Mannich reaction asymmetric complex

Mannich reaction. A complex derived from (r-BuOjaHf, imidazole and 6,6 -dibromo-BINOL is air-stable. It is capable of asymmetric induction in catalyzing the Mannich reaction (80-90% ee). ... 

The studies summarized above clearly bear testimony to the significance of Zr-based chiral catalysts in the important field of catalytic asymmetric synthesis. Chiral zircono-cenes promote unique reactions such as enantioselective alkene alkylations, processes that are not effectively catalyzed by any other chiral catalyst class. More recently, since about 1996, an impressive body of work has appeared that involves non-metallocene Zr catalysts. These chiral complexes are readily prepared (often in situ), easily modified, and effect a wide range of enantioselective C—C bond-forming reactions in an efficient manner (e. g. imine alkylations, Mannich reactions, aldol additions). 

Mannich reactions give rise to (i-amino carbonyl compounds which are amenable to further synthetic manipulations. Numerous stereoselective variants have been achieved by means of different types of catalysts including both metal complexes and organic molecules. In 2004, the groups of Akiyama and Terada independently selected this transformation as a model reaction for the introduction of a novel chiral motif to asymmetric catalysis [14, 15]. 

A direct catalytic asymmetric Mannich reaction using unmodified ketones was reported using cooperative catalysis of a AlLibis((i )-binaphthoxide) complex ((.R)-ALB) and La(0Tf)3-nH20 [27,28]. It was also reported that enantiose-lective and diastereoselective catalytic nitro-Mannich reactions of N-phosphi-noylimines proceeded smoothly using the complex of ALB and ferf-BuOK [29, 30] [(Eq. (5)]. 

Shibasaki and coworkers have conducted extensive research on the use of hetero-bimetallic complexes as catalysts for asymmetric synthesis [11]. The reactions are catalyzed by heterobimetallic complexes that function as both a Lewis acid and a Bronsted base. Among these, LaLi3tris(binaphthoxide) catalyst 1 (LLB) was proven to be an effective catalyst in direct asymmetric aldol reactions (Fig. 1) [12]. On the basis of this research, Shibasaki et al. reported the first report of a direct catalytic asymmetric Mannich reaction [13],... 

In 1998, Lectka and coworkers reported the asymmetric Mannich reaction of a-iminoesters catalyzed by a BINAP-Ag(I) complex (Scheme 9.14).25... 

In addition, Ir-complexes of DIFLUORPHOS (81) have been used in the asymmetric hydrogenation of quinolines (07SL2743). Very recently, its Cu(I)-complex (as CuOAc-DIFLOURPHOS) was identified as the catalyst of choice for the asymmetric reductive Mannich reaction of ketimines (93a-c) with a broad substrate scope providing high enantio- and diastereoselectivities (Scheme 19, 08JA16146). 

For example, an effective procedure for the synthesis of LLB (where LL = lanthanum and lithium) is treatment of LaCls 7H2O with 2.7 mol equiv. BINOL dilithium salt, and NaO-t-Bu (0.3 mol equiv.) in THF at 50 °C for 50 h. Another efficient procedure for the preparation of LLB starts from La(0-/-Pr)3 [54], the exposure of which to 3 mol equiv. BINOL in THF is followed by addition of butyllithium (3 mol equiv.) at 0 C. It is worthy of note that heterobimetallic asymmetric complexes which include LLB are stable in organic solvents such as THF, CH2CI2 and toluene which contain small amounts of water, and are also insensitive to oxygen. These heterobimetallic complexes can, by choice of suitable rare earth and alkali metals, be used to promote a variety of efficient asymmetric reactions, for example nitroaldol, aldol, Michael, nitro-Mannich-type, hydrophosphonylation, hydrophosphination, protonation and Diels-Alder reactions. A catalytic asymmetric nitroaldol reaction, a direct catalytic asymmetric aldol reaction, and a catalytic asymmetric nitro-Mannich-type reaction are discussed in detail below. 

The examples outlined in this chapter show that carbohydrates are efficient stereodifferentiating auxiliaries, which offer possibilities for stereochemical discrimination in a wide variety of chemical reactions. Interesting chiral products are accessible, including chiral carbo- and heterocycles, a- and 3-amino acid derivatives, 3-lactams, branched carbonyl compounds and amines. Owing to the immense material published since the time of the earlier review articles on carbohydrates in asymmetric synthesis [9,10], the examples discussed in this chapter necessarily focused on the use of carbohydrates as auxiliaries covalently linked to and cleavable from the substrate. Given the scope of this chapter, a discussion of other interesting asymmetric reactions has not been permitted — for example, reactions in which carbohydrate-derived Lewis acids, such as cyclopentadienyl titanium carbohydrate complexes, exhibit stereocontrol in aldol reactions [180]. Similarly, processes in which in situ glycosylation induces reactivity and stereodifferentiation — for example, in Mannich reactions of imines [181] — have also been excluded from this discussion. 

Scheme 46 Asymmetric catalytic Mannich reaction catalyzed by cationic Pd(II) complex as Lewis acid...

A. S. Demir, S. Basceken, Tetrahedron Asymmetry 2013, 24, 515-525. Study of asymmetric aldol and Mannich reactions catalyzed by proline-thiourea host-guest complexes in nonpolar solvents. 

Scheme 10 A catalytic asymmetric 5yn-selective nitro-Mannich reaction promoted by heterobimetallic Cu/Sm/dinucleating Schiff base complexes...

To test this concept, we applied [Cu" (trisox)] complexes in the asymmetric Mannich reaction [24] of a P-ketoester with an activated JV-tosyl-a-imino ester, a reaction that had been previously reported by Jorgensen et al. [25] using chiral copper(II)-BOX catalysts (10mol%). After optimization of the reaction conditions, the reaction product was obtained with an excellent enantiomeric excess of 90% using 10 mol% of the catalyst (Table 15.2) [24a]. 

Asymmetric Mannich-type reaction is a versatile method to prepare nonracemic P-amino carbonyl compounds, which can be transformed into P-lactams or related compounds. Lectka and coworkers have shown that a BINAP-silver(I) complex acts as asymmetric catalyst in the reaction of a-imino esters for the first time in 1998 [58]. The chiral silver (I) catalyst has been further applied to asymmetric ene reactions of a-imino esters [59, 60]. In contrast, Hoveyda and co workers have developed a new chiral silver(I) catalyst using iso-Leu-derived phosphine (44) as a chiral ligand, which promotes asymmetric Mannich reaction of silyl... 

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