Catalyst additives second generation

The LLB catalysts requires at least 3.3 mol% of asymmehic catalyst for efficient nitro-aldol reactions, and the reactions are rather slow (first generation). Second-generation LLB catalysts are prepared by addition of 1 equiv of H2O and 0.9 equiv of n-BuLi. The second-generation-catalysts are more reactive than the first generation LLB as shown in Eq. 3.80. The proposed mechanism of asymmetiic niti o-aldol reaction using these catalysts is presented in Scheme 3.20. ... 

Olefin metathesis is one of the most important reaction in organic synthesis [44], Complexes of Ru are extremely useful for this transformation, especially so-called Grubbs catalysts. The introduction of NHCs in Ru metathesis catalysts a decade ago ( second generation Grubbs catalysts) resulted in enhanced activity and lifetime, hence overall improved catalytic performance [45, 46]. However, compared to the archetypal phosphine-based Ru metathesis catalyst 24 (Fig. 13.3), Ru-NHC complexes such as 25 display specific reactivity patterns and as a consequence, are prone to additional decomposition pathways as well as non NHC-specific pathways [47]. 

A synthesis of 5//-pyrrolo[l,2-r] imidazole 105 has been developed via a chemoselective addition/dehydration of acetaldehyde on diiodo imidazole 103 giving the vinylic imidazole 104. This compound, treated under the metathesis condition in the presence of the second-generation Grubbs catalyst, gave the final product 105 (Scheme 11) <2003TL1379>. 

As shown in Tab. 11.7 for the RCM of diethyl diallylmalonate, the original catalyst (10) suffered complete loss of metathesis activity after only two runs (entry 1). On the other hand, the second generation catalyst (55) retained modest activity in the third consecutive run (entry 2). As in the prior study [18], the addition of a terminal olefin additive was required to extend the catalyst lifetime past four runs (entry 3). Use of triphenylphosphine as a second additive just ten minutes before filtration led to further improvements in activity during catalyst reuse. However, as mentioned previously, the use of additives is somewhat wasteful and exclusive, since... 

Employing protic and halide additives can effectively reverse the deleterious effect with aliphatic amines [8, 11]. The optimum results are obtained when ammonium iodide is employed as the addihve in combination with the second-generation rhodium-iodide catalyst. Under these conditions, a variety of aliphatic amines can be used to generate the aminotetrahn products in high yields and with excellent enantiomeric excess (Scheme 9.4). From a technical perspective, ammonium iodide benefits from being a combined proton and iodide source that is air-stable and nonhygroscopic. 

To improve these selectivities, Hashimoto studied several catalysts that had been found highly effective for enantioselective C—H insertion reactions. The new catalysts incorporated an additional benzene in the naphthyl system to increase the steric bias of the catalyst. By using the second-generation catalysts in trifluorotoluene as solvent, at 0 °C, and short reaction times gave ee ratios of 68-92%. Lowered reaction temperature generally resulted in reduced chemical yields but did not erode the ee ratio. Tether lengths one smaller or one larger also tended to erode the ee ratio (Scheme 4.73). 

The two-directional tandem metathesis of 1 to 2 proceeded smoothly using 20 mol % of the second generation Grubbs catalyst (now commercially available only from Aldrich and from Materia) under an atmosphere of ethylene. The conversion of 2 to 3 took advantage of the differing reactivity of the two ketones. Addition of hydride to 2 from the less hindered face of the less hindered ketone delivered 4. 

Significant improvement in the catalytic activity of ALB was realized without any loss of enantioselectivity by using the second-generation ALB [27] generated by the self-assembled complex formation of ALB with alkali metal-malonate or alkoxide. This protocol allowed the catalyst loading to be reduced to 0.3 mol %, for example, the Michael addition of methyl malonate to cyclohexenone catalyzed by the self-assembled complex of (ff)-ALB (0.3 mol %) and KO Bu (0.27 mol %) in the presence of MS 4A gave the adduct in 94% yield and 99% ee [28]. This reaction has been successfully carried out on a 100-g scale wherein the product was purified by recrystallization. The kinetic studies of the reactions catalyzed by ALB and ALB/Na-malonate have revealed that the reactions are second-order to these catalysts (the rate constant ALB = 0.273 M 1h 1 ALB/Na-maionate = 1-66 M 1h 1) [27]. This reaction was used as the first key step for the catalytic asymmetric total synthesis of tubifolidine (Scheme 8D. 11) [28]. 

---