Organocatalytic phase-transfer catalysts

Organocatalytic asymmetric carbonyl reductions have been achieved with boranes in the presence of oxazaborolidine and phosphorus-based catalysts (Section 11.1), with borohydride reagents in the presence of phase-transfer catalysts (Section 11.2), and with hydrosilanes in the presence of chiral nucleophilic activators (Section 11.3). 

The asymmetric organocatalytic transformation of a ketone into an alcohol may be realized with the combination achiral silanexhiral phase-transfer catalyst, such a quaternary ammonium salt. The final alcohol is then recovered by an additional hydrolytic step. The asymmetric reduction of aryl alkyl ketones with silanes has been reported (ee-values up to 70%), the catalysts utilized being ammonium fluorides prepared from the quinine/quinidine series (e.g., 18 in Scheme 11.6) [19]. (For experimental details see Chapter 14.21.1). The more appropriated silanes were (Me3SiO)3SiH or (MeO)3SiH (some examples are... 

Abstract The organocatalytic asymmetric Mannich reaction and the related aza-Morita-Baylis-Hillman have been reviewed. The activities in this field have been snbdivided based on the types of catalysts that have been ntilized, which includes catalysis by enamine-forming chiral amines, chiral Br0nsted bases, chiral Brpnsted acids, and phase-transfer catalysts. 

An organocatalytic asymmetric hydroxylation of oxindoles by molecular oxygen as an oxidant using a phase-transfer catalyst was reported by Itoh et ai, in 2008. The use of O2 as the oxidant was a paramount process, because it is inexpensive and environmentally benign. In these conditions, the reaction of a series of 3-substituted oxindoles in the presence of a cinchonidine-derived... 

Recently, considerable efforts have been made to discover new organocatalytic systems for asymmehic epoxidation. In 2003, A arwal and coworkers reported that the asymmetric epoxidation of olefins proceeded in good yields and with moderate enantioselectivities using Oxone (Wako Chemicals, Osaka, Japan) as an oxidant in the presence of a 48-type catalyst (Scheme 1.22) [261]. According to their proposal, the protonated ammonium salt species can act not only as a phase-transfer catalyst to carry the real oxidant species to the organic phase but also as a promoter to activate the chiral oxidant via hydrogen-bonding stabilization, as depicted in 63. 

The power of this phase-transfer method is also emphasized by the economics of the process. It was reported that the cost of producing the desired (S) enantiomer on the basis of the asymmetric organocatalytic alkylation route using an amount of catalyst below 10 mol% was significantly lower than the cost of producing the isomer by a resolution process [50],... 

The direct enantioselective organocatalytic a-fluorination can also be performed with cinchona alkaloid derivatives as catalyst under phase-transfer reaction conditions [25]. The fluorination reaction by NFSI of / -ketoesters 21, readily enolizable substrates, generated a stereogenic quaternary C-F bond in high yields and with enantioselectivities up to 69% ee for the optically active products 26 (Eq. 6). 

A related example of an organocatalytic asymmetric Mannich reaction that makes use of an aqueous biphasic system (aq. K2CO3/toluene) was reported by Ricci et al. Catalysts 19 derive from quinine and act as typical phase-transfer reagents. Active methylene compounds are used as donors, and 7V-Boc and A-Cbz protected a-amido sulfones as precursors of TV-prolcclcd imines (Scheme 1.9). ... 

On the other hand, Palomo et al. have developed efficient organocatalytic asymmetric aza-Henry reactions under phase-transfer conditions. This method was based on the reaction of a nitroalkane with an azomethine generated from an a-amido sulfone promoted by CSOH.H2O as a base in toluene and in the presence of cinchonine-derived ammonium catalysts. The corresponding. syw-products were obtained in good yields, moderate to good diastereoselectivities (10-86% de) and moderate to excellent enantioselectivities... 

This chapter has presented motivating appUcations of organocatalysis in the synthesis of relevant biological active compounds. The most common organocatalytic approaches, such as aminocatalysis, hydrogen bond catalysis, cinchona alkaloids catalysts, and phase-transfer catalysis have been covered. We hope the reader now... 

Synthesis of eicosanoid 555 commenced with a stereoselective organocatalytic cyclopropanation achieved by reacting bromoacetate 559 with Michael acceptor 560 in the presence of dimeric catalyst 561. As the authors were not able to resolve product 562 using an enantioselective HPLC phase, the exact enantiomeric excess could not be determined oti this stage but was found to be satisfactory for the rest of the sequence. With respect to the synthesis of lactonealdehyde 556, the cyclopropanation was carried out by adding the Weinreb- m dt 563 to enone 564 to furnish the key intermediate 565, which was transferred further into 556 in a similar manner (474) (Scheme 118). 

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