Cross-coupling electrophiles

The late Professor J. K. Stille pioneered the development of a very effective and versatile palladium-mediated C-C bond forming method - the palladium-catalyzed cross-coupling of organic electrophiles with organostannanes.48 This process continues to enjoy much success in organic synthesis because it proceeds in high yields under mild reaction conditions and because it tolerates a... 

Optically active (Z)-l-substituted-2-alkenylsilanes are also available by asymmetric cross coupling, and similarly react with aldehydes in the presence of titanium(IV) chloride by an SE process in which the electrophile attacks the allylsilane double bond unit with respect to the leaving silyl group to form ( )-s)vr-products. However the enantiomeric excesses of these (Z)-allylsilanes tend to be lower than those of their ( )-isomers, and their reactions with aldehydes tend to be less stereoselective with more of the (E)-anti products being obtained74. 

The procedure in Section C is representative of the synthesis of non-natural a-amino acids featuring the palladium cross coupling reaction of a (1-alaninc organozinc derivative with aromatic electrophiles. This methodology has been successfully extended with modifications to both the electrophile and the catalyst as shown in the Table. 

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... 

Transition metal catalysed cross-coupling reactions of organometalUc reagents containing Zn, Si, Mg, Sn or B with organic electrophiles in the presence of group 8-10 metals, notably Ni and Pd, are routinely the method of choice, both in academia and industry, for the preparation of C-0, C-S, C-H, C-N and C-C bonds [1]. 

Cross-coupling reactions resulting in C-C bond formation are normally classified according to the nature of the organometallic reagent and the organic electrophile. Scheme 6.4 summarises, broadly, the names and reaction partners of the most common of these transformations. 

Hydroboration of alkenes or alkynes followed by cross-coupling with organic electrophiles provides a straightforward method for the carbon-carbon bond formation (Scheme 1-19). The hydroboration of thioalkynes with catecholborane in the presence of a nickel or palladium catalyst yields P-(aLkylthio)-l-alkenylboronates (72a)... 

The use of enol- and phenol-esters in cross-coupling reactions is a valuable protocol, as it gives an indirect way to involve readily available phenols and carbonyl compounds as the electrophilic components of cross-couplings (Equation (22)) ... 

As Pd° and Ni° are capable of oxidative addition by C—S bonds, organosulfur compounds can take part in cross-coupling reactions as electrophilic reagents. Due to the formation of stable Pd—S... 

The Zn11 cation may lend soft electrophilic assistance for transmetalation. The most efficient such assistance is in the intramolecular chelating mode, which is exemplified by cross-coupling of... 

Simple Pd salts and complexes which contain neither phosphines nor any other deliberately added ligands are well known to provide catalytic activity in cross-coupling reactions. Such catalytic systems (often referred to as ligand-free catalysts ) often require the use of water as a component of the reaction medium.17 In the majority of cases such systems are applicable to electrophiles easily undergoing the oxidative addition (aryl iodides and activated bromides), although there are examples of effective reactions with unactivated substrates (electron-rich aiyl bromides, and some aryl chlorides).18,470... 

As described above, our synthetic strategy involves the convergent construction of the central cyclopentanone ring with a carbonylative cross-coupling reaction and a photo-Nazarov cyclization reaction (Chart 2.2). The electrophilic coupling component 51 was synthesized by an intramolecular Diels-Alder reaction [34] and the nucleophilic coupling component 52 by a vinyiogous Mukaiyama aldol reaction [35]. 

Aryl fluorosulfonates have recently been reported as less expensive alternatives to aryl inflates. Compound 3 has been synthesized in 50% isolated yield using 4-nitrophenyl fluorosulfonate as the electrophilic partner in the cross-coupling reaction. Roth, G. R. Fuller, C. E. J. Org. Cham. 1901,56,3493-3496. 

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