Alkyl-aryl coupling reaction

Protection of allylic amines with a f-butoxycarbonyl (Boc),benzyloxycar-bonyl (Cbz), or p-methoxybenzyloxycarbonyl (PMB) group furnished the desired 9-BBN derivative for the coupling reaction [106, 107, 119]. The alkyl-vinyl and alkyl-aryl coupling reactions readily proceed on the solid-phase which was demonstrated in the preparation of members of several structurally distinct PG classes (47) [120]. 

Cross coupling between an aryl halide and an activated alkyl halide, catalysed by the nickel system, is achieved by controlling the rate of addition of the alkyl halide to the reaction mixture. When the aryl halide is present in excess, it reacts preferentially with the Ni(o) intermediate whereas the Ni(l) intermediate reacts more rapidly with an activated alkyl halide. Thus continuous slow addition of the alkyl halide to the electrochemical cell already charged with the aryl halide ensures that the alkyl-aryl coupled compound becomes the major product. Activated alkyl halides include benzyl chloride, a-chloroketones, a-chloroesters and amides, a-chloro-nitriles and vinyl chlorides [202, 203, 204], Asymmetric induction during the coupling step occurs with over 90 % distereomeric excess from reactions with amides such as 62, derived from enantiomerically pure (-)-ephedrine, even when 62 is a mixture of diastereoisomcrs prepared from a racemic a-chloroacid. Metiha-nolysis of the amide product affords the chiral ester 63 and chiral ephedrine is recoverable [205]. 

Scheme 20. Reaction conditions for alkyl-vinyl and alkyl-aryl coupling ...

An important feature of the Suzuki reaction is that it allows cr/Z Z-alkenyl or alkyl-aryl coupling of fi-a//cy/-9-borabicyclo[3.3.3]nonane derivatives with haloalkenes and haloarenes without concomitant p-hydride elimination. The required organoboranes are obtained by hydroboration of the appropriate alkenes or functionally substituted alkenes with 9-BBN. The coupling reaction tolerates the presence of functional groups in both reaction partners, thus circumventing a requirement of their prior pro-tection. ... 

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... 

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... 

The first synthesis of soluble PPPs having long alkyl side chains was carried out with a Ni-catalyzed aryl/aryl coupling reaction of 1,4-dibromoben-zenes (24) bearing long alkyl chains in the 2- and 5-positions (Scheme 9) [36]. 

Indoles with carbocyclic halogen or triflate substituents are potential starting materials for vinylation, arylation and acylation via palladium-catalysed pro-cesses[l]. Indolylstannanes. indolylzinc halides and indolylboronic acids are also potential reactants. The principal type of substitution which is excluded from such coupling reactions is alkylation, since saturated alkyl groups tend to give elimination products in Pd-catalysed processes. 

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). 

Carbamates can be used as protective groups for amino acids to minimize racem-ization in peptide synthesis. Racemization occurs during the base-catalyzed coupling reaction of an A-protected, carboxyl-activated amino acid and takes place in the intermediate oxazolone that forms readily from an A-acyl-protected amino acid (R = alkyl, aryl) ... 

The synthetic applicability is rather limited, due to the various side-reactions observed, such as eliminations and rearrangement reactions. The attempted coupling of two different alkyl halides in order to obtain an unsymmetrical hydrocarbon, usually gives the desired product in only low yield. However the coupling reaction of an aryl halide with an alkyl halide upon treatment with a metal (the Wurtz-Fittig reaction) often proceeds with high yield. The coupling of two aryl halides usually does not occur under those conditions (see however below ) since the aryl halides are less reactive. 

This organometallic coupling reaction is useful in organic synthesis because it forms carbon-carbon bonds, thereby making possible the preparation of larger molecules from smaller ones. As the following examples indicate, the coupling reaction can be carried out on aryl and vinylic halides as well as on alkyl halides. 

The occurrence of arenediazo alkyl and aryl ethers as intermediates has been discussed since 1870, when Kekule and Hidegh postulated that in the azo coupling reaction of benzenediazonium salts with phenol, 4-phenylazophenol is formed via the diazo phenyl ether. The analogous problem for diazo methyl ethers was first discussed by von Euler (1903). 

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