Heterocycle-based organocatalysts

Indollne-2-carboxylic acid [79815-20-6] M 163.2, m 177"(dec), [a] -114" (c 1, N HCl). It is purified as the racemate (see [78348-24-0] in Heterocyclic Compound, Chapter 4). The S-(-)-hydrochloride [82923-76-0] M 199.7, m 133"(dec), [a] -70" (c 1, EtOH) crystallises from Et20/propan-2-ol. It is a proline based organocatalyst which promotes the enantioseleetive formation of cyclopropanes by reaction between 2-(dimethyl- 4-sulfanylidene)-l-phenyl-ethanone (for stable sulfonium ylides see Ratts Yao J Org Chem 31 1185 1966) and but-2-enals in high yields and very high stereoselectivity involving Direct Electrostatic Activation (DEA) [Kunz Mac Millan Chem Soc 127 3240 2005.]... 

Sterically and electronically tuneable and bifunctional organocatalysts based on diamides derived from proline are particularly selective in reactions of heterocyclic ketones with aldehydes.109... 

Abstract. Within the context of Lewis base catalysis /V-heterocyclic carbenes represent an extremely versatile class of organocatalyst that allows for a great variety of different transformations. Starting from the early investigations on benzoin, and later Stetter reactions, the mechanistic diversity of /V-hctcrocyclic carbenes, depending on their properties, has led to the development of several unprecedented catalytic reactions. This article will provide an overview of the versatile reactivity of A-heterocyclic carbenes. 

Recently, the reactivity (base, nucleophile, catalyst) and the role in modem organic synthesis of N-heterocyclic carbenes (cychc carbenes bearing at least one amino substituent) has been set-up by Ender et al. [60,61]. The possible utilization of NHCs as ligands for transition-metal catalyst [62,63] and as organocatalyst has been emphasized [61]. The inversion of the normal reactivity (umpolung) induced via NHCs has been extensively discussed. Classical carbon-carbon-bond-forming reactions (benzoin condensation, Stetter reaction, etc.) have been re-examined using ionic liquids as pre-catalysts in the presence of bases. 

Since the bulk properties of PLA are highly dependent on the stereoregularity or the tacticity of the polymer, i the development of catalysts for rac-lactide (or meso-lactide) polymerization has been focused on achieving stereoselectivity. 2 2 " Numerous organocatalysts such as A-heterocyclic carbenes (NHCs) and phosphine-based compounds " have been investigated for the controlled ROP of lactide. 

A range of metal-free organocatalysts have been used to good effect in the kinetic resolution of alcohols. A number of enantiomerically pure 4-aminopyridine-based catalysts effect kinetic resolution with high S values. These include the conforma-tionallyrestricted2,3-dihydroimidazo[l,2-a]pyridine (12.98) and the atropiso-meric catalyst (12.99). N-heterocyclic carbenes also function as nucleophilic... 

A combination of organocatalysts, the prolinol silylether 17b and an A-heterocyclic carbene (NHC), was used by Cordova and co-workers [64] for the related asymmetric P-boration of cinnamaldehyde. While the secondary amine served to activate the enal through the formation of a chiral iminium ion intermediate, the NHC functioned as a Lewis base forming the nucleophilic adduct with diborate. The product was treated in situ with a stabilized phosphorus ylide affording a synthetically useful chiral allylboronate (Scheme 14.22). A 50 mol% loading of amine was needed to reach reasonable enantioselectivity (60% ee). Lowering of the amine loading to 10 mol% caused a drop in the enantioselectivity (34% ee). 

Figure 1.6 Representative examples of ptoline-based heterocyclic organocatalysts.

For a long period, chiral Lewis acids were the most studied catalysts. Only recently have chiral bases, Br0nsted acids, and N-heterocyclic carbenes been utilized as effective organocatalysts for the oxa-hetero-Diels-Alder reaction. 

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