Desymmetrizations organocatalytic

The intramolecular aldol reaction of triketones with asymmetric desymmetrization has been known for a long time. When Eder, Sauer, and Wiechert [97, 98], and in parallel Hajos and Parrish [99-101] reported this reaction in the early 1970s it was the first example of an asymmetric catalytic aldol reaction, and one of the first examples of an organocatalytic asymmetric synthesis [104]. 

The field of organocatalytic enantioselective anhydride transformations has seen tremendous progress during recent years. For example, the alcoholytic desymmetrization of meso anhydrides, effected by stoichiometric quantities of inexpensive and readily available cinchona alkaloids, has been developed to a very practical level, and several applications, e.g. for the synthesis of enantiomerically pure... 

High enantiomeric excess in organocatalytic desymmetrization of meso-diols using chiral phosphines as nucleophilic catalysts was achieved for the first time by Vedejs et al. (Scheme 13.21) [36a], In this approach selectivity factors up to 5.5 were achieved when the C2-symmetric phospholane 42a was employed (application of chiral phosphines in the kinetic resolution of racemic secondary alcohols is discussed in Section 12.1). A later study compared the performance of the phos-pholanes 42b-d with that of the phosphabicyclooctanes 43a-c in the desymmetrization of meso-hydrobenzoin (Scheme 13.21) [36b], Improved enantioselectivity was observed for phospholanes 42b-d (86% for 42c) but reactions were usually slow. Currently the bicyclic compound 43a seems to be the best compromise between catalyst accessibility, reactivity, and enantioselectivity - the monobenzoate of hydrobenzoin has been obtained with a yield of 97% and up to 94% ee [36b]. 

It should finally be mentioned that chiral base methodology is not limited to the desymmetrization of meso-epoxides but also enables kinetic resolution of racemic epoxides [57, 63, 65], This (organocatalytic) type of reaction seems, however, to be less prominent than the desymmetrization of meso-epoxides. Some examples of kinetic resolution of chiral epoxides are summarized in Scheme 13.35. 

Although the use of asymmetric Baeyer-Villiger reactions for desymmetrization of several types of prochiral ketone using enzymes or metal-catalyzed systems is well established [81], few studies have been conducted on organocatalytic variants. An interesting organocatalytic Baeyer-Villiger reaction has been reported in which the planar-chiral bisflavin 32 (Fig. 12.12) promotes desymmetrization... 

Scheme 21 Organocatalytic desymmetrization approach towards (+)-cocaine (92)...

An organocatalytic desymmetrization of a /neso-anhydride was also the starting point in a recent efficient protecting group-free total synthesis of the monoterpenoid... 

Pinto, N., RetaUleau, R, Voituriez, A., Marinetti, A. (2011). Organocatalytic enantioselective desymmetrization of cychc enones via phosphine promoted [3+2] annulations. Chemical Communications, 47, 1015-1017. 

SCHEME 6.44 Organocatalytic desymmetrization of the meso-anhydride 276 in the syntheses of the monoterpenoid indole alkaloids ( )- and (Z)-alstoscholarine (275). 

Scheme 44.14 Synthesis of BAY 10-888 through an organocatalytic desymmetrization reaction.

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