Meso cyclic

Enantioselective alcoholysis of racemic, prochiral, or meso cyclic anhydrides can be catalyzed by hydrolases, yielding the corresponding monoesters (Eigure 6.25). In most cases, the enantioselectivity was moderate ]75-77]. Organometallic catalysts or organocatalysts such as cinchona alkaloids are often more efficient than enzymes for the stereoselective ring opening of cyclic anhydrides. 

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... 

Scheme 1.65 Cu-catalysed desymmetrization of meso cyclic ally lie bisdiethylpho-sphate with ZnEt2 in the presence of P-aminosulfonamide ligands.

Enantioselective desymmetrization of the seven-membered meso-cyclic disulfide 128 (n = 3, R = Me) by desulfurization with a chiral rert-aminophospine, gave 129 (n = 3, R = Me) in modest yields with up to 30% ee <00JCS(P1)1595>. 

Nagao has disclosed bifunctional chiral sulfonamide 69 as being effective for the thiolytic ASD of meso-cyclic anhydrides in up to 98% ee when employed at the 5 mol% level for 20 h at room temperature in ether [228], Catalyst 69 is a 1,2-diamine derivative in which one of the nitrogens presents as an acidic NH group (part of an electron deficient aryl sulfonamide) and the other as a nucleophihc/basic teri-amine group with the intention to act synergistically in activation of the substrate carbonyl function and thiol nucleophile respectively (Fig. 16) [228],... 

Scheme 8E.15. Desymmetrization of seven-membered meso-cyclic compound.

Banfi and co-workers have also employed similar methodology to access meso-cyclic yS-turn scaffolds by the tandem U-MCR/RCM procedure generating such macrocyclic structures as 87 [73]. 

Desymmetrization of prochiral cyclic anhydrides In the presence of the chiral nucleophilic catalyst (e.g. A, Scheme 13.1, top) one of the enantiotopic carbonyl groups of the prochiral (usually meso) cyclic anhydride substrate is selectively converted into an ester. Application of catalyst B (usually the enantiomer or a pseudoenantiomer of A) results in generation of the enantiomeric product ester. Ideally, 100% of one enantiomerically pure product can be generated from the starting anhydride. No reports of desymmetrizing alcoholyses of acyclic meso anhydrides appear to exist in the literature. 

Y. Y. Chu, Y. Synthetic studies on d-biotin, part 6 an expeditious and enantiocontrolled approach to the total synthesis of d-biotin via a polymer-supported chiral oxazaborolidine-cata-lyzed reduction of meso-cyclic imide strategy. Synthesis 2003, 2155-2160. 

Type II Alcoholative ASD of Achiral/meso-Cyclic Anhydrides... 

In 2000, Deng reported that commercially available Sharpless ligands also catalyze the highly enantioselective alcoholysis of meso-cyclic anhydrides [179]. 

Surprisingly few studies have been directed towards the development of noncinchona alkaloid-based catalysts for the alcoholative ASD of meso-anhydrides, or indeed any of the enantioselective alcoholysis processes. Uozumi has reported a series of (2S, 4R)-4-hydroxyproline-derived 2-aryl-6-hydroxyhexahydro-lfi-pyr-rolo[l,2-c] imidazolones which mediate the methanolytic ASD of ds-hexa-hydrophthalic anhydride in up to 89% ee when employed at the 10 mol% level for 20 h at —25 °C in toluene [186]. Additionally, Nagao has described the use of a bifunctional chiral sulfonamide for the thiolytic ASD of meso-cyclic anhydrides in up to 98% ee when employed at the 5 mol% level for 20 h at rt in ether [187]. 

A highly regio-, diastereo-, and enantioselective desymmetrisation of five-, six-, and seven-membered meso-cyclic allylic bis-diethyl phosphates (104), (105) and (106), was achieved with diethylzinc using catalytic amounts of [Cu(OTf)]2, CgHg and phosphoramidite ligands (107). The addition of diethylzinc to cyclopentene, cyclohexene, and cycloheptene bis-diethyl phosphates, provided allylic monophosphates (108), (109) and (110) with enantiomeric excess of up to 87, 94 and >98%, respectively (Scheme 28). ... 

