Zincate, lithium

In the second half of this section, we will discuss the mechanistic understanding of this chiral addition with lithium acetylide, the cornerstone of the first manufacturing process. Based on the mechanism of asymmetric lithium acetylide addition, we will turn our attention toward the novel highly efficient zincate chemistry. This is an excellent example in which mechanistic studies paid off handsomely. 

We came up with the idea of using a dummy ligand, as shown in Scheme 1.23 [34]. Reaction of dimethylzinc with our chiral modifier (amino-alcohol) 46 provided the methylzinc complex 62, which was subsequently reacted with 1 equiv of MeOH, to form chiral zinc alkoxide 63, generating a total of 2 moles of methane. Addition of lithium acetylide to 63 would generate an ate complex 64. The ate complex 64 should exist in equilibrium with the monomeric zincate 65 and the dimer 66. However, we expected that the monomer ate complex 64 and the mono-... 

The first structurally characterized triarylzincate [Li(TMEDA)2][Zn 2,4,6-(Pr1)3G6H2 3] 59 was a byproduct of the lithiation of VC13(THF)3 with Li(2,4,6-(Pr1)3C6H2)3, in which the vanadium compound had been pre-reduced with metallic zinc.116 In the solid state, the compound consists of isolated, tetrahedrally coordinated lithium ions and trigonal-planar tris(tris(isopropyl)phenyl)zincate ions. The Zn-G bonds are equidistant (2.039(7) A), but the C-Zn-C bond angles are variable, ranging from 112.2(3)° to 125.4(3)°. 

Four equivalents of lithium phenylacetylide reacted with bis bis(trimethylsilyl)amido zinc (Scheme 51) to form the ion-paired dilithiotetra(phenylacetylido)zincate 65, whose structure is shown in Figure 33.121 The zinc-carbon bonds (2.05 A) are somewhat longer than those observed in the tri(phenylacetylido)zincate 62a, due to the increase in both the coordination number and the negative charge on the ion. Each lithium ion is associated with the zincate ion through coordination to two of the triple bonds. 

The reaction of diorganozincs bearing bulky trimethylsilyl-substituted methyl groups and methyl- or phenyllithium in the presence of the 1,3,5-trimethyl-1,3,5-triazacyclohexane (TAGH), Scheme 53, afforded the corresponding lithium zincates as poorly soluble ion pairs.124... 

If the nucleophile R1 is replaced with bis(trimethylsilyl)amide, Scheme 54, a much more soluble lithium zincate 69 is isolated as a contact ion pair. A further increase in the steric bulk of either the organic substituents of the diorganozinc or of the nucleophile gave equilibria from which no organozincates could be isolated. 

Mixtures of hexamethyldisilazane, /z-butyllithium, and dimethylzinc reacted, Scheme 55, with the formation of a lithium zincate 70. In the solid state, Figure 37, 70 consists of four-membered, -symmetric LiN2Zn rings, which form a polymeric structure through bridging methyl groups from zinc to lithium.126... 

Scheme 3.10. Diastereoselectivity in 1,4-addition of stannyl-lithium, cuprate, and zincate reagents to enantiopure 4-heteroatom-substituted 2-enoates [59],...

According to NMR data, reaction of lithium tetramethylpiperidine (TMP) and t-Bu2Zn, in a 1 1 molar ratio (Scheme 6) affords the heteroleptic zincate [f-Bu2Zn(TMP)]Li (36) . An interesting feature of this compound is that it is capable of metalate arenes that contain a directing metalating group (DMG) in ortho-posilion and thus allow further derivatization by reaction of the zincate intermediate with electrophiles (E+). 

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