Desymmetrisation of epoxides

A large group of catalysts performed well in the opening of derivatives of ds-stilbene oxide 21.131 (R = Ar). A high level of enantioselectivity was attained with the axially chiral phosphoramide 21.140, BINAPO 21.14,  

In the case of the less sterically demanding aliphatic 21.131 [e.g. R = CH20Bn) and cyclic epoxides 21.136, the selectivity with these catalysts dropped to a modest level and helow. Cyclooctene oxide 21.136 ( = 8) proved to be a particularly difficult substrate, displaying low reactivity and selectivity with most of the Lewis bases except for the pinene-derived bipyridine mono-AT-oxide 21.23, which furnished the corresponding chlorohydrin in 90% ee. Catalyst 21.23 was also active with other cyclic 

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Enantioselective vanadium and niobium catalysts provide chemists with new and powerful tools for the efficient preparation of optically active molecules. Over the past few decades, the use of vanadium and niobium catalysts has been extended to a variety of different and complementaiy asymmetric reactions. These reactions include cyanide additions, oxidative coupling of 2-naphthols, Friedel-Crafts-type reactions, pinacol couplings, Diels-Alder reactions, Mannich-type reactions, desymmetrisation of epoxides and aziridines, hydroaminations, hydroaminoalkylations, sulfoxida-tions, epoxidations, and oxidation of a-hydroxy carbo) lates Thus, their major applications are in Lewis acid-based chemistiy and redox chemistry. In particular, vanadium is attractive as a metal catalyst in organic synthesis because of its natural abundance as well as its relatively low toxicity and moisture sensitivity compared with other metals. The fact that vanadium is present in nature in equal abundance to zinc (albeit in a more widely distributed form and more difficult to access) is not widely appreciated. Inspired by the activation of substrates in nature [e.g. bromoperoxidase. 

Epoxides are effectively ring-opened in the presence of lanthanide salts, and Schaus and Jacobsen have shown that the asymmetric desymmetrisation of cyclic mesu-epoxides with TMSCN can be achieved with up to 92% ee using ytterbium... 

Antilla developed a catalytic enantioselective desymmetrisation of meso-epoxides with thiols by using chiral lithium phosphate 17. A wide range of epoxides and aromatic thiols were observed with high enantioselectivities (Scheme 2.12). ... 

Scheme 2.12 Enantioselective desymmetrisation of meso-epoxides with thiols with the use of chiral lithium(i) phosphate.

Figure 21.6 Catalysts for desymmetrisation of meso-epoxides and their scope.

Applications of the AD to epoxide transformation propranolol and diltiazem Part V - Jacobsen Epoxidation Part VI - Desymmetrisation Reactions Opening anhydrides Opening epoxides... 

The starting material for the next desymmetrisation comes from an interesting reaction first described in chapter 19. The Pd-catalysed attack of AcOH on the mono-epoxide ( )-35 gives the racemic monoester 36. In order to convert this to a single enantiomer it is first made into the meso diester13 37. 

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