Organocatalytic reactions, enantioselection protonation

In the previons section, secondary chiral amines were employed that give rise to enamine formation npon reaction with ketones or aldehydes. Chiral tertiary amines, unable to form enamines, are nevertheless capable of inducing enantioselectivity in case substrates are used that contain sufficiently acidic protons such as aldehydes, ketones or active methylene compounds [33]. The cinchona alkaloids, by far the most versatile source of Brpnsted base catalysts, have played a prominent role in various types of asymmetric organocatalytic reactions [34], which is also true for the Mannich reaction. 

Quite surprisingly, whereas the chemistry of silyl enolates is considered as one of the cornerstones in organic synthesis, only a few papers have been devoted to organocatalytic enantioselective protonation of this class of substrates. The first organocatalyzed process was reported by Levacher et al. [33] by making use of cinchona alkaloids as catalysts and a latent source of hydrogen fluoride. The mechanism postulated by the authors is illustrated in Scheme 3.38. Basically, the reaction between benzoyl fluoride and ethanol in the presence of a catalytic amount of... 

The Muzart group reported an organocatalytic protonation reaction based on an in situ-formation of the required enolate by photochemical tautomerization of the chiral ammonium enolate 26 as an initial step [21]. The ammonium ion in 26 functions as the chiral proton source. Subsequent esterification affords the desired car-boxylate 20 in up to 65% yield and enantioselectivity in the range 40-85% ee. An example is shown in Scheme 9.8. The best results were obtained by use of the secondary, N-isopropyl-substituted aminobornanol for formation of the chiral ammo-... 

A key step in the total synthesis of the marine metabolite (—)-solanopyrone D (161) is the enantioselective organocatalytic intramolecular Diels-Alder reaction of the trienal (158) to the decalin aldehyde (160) in the presence of the imidazolidinone catalyst (159) (Scheme 45).187 Protonated 1,2-diamino-1,2-diphenylethane has been... 

A successful asymmetric organocatalytic based C=0 reduction with the Hantzsch ester was not reported until very recently. Terada and Toda developed a relay catalysis that combined Rh(ll) and a chiral phosphoric acid catalyst in a one-pot reaction (Scheme 32.15). In this reaction sequence, a rhodium carbene (I) forms in the first step and is followed with an intramolecular cyclization to afford carbonyl ylide intermediate II or oxidopyrylium III. These intermediates are protonated by 7 to yield the chiral ion pair between isobenzopyrylium and the conjugate base of 7 (IV). Intermediate IV is further reduced in situ by Hantzsch ester Id to produce the isochroman-4-one derivative 67, which is finally trapped with benzoyl chloride to afford the chiral product 68. Surprisingly, the reaction sequence proceeds well to give racemic product even without the addition of chiral 7, while giving rise to the desired product with high enantioselectivity in the presence of chiral Br0nsted acid 7 [38]. 

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