Asymmetric reactions desymmetrizations

Precursor of Useful Chiral Ligands. OPEN is widely used for the preparation of chiral ligands. Organometallic compounds with these ligands act as useful reagents or catalysts in asymmetric induction reactions such as dihydroxylation of olefins, transfer hydrogenation of ketones and imines, Diels-Alder and aldol reactions, desymmetrization of meso-diols to produce chiral oxazolidinones, epoxidation of simple olefins, benzylic hydroxylation, and borohydride reduction of ketones, imines, and a,p-unsaturated carboxylates. ... 

The most powerful approaches, which can be used with several different enzyme systems, lead to a single enantiomer as the product in high yield and do not rely on a classic resolution approach in which the unwanted enantiomer is discarded. These approaches include dynamic kinetic resolutions, der-acemizations, and asymmetric and desymmetrization reactions (49, 50). In some cases, a chemical catalyst may be available to recycle the unwanted isomer in the same reactor vide infra). It is sometimes possible to racemize the unwanted isomer of the substrate and then to perform the reaction again (51). 

The BINOL-Ti catalyst can also be used for the carbonyl-ene reaction with formaldehyde or vinyl and alkynyl analogues of glyoxylates in an asymmetric catalytic desymmetrization (vide infra) approach to the asymmetric synthesis of isocarbacycline analogues (Scheme 7) [31a, 31b]. 

CIL 90 in combination with phthalic acid efficiently catalyzed asymmetric reactions of cyclic ketones 93 with diarylhydroxymethane derivatives 94, affording alkylation products 95 with yields from moderate to high and a broad range of enantiomeric excess (8-87% ee) [104] (Scheme 22.29). Presumably, ketone 93-derived enamines and alcohol 94-sourced diarylmethyl cations were intermediates in these reactions. Desymmetrization products 95 [R, = CH2CH(R)CH2]... 

In contrast, Cozzi and Umani-Ronchi found the (salen)Cr-Cl complex 2 to be very effective for the desymmetrization of meso-slilbene oxide with use of substituted indoles as nucleophiles (Scheme 7.25) [49]. The reaction is high-yielding, highly enantioselective, and takes place exclusively at sp2-hybridized C3, independently of the indole substitution pattern at positions 1 and 2. The successful use of N-alkyl substrates (Scheme 7.25, entries 2 and 4) suggests that nucleophile activation does not occur in this reaction, in stark contrast with the highly enantioselective cooperative bimetallic mechanism of the (salen)Cr-Cl-catalyzed asymmetric azidolysis reaction (Scheme 7.5). However, no kinetic studies on this reaction were reported. 

In an asymmetric synthesis, the enantiomeric composition of the product remains constant as the reaction proceeds. In practice, ho vever, many enzymatic desymmetrizations undergo a subsequent kinetic resolution as illustrated in Figure 6.5. For instance, hydrolysis of a prochiral diacetate first gives the chiral monoalcohol monoester, but this product is also a substrate for the hydrolase, resulting in the production of... 

Other reactions not described here are formal [3 -i- 2] cycloadditions of a,p-unsaturated acyl-fluorides with allylsilanes [116], or the desymmetrization of meso epoxides [117]. For many of the reactions shown above, the planar chiral Fe-sandwich complexes are the first catalysts allowing for broad substrate scope in combination with high enantioselectivities and yields. Clearly, these milestones in asymmetric Lewis-base catalysis are stimulating the still ongoing design of improved catalysts. 

The catalytic enantioselective desymmetrization of meso compounds is a powerful tool for the construction of enantiomerically enriched functionalized products." Meso cyclic allylic diol derivatives are challenging substrates for the asymmetric allylic substitution reaction owing to the potential competition of several reaction pathways. In particular, S 2 and 5n2 substitutions can occur, and both with either retention or inversion of the stereochemistry. In the... 

Formal hydration of the double bond appeared by the hydroboration-oxidation sequence. Desymmetrization reactions with catalytic asymmetric hydroboration are not restricted to norbornene or nonfunctionalized substrates and can be successfully applied to meso bicyclic hydrazines. In the case of 157, hydroxy derivative 158 is formed with only moderate enantioselectivity both using Rh or Ir precatalysts. Interestingly, a reversal of enantioselectivity is observed for the catalytic desymmetrization reaction by exchanging these two transition metals. Rh-catalyzed hydroboration involves a metal-H insertion, and a boryl migration is involved when using an Ir precatalyst (Equation 17) <2002JA12098, 2002JOC3522>. 

Related catalytic enantioselective processes [115] Two catalytic procedures for asymmetric addition of cyanides to meso epoxides have been reported [116]. One is the result of work carried out in these laboratories, shown in Eq. 6.24, promoted by Ti-peptide chiral complexes, while the other, developed by Jacobsen and Schaus, is a Yb-catalyzed enantioselective reaction that is effected in the presence of pybox ligands (Eq. 6.25) [117]. Although the Shibasaki method (Eq. 6.21) is not as enantioselective as these latter methods, it has the advantage that it accomplishes both the epoxidation and subsequent desymmetrization in a single vessel. 

The process of obtaining homochiral product from a prochiral starting material is known as asymmetrization. This encompasses reactions where a faster rate of attack of a reactive species occurs on one enantiotopic face of a prochiral trigonal biplanar system, or at one enantiotopic substituent of a C2 symmetrical system, resulting in the preferential formation of one product enantiomer. The latter is also frequently referred to as the meso-trick or desymmetrization . These transformations can be more easily defined in pictorial form (Figure 1.8). 

Nugent, W. A. (1998) Desymmetrization of meso-epoxides with halides A new catalytic reaction based on mechanistic insight, J. Am. Chem. Soc., 120 7139-7140. Bruns, S. Haufe, G. (1999) Catalytic asymmetric ring opening of epoxides to chlorohydrins with mild chloride donors and enantiopure titanium complexes.. 

RECENT ADVANCES IN CATALYTIC ASYMMETRIC DESYMMETRIZATION REACTIONS... 

Burke and Jiang have utilized Trost s ligand and the asymmetric ally lie alkylation to desymmetrize a tetraol diacetate as a potential route to a fragment of haU-chondrin B. Unfortunately, enantioselectivity was not determined in this reaction, although optical rotation suggests measurable selectivity ... 

Jeong and coworkers have executed a desymmetrization of a dienyne by asymmetric Pauson-Khand-type reaction. Intriguingly, the use of a Rh catalyst resulted in preferential formation of one diastereomer, while a switch to the analogous Ir system provided the other diastereomer in excellent selectivity [Eq. (10.62)] the system has been shown to be tolerant of oxygen in the linker as well as modest substitution on the alkyne (Ph) ... 

Landais has extended his desymmetrization of dienes from dihydroxylation approaches to a cyclopropanation reaction. A Cu-pybox complex provides the highest enantioselectivities and good diastereoselectivity in the asymmetric cyclopropanation of the silyl-substituted cyclopentadiene 210 ... 

Catalytic asymmetric desymmetrization as a field is still growing, with new applications appearing weekly. It is evident that advances in this subfield have kept in step with advances in catalysis as a whole. Some spectacular successes have been reported in recent years, and this strategy has been applied to many new reactions. Willis mentions in conclusion to his 1999 review of this field that desymmetrization reactions involving catalytic enantioselective construction of C—C bonds are... 

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