Cross alkyl electrophile

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... 

Netherton M, Fu GC (2005) Palladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 Neumann H, see Jacobi von Wangelin A (2006) 18 207-221... 

Palladium- or nickel-catalyzed cross-coupling reactions Use of Alkyl Electrophiles Containing I, Br, Cl, and OTs... 

All of the alkyl electrophiles shown in Schemes 73-78 are primary alkyl derivatives. On the other hand, cross-coupling of primary alkylzincs with secondary alkyl iodides and bromides was shown to be feasible with 4% Ni(COD)2, 8% s-Bu-Pybox (3) and DMA(N,N-Dimethylacetamide)88k (Scheme 79). More recently, a modification of this procedure through the use of -Pr-Pybox and 7 1 DMI/THF, where DMI is 1,3-dimethyl-2-imidazolidinone, in place of v-Bu-Pybox (3) and DMA has been shown to permit enantioselective alkylation of racemic secondary a-bromoamides with organozincs210 (Scheme 79). 

Scheme 5.15 Cross-coupling of alkenyl-Grignard reagents with alkyl electrophiles.

Abstract For many years, unactivated alkyl electrophiles that contain p hydrogens were generally regarded as unsuitable partners for palladium-catalyzed cross-coupling reactions. Recently, however, a series of studies have established that palladium complexes can in fact couple a range of alkyl electrophiles with a variety of organometallic reagents. 

Fig.l Cross-coupling reaction of unactivated alkyl electrophiles showing intramolecular p-hydride elimination (undesired) and intermolecular transmetalation (desired). 

Palladium-Catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles 87... 

Due to concern about these issues, in combination with early interest and success in coupling aryl and vinyl electrophiles, progress toward the development of palladium- or nickel-based methods for cross-coupling alkyl halides/ sulfonates has been relatively slow. However, during the past decade (particularly the last few years), important advances have been described that clearly demonstrate that the aforementioned obstacles can be overcome and that the development of general catalysts for coupling alkyl electrophiles is a realistic objective. 

The attractiveness of organo-9-BBN derivatives as coupling partners is largely due to their accessibility via the hydroboration of alkenes and alkynes on the other hand, they suffer from the drawbacks of not being easily manipulated in air or commercially available. In contrast, boronic acids are air-stable, and a large number and variety are commercially available. Consequently, the development of methods for cross-coupling alkyl electrophiles with boronic acids is undoubtedly an important objective. 

The Suzuki cross-coupling methods described in Sect. 2.1 establish that palladium complexes that bear electron-rich trialkylphosphines of the appropriate size can serve as effective catalysts for reactions of alkyl electrophiles. Naturally, it was of interest to determine if non-phosphine ligands that are bulky and electron-rich can also furnish active catalysts. 

Table 4 Negishi cross-coupling reactions of alkyl electrophiles and organozinc halides...

Two reports have described palladium-catalyzed Stille cross-couplings of unactivated alkyl electrophiles. Specifically, these investigations by Fu demonstrate that primary alkyl bromides and iodides can be coupled with vinylstannanes [27,28] and arylstannanes [28] (Eq. 10). 

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