Stereospecificity Claisen rearrangement

Both sequences utilized a stereospecific Claisen rearrangement to convert a pentenose intermediate to the branched-chain amide which... 

When ethyl trifluoroacetylacetate is treated with an allylic alkoxide, tran-sesterification is followed by ester enolate Claisen rearrangement m a process that on decarboxylation yields stereospecifically the tnfluoromethyl ketone product [22] (equation 19)... 

N,O-acetal intermediate 172, y,<5-unsaturated amide 171. It is important to note that there is a correspondence between the stereochemistry at C-41 of the allylic alcohol substrate 173 and at C-37 of the amide product 171. Provided that the configuration of the hydroxyl-bearing carbon in 173 can be established as shown, then the subsequent suprafacial [3,3] sigmatropic rearrangement would ensure the stereospecific introduction of the C-37 side chain during the course of the Eschenmoser-Claisen rearrangement, stereochemistry is transferred from C-41 to C-37. Ketone 174, a potential intermediate for a synthesis of 173, could conceivably be fashioned in short order from epoxide 175. 

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... 

An interesting procedure has been developed by Vat le to obtain C-5 branched-chain sugars [189]. It also takes advantage of the stereospecificity of the Claisen rearrangement of allyl (vinylsulfinyl) ether 158 derived from a 4,5-unsaturated sugar. An acrylic derivative 159 is formed in the process by elimination of sulfenic acid (Scheme 53). 

The diastereomerically pure camphor-based 1,3-oxathiane 36, formed by the reaction of a,(S-unsaturated aldehydes with the hydroxythiol 37, undergoes a stereospecific ketene Claisen rearrangement with dichloroketene to give the stereo-pure 10-membeted thiolactone <02CC2534>. 

The quaternary center was constructed stereospecifically by Claisen rearrangement (Scheme 46). The necessary enol ether was obtained by reaction of the secondary alcohol of 399 with ethyl vinyl ether and mercuric acetate. To change the polarity of the endocyclic double bond, the unsaturated ketone was reduced with lithium aluminum hydride to the allylic alcohol, 400, at low temperature. Then, prolonged heating with xylene led to the aldehyde, 401. Protection of the secondary alcohol was achieved by bromoether formation with W-bromosuccinimide in acetonitrile before the aldehyde of 402 was reacted with methyllithium. The epimeric mixture of secondary alcohols was protected as acetates 403. Then, the cyclic ketone... 

Along with the Claisen rearrangement, other related reactions are applicable for the preparation of natural products. For instance a [2.3]-Wittig reaiTangement is one step in the stereospecific synthesis of HMG-CoA reductase inhibitor pravastatin and in the total synthesis of the HMG-CoA synthase inhibitor 1233A according to the general scheme (equation 253). 

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]. 

A further advantage of the c/s-oriented 4,6 Claisen rearrangement is the stereospecific alkylation of decalin and hydrindane systems4 9 420. Further examples are reported in refs 167. 240 and 421-425. 

The aqueous Claisen rearrangement was successfully applied to the stereospecific angular alkylation of [4.5.5.5]fenestrenes146. 

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