Copper-catalyzed cross-coupling of nonactivated secondary alkyl halides and tosylates with secondary alkyl Grignard reagents

Practical catalytic cross-coupling of secondary alkyl electrophiles with secondary alkyl nucleophiles under Cu catalysis has been realized. The use of TMEDA and LiOMe is critical for the success of the reaction. This cross-coupling reaction occurs via an S(N)2 mechanism with inversion of configuration and therefore provides a general approach for the stereocontrolled formation of C-C bonds between two tertiary carbons from chiral secondary alcohols.     

Cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic and benzylic Grignard reagents and their application to tandem radical cyclization/cross-coupling reactions

Details of cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic Grignard reagents are disclosed. A combination of cobalt(II) chloride and 1,2-bis(diphenylphosphino)ethane (DPPE) or 1,3-bis(diphenylphosphino)propane (DPPP) is suitable as a precatalyst and allows secondary and tertiary alkyl halides--as well as primary ones--to be employed as coupling partners for allyl Grignard reagents. The reaction offers a facile synthesis of quaternary carbon centers, which has practically never been possible with palladium, nickel, and copper catalysts. Benzyl, methallyl, and crotyl Grignard reagents can all couple with alkyl halides. The benzylation definitely requires DPPE or DPPP as a ligand. The reaction mechanism should include the generation of an alkyl radical from the parent alkyl halide. The mechanism can be interpreted in terms of a tandem radical cyclization/cross-coupling reaction. In addition, serendipitous tandem radical cyclization/cyclopropanation/carbonyl allylation of 5-alkoxy-6-halo-4-oxa-1-hexene derivatives is also described. The intermediacy of a carbon-centered radical results in the loss of the original stereochemistry of the parent alkyl halides, creating the potential for asymmetric cross-coupling of racemic alkyl halides.     

Iron nanoparticles in the coupling of alkyl halides with aryl Grignard reagents

Iron nanoparticles, either formed in situ stabilized by 1,6-bis(diphenylphosphino)hexane or polyethylene glycol (PEG), or preformed stabilized by PEG, are excellent catalysts for the cross-coupling of aryl Grignard reagents with primary and secondary alkyl halides bearing beta-hydrogens and they also prove effective in a tandem cyclization/cross-coupling reaction.     

Nickel-catalyzed migratory alkyl–alkyl cross-coupling reaction

The selective cross-coupling of activated electrophiles with unactivated ones has been regarded as a challenging task in cross-electrophile couplings. Herein we describe a migratory cross-coupling strategy, which can overcome this obstacle to access the desired cross-coupling products. Accordingly, a selective migratory cross-coupling of two alkyl electrophiles has been accomplished by nickel catalysis. Remarkably, this alkyl–alkyl cross-coupling reaction provides a platform to prepare 2°–2° carbon–carbon bonds from 1° and 2° carbon coupling partners. Preliminary mechanistic studies suggest that chain-walking occurs at both alkyl halides in this reaction, thus a catalytic cycle with the key step involving two alkylnickel(ii) species is proposed for this transformation.

The selective cross-coupling of activated electrophiles with unactivated ones has been regarded as a challenging task in cross-electrophile couplings.     

Cross-coupling of alkyl halides with Grignard reagents using nickel and palladium complexes bearing eta(3)-allyl ligand as catalysts

The cross-coupling of Grignard reagents with alkyl bromides and tosylates has been achieved by the use of eta(3)-allylnickel and eta(3)-allylpalladium complexes as catalysts.     

Analysis of key steps in the catalytic cross-coupling of alkyl electrophiles under Negishi-like conditions

The use of tpy'(tpy'= 4,4',4'-tri-tert-butyl-terpyridine) as a ligand for nickel allows for the isolation of a Ni(I)-alkyl complex and a Ni(II)-alkyl halide complex, both of which can be used as mechanistic probes of key steps in alkyl cross-coupling reactions.     

Nickel-catalyzed cross-coupling of unactivated alkyl halides and tosylate carrying a functional group with alkyl and phenyl Grignard reagents

By the use of catalytic amounts of a nickel salt and a 1,3-butadiene, primary and secondary alkyl Grignard reagents undergo cross-coupling with alkyl bromides, iodide, and tosylate carrying a functional group such as amide, ester, and ketone at 0 °C in THF. The present procedure provides a simple, convenient, and practical method for construction of carbon chains in the presence of various functional groups. PhMgBr also gave the corresponding coupling product in a moderate yield.     

