Dialkylzinc addition to aldehydes

Alkaloid catalyst Reaction time (h) Reaction temperature (°C) Yield (%) ee [%) Configuration 

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Since the discovery of amino alcohol induced dialkylzinc addition to aldehydes, many new ligands have been developed. It has recently been reported that chiral amino thiols and amino disulfides can form complexes or structurally strained derivatives with diethylzinc more favorably than chiral amino alcohols and thus enhance the asymmetric induction. Table 2 15 is a brief summary of such chiral catalysts. 

Another significant development in oxazoline chemistry is the application of oxazoline-containing ligands for asymmetric catalysis, such as palladium-catalyzed allylic substimtions, Heck reactions, hydrogenations, dialkylzinc additions to aldehydes, and Michael reactions. The discovery of diastereoselective metalation of chiral ferrocenyloxazolines has further expanded the availability of chiral ligands for metal-catalytic reactions. 

Scheme 1 Chiral amino alcohol catalyzed asymmetric dialkylzinc addition to aldehydes...

The key point of this scenario is to assume a priori that XY promotes the product of opposite configuration to X. In addition, additive dimers and not monomers are considered as catalytically active species, opposing the commonly accepted mechanism for typical dialkylzinc additions to aldehydes catalyzed by Vamino alcohols [ 18]. 

Only few reports deal with the use of mineral supports for immobilising chiral auxiliaries able to. activate dialkylzinc addition to aldehyde (Scheme 10). 

Chiral Lewis acidic catalysts derived from p-amino alcohols constitute a major field of recent development. These reagents have been used for enantioselective reduction of ketones and for dialkylzinc additions to aldehydes. 

A very similar model can be invoked to explain the results of catalytic enantioselective dialkylzinc additions to aldehydes. The catalysts used in these reactions are invariably lithium- or zinc-centered Lewis acids. The transition structure shown in Figure has been put forward by several groups... 

Figure 52 A model for catalytic asymmetric dialkylzinc additions to aldehydes...

One of the earUest demonstrations of the viability of a combinatorial approach in the discovery of asymmetric reactions was reported by Elhnan in 1995 [7]. The Berkeley team s selection of the dialkylzinc addition to aldehydes (Scheme 2) to gauge the potential utility of a combinatorial approach was based on several factors ... 

In this section, the asymmetric synthesis of the vicinal thio- and selenoalcohols 42 — 45 is described based on the highly enantio- and diastereoselective addition of diethylzinc reagent to racemic a-thio- and selenoaldehydes 41, catalyzed by 20o (( —)-DFPE) and S,R)-2Qo ((+)-DFPE) (Scheme 3-20). Although the enantio-selective addition of dialkylzinc reagents to achiral aldehydes using chiral catalysts has been well investigated [10], there are no known catalytic enantio- and di-asteroselective dialkylzinc additions to aldehydes with chiral centers, except for the alkylation of a-methyl- [58, 59], a-chloro- [59], and j5-alkoxyaldehydes [60]. The reaction of diethylzinc with racemic a-thio- and selenoaldehydes 41 was carried out in the presence of 20o or (S,il)-20o (5 — 50 mol%) in hexane at room temperature for 12 —16h. The results are summarized in Table 3-11. 

A complementary reaction towards the construction of secondary alcohols consists of a dialkylzinc addition to aldehydes in the presence of substoichiometric amounts of suitable chiral ligands, mostly amino alcohols [42-44]. For this reaction, which already is one of the classical asymmetric catalytic syntheses, three structurally related catalyst precursors have been described. 

The ionic liquids, [BMIMjBr, [BMIM][BF4], [BMIMjlPFe], [BDMIM][BF4], and [BPY][BF4], were examined as the solvent media for dialkylzinc addition to aldehydes giving the corresponding alcohols. The ionic liquid [BPY][BF4] was found to be the solvent of choice, giving the best yields, and was found to be easily recovered and reused [226] (Scheme 5.2-95). It was found that the imidazoUum salts react with diethyl zinc to form a carbene complex of zinc, but the 2-methylimidazolium or pyridinium salts did not react and hence could be recycled. 

Figure 6.1 Mechanism of catalysed dialkylzinc addition to aldehyde...

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