Enantioselective catalyst reactivity

The corresponding A-butyloxazaborolidine is also frequently used as a catalyst. The enantioselectivity and reactivity of these catalysts can be modified by changes in substituent groups to optimize selectivity toward a particular ketone.150 Catecholborane can also be used as the reductant.151... 

Some neutral rhodium catalysts with chiral ligands, such as MCCPM 9 (see Scheme 33.3) [20c], Cy,Cy-oxoProNOP 15, and Cp,Cp-IndoNOP 18, demonstrate excellent enantioselectivities and reactivities in the hydrogenation of a-ketoesters and ketoamides indeed, they compare well with ruthenium-based catalysts (Table 33.2). Togni et al. have successfully used the Josiphos 47 ligand for the hydrogenation of ethyl acetoacetate [27], while the use of MannOPs has led to somewhat high enantioselectivities [18]. 

Covalent attachment chiral Co(salen) complexes to polystyrene and silica gave efficient and highly enantioselective catalysts for the hydrolytic kinetic resolution (HKR) of terminal epoxides, including epichlorohydrin. These systems provide practical solutions to difficulties with the isolation of reaction products from the HKR. Removal of the supported catalyst by filtration and repeated recycling was demonstrated with no loss of reactivity or enantioselectivity. The immobilised catalysts have been adapted to a... 

Amino Ketones Amino ketones and their hydrochloride salts can be effectively hydrogenated with chiral rhodium catalysts (Tab. 1.9). The rhodium precatalysts, combined with chiral phosphorous ligands such as BPPFOH [10b], MCCPM [24f-k], Cy,Cy-oxo-ProNOP [79c, e], Cp,Cp-oxoProNOP [79c, e], and IndoNOP [79g], have provided excellent enantioselectivity and reactivity for the asymmetric hydrogenation of a, yS, and y-al-kyl amino ketone hydrochloride salts. 

It was clear that 1 would be derived from a Diels-Alder adduct. There has been a great deal of work in recent years around the development of enantioselective catalysts for the Diels-Alder reaction, but the catalysts that have been developed to date only work with activated dienophile-diene combinations. For less reactive dienes, it is still necessary to use chiral auxiliary control. One of the more effective of those was the known camphor-derived tertiary alcohol, so that was used in this project. Diels-Alder cycloaddition of the diene 4 with the enantiomerically-pure enone 5 led to the adduct 6 with high diastereocontrol. Oxidative cleavage led to the acid 7, which was carried on to the bis-enone I. 

For the synthesis of bidentate ligands, supramolecular approaches have led to a renaissance in homogeneous catalyst discovery (Chapters 2, 4, 8, 9,10), and in a few cases even monodentate ligands have been modified in a supramolecular fashion (Chapter 8, Section 8.2). Combinations of monodentate ligands can be left to chance and in several instances this has led to successful, new catalysts [96]. Such heterocombinations can form spontaneously for steric or electronic reasons or the reactivity of the combinations can be different such that on certain occasions highly enantioselective catalysts are obtained. There are many ways to synthesize the desired heterocombinations selectively and the ionic modification outlined in Section 10.4 is only one of them since nitration (followed by reduction to amines) and sulfonation are robust methods, the ionic route may prove useful. Hydrogen bonding between different donor-acceptors (Chapters 2 and 8), Lewis add-base interactions (Chapter... 

An allylic halide has been used to give a better result than the corresponding allylic acetate (Scheme 8E.21) [134]. Notably, only 0.05 mol% of catalyst was sufficient to produce the enantiopure product in 96% yield. To achieve high enantioselectivity, the reactivity of the substrate had to be modulated by slow addition of the nucleophile, This deracemization strategy offers an efficient alternative method for the preparation of hydroxylactone, which has served as a synthetically useful building block for various natural product syntheses [135,136]. 

Phosphines ligands that have chirality from ferrocenes have been implemented in the iridium-catalyzed asymmetric hydrogenation of imine with moderate enantioselectivities for Novartis s manufacture of metolachlor. Electronic modifications of these ferrocenyl ligands have increased the enantioselectivity and catalyst reactivity for Lonza s asymmetric hydrogenation processes of biotin and 2-substituted piperazines, intermediates for several pharmaceutical drugs. 

The reusability of the catalyst system was also examined in the hydrogenation of (Z)-methyl 2-acetamidobut-2-enoate. Using the filtration-recovered catalyst, the hydrogenation proceeded with near-quantitative conversion and constant enantioselectivity (96-92% ee) for at least 10 cycles and with a standard reaction time of 20 h. The reaction profile of the hydrogenation showed that the catalyst reactivity declined with consecutive runs, presumably due to partial catalyst decomposition during catalyst recovery. 

Since the diphosphine is appreciably more electron-rich than is BINAP, the major ruthenium complex is a more active hydrogenation catalyst than the parent. Increased electron-rich ligation may be the reason for the success of heterocyclic analogues of BINAP in which the binaphthalene is replaced by a bi(ben-zothiophene) or biindolyl the resulting Ru complexes are effective both in terms of enantioselectivity and reactivity [139]. Readers of the related Chapter 6.1 on the asymmetric hydrogenation of carbonyl compounds will encounter the Ru complexes of ligands in the DUPHOS family, where the ease of modification of the alkyl substituents of the phospholane enhances the power of the system, since it permits the easy optimization of ee for any substrate [140]. 

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