Claisen rearrangement stereochemical course

The stereochemical outcome of the reaction is determined by the geometry of the transition state for the Claisen rearrangement a chairlike conformation is preferred,and it proceeds strictly by an intramolecular pathway. It is therefore possible to predict the stereochemical course of the reaction, and thus the configuration of the stereogenic centers to be generated. This potential can be used for the planning of stereoselective syntheses e.g the synthesis of natural products. 

Alkoxyallenes turned out to be excellent starting materials also for the synthesis of highly functionalized 1,3-dienes, two examples being depicted in Schemes 8.61 and 8.62. As described by Kantlehner et al., 1,3-dienes such as 238 were obtained from methoxyallene derivative 50 by condensation with CH-acidic compounds 237 [135]. Hoppe and co-workers explored the stereochemical course of the allene Claisen rearrangement under Johnson s conditions, e.g. the reaction of 239 with trimethyl orthoacetate, which furnished intermediate 240 followed by rearrangement to the isomeric dienes 241a,b [136],... 

The configuration of the Claisen rearrangement product (J )-( )-2,4-dimethyl-4-heptenoic acid (see p 422)144 was determined by correlation with a reference sample of (f )-4,6-dimethyl-6-nonen-3-one (1) prepared from 3-pentanone employing the RAMP-hydrazone method221. Configurational assignment thus rests on the well-established stereochemical course of the Enders method 222. 

The arylsulfonyl carbanion accelerated Claisen rearrangement is completely regioselective and has also been found to be highly diastereoselective (Scheme 2). The stereochemical course of the reaction conforms to the familiar chair-like transition state model usually invoked for the classic thermal process. Recently, high degrees of asymmetric induction have been observed in tlie rearrangements of chiral cyclic phosphoramidate stabilized carbanion derivatives. ... 

The aza-Claisen rearrangement of A -allylenammes is a versatile alternative to its oxygen counterpart as the initially formed products are readily transformed to (E)-y,<5-unsaturated aldehydes on hydrolysis. In the thermal, as well as in the catalyzed rearrangement, U-doublc-bond geometry is preferred. For example. 2-methyl-2-phenyl-3-pentenal (2) is obtained from A -allylenamine 1 with moderate EjZ selectivity [(EjZ) 87 13]345. The nitrogen substituent does not significantly influence the stereochemical course of the reaction. 

As some Claisen rearrangements, particularly the ester enolate Claisen rearrangements, allow the product stereochemistry to be accurately predicted the question of whether the rearrangement proceeds through a chair- or boatlike transition state is crucial for the prediction of the stereochemical course of the rearrangement. 

With respect to the stereochemical course of the acetylene Claisen rearrangement, problems arise with control of the vinyl ether double-bond geometry. High selectivity should be observed in the rearrangement of cyclic substrates 6. However, the stereochemistry of the products were not reported in this case670. 

Fig. 2.4 Proposed stereochemical course of the Cu" (box)-catalyzed Claisen rearrangement.

Scheme 2.7 Stereochemical course of the sequential Claisen rearrangement intramolecular carbonyl-ene reaction.

Fig. 2.5 Proposed stereochemical course of the of Pd"-catalyzed asymmetric Claisen rearrangement.

The Claisen rearrangement [5], the intramolecular reaction of allyl enol ethers 1 to y,<5-unsaturated carbonyl compounds 3, has become a valuable tool for organic synthesis [6]. The sigmatropic process allows a significant alteration of the molecular framework within a single step. The concerted mechanism involves a highly organized transition state 2 that often directs the stereochemical course in the reaction of substituted derivatives and enables the simultaneous formation of two asymmetric centers (Scheme 1). 

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