Nickel-catalyzed reductive coupling of unactivated alkyl bromides and aliphatic aldehydes

A mild, convenient coupling of aliphatic aldehydes and unactivated alkyl bromides has been developed. The catalytic system features the use of a common Ni(ii) precatalyst and a readily available bioxazoline ligand and affords silyl-protected secondary alcohols. The reaction is operationally simple, utilizing Mn as a stoichiometric reductant, and tolerates a wide range of functional groups. The use of 1,5-hexadiene as an additive is an important reaction parameter that provides significant benefits in yield optimizations. Initial mechanistic experiments support a mechanism featuring an alpha-silyloxy Ni species that undergoes formal oxidative addition to the alkyl bromide via a reductive cross-coupling pathway.

Aliphatic aldehydes and alkyl bromides are reductively coupled using nickel catalysis. A BiOX ligand and 1,5-hexadiene paired with a silyl chloride and Mn as the terminal reductant are important features of the process.     

Tin-catalyzed conversion of trioses to alkyl lactates in alcohol solution

Tin chlorides, SnCl2 and SnCl4.5H2O are excellent catalysts for the reactions of trioses, dihydroxyacetone and glyceraldehyde with alcohols (MeOH, EtOH and nBuOH) to give alkyl lactates, whose reaction mechanism involves the intermediary formation of pyruvic aldehyde followed by its esterification, which is distinctively promoted by tin halides.     

A structure-activity study of Ni-catalyzed alkyl-alkyl Kumada coupling. Improved catalysts for coupling of secondary alkyl halides

A structure-activity study was carried out for Ni catalyzed alkyl-alkyl Kumada-type cross coupling reactions. A series of new nickel(II) complexes including those with tridentate pincer bis(amino)amide ligands ((R)N(2)N) and those with bidentate mixed amino-amide ligands ((R)NN) were synthesized and structurally characterized. The coordination geometries of these complexes range from square planar, tetrahedral, to square pyramidal. The complexes had been examined as precatalysts for cross coupling of nonactivated alkyl halides, particularly secondary alkyl iodides, with alkyl Grignard reagents. Comparison was made to the results obtained with the previously reported Ni pincer complex [((Me)N(2)N)NiCl]. A transmetalation site in the precatalysts is necessary for the catalysis. The coordination geometries and spin-states of the precatalysts have a small or no influence. The work led to the discovery of several well-defined Ni catalysts that are significantly more active and efficient than the pincer complex [((Me)N(2)N)NiCl] for the coupling of secondary alkyl halides. The best two catalysts are [((H)NN)Ni(PPh(3))Cl] and [((H)NN)Ni(2,4-lutidine)Cl]. The improved activity and efficiency was attributed to the fact that phosphine and lutidine ligands in these complexes can dissociate from the Ni center during catalysis. The activation of alkyl halides was shown to proceed via a radical mechanism.     

Kumada coupling of aryl, heteroaryl, and vinyl chlorides catalyzed by amido pincer nickel complexes

A series of amido pincer complexes of nickel were examined for their catalysis in the Kumada cross-coupling reaction. The P,N,O-pincer nickel complexes tested are active catalysts for the cross-coupling of aryl, heteroaryl, and vinyl chlorides with aryl Grignard reagents. The reactions can proceed at room temperature and tolerate functional groups in aryl chlorides with the aid of LiCl and ZnCl(2) additives.     

New procedure for synthesis alkyl esters of 5-acetyl-2-furan-carboxylic acid alkyl ester

The possibility to synthesize alkyl esters of 5-acetyl-2-furan-carboxylic acid by the reaction of 5-acetyl-2-furan with CCl₄ and aliphatic alcohols under the action of iron-containing catalysts was studied.

     

Silver-catalyzed cross-coupling reactions of alkyl bromides with alkyl or aryl Grignard reagents

Treatment of secondary or tertiary alkyl bromides with alkyl Grignard reagents in the presence of catalytic amounts of silver bromide and potassium fluoride in CH₂Cl₂ afforded the corresponding cross-coupling products in reasonable yields. Moreover, silver showed catalytic activity for the cross-coupling reactions of alkyl bromides with aryl Grignard reagents.     

Pd-catalyzed cross-coupling reactions of alkyl halides

Cross-coupling reactions have become indispensable tools for creating carbon-carbon (or heteroatom) bonds in organic synthesis. Like in other important transition metal catalyzed reactions, such as metathesis, addition, and polymerization, unsaturated compounds are usually employed as substrates for cross-coupling reactions. However during the past decade, a great deal of effort has been devoted to the use of alkyl halides as saturated compounds in cross-coupling reactions, which has resulted in significant progress in this undeveloped area by introducing new effective ligands. Many useful catalytic systems are now available for synthetic transformations based on C(sp(3))-C(sp(3)), C(sp(3))-C(sp(2)) and C(sp(3))-C(sp) bond formation as complementary methods to conventional C(sp(2))-C(sp(2)), C(sp(2))-C(sp) and C(sp)-C(sp) coupling. This tutorial review summarizes recent advances in cross-coupling reactions of alkyl halides and pseudohalides catalyzed by a palladium complex.     

