Silyl enol ethers Claisen rearrangement

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. 

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 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 Claisen rearrangement was used in the asymmetric total synthesis of (+)-9(ll)-dehydroestrone methyl ether (5), a versatile intermediate in the synthesis of estrogens5 (Scheme 1. If). The key feature of the synthesis is the successful development of the asymmetric tandem Claisen-ene sequence. Thus, a solution of the cyclic enol ether 6 in toluene was heated in a sealed tube at 180 C for 60 hours to afford the product 9 in 76% isolated yield after deprotection of the silyl enol ether. The Claisen rearrangement of the allyl vinyl ether 6 occurred stereoselectively to give an intermediate (7), in which the 8,14-configuration was 90% syn. The stereoselectivity in the Claisen rearrangement can be explained... 

Very few pericyclic reactions of carbene complexes have been studied that are not in the cycloaddition class. The two examples that are known involve ene reactions and Claisen rearrangements. Both of these reactions have been recently studied and thus future developments in this area are anticipated. Ene reactions have been observed in the the reactions of alkynyl carbene complexes and enol ethers, where a competition can exist with [2 + 2] cycloadditions. Ene products are the major components firom the reaction of silyl enol ethers and [2 + 2] cycloadducts are normally the exclusive products with alkyl enol ethers (Section 9.2.2.1). As indicated in equation (7), methyl cyclohexenyl ether gives the [2 -t- 2] adduct (84a) as the major product along with a minor amount of the ene product (83a). The t-butyldimethylsilyl enol ether of cyclohexanone gives the ene product 9 1 over the [2 + 2] cycloadduct. The reason for this effect of silicon is not known at this time but if the reaction is stepwise, this result is one that would be expected on the basis of the silicon-stabilizing effect on the P-oxonium ion. 

In detail, the first step is a Cope rearrangement - a [3,3]-sigmatropic rearrangement involving nothing but carbon atoms 167. This step is unfavourable because it transforms a stable cyclohexane into an unstable It, C-dccadicnc. The product 168 is a minor component in the equilibrium. What drives the reaction forward is a favourable Claisen-Ireland rearrangement on the silyl enol ether 168. This step is favourable because it creates a carbonyl group (the ester in 165) at the expense of an alkene. 

CLAISEN-IRELAND Rearrangement Rearrangement of allyl phenyl ethers to o-(or p)-allylphenols or of allyl vinyl ethers to y,8-unsaturated aldehydes or ketones (Claisen). Rearrangement of allyl esters as enolate anions or silyl enol ethers to y,5-unsaturated acids (Ireland). Also rearrangement of N-allylanilines (an aza-Cope rearrangement) (see 1st edition). 

Claisen rearrangement of ally silyl ethers (4,307-308). Katzenellenbogen and Christy have extended the rearrangement of silyl enol ether derivatives of allylic acetates to y,S-unsaturated acids to systems in which a trisubstituted double bond is generated. Thus 3-acetoxy-2-methyl-l-nonene (1) was treated with lithium N-isopropylcyclohexylamide (LilCA) in THF at -78° and then with f-butyldimethylchlorosilane to give the f-butyldimethylsiloxyvinyl ether... 

Ireland-Claisen Rearrangement. Silyl enol ethers of allyl esters undergo highly stereoselective Ireland-Claisen rearrangement to afford 4-pentenoic acids. The structure of the ester and the reaction conditions dictate the stereoselectivity. It has seen wide synthetic application, e.g. the construction of unnatural (—)-trichodiene (eq 30). ... 

This gentle variant of the Claisen Rearrangement employs the allyl ester of a carboxylic acid instead of an allyl vinyl ether. The ester is converted to its silyl-stabilized enolate (silyl ketene acetal), which rearranges at temperatures below 100 °C. 

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