Desymmetrization strategy

Another way of constructing axially chiral binaphthyls under nickel catalysis involves an enantioselective desymmetrization strategy. Thus, dinaphthothiophene... 

The enantioselective desymmetrization strategy can also be used for the palladium-catalyzed cross-coupling reactions with Grignard reagents. Thus, in the... 

Desymmetrization strategy in enantioselective oxonium ylide formation/[l,2]-shift reaction has been reported by Doyle and co-workers.With dirhodium(ii) tetrakis[methyl l-(3-phenylpropanoyl)-2-oxoimidazolidine-4(3 )-carboxylate] [Rh2(43 -MPPIM)4] as the catalyst, up to 88% ee is obtained (Equation (7)). 

Inoue, M., Lee, N., Kasuya, S., Sato, T., Hirama, M., Moriyama, M., and Fukuyama, Y. (2007) Total synthesis and bioactivity of an unnatural enantiomer of merrilactone a development of an enantioselective desymmetrization strategy. Journal of Organic Chemistry, 72, 3065-3075. 

Although the hydroacylation reactions of simple alkynes will not generate new stereogenic centers on the alkyne moiety, nevertheless, the asymmetric intramolecular hydroacylation reactions of alkynes have emerged by applying either kinetic resolution or a desymmetrization strategy. 

NHC catalysis has been efficiently employed in an intramolecular crossed-benzoin reaction of symmetrical reactants. This desymmetrization strategy can be applied to (g) asymmetric synthesis with chiral NHCs. As an example, bis(acyloin) (91) containing three contiguous quaternary bridgehead chiral centres was synthesized and structurally characterized by X-ray crystallography. 

In another example of the power of amine nucleophiles in the AAA reaction, Trost reported a highly enantioselective route to mannostatin A (77), a specific nanomolar inhibitor of a-D-mannosidase. Once again a desymmetrization strategy was employed, cyclizing meso substrate 75 in an intramolecular AAA reaction to give adduct 76. While other ligands provided inefficient in this task, the diphenylphosphino benzoic acid-based ligand 59 delivered key intermediate 76 in 97% ee, which was subsequently converted to mannostatin A (77). 

Yadav JS, Rao KVR, Ravindar K, Subba Reddy BV. Total synthesis of (+)-bourgeanic acid utilizing desymmetrization strategy. Eur. J. Org. Chem. 2011 58-61 and references therein. 

Inoue M, Lee N, Kasuya S, Sato T, Hirama M, Moriyama M, Fukuyama Y. Total synthesis and bioactivity of an uimatural enantiomer of merrilactone A development of an enantioselective desymmetrization strategy. J. Org. Chem. 2007 72 3065-3075. 

The 6,8-dioxabicyclo[3.2.1]octane skeleton has been a common structural subunit in natural products. A conceptually new strategy affording these structures is described by Burk et al. [Eqs. (6.67) and (6.68)]. For the syntheses of (+)-exo-brevicomin, they used desymmetrization of triene 97, derived from diol 96 with C2 symmetry, via ring-closing metathesis. Enantiomerically enriched (- -)-ent/o-brevicomm... 

Whatever the nomenclamre, the concept of an enantioselective desymmetrization can be a powerful strategy when executed efficiently. The ability of the reaction to simultaneously control multiple stereogenic centers in a single transformation is attractive. The caveat that must be applied is that the substrates are not always readily available and the success of the reaction may be greatly tempered by the difficulty of accessing the starting material. ... 

Desymmetrizations by C—H insertion using diazo decomposition strategies is well established. Chiu and coworkers have recently applied this strategy to the oxabicyclic system 195. A ferf-leucine-derived Rh(II) catalyst provided the best results [Eq. (10.58a)]. Wardrop and coworkers have applied a similar strategy en route to sordidin unfortunately, both yield and ee proved to be suboptimal [Eq. (10.58b)] ... 

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... 

One question of course was, what the scope and limitations of the new catenane synthesis were and how the yields of the catenane could be increased. The first step towards greater variability of this synthesis was the stepwise sequence shown in Scheme 8. It permits the generation of macrocycles which are desymmetrized with respect to their two dicarboxylic amide building blocks. Many catenanes with such wheels can be synthesized by this strategy.26 It turned out that the product... 

An enantioselective aza-Wittig strategy has been employed in the desymmetrization of prochiral 1,3-diketoazides, to produce /3-quaternary azacycles.241... 

Neri, C. Williams, J. M. J. New routes to chiral Evans auxiliaries by enzymatic desymmetrization and resolution strategies. Adv. Synth. Catal. 2003, 345, 835-848. 

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