Electrophile alkyl

Reactions with Aldehydes and Ketones. An important use for alkylphenols is ia phenol—formaldehyde resias. These resias are classified as resoles or aovolaks (see Phenolic resins). Resoles are produced whea oae or more moles of formaldehyde react with oae mole of pheaol uader basic catalysis. These resias are thermosets. Novolaks are thermoplastic resias formed whea an excess of phenol reacts with formaldehyde under acidic conditions. The acid protonates formaldehyde to generate the alkylating electrophile (17). 

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... 

In a few interesting cases, adducts decompose via reactions in which DNA serves as a leaving group and the original DNA-alkylating electrophile is regenerated. Reversible... 

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... 

Subsequent ion exchange of the metal cation with the quaternary ammonium ion catalyst provides a lipophilic ion pair (step 2), which either reacts with the requisite alkyl electrophile at the interface (step 3) or is partitioned into the electrophile-containing organic phase, whereupon alkylation occurs and the catalyst is reconstituted. Enantioselective PTC has found apphcation in a vast number of chemical transformations, including alkylations, conjugate additions, aldol reactions, oxidations, reductions, and C-X bond formations." ... 

When structurally alerting compounds (e.g. those possessing alkylating electrophilic centres) have given negative results in the standard battery. 

The composition of the products from the alkylation of lithiated 3,6-dialkoxy-2,5-dihydropy-razines with bis-alkylating reagents depends on the equivalents of electrophile employed. For example, with three equivalents of bis-alkylating electrophiles, (25)-2,5-dihydro-2-isopropyi-3,6-dimethoxy-5-methylpyrazine (I) gives high yields of the 1 1 adducts 2 or 5 with > 97% de2. These products can be further converted to the bicyclic systems (3 and 6. respectively) which, upon hydrolysis, give optically pure cyclic amino acids (4 and 7). Methyloxirane is used as an acid scavenger in order to release the free amino acid zwitterion. 

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

Whereas allyl, benzyl and propargyl electrophiles are among the most reactive towards Pd, Ni and other transition metals, ordinary alkyl halides and related alkyl electrophiles that are not /3, -unsaturated are among the least reactive carbon electrophiles with respect to oxidative addition to Pd or Ni. Most of the alkyl derivatives are also associated... 

In the following two sections, recent advances in the Pd- or Ni-catalyzed alkylation with alkylmetals (Section III.E.2) and with alkyl electrophiles (Section . . ) will be discussed. 

Another major approach to the Pd- or Ni-catalyzed alkylation with alkyl electrophiles is to use bulky and highly nucleophilic trialkylphosphines to promote slow oxidative addition. Screening of several trialkylphosphines as well as several widely used tri-arylphosphines for the Pd-catalyzed reaction of n-BuZnBr with Br(CH2)3OBn led to the following results Firstly, most of the conventional triarylphosphines including PPh3, TFP... 

SCHEME 76. Pd-catalyzed alkylation of organozincs with primary alkyl electrophiles... 

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). 

Table 1 Chiral-selective Alkylations Electrophile Di. D2 Carboxylic acid...

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

---