Nickel-catalyzed cross-coupling reaction of grignard reagents with alkyl halides and tosylates: remarkable effect of 1,3-butadienes

A new method for the cross-coupling reaction of Grignard reagents with alkyl chlorides, bromides, and tosylates has been developed by the use of a nickel catalyst in the presence of a diene as an additive. This reaction proceeds efficiently at 0-25 degrees C in THF using primary and secondary alkyl and aryl Grignard reagents. Nickel complexes bearing no phosphine ligands, such as NiCl2, Ni(acac)2, and Ni(COD)2, afford the coupling products in good yields, whereas NiCl2(PPh3)2 and NiCl2(dppp) were less effective. 1,3-Butadiene shows the highest activity as an additive for the present coupling reaction. A plausible reaction pathway was proposed.     

Control of Vicinal Stereocenters through Nickel-Catalyzed Alkyl–Alkyl Cross-Coupling

Vicinal stereocenters are found in many natural and unnatural compounds. Although metal-catalyzed cross-coupling reactions of unactivated alkyl electrophiles are emerging as a powerful tool in organic synthesis, there have been virtually no reports of processes that generate, much less control, vicinal stereocenters. In this investigation, we establish that a chiral nickel catalyst can mediate doubly stereoconvergent alkyl–alkyl cross-coupling, specifically, reactions of a racemic pyrrolidine-derived nucleophile with cyclic alkyl halides (as mixtures of stereoisomers) to produce vicinal stereocenters with very good stereoselectivity.     

Synthesis of sulfated alkyl oligosaccharides with potent anti-HIV activity

Sulfated alkyl malto- and laminari-oligosaccharides with potent anti-human immunodeficiency virus (HIV) activities were synthesized. Present work focusses on the syntheses of high anti-HIV active compounds from low molecular weight carbohydrates which will react selectively with AIDS virus protein only. A surface-active agent type compound consisting of both hydrophilic sulfated oligosaccharide and hydrophobic alkyl group portion was prepared. Individual pure malto-oligosaccharides from malto-tetraose to -heptaose and laminarioligosaccharides from laminari-pentaose to -nonaose were used as the starting carbohydrates. Synthesis of peracetylated alkyl oligosaccharide was carried out with β-peracetylated oligosaccharides and corresponding alcohols by using Lewis acid catalysts. Sulfation was performed with sulfur trioxide-pyridine complex. The anti-HIV activity was assayed by means of MT-4 cells and HIV-1 or HIV-2 viruses. Almost all sulfated alkyl oligosaccharides exhibited potent inhibitory effects on HIV infection. Sulfated alkyl laminari-oligosaccharides which have various kind of aklyl portion such as fluoro alkyl, chiral alkyl, cyclic alkyl, and phenyl alkyl were also examined. In addition, this study also provides an assessment of activity levels of sulfated alkyl oligosaccharides in small mammals.     

Cross-couplings of unactivated secondary alkyl halides: room-temperature nickel-catalyzed Negishi reactions of alkyl bromides and iodides

The development of a nickel- or palladium-catalyzed method for cross-coupling unactivated secondary alkyl halides has been a long-standing challenge in synthetic chemistry. This communication describes a simple catalyst system-Ni(cod)2/s-Bu-Pybox-that achieves room-temperature Negishi reactions of an array of functionalized primary and secondary alkyl bromides and iodides.     

Iron-catalyzed Grignard cross-coupling with alkyl halides possessing beta-hydrogens

Tris(acetylacetonato)iron(III) (Fe(acac)(3)) was found to be an efficient catalyst for the cross-coupling reaction between aryl Grignard reagents and alkyl halides possessing beta-hydrogens. The reaction is applicable to secondary alkyl halides as well as primary ones. [reaction: see text]     

Palladium-catalyzed coupling of thiol esters with aryl and primary and secondary alkyl organoindium reagents

Thiol esters and organoindium reagents undergo palladium-catalyzed cross-coupling under mild conditions to give ketones in moderate to excellent yields. Aryl and primary/secondary alkyl organoindium reagents can be used as coupling partners. This method has two advantages over the cross-coupling of thiol esters with boron and tin reagents: (1) no added copper reagent is required to mediate the reaction and (2) for the case of alkyl transfer, no added base is required to activate organoindium reagents for cross-coupling as is required for the coupling of alkyl boron reagents with thiol esters.