Desymmetrization analog

Subsequent to the development of the (salen)Cr-catalyzed desymmetrization of meso-epoxides with azide (Scheme 7.3), Jacobsen discovered that the analogous (salen)Co(n) complex 6 promoted the enantioselective addition of benzoic acids to meso-epoxides to afford valuable monoprotected C2-symmetric diols (Scheme 7.15) [26], Under the reaction conditions, complex 6 served as a precatalyst for the (salen) Co(iii)-OBz complex, which was fonned in situ by aerobic oxidation. While the enantioselectivity was moderate for certain substrates, the high crystallinity of the products allowed access to enantiopure materials by simple recrystallization. 

The high chemoselectivity for the Baeyer-Villiger process was utilized in the synthetic elaboration of another hetero-bicyclic substrate. The biooxidation only provides the expected unsaturated lactone in a desymmetrization reaction without compromising the olefin functionality. The biotransformation product was then converted to pivotal intermediates for C-nucleosides like showdomycin, tetrahydro-furan natural products like kumausyne, and goniofufurone analogs in subsequent chemical operations (Scheme 9.17) [161]. 

Trost and co-workers have explored asymmetric transition metal-catalyzed allylic alkylations. Details on this subject have been well reviewed by Trost and others.90 With the use of asymmetric palladium-catalyzed desymmetrization of meso-2-ene-l,4-diols, cw-l,4-dibenzoy-loxy-2-cyclopentene can be converted to the enantiometrically pure cA-4-tert-butoxycar-bamoyl-l-methoxycarbonyl-2-cyclopentene.91 The product is a useful and general building block for synthesis of carbocyclic analogs of nucleosides as presented in Scheme 5.12. 

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) ... 

There have been a number of syntheses where the requisite stereochemistry has been introduced by the asymmetric desymmetrization of a variety of glutaric acid analogs... 

BINOL-Ti catalysis is also applicable to carbonyl-ene reaction with formaldehyde or vinylogous and alkynylogous analogs of glyoxylates in the catalytic desymmetrization (vide infra) approach to the asymmetric synthesis of isocarbacycline analogs (Scheme 8C.7) [24],... 

A plane of chirality is encountered in molecules in which a molecular plane is desymmetrized by a bridge (ansa compounds and analogs). Examples include the paraphane derivatives XXXV and XXXVI, and wwts-cycloalkenes (XXXVII). 

This methodology has been used to provide efficient protocols for the asymmetric allylic alkylation of p-keto esters, ketone enolates, barbituric acid derivatives, and nitroalkanes. Several natural products and analogs have been accessed using asymmetric desymmetrization of substrates with carbon nucleophiles. The palladium-catalyzed reaction of a dibenzoate with a sulfonylsuccinimide gave an advanced intermediate in the synthesis of L-showdomycin (eq 3). ... 

There is a frequently noted incompatibility of organoiithiums with many chiral Lewis acids, which are often employed for asymmetric openings of epoxides [99]. Analogous Lewis base-catalyzed reactions are rare [100]. However, activation by Lewis acids, such as BFj OEt2, is necessary for the opening of less reactive epoxides [101]. While organoiithiums are rarely employed, applications of hetero-nucleophiles are well known in enantioselective desymmetrizations of meso-epoxides [102]. 

Tetrasubstitution of one of the ethylene molecules in the symmetric coplanar arrangement desymmetrizes the pathway of least motion - or highest symmetry - from D2/1 to in which the highest occupied orbital of the reactant pair in Fig. 6.6 correlates no better with that of the tetrasubstituted cyclobutane than do the analogous MOs in Fig. 6.2 ... 

BINOL-Ti-catalyzed carbonyl-ene reaction of glyoxylate has also been applied to the asymmetric desymmetrization of prochiral ene substrates with planar symmetry and kinetic optical resolution of racemic ether. As shown in Scheme 14.55, optically active products can be obtained with extremely high enantiomeric excesses [140]. The asymmetric desymmetrization of meso olefin derivative via BINOL-Ti-catalyzed carbonyl-ene reaction of formaldehyde, vinyl and alkynyl analogs of glyoxylates has been applied to the synthesis of isocarbocycline analogs [141]. 

Desymmetrization of bicyclo[32.1]oct-6-en-3-one 79 toward both enantiomers of carba-analogous Showdomycin ((+)-81 (-)-81) using two BVMOs (top) [135] regioseiective kinetic resoiution of p-aminoketones 82 toward p-amino acids 84 (bottom) [136,137]. 

The chemical method for the synthesis of P2 moiety suffers from at least 50% yield loss in the resolution process [164]. Biocatalytic desymmetrization of substituted pyrrolidines to give the desired enantiomer is an attractive approach to access proline analogs. 

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