Ireland-Claisen rearrangement stereochemistry

The stereochemistry of Ireland-Claisen rearrangements of cyclic compounds is sometimes indicative of reaction through a boat TS. For example, the major product from 2-cyclohexenyl propanoate is formed through a boat TS.244... 

The synthesis in Scheme 13.44 is also based on a carbohydrate-derived starting material. It controlled the stereochemistry at C(2) by means of the stereoselectivity of the Ireland-Claisen rearrangement in Step A (see Section 6.4.2.3). The ester enolate was formed under conditions in which the T -enolate is expected to predominate. Heating the resulting silyl enol ether gave a 9 1 preference for the expected stereoisomer. The... 

Using this methodology, the first total synthesis of the natural product (-)-(19R)-ibogamin-19-ol was reported [106]. The crucial ISQ core containing the entire configurational stereochemistry of the final target compound was prepared in 15 steps. The two key steps involved chirality transfer in an Ireland-Claisen rearrangement and an intramolecular nitrone-olefin 1,3-dipolar cycloaddition described earlier. 

Protection of the primary and acylation of the secondary alcohol prepares the way for an Ireland-Claisen rearrangement. The E-enolate is produced and the [3,3] sigmatropic rearrangement transmits the chirality across the alkene to set up two new centres. The mechanism of the Ireland-Claisen rearrangement is described above 94 and occurs suprafacially across the backbone of the molecule through a chair-like transition state. We hope you agree both with the relative stereochemistry of the new centres and the E stereochemistry of the new alkene. 

Addition of lithium enolate (56) to trifluorocrotonate (55) proceeded smoothly in almost quantitative yields with excellent stereoselectivity. The intramolecular chelation in 57 retards the retro-aldol reaction. On the other hand, nonfluorinated crotonate (59) provided 60 in a poor yield because of the faster retro-aldol reaction [26]. The stereochemistry of the chelated intermediate (57) was proven by trapping 57 as its ketenesilylacetal (61). Pd-catalyzed Ireland-Claisen rearrangement of 61 proceeded stereospecifically to give a single stereoisomer (62), suggesting a rigid control of the three consecutive stereocenters (Scheme 3.12) [27]. 

Allylic alcohol 846 is instrumental in controlling the stereochemistry in the synthesis of (+ )-roccellaric acid (864) [231] (Scheme 115). The key step is an Ireland-Claisen rearrangement of propionate 861, which produces 862 as a mixture of isomers (epimeric at the methyl group). The minor diastereomer is removed at the lactone stage (863). Debenzylation and oxidation of the alcohol to an acid furnishes the natural product. 

In 1972, Ireland and Mueller reported the transformation that has come to be known as the Ireland-Claisen rearrangement (Scheme 4.2) [1]. Use of a lithium dialkylamide base allowed for efficient low temperature enolization of the allyUc ester. They found that sUylation of the ester enolate suppressed side reactions such as decomposition via the ketene pathway and Claisen-type condensations. Although this first reported Ireland-Claisen rearrangement was presumably dia-stereoselective vide infra, Section 4.6.1), the stereochemistry of the alkyl groups was not an issue in its application to the synthesis of dihydrojasmone. 

One of the many attractive features of the Ireland-Claisen rearrangement lies in its abiUty to reUably transfer stereochemistry to one or two newly formed sp stereocenters (C2 and/or C3 of the pentenoic acid) as well as to the resulting C4—C5 alkene. It has been found that the stereochemical outcome of the rearrangement may be governed by a variety of influences, some easily rationaUzed and others more subtle. 

Also in 1993, Hauske and JuUn reported a similar Ireland-Claisen rearrangement of an acyclic C6 carbamate (Scheme 4.35) [39]. The authors examined three different silyl ketene acetals in the rearrangement, although no experimental details were provided. AU three examples apparently proceeded with complete facial selectivity with respect to the allyUc alkene to afford the syn stereochemistry between the aUyl group and the NHBoc group in the conformation shown. The same rationale for facial selectivity can be applied as for Mulzer s results in the previous scheme. The reason for the low C2,C3 synjanti diastereoselectivity in the propionate example was not addressed. A lack of control of enolate geometry or post-rearrangement epimerization are both possible. 

Burke et al. employed a cyclic variant of the glycolate Ireland-Claisen rearrangement in the asymmetric synthesis of (-I-)-breynolide (Scheme 4.128) [122]. The rearrangement of the Z-silyl ketene acetal via a boat transition state generated the C3,C4 stereochemistry of the natural product in high yield and stereoselectivity. 

Draw transition state structures that rationalize the stereochemistry of the two Ireland-Claisen rearrangements shown in Eq. 15.45. 

The Ireland-Claisen reaction of ( )-vinylsilanes has been applied to the stereoselective synthesis of syn- and c/nti-2-substituted 3-silyl alkcnoic acids. a R-2-Alkyl-3-silyl acids are prepared by rearrangement of ( )-silyl ketene acetals which are generated in situ from the kinetically formed (Z)-enolate of the corresponding propionate ester40. Chelation directs the stereochemistry of enolization of heteroelement-substituted acetates in such a way that the syn-diastereomers are invariably formed on rearrangement403. 

The Ireland modification utilizes silyl ketene acetals derived from allyl ester eno-lates and provides a general method to effect stereocontrolled Claisen rearrangements under mild conditions, making it possible to apply the reaction to acid-sensitive and thermally labile substrates. Moreover, by proper choice of the reaction conditions, one can control the geometry of the enol ethers and hence the stereochemistry of the new C-C bond that is produced in the rearrangement step." ... 

The Simmons-Smith cyclopropanation reaction Stereochemically controlled epoxidations Regio- and Stereocontrolled Reactions with Nucleophiles Claisen-Cope rearrangements Stereochemistry in the Claisen-Cope rearrangement The Claisen-Ireland rearrangement Pd-catalysed reactions of allylic alcohols Pd-allyl acetate complexes Stereochemistry of Pd-allyl cation complexes Pd and monoepoxides of dienes The control of remote chirality Recent developments Summary... 

Stereochemical control of enolization of esters. In continuation of studies on the Claisen rearrangement of allyl esters (4, 307-308), Ireland and Willard have observed that the stereochemistry of enolization of these esters (1) and (2) can be controlled to a marked extent by the solvent used. Thus Claisen rearrangement of (1) through the enolate obtained in THF alone gives the acids (3) and... 

In the total synthesis of the esterase inhibitor ( )-ebelactone A, Paterson and Hulme applied an aldol-Claisen strategy for a relay of 1,2-syn into 1,5-syn relative stereochemistry (Scheme 25). - i3,ii4 critical Ireland ester enolate rearrangement could be performed without protecting the C9 ketone to give ester (137) in 74% overall yield. ... 

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