Metallation-transmetallation-acylation

Various polyfunctionalized a,/3-alkynyl ketones were easily prepared from many simple or functionalized terminal alkynes according to a one-pot procedure metallation-transmetallation-acylation (Scheme 13.26) [29]. 

Treatment of lithium enolate species, such as 7, with a variety of metal halide species produces enolates with different reactivities in particular, diethylaluminum(IH) and copper(I) species have been found to profoundly alter stereodifferentiation in reactions of iron acyl enolates (see Section D.1.3.4.2.5.1.). It has not been established whether complex formation or discrete ti ansmetalation occurs usually, a temperature increase from — 78 °C to — 42 °C is required for maximum effect, suggesting that cation exchange is responsible. In some cases, such additives exert an influence at —78 °C13, and this has been attributed to simple Lewis acid-type interactions with the substrate instead of transmetalation of the enolate species. For simplicity, when such additives are allowed to react with enolate species at temperatures of — 42 =C and above prior to the addition of other reagents, the process shall be referred to as transmetalation. 

The direct transmetallation of alkenyl, acyl, and alkylzirconocenes to a copper catalyst and subsequent conjugate addition is also possible without a detour via another metal like zinc. For example, Wipf and Takahashi182 reported the highly diastereoselective 1,4-addition of in situ-prepared alkylzirconocenes (e.g., 246) to chiral N-acyl oxazolidinone 245 and similar substrates in the presence of BF3 OEt2 and catalytic amount of CuBr-SMe2, giving adducts of the type 247 with moderate to good yield (Equation (13)). 

In the initial studies about the reaction of /V.zV-disubstituted formamides with alkaline metals to give glyoxylic amides, the participation of carbamoyl metal derivatives as intermediates was postulated83. The first preparation of the carbamoyllithium 77 was described two years later by a mercury-lithium transmetallation from compound 76 at —75 °C (Scheme 20)84. The authors proposed also an aminocarbene structure 78 and studied its reactivity with methanol, methyl iodide, carbonyl compounds, esters, acyl chlorides, mercury(II) chloride and tri-n-butyltin chloride providing compounds 79. 

The reactions may also be carried out under an atmosphere of carbon monoxide, CO (Scheme 10.22), when the usual catalytic cycle occurs. CO inserts easily into the palladium complex Ar-Pd -X. The aryl ligand migrates on to the carbonyl group to form a metal-acyl species, X-Pd - C(0)Ar. A transmetallation-reductive elimination sequence follows, forming the ketone and regenerating the Pd catalyst. 

The method was made considerably more general by inclusion of a catalytic amount of a palladium(O) complex during addition of the organometallic. Alkenylcopper reagents actually react relatively slowly with acid halides but, in a fashion analogous to other alkenyl metal species (see Section 1.13.4), they may be readily transmetallated to form an acylpalladium(II) complex which then undergoes reductive elimination to the product (Scheme 29)." A further discussion of acylation mediated by palladium complexes is included in Section 1.13.4. Interestingly, a,P-unsaturated acid chlorides react under these conditions to form divinyl ketones. 

An interesting metal effect was observed in the aldol condensations of the enolate derived from the iron acetyl complex (r)"-C HdFe(CO)(PPhd(COMe) with aldehydes [56,57]. Although the lithium enolate did not show any selectivity, the corresponding aluminum enolate by transmetalation with Et.AlCl exhibited exceptionally high diastereoselectivity (>99% de). The resultant P-hydroxy acyl complexes are transformed to P-hydroxy acids on decomplexation with Br.. 

This section mainly deals with Pd-catalyzed reactions of aryl, alkenyl, benzyl, alkyl, and acyl electrophiles with metal nucleophiles M = Si, Ge, Sn, B, and transition metals) leading to carbon-metal bond formation (Scheme 1). Allylic and related metallations are described in Sect. V.2.3.3, The reaction mechanism is generally believed to involve, firstly, oxidative addition of R—X to a Pd(0) species second, transmetallation of the resulting Pd(II) species with M—M and finally, reductive elimination forming R—M and the active Pd(0) species. However, another catalytic cycle via oxidative addition of M—M to Pd(0) species is also proposed. ... 

Elaborations of the oxazole scaffold included the first stepwise and mild functionalization performed through subsequent Mg or Zn metallation steps in positions 2, 4, and finally 5. The metallation allowed reactions with electrophiles, Negishi cross-couplings, Pd-catalyzed Negishi acylations, Sono-gashira couplings and, after transmetallation with Cu, allylations (130L6162). 

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