Hayashi-Jorgensen catalysts

The most efficient catalysts in water and ball mill, 0-lanroyl-derived catalyst Cl and Hayashi-Jorgensen catalyst C8 were used with a variety of aldehydes and nitroalkenes in aqneons solution, as well as in the ball mill (Scheme 2.31). The yields and diastereoselectivities were high in solution and in the ball mill (Table 2.27). 

Not only alcohols can be used with the MacMillan catalyst-isolated and stable carbenium ions are also suitable partners for the reaction [30], Tropylium tetrafluor-oborate is commercially available, and it is a stable carbenium ion that can be used in this type of reaction without any precautions. However, other carbenium ions are less stable and are difficult to generate they can be obtained using the conditions described by Mayr in his papers as unstable soUds. Although the appH-cation of an Sul-type reaction with alcohols seems to be Umited to the use of the MacMillan catalyst, the Hayashi-Jorgensen catalyst is also suitable for this transformation [31]. 

After the rediscovery of (S )-proline-catalysed reactions in 2000 and the discovery of the outstandingly efficient family of Jorgensen-Hayashi s catalysts in 2005, many research groups around the world have struggled in the search for different and more efficient chiral amino-catalysts, based on the pyrrolidine scaffold. A huge number of steric and electronic structural variations have been proposed along the way, sometimes resulting in the... 

Maltsev, O. V. A. O. Chizhov and S. G. Zlotin (2011). "chiral ionic liquid/esi-ms methodology as an efficient tool for the study of transformations of supported organocatalysts deactivation pathways of jorgensen-hayashi-type catalysts in asymmetric michael reactions." Chemistry, Vol.l7, No.22, (May 23, 2011), pp. 6109-6117, ISSN 1521-3765... 

Hayashi catalyst Figure 33.4 Hayashi and Jorgensen catalysts. 

Jorgensen and co-workers reported the enantioselective a-sulfenylation of aldehydes catalyzed by 6b (Equation 10.16) [34]. Hayashi et al. reported the 1,4-addition reaction of acetaldehyde with nitrostyrene in the presence of 6a (Scheme 10.17) [35]. The introduction of a siloxy group into proline increased its catalytic activity, thus allowing for a decrease in catalyst load and reaction time without compromising the... 

In contrast to the plethora of methodologies showing stereoselective applications of the Jorgensen-Hayashi catalyst (Chapter 8), a few reports have addressed the catal3dic ability of prolinol carbon-ethers in asymmetric synthesis. These procedures focused on the employment of commercially available (5)- or (R)-2-metho3qmiethylpyrrolidine, a scaffold originally... 

Prolinol silyl ethers were introduced independently by Jorgensen and Hayashi in 2005 (Figure 8.1) and this catalyst type quickly became one of the privileged structures in the asymmetric organocatalysis. ... 

The 0-TBS-hydro>y-diphenylprolinol silyl ethers 14, analogues of the Jorgensen-Hayashi catalyst 3a, were tested in 2008 by List and coworkers for the challenging catalytic asymmetric Michael reactions of acetaldehyde with nitroalkenes. While 4-hydroxy-proline derivative 14a displayed diminished activity, but slightly better enantioselectivity with respect to 3a, the 3-hydroxy-proline derivative 14b gave in this case very poor results (Scheme 11.12). 

Scheme 11.12 Asymmetric Michael addition between acetaldehyde and ( )-p-nitro-styerene catalysed by Jorgensen-Hayashi catalyst 3a and by diphe-nylprolinol silyl ethers 14.

Recently, Mayr and coworkers examined in detail the reactivity of catalysts (S )-34 and (S)-35d, comparing them to the Jorgensen-Hayashi-silylated (5)-a,a-diphenyl-prolinol 3a. While X-ray structures of the enamines deriving from (S)-34 and (S )-35d confirmed an almost perfect planarity of the enamine nitrogen, the high reactivity of catalyst (5)-35d was found to be due to a hyperconjugative interaction of ac si with 7i cn) increasing its Lewis basicity. ... 

Mechanism After the first report of iminium activation by MacMillan et al. in 2000, many studies have been made in this area. Two of the most important famihes of catalysts are MacMillan s catalysts and the TMS O-protected diaryl substituted prolinols developed independently by Jorgensen and Hayashi in 2005. 

In 2005 Jorgensen [12] and Hayashi [13] developed almost at the same time diarylproHnol derivahves protected as silyl ethers (Figure 33.4) as a suitable catalysts for inline and enamine achvation. 

As detailed in Scheme 42.23, the one-pot synthesis of ABT-341, potentially useful in the therapy for type 2 diabetes, was designed around the highly stereoselective Michael addition of acetaldehyde 90 to nitroalkene 91 catalyzed by the Jorgensen-Hayashi catalyst (R)-27. Then, exploiting the reactivity of the resulting nucleophilic intermediate 92, a domino transformation was carried out the... 

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