J0rgensen-Hayashi catalyst

An organocatalytic (j0rgensen-Hayashi catalyst 1) domino Micliael/Michael/aldol condensation was used to prepare a hexahydronaphtlialenone (+)-121 m route to the natural product (+)-galbulin (Scheme 7.22). In this case, it was proposed that an iminium salt 118 (activated from the re face) and an enamine species 117 were preformed. Following a kinetic asymmetric transformation (KAT) of the racemic precursor 115, the intermediate 119 is first formed through an intermolecular Michael reaction. A second intramolecular Michael reaction occurs and the intermediate 120 forms, and finally an acid-initiated aldol condensation... 

In 2009, Christmann and co-workers [111] disclosed a Ranhut-Currier-type intramolecular Michael reaction via dienamine activation for the construction of iridoid framework. Catalyzed by J0rgensen-Hayashi catalyst 7, the reaction proceeded well to afford the cyclopentene derivatives including (+)-rotundial in moderate to good yields with good enantioselectivities (Scheme 5.53). 

Following this, Chen and co-workers [43,44] successfully reported an aza-HAD (Scheme 6.16). They applied the J0rgensen-Hayashi catalyst 46 for catalytic HOMO activation of aldehydes 66 that readily underwent DA with enimine 73 to give optically active piperidine derivatives 74. The adducts 74 were obtained in moderate... 

It is interesting to note that the same chemistry starting from the corresponding allylic alcohols is possible providing the in situ oxidation (e.g., Mn02 or TPAP/NMO) followed by the enantioselective bromomalonate-promoted cyclopropanation with the J0rgensen-Hayashi catalyst B [36, 37]. 

Two complementary thia-Michael/aldol [28] and Michael/aldol [29] strategies from alkylideneindolones involving either a bifunctional tertiary amine-thiourea or the J0rgensen-Hayashi catalyst I have also been proposed contemporaneously. 

SCHEME 9.16 Tandem reaction combining a J0rgensen-Hayashi catalyst and an (R)-proline catalyst. 

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 nitroaUcene 91 catalyzed by the j0rgensen-Hayashi catalyst (R)-27. Then, exploiting the reactivity of the resulting nucleophilic intermediate 92, a domino transformation was carried out the... 

Very recently, Rovis et al. [20] reported the application of combined enamine and carbene catalysis in the diastereo- and enantioselective synthesis of functionalized cyclopentanones (Scheme 43.10). The authors proposed that the secondary amine catalyst was capable of epimerizmg the a-position of the intermediate aldehyde to form an equilibrium between two diastereomers. Then the chiral triazohum catalyst preferred cyclization with only one of these diastereomers to the final product. The second step of this reaction could be considered analogous to a dynamic kinetic resolution because the j0rgensen-Hayashi amine catalyst would be able to interconvert the two diastereomers. 

Not only alcohols can be used with the MacMiUan 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 soHds. Although the appH-cation of an SNl-type reaction with alcohols seems to be Hmited to the use of the MacMiUan catalyst, the Hayashi-J0rgensen catalyst is also suitable for this transformation [31]. 

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 families of catalysts are MacMillan s catalysts and the TMS O-protected diaryl substituted prolinols developed independently by j0rgensen and Hayashi in 2005. 

In 2005 j0rgensen [12] and Hayashi [13] developed almost at the same time diarylprolinol derivatives protected as silyl ethers (Figure 33.4) as a suitable catalysts for rmtne and enamtne activation. 

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