Organocatalysts quinine

The intramolecular aldol reaction can also proceed with high enantioselectivity. Daniel Romo of Texas A M University has shown (/ Org. Chem. 2005, 70,2835) that a quinine-derived organocatalyst Q works well for the cyclization of aldehyde acids such as 6 to the bicyclic p-lactone 8. Both 5- and 6-... 

Karl Anker Jorgensen of Aarhus University, Denmark has found (J. Am. Chem. Soc. 2005, /27, 3670) that face-selective addition can also be carried out on an activated aromatic ring. In this work, the chirality is delivered by a quinine-derived organocatalyst. 

Low cost Organocatalysts from Nature, such as proline and quinine acetate, are inexpensive and bio-renewable... 

Economic and practical reasons, in addition to green concerns, have meant that many of the first generation of asymmetric organocatalysts have been either natural molecules, such as nomicotine [52] and proline [40], derived directly from the chiral pool (Figure 7.1), or simple derivatives thereof, such as quinine acetate [53] and 5,5-dimethyl thiazolidinium-4-carboxylate (DMTC) [54], which are expected to be either biodegradable or biotransformable, with little impact on the environment. [54]. 

An interesting recent publication of an enantioselective transformation using quinine as an organocatalyst suggests the following transition state ... 

In 2007, Jorgensen and coworkers reported an asymmetric a-arylation of [1-ketoester 101 under homogeneous condition using (—)-quinine as organocatalyst (Scheme 6.30) [58]. They demonstrated that the reaction of [hkctoesters 101 with 1,4-quinone 102 could be a good strategy of enantioselective a-arylation for aromatic... 

Yan and co-workers have also utilized bromomalonate 22, but using a nitro-olefin as the electrophile and a P-aminoalcohol quinine derivative 27 as the organocatalyst (Scheme 1.7) [8]. No retro-Michael reaction appears to have been observed. 

With respect to the use of Cinchona alkaloid-derived organocatalysts, the first example of asymmetric Michel addition of ketones to enones appeared in 1979 when Trost illustrated, during the total synthesis of the sesquiterpene ( )-hirsutic acid C [101], a stereoselective (30% ee) quinine (59)-catalyzed intramolecular conjugate addition of an intermediate functionalized cyclohexanone (Scheme 2.32). 

Cyclopentenone as well as acyclic enones have been productively used in the conjugate addition with aromatic and aliphatic thiols employing catalysts 203 [383] and 204 [384] (Fig. 2.28). Quinine-derived urea catalyst 203 is a very active organocatalyst for the addition of aromatic nucleophiles to cyclic and acyclic enones working at rt under very low loading conditions (0.1 mol%) [383]. 

Garcia-Tellado and his coworkers have reported an organocatalyzed 1,3-dipolar cycloaddition of alkynoate 231 and nitrones 230 in the presence of triphenylphos-phane, quinine or quinuclidine on water [91], affording 2,3-dihydroxazoles 232, Scheme 3.74 [92], Initial addition of the organocatalyst (e.g., quinine, quinuclidine or Ph P) to alkynoate 231 generated the zwitterionic allenolate. Regioselective... 

The addition of diphenyl phosphite to ketimines derived from isatin was attempted using several Cinchona derived organocatalysts. The best results were achieved with a quinine-derived bifunctional squaramide (Q-SQ 1),... 

Brpnsted bases have been explored in cooperative catalysis to deprotonate substrates that subsequently add to metal-activated electrophiles. Regarding the use of these organocatalysts in cooperative catalysis, the combination of quinine and quinine-derived thiourea organocatalysts with Cu(II)-PhBox and Cu(OTf) has been employed in aza-Henry [23] and... 

The first highly enantioselective epoxidation of cyclic enones was developed by List et al. by using hydrogen peroxide as the oxidant and a chiral primary amine salt as the organocatalyst. A series of primary amine salts were investigated for this reaction and the best results were obtained with a quinine-derived primary amine salt, which provided excellent enantioselectivities of up to 99% ee for a variety of cyclic enones, as shown in Scheme 7.7. 

An enantioselective, one-pot sequence of Mannich reaction and hydroamination, catalysed by a combination of the quinine-derived organocatalyst (185) and gold(I)-... 

The multi-functional organocatalyst (379), combining the features of quinine, t-leucine, and thiourea, was employed to attain the Michael addition of phthalides to nitroalkenes RCH=CHN02, which afforded (380) with <98% ee and >19 1 dr Thiourea (381) (10mol%) has been reported to catalyse the addition of 3-aminooxindoles to nitroalkenes RCH=CHN02 in CH2CI2 at 0°C adducts (382)... 

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