Transmetalation zinc enolates

The addition of carbonyl compounds towards lithiated 1-siloxy-substituted allenes does not proceed in the manner described above for alkoxyallenes. Tius and co-work-ers found that treatment of 1-siloxy-substituted allene 67 with tert-butyllithium and subsequent addition of aldehydes or ketones led to the formation of ,/i-unsaturated acyl silanes 70 (Scheme 8.19) [66]. This simple and convenient method starts with the usual lithiation of allene 67 at C-l but is followed by a migration of the silyl group from oxygen to C-l, thus forming the lithium enolate 69, which finally adds to the carbonyl species. Transmetalation of the lithiated intermediate 69 to the corresponding zinc enolate provided better access to acylsilanes derived from enolizable aldehydes. For reactions of 69 with ketones, transmetalation to a magnesium species seems to afford optimal results. 

This reaction sequence has been extended to lithium enolates. The deprotonation of the aminoester 54 with LDA followed by a transmetalation with zinc bromide in ether furnishes a zinc enolate, which readily adds to the double bond providing the proline derivative 55 in high diastereoselectivity (Scheme 23) . ... 

An interesting variation of this methodology was developed whereby zinc enolates 127 were employed giving 2-ester-substituted pyrrolidines 128-13060c. The enolates 127 were obtained via transmetallation of lithium ester enolates 126 with ZnBr2 (equation 59). 

On the other hand, the O-metallated structure E is also observed, for example when a zinc enolate is prepared by transmetallation of a lithium enolate with a Zn(II) salt5. 

Three approaches to zinc enolates are commonly adopted the process associated to the classical Reformatsky reaction is based on the insertion of Zn(0) into the carbon—halogen bond of an a-haloester. Two additional routes involve (i) transmetallation of a lithium enolate with a Zn(II) salt (Section V.A) and (ii) the transition-metal-catalysed conjugate addition of diethylzinc to Michael acceptors (Section V.B). 

Using l-(2-nitrovinyl)pyrrolidines 108 or 111 as Michael acceptors, the addition of the Reformatsky reagent is followed by amine elimination. A formal vinylic substitution ensues, which can take advantage of the presence of stereocenters in the pyrrolidine moiety, affording new chiral nitroolefins 110151 and 113152, as reported in equations 64 and 65, respectively. In both cases, zinc enolates 109 and 112 are prepared by lithia-tion/transmetallation of the parent ester. 

The most general route to transition metal enolates involves lithiation of an enolisable substrate followed by transmetallation with a proper metal halide several reports are available in the literature where zinc enolates are prepared via lithium/zinc exchange, and selected examples are discussed henceforth. 

Transmetallation of 12 with a catalytic amount of the higher order cyanocuprate Me2Cu(CN)Li2, in the presence of Me3ZnLi and with slow addition of enone 7 led first to the initial conjugate addition product 14, then to zinc enolate 15 after Cu-to-Zn transmetallation. The third component, the electrophile, either an aide-... 

Amide 9 is enolizable and carries an oxazolidinone auxiliary. Addition of ZnCb leads to transmetallation and formation of a zinc enolate. 

Z-enolate 40 is formed which can be explained by the Ireland model. There, the allyl residue interacts to a lesser extent with the LDA framework than with the sterically demanding dimethyl alkyl residue. Transmetallation with ZnCb delivers the chiral zinc enolate 40. 

Thus, we set out to determine whether we could directly observe and identify the unreactive species, and this is when we turned to in situ IR for insights. It seemed reasonable that a hthium-to-zinc transmetallation was a likely cause of the observed attenuated reactivity. It is well established that zinc enolates are much less reactive than the corresponding lithium enolates. The addition of... 

Heterocycles. A route to 2,3-disubstituted furans takes advantage of the Cu-Zn-transmetallation (with ZnCl2) from enolates derived from conjugate organocuprate addition to enones, and aldol reaction of zinc enolates to an alkoxyacetaldehyde. ... 

The nickel-catalyzed reductive coupling reaction of methyl vinyl ketone with enyne 43 bearing a P-dicarbonyl moiety proceeds with liberation of the P-dicarbonyl enolate (Scheme 5.56) [39]. Reductive coupling of 43 with enone would afford nickelaoxacyclooctadiene 44. Transmetalation is accompanied by carbonickelation to yield 45. Intermediate 45 engages in P-carbon elimination through a six-membered cyclic transition state to liberate nickel enolate 46, which should be transformed to the corresponding zinc enolate to complete the catalytic cycle, and zinc enolate 47, which is eventually protonated upon hydrolysis. 

The transmetallation of alkali enolates 164 (M = Li, Na, K) with metal salts (M Y L, ) is a general method for the preparation of a large variety of enolates 165, provided that is less electropositive than M. It is particularly suitable for such enolates 165 whose reactivity and/or selectivity is tuned by additional ligands L. Thus, a variety of magnesium, boron, aluminum, siUcon, tin, titanium, zirconium, and zinc enolates become readily available (Scheme 2.48) [2c,d]. Usually, the configuration of the enolates is maintained during the transmetallation, but cis-tmns isomerization in the transmetallated enolates occur occasionally. Individual examples will be discussed with their applications in asymmetric syntheses. 

The catalytic cycle, also shown in Scheme 5.101, as proposed by Cozzi and coworkers [160a, 193], postulates that a nickel enolate 386 forms spontaneously from a Ni(0) species and bromoacetate. This enolate is unable to react with the imine. It is transmetallated, however, into a zinc enolate that is believed to exist in an equilibrium between C-bound tautomer 387 and O-bound tautomer 388. Concomitantly, NiMeX forms that undergoes a coupling to ethane under regeneration of the Ni(0) species. The zinc enolate 387 or 388 finally adds to the... 

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