There has been considerable interest in the stereoselective ring opening of meso-cyclic anhydrides. The stereoselective alcoholysis of these anhydrides is particularly attractive as the resulting hemiesters are used as versatile intermediates in the construction of many bioactive compounds [1], Much effort has, therefore, been devoted to the development of efficient enzymatic and nonenzymatic catalytic systems for this reaction [2], Among the stereoselective catalysts developed to date,... 

However, highly interestingly, unusual concentration and temperature effects on the enantioselectivity were observed by Song and coworkers [11a]. As shown in Figure 11.2, the enantioselectivity in the methanolytic desymmetrization reaction of the meso-cyclic anhydride IS increases with increasing dilution of the reaction mixture and on raising the reaction temperature from —20 to 20 °C. 

The enantiomerically enriched 4-hydroxyenones 32 are an important class of chiral building blocks. This class of molecules has generally been obtained by the enzymatic or nonenzymatic catalytic desymmetrization of meso-cyclic diols 31 (or their derivatives) that can be prepared from the meso-endoperoxides 30 [32]. It is also well known that achiral bases such as NEt3 can promote the Kornblum-DeLaMare rearrangement of the meso-endoperoxides 30 [33]. This process is believed to proceed via the E2... 

Diaryl-1,3-butadienes are obtained from ArCOMe directly by the reaction with Sml2 and AC2O in refluxing THF. ° Transannular addition of ketyl species generated from meso-cyclic ketones to a double bond is quite efficient. 

A few seven-membered cyclic sulfites derived from dl- and meso-2,5-hexanediols rearranged to cis- and /rans-2,5-dimethyltetrahydrofuran (96a and 96b) when allowed to stay at room temperature. The meso cyclic sulfite... 

Seven-membered meso-cyclic sulfate 291 also undergoes ring opening with sodium diethylphosphite in DMF to give diethylphosphono alcohol 292, which after hydrolysis (95TA3055) is finally converted into optically active hydantoins 293 (Scheme 74). 

Enantioselective copper-catalyzed desymmetrization of meso cyclic allylic bisdiethyl-phosphates has alsobeen conducted with dialkylzinc reagents. Piarulli and Gennari initially showed that the copper(l) complex of a chiral Schiff base catalyzed tlie enantioselective desymmetrization of 4-cyclopentene-l,3-bis(diethylphosphate) with diethyzinc (Equation 20.75). Piarulli, Gennari, and Feringa then improved upon the enantioselectivities... 

DESYMMETRiZATiON OF meso-CYCLic KETONES 13 To a solution of ketone 13 (0.10 mmol) and the chiral catalyst solution prepared beforehand (0.005 mmol... 

Scheme 4.4 Desymmetrization of meso cyclic ketones and kinetic resolntion of racemic 2-arylcyclohexanones by enantioselective Baeyer—VUliger oxidation.

Zhou, L., Liu, X., Ji, J., Zhang, Y, Hu, X., Lin, L., Feng, X. (2012). Enantioselective Baeyer-Villiger oxidation desymmetrization of meso cyclic ketones and kinetic resolution of racemic 2-arylcyclohexanones. Journal of the American Chemical Society, 134, 17023-17026. 

SCHEME 71 Desymmetric hydrogenation of a meso-cyclic acid anhydride. 

In Volumes 3 and 4, there are chapters describing stereo-specific polymerization of vinyl and cyclic monomers, formation of isotactic and syndiotactic polymers, and polymerization of racemic (as well as meso) cyclic monomers. 

When an anhydride such as succinic anhydride is reacted with a racemic alcohol in organic solvent with a lipase, an enantioselective resolution can be achieved [89]. The enantioselective opening of racemic or meso cyclic anhydrides can constitute a good method for the preparation of nearly optically pure esters [90-93]. Examples of these reactions are depicted in Scheme 13. 

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