Alkyl cross-coupling reaction

Cardenas, D. J. Towards efficient and wide-scope metal-catalyzed alkyl—alkyl cross-coupling reactions. Angew. Chem. Int. Ed. 1999,... 

Fig. 40 Alkyl-alkyl cross-coupling reactions catalyzed by Pd(0) complexes...

Alkyl-alkyl cross-coupling reactions have historically been the most difficult to realize. Among the many obstacles to the effective development of such a system are the lower reactivity of alkyl groups relative to alkenyl and aryl groups, as well as side processes such as -hydride elimination that are accessible with alkyl substrates. More reports by Fu et al. have disclosed successful alkyl cross-coupling protocols... 

Scheme 2-31. Alkyl-alkyl cross-coupling reaction catalyzed by Cu(l)-salts.

Of-Silylalkanenitriles couples with aryl halides to give a variety of cx-arylalkanenitriles (Scheme 3-169). On the other hand, alkyl cross-coupling reaction using alkylsilane reagents as nucleophiles is successful only with... 

Ishiyama T, Abe S, Miyaura N, Suzuki A. Palladium-catalyzed alkyl-alkyl cross-coupling reaction of 9-Alkyl-9-BBN derivatives with iodoalkanes possessing (i-hydrogens. Chem. Lett. 1992 21(4) 691-694. 

Moderate yields of acids and ketones can be obtained by paHadium-cataly2ed carbonylation of boronic acids and by carbonylation cross-coupling reactions (272,320,321). In an alternative procedure for the carbonylation reaction, potassium trialkylborohydride ia the presence of a catalytic amount of the free borane is utilized (322). FiaaHy, various tertiary alcohols including hindered and polycycHc stmctures become readily available by oxidation of the organoborane iatermediate produced after migration of three alkyl groups (312,313,323). 

Alkyl- and aryl-pyridazines can be prepared by cross-coupling reactions between chloropyridazines and Grignard reagents in the presence of nickel-phosphine complexes as catalysts. Dichloro[l,2-bis(diphenylphosphino)propane]nickel is used for alkylation and dichloro[l,2-bis(diphenylphosphino)ethane]nickel for arylation (78CPB2550). 3-Alkynyl-pyridazines and their A-oxides are prepared from 3-chloropyridazines and their A-oxides and alkynes using a Pd(PPh3)Cl2-Cu complex and triethylamine (78H(9)1397). 

Our group has recently developed an alternative method for alkyl-(hetero)aryl- as well as aryl-heteroaryl cross coupling reactions catalyzed by iron salts.3 4 This methodology was inspired by early reports of Kochi et al.5>6 on iron-catalyzed cross coupling of vinyl halides and is distinguished by several notable advantages. 

It has been shown that cross-coupling reactions constitute a very mild method to introduce different alkyl and aryl groups to the most active C-3 position of the pyrazinone ring [26]. The broadly functionahzed 2-azadiene system of the title compounds was studied in cycloaddition reactions with various electron-reach and electron-poor dienophiles to provide highly substituted heterocycles [24]. 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Pa]ladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 Nicolaou KC, King NP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natmal Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

Rehahn et al. [35] recently presented the synthesis of constitutionally homogeneous oligophenylenes, 22a/b, with 2,5-alkyl substituents located on the central aromatic ring, generated via the cross-coupling reaction of Suzuki. They are exclusively linked in the para-positions and composed of 3 -15 benzene rings. 

Scheme 29 Iron-catalyzed cross coupling reaction of aryl Grignard reagents with alkyl halides...

Although the formation of tetraalkylferrates, for example, in the first step of a cross-coupling reaction starting from Fe(-i-3)-salts and alkyl Grignard reagents, seems possible, until now there is no analytical or spectroscopic proof for such a species. In fact, it was shown that Fe(-i-3) is reduced by MeLi or MeMgBr to Fe(-i-2) under release of ethane [5, 6]. 

The hydrosi(ly)lations of alkenes and alkynes are very important catalytic processes for the synthesis of alkyl- and alkenyl-silanes, respectively, which can be further transformed into aldehydes, ketones or alcohols by estabhshed stoichiometric organic transformations, or used as nucleophiles in cross-coupling reactions. Hydrosilylation is also used for the derivatisation of Si containing polymers. The drawbacks of the most widespread hydrosilylation catalysts [the Speier s system, H PtCl/PrOH, and Karstedt s complex [Pt2(divinyl-disiloxane)3] include the formation of side-products, in addition to the desired anh-Markovnikov Si-H addition product. In the hydrosilylation of alkynes, formation of di-silanes (by competing further reaction of the product alkenyl-silane) and of geometrical isomers (a-isomer from the Markovnikov addition and Z-p and -P from the anh-Markovnikov addition. Scheme 2.6) are also possible. 

Phosphine ligands based on the ferrocene backbone are very efficient in many palladium-catalyzed reactions, e.g., cross-coupling reactions,248 Heck reaction,249 amination reaction,250 and enantioselective synthesis.251 A particularly interesting example of an unusual coordination mode of the l,l -bis(diphenylphosphino)ferrocene (dppf) ligand has been reported. Dicationic palladium(II) complexes, such as [(dppf)Pd(PPh3)]2+[BF4 ]2, were shown to contain a palladium-iron bond.252,253 Palladium-iron bonds occur also in monocationic methyl and acylpalladium(II) complexes.254 A palladium-iron interaction is favored by bulky alkyl substituents on phosphorus and a lower electron density at palladium. 

Branchaud and coworkers have used cobaloximes as alkyl radical precursors for the cross-coupling reaction with nitronates.57 This method is very useful for producing branched-chain monosaccharides, as shown in Eq. 5.39.57b... 

Oxidative cross-coupling reactions of alkylated derivatives of activated CH compounds, such as malonic esters, acetylacetone, cyanoacetates, and certain ketones, with nitroalkanes promoted by silver nitrate or iodine lead to the formation of the nitroalkylated products.67 This is an alternative way of performing SRN1 reactions using a-halo-nitroalkanes. 

Anionic complexes of boron (boronates, borinates, etc.) have been introduced as convenient reagents in cross-coupling reactions of broad scope, particularly interesting for the transfer of alkynyl and primary alkyl residues, which cannot be accomplished using the standard protocols of the Suzuki-Miyaura reaction. Readily available Ph4BNa can be used as a convenient reagent for phenylation in place of the much more expensive PhB(OH)2, and all four phenyl groups can be utilized when the reaction is carried out with a phosphine-free catalyst in aqueous solutions.244... 

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