Enantioselective Claisen Rearrangements

R)-Pantolactone is also prepared in a sequence involving Claisen rearrangement of the chiral glycolate (24), although with poor enantioselectivity... 

There are a number of powerful synthetic reactions which join two trigonal carbons to form a CC single bond in a stereocontrolled way under proper reaction conditions. Included in this group are the aldol, Michael, Claisen rearrangement, ene and metalloallyl-carbonyl addition reactions. The corresponding transforms are powerfully stereosimplifying, especially when rendered enantioselective as well as diastereoselective by the use of chiral controller groups. Some examples are listed in Chart 20. 

By employing optically active enol borinates instead of silylketene acetals, the Ireland-Claisen rearrangement has been further developed to an enantioselective... 

Claisen rearrangements with 74 -, Diels-Alder reactions with 74 -, enantioselective reactions 74... 

Single isobacteriochlorin stereoisomers even in enantiomcrically pure form can be obtained230 when the Claisen rearrangement is performed with the pure hematoporphyrin stereoisomers23d which can be prepared by stereogenic enantioselective reduction from diacetyl deuteroporphyrin dimethyl ester. 

Because of the nature of the transition state in the pericyclic mechanism, optically active substrates with a chiral carbon at C-3 or C-4 transfer the chirality to the product, making this an enantioselective synthesis (see p. 1451 for an example in the mechanistically similar Claisen rearrangement). ... 

In 1997 the first asymmetric aza-Claisen rearrangement was reported by Overman et al. [55], which made use of diamines as bidentate ligands for Pd(II), allowing for moderate enantioselectivities. In the same year, Hollis and Overman described the application of the planar chiral ferrocenyl palladacycle 38 as a catalyst for the enantioselective aza-Claisen rearrangement of benzimidates 39 (Fig. 19) [56]. A related ferrocenyl imine palladacycle provided slightly inferior results, while a benzylamine palladacycle lacking the element of planar chirality was not able to provide any enantioselectivity [57]. 

A significant breakthrough was achieved by Overman and Donde in 1999 they reported the first highly selective catalyst 41 for the aza-Claisen rearrangement of benzimidates 39 (Fig. 20) [58]. Enantioselectivities were in most cases good to very good. 

Moyano A, Rosol M, Moreno RM, Lopez C, Maestro MA (2005) Oxazoline-mediated interannular cyclopalladation of ferrocene chiral palladium(II) catalysts for the enantioselective Azti-Claisen rearrangement. Angew Chem Int Ed 44 1865-1869... 

Weiss ME, Fischer DF, Xin ZQ, Jautze S, Schweizer WB, Peters R (2006) Practical, highly active, and enantioselective ferrocenyl-imidazoline palladacycle catalysts (FIPs) for the Aza-Claisen rearrangement of A-para-methoxyphenyl trifluoroacetimidates. Angew Chem Int Ed 45 5694-5698... 

The Claisen rearrangement has attracted much attention as an attractive tool for the construction of new carbon-carbon bonds. Various catalytic systems have been developed to afford enantioselective versions of this process. On the other hand, relatively few chiral sulfur-containing ligands have been investigated for this type of reaction. As an example, Taguchi et al. have... 

Wipf and coworkers used a Claisen rearrangement of allyl phenyl ethers 4-309 followed by an enantioselective carboalumination using the chiral Zr-complex 4-310 and trimethyl aluminum (Scheme 4.67) [104]. After an oxidative work-up of the intermediate trialkylalane, the corresponding alcohols 4-311 were obtained with up to 80% ee and 78% yield. One can also transfer an ethyl group using triethyl aluminum with even better ee-values (up to 92%), but the yields were rather low (42%) due to a more sluggish oxidative cleavage of the Al-C bond. 

The Claisen rearrangement of allyl vinyl ethers is a classic method for the stereoselective synthesis of y,J-unsaturated esters. The allylic C-H activation is an alternative way of generating the same products [135]. Reactions with silyl-substituted cyclohexenes 197 demonstrate how the diastereoselectivity in the formation of 198 improves (40% to 88% de) for the C-H insertion reactions as the size of the silyl group increases (TMS to TBDPS) (Tab. 14.14). Indeed, in cases where there is good size differentiation between the two substituents at a methylene site, high diastereo- and enantioselectivity is possible in the C-H activation. 

Bis(oxazoline) ligands have also been employed in the catalytic enantioselective aza-Claisen rearrangement of allylic imidates, " chirality recognition in the determination of the ee of l,l -bi-2-naphthol, " and the enantioselective formation of double and triple helicates. 

The enantioselective a-allylation of a ketone has become increasingly important. Martin Hiersmann of the Technische Universitat Dresden reports (Tetrahedron Lett. 2004,45, 3647) that a-ketoesters readily form enol ethers, such as 6. On exposure to an enantiomerically-purc Cu catalyst, the enol ethers undergo facile Claisen rearrangement, leading to the allylated ketone (e.g. 7) with high enantiomeric... 

In an attempt to achieve an enantioselective Eschenmoser-Claisen rearrangement with amide salts 6, (2R,5R)-l-(fluoroacetyl)-2,5-dimethylpyrrolidine was methylated to give chiral 6d. 5 Reaction of 6d with the lithium salt of (fj-crotyl alcohol gives amide 7d as a mixture of diastereomers, in which the. vj rt-isomers predominate. 

The method involves a highly enantioselective rearrangement of an epoxide and a subsequent Ireland-Claisen rearrangement (see Scheme 31). The enolate Claisen rearrangements of [4-7- /4-4-(l-acyloxy-2,4,6-octatrienyl)]tricarbonyl iron complexes... 

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