel iron-catalyzed oxidative coupling of indoles with α-amino carbonyl compounds has been developed. The transformation provides an attractive approach to the synthesis of 3-acylindoles, with the advantages of easily available starting materials and high functional group tolerance. Furthermore, control experiments imply that a radical process maybe involved in this reaction.     

Photocatalytic aerobic cross-coupling reaction of N-substituted anilines with N-aryl glycine esters: Synthesis of α-aryl α-amino esters

A novel photocatalytic cross dehydrogenative coupling reaction of N-aryl glycine esters with N-substituted anilines has been developed. The reaction proceeds effectively using methylene blue as a photocatalyst under visible light irradiation without any metal, chemical oxidant or additive. A variety of α-aryl α-amino derivatives were prepared in moderate to excellent yields with a high para-regioselectivity.