Claisen orthoester rearrangement

Both the exchange and elimination are catalyzed by the addition of a small amount of a weak acid, such as propanoic acid. These reactions are usually conducted at the reflux temperature of the orthoester, which is about 110°C for the trimethyl ester and 140° C for the triethyl ester. Microwave heating has been used and is reported to greatly accelerate orthoester-Claisen rearrangements.232... 

The mechanism and stereochemistry of the orthoester Claisen rearrangement is analogous to the Cope rearrangement. The reaction is stereospecific with respect to the double bond present in the initial allylic alcohol. In acyclic molecules, the stereochemistry of the product can usually be predicted on the basis of a chairlike TS.233 When steric effects or ring geometry preclude a chairlike structure, the reaction can proceed through a boatlike TS.234... 

Scheme 6.15 gives some representative examples of the orthoester Claisen rearrangement. Entry 1 is an example of the standard conditions for the orthoester Claisen rearrangement using triethyl orthoacetate as the reactant. The allylic alcohol is heated in an excess of the orthoester (5.75 equivalents) with 5 mol % of propanoic acid. Ethanol is distilled from the reaction mixture. The E-double bond arises from the chair TS. 

A. Claisen Rerrangements of Ketene Aminats and Imidates. A reaction that is related to the orthoester Claisen rearrangement utilizes an amide acetal, such as dimethylacetamide dimethyl acetal, in the exchange reaction with allylic alcohols.257 The products are y, 8-unsaturated amides. The stereochemistry of the reaction is analogous to the other variants of the Claisen rearrangement.258... 

Scheme 4.22 Asymmetric synthesis of allene 89 by the orthoester Claisen rearrangement.

Scheme 18.43 Stereoselective synthesis of enprostil by orthoester-Claisen rearrangement [125a] (THP = tetrahydropyranyl).

Organoaluminum compounds, reaction with imino carbocations, 66, 189 Orthoester Claisen rearrangement, 66, 22 Orthoformic acid, triethyl ester, 65, 146 Oxalic acid, diethyl ester, 65, 146... 

Claisen-Ireland rearrangement of 239 followed by DIBALH reduction gives a mixture of syn and anti isomers 240 (equation 194)34-347. In a similar manner, orthoester Claisen rearrangements of 241 give stereoselectively the corresponding chiral allylsilanes 242 (equation 195)348. 

For the application of the Johnson orthoester Claisen rearrangement to a similar system see A. Srikrishna and R. Viswajanani, Tetrahedron Lett., 1996, 37, 2863. 

The success of the Claisen-Cope rearrangement need not be limited to the production of aldehydes via enol ethers. Allylic alcohol (58) is successively transposed into a mixture of allylic isomers (59 Scheme 4), and is subjected to an orthoester Claisen rearrangement at 150 "C to provide ester (61). The moderate temperature of the Claisen step permits the isolation of an intermediate (c/. Scheme 3) prior to the final Cope rearrangement (195 C) to. y-unsaturated esters (60). The esters (60) are a 55 45 mixture of ( )- and (Z)-double bond isomers owing to the near equal steric bulk of the methyl and acetic acid residues in the transition state for the Cope rearrangement. ... 

The synthetic utility of this process can be seen by evaluating the examples in Table 2. For example, because the cyclopropane serves as a pseudo alkene and because the [1.5] shift requires a six-memb ed transition state, it relates conceptually to the Cope and Claisen rearrangements. The 7,8-unsaturated carbonyl compounds in Table 2 are those that would otherwise be obtained via Claisen or orthoester Claisen rearrangements, which are normally effected under strongly acidic or strongly basic conditions (Scheme 3). 

Later work showed that such displacements can be effected with a BusSnCu reagent [83], With this reagent secondary mesylates afford allenylstannanes as the exclusive kinetic products (Eq. 68). The configuration of the allenic products was confirmed by an independent synthesis involving an orthoester Claisen rearrangement (Eq. 69). 

Allylic alcohols undergo symmetry-allowed orthoester Claisen rearrangement, when treated with trialkyl orthoacetate in the presence of an acid catalyst. When this reaction is applied to 2-butyne-l,4-diols, one of the products formed is a 1,3-diene. 1,3-Dienes also result when this reaction is performed on bisally lie alcohols (equation 91). Regiospe-cific conversion of allylic alcohols to two-carbon extended dienoate esters, by performing an orthoester Claisen rearrangement with phenylsulhnyl orthoacetate, has been described (equation 92). ... 

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