Organocatalysts diarylprolinol silyl ether

SCHEME 5.2. Reusable diarylprolinol silyl ether organocatalysts. 

In 2009, Lin et al. reported an enantioselective synthesis of an important Janus kinase inhibitor, INCBO18424, the key step of which was an asymmetric aza-Michael addition of pyrazoles to an a,p-unsaturated aldehyde catalysed by a chiral diarylprolinol silyl ether. The use of benzoic acid or 4-nitrobenzoic acid as an additive was shown to increase the reaction rate. The highest enantioselectivities of up to 93% ee were observed for the reactions using the more sterically hindered organocatalysts (Scheme 1.68). 

In 2009, a diarylprolinol silyl ether was involved as an organocatalyst in an asymmetric domino aldol-oxa-Michael reaction occurring between salicy-laldehyde and senecialdehyde. As shown in Scheme 2.28, this process generated the corresponding chiral tricyclic systems in good yields and high enantioselectivities of up to 98% ee. One of these products could be further converted into 4-dehydroxydiversonol. 

On the other hand, a diarylprolinol silyl ether salt was demonstrated by Hayashi et al. to be an efficient organocatalyst for the enantioselective Diels-Alder reaction of cyclopentadiene with a,p-unsaturated aldehydes performed in water. Under these solvent-free conditions, the cycloadducts were obtained in high yields with good exo selectivities and excellent enantioselectivities of up to 99% ee (Scheme 6.5). The authors have examined the role of water and demonstrated that it accelerated the reaction and increased the enantioselectivity. 

An A-Boc sulfone derivative has been used for in situ generation of an a-keto imine, which undergoes an asymmetric Mannich reaction, using a diarylprolinol silyl ether (17) as organocatalyst." 0... 

Organocatalysts To date, the main classes of organocatalysts that have been used are [42] imidazolidinone, diarylprolinol silyl ether, cinchona alkaloid, and phosphoric acid and thiourea derivatives. Essentially, two modes of activation can be considered the reversible formation of iminiums/enamines (covalent activation) with a,P-unsaturated aldehydes and ketones in the presence of primary or secondary chiral amines (Figure 35.1), and activation via hydrogen-bond formation (non-covalent activation) when chiral catalysts bearing hydrogen-bond donors are used (Figure 35.2). 

Recently, Chen, Jorgensen, and coworkers discovered a novel activation mode by the condensation of chiral amines with polyenals 37 to generate reactive trien-amine intermediates J that can participate in asymmetric Diels-Alder reactions with different classes of dienophiles (Scheme 38.12) to afford cycloadducts 38 [20]. With the use of chiral diarylprolinol silyl ether 40 as organocatalysts, various spi-rocyclic oxindoles 41 and multifunctional cyclohexenes 43 can be obtained in high... 

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