Silyl enolate Claisen rearrangement

This effect is the basis of the synthetic importance of ester enolate Claisen rearrangements in which enolates or silyl enol ethers of allylic esters are rearranged into 4-pentenoate esters. 

The stereoselectivity of ester enolate Claisen rearrangements can also be controlled by specific intramolecular interactions.168 169 The enolates of a-alkoxy esters give the Z-silyl derivatives because of chelation by the alkoxy substituent. 

Excellent experimental technique was required to effect formation of the monensin cA> ring system (218) via silyl ester enolate Claisen rearrangement of acid (216) and alcohol (217) (Scheme 42). Ester... 

Marshall, J. A. Stereochemical control in the ester enolate Claisen rearrangement. Stereoselectivity in silyl ketene acetal formation. Chemtracts Org. Chem. 1991,4,154-157. 

The Ireland contribution to nonactic acid synthesis, outlined in Scheme 4.32, involves a selective silyl ketene acetal formation and Claisen rearrangement in the key step. D-Mannose (209) was readily converted in a straightforward manner to dihydrofuran 212 via 210 and 211 in 36% overall yield. Esterification of the free alcohol with propionyl chloride followed by the an enolate Claisen rearrangement afforded a mixture (89 11) of tetrahydrofuryl propionates 213 after catalytic reduction. 

Iron(tricarbonyl) was employed to control the diastereofacial selectivity in the enolate Claisen rearrangement of some trienyhc esters. Trienylic esters 137 and 139 underwent successful enolate Claisen rearrangements to afford 141 when treated with 1.05-1.15 equiv. of KHMDS in THF with 23% HMPA as cosolvent and 1.2 equiv. of TBDMSCl as an internal silylating agent (equation 67). Compound 137 yielded carboxylic acid 141 in 70-80% as a single diastereomer, while the yield from compound 139 was 45-50%. TBDMSOTf was used as an internal silylating agent for esters 138 and 140. In contrast to the results obtained with 137 and 139, inseparable mixtures of diastereomers 142 and 143 were obtained in 85-95% yield. 

Other donor substituents, e.g., trimethylsilyloxy, at C(2) are strongly accelerating. This effect is the basis of the synthetic importance of ester enolate Claisen rearrangements, in which enolates or silyl ketene acetals of allylic esters are rearranged into 4-pentenoate esters. This reaction is known as the Ireland-Claisen rearrangement. 

Simple Enolate Claisen Rearrangement 215 Tab. 5.1.1 Half-life times for rearrangement of silyl ketene acetals at 32°C. 

The initial synthetic applications of the ester enolate Claisen rearrangement were reported from the Ireland group. Silyl ketene acetal generated from 143 readily rearranged to the carboxylic acid 144 in moderate yield and diastereoselectivity. The product 144 was subsequently elaborated for the completion of the total synthesis of lasalocid... 

A highly successful route to stereoisomers of substituted 3-cyclohexene-l-carboxylates runs via Ireland-Claisen rearrangements of silyl enolates of oj-vinyl lactones. The rearrangement proceeds stereospeaifically through the only possible boat-like transition state, in which the connecting carbon atoms come close enough (S. Danishefsky, 1980 see also section 4.8.3, M. Nakatsuka, 1990). 

The ester 7-1 gives alternative stereoisomers when subjected to Claisen rearrangement as the lithium enolate or as the silyl ketene acetal. Analyze the respective transition structures and develop a rationale to explain these results. 

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... 

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],... 

The stereochemistry of the silyl enol ether Claisen rearrangement is controlled not only by the stereochemistry of the double bond in the allyhc alcohol but also by the stereochemistry of the silyl enol ether. For the chair transition state, the configuration at the newly formed C—C bond is predicted to be determined by the E- or Z-configuration of the silyl enol ether. 

Sigmatropic rearrangements proceed via closed transition states in the Claisen-Ireland variation a silyl-enol ester, 27 or 28, is used, which may be selectively generated in (Z) or (E) configuration12 (Section A. 1.6.3.1.). As shown in the transition states 32 and 29, this results in the formation of 30/31 and 33/34. 

Another interesting variant of Claisen rearrangement has been introduced by Ireland [149], and used by his group in carbohydrate chemistry. The starting compound is again an allylic alcohol that is esterified by a suitable carboxylic acid. This ester is enolized in basic medium, and quenching of the intermediate enolate at low temperature gives a ketene silyl... 

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