Ireland-Claisen reaction diastereoselectivity

The sequential Michael addition/Ireland-Claisen reactions proceed with high diastereoselectivity in one pot. Preparation of the lithium enolate 68 with LDA in THF at —78 °C followed by the addition of the allylic ester acceptor 67 leads to the smooth conjugate addition, whose stereoselectivity was more than 98% diastereomeric excess. The ketene silyl acetal 70, which was formed by the trapping of the Michael addition intermediate 69 with TMSCl, underwent Ireland-Claisen rearrangement in the presence of PdCl2(PhCN)2... 

The Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

Ireland-Claisen rearrangement as an alternative approach to the syn isomer with a high degree of diastereoselectivity was also examined. This reaction might be similar to the system of ester-enolate [2,3]-Wittig shift in the case of OR (R=protective group). 

Figure 7.1. Origin of diastereoselectivity in Ireland-Claisen step of the cascade reaction.

In the enantioselective total synthesis of p-lactone enzyme inhibitor (-)-ebelactone A and B, I. Paterson and coworkers constructed seven stereocenters and a trisubstituted alkene plus a very sensitive p-lactone ring. The backbone of their strategy applied an aldol reaction / Ireland-Claisen rearrangement sequence and used minimal functional group manipulation. The Ireland-Claisen rearrangement was performed in the presence of an unprotected ketone moiety and set a precedent for this protocol. The diastereoselectivity was 96 4, indicating highly ( )-selective silylketene acetal formation. 

Alternatively, the central synthetic building block can also be generated via a diastereoselective Ireland-Claisen rearrangement of butenyl methoxyacetate. Introduction of the styryl fragment results from a Horner-Wadsworth-Emmons reaction. The remainder of the synthesis is closely related to the sequence described above. [51, 52]... 

The Ireland-Claisen rearrangement is not limited to allylic esters, but can also be applied to propargylic glycolates [14]. In the rearrangement of several pro-pargylic esters 14 the diastereoselectivity (ds), the allenic a-hydroxyacids 15 are formed with, was always very high (Scheme 5.2.6, Table 5.2.3). In this reaction, LHMDS in THF is the best base/solvent combination, LDA gave no desired product, and the use of ether and dimethoxyethane resulted in a decrease of both yield and diastereoselectivity. 

McIntosh has recently reported the Ireland-Claisen rearrangement of the substituted bis-allylic ester 125. The reaction proceeds via the chair-like arrangement 126, which avoids steric repulsion between 0-silyl moiety and neighboring choro substituent. The facile reaction generates trisubstituted exo-alkene 127 in high yield excellent diastereoselection. ... 

In course of studies toward the synthesis of (+)-zaragozic acid C, Rizzacasa has described the Ireland-Claisen rearrangement of 147 which incorporates a benzyloxy substituent at the yff-position. To avoid elimination, enolization is conducted at -100 °C and (Z)-enolate was preferentially formed due to chelation. The reaction proceeds via a chair-like arrangement to yield 148 with moderate diastereoselectivity. ... 

Silyl-substituted ally methoxyacetate 1 undergoes the Claisen-Ireland rearrangement to diastereoselectively give optically active allylic silane 2 as exemplified by Scheme 5.1. The resulting silane is employed for asymmetric addition to both aliphatic and aromatic acetals 3a and 3b in the presence of MejSiOTf, giving rise to homoallylic ethers 4a and 4b, respectively, with high diastereo- and enantioselec-tivities [4]. The whole sequence of reactions is an example of 1,4- and 1,5-remote... 

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