Keten-Claisen-rearrangement

The mild reaction conditions and the obviously high potential driving force of the ketene Claisen rearrangement recommended the use of the process for more complex systems. The first series of this type of reaction suffered from severe limitations. On the one hand, only electron-deficient ketenes added to the allylamines, and useful yields of the lactams had exclusively been achieved by employing dichloroketene [57, 58 a]. On the other hand, the rearrangement was restricted to either monosubstituted olefins in the amino fragment or the... 

Originally, ketene Claisen rearrangements were described by BeUus and Malherbe in the reaction of aUyl sulfides and dichloroketene (a) Malherbe R, BeUus D (1978) Helv Chim Acta 61 1768 (b) Malherbe R, Rist G, BeUus D (1983) J Org Chem 48 860... 

Asymmetric induction has been reported for a ketene Claisen rearrangement of the adducts of dichloroketene to chiral allyl thioethers as a route to precursors of optically active y-butyrolactones [504], An example of this sigmatropic step is given hereafter. 

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>. 

Ketene Claisen rearrangement. Dichlorokelene (1) reacts with the allylic sulfide 2 to give the expected [2 + 2] cycloadduct (3) and the S-phenyl ester of the unsaturated acid (4). The latter product is evidently formed by a Claisen rearrangement of a 1,3-dipolar intermediate (a). Products related to 4 are also obtained from allylic ethers and selenides in fact, in the case of allylic ethers only the rearranged esters are usually isolable. 

The stereoselective ketene-Claisen rearrangements of optically active cyclic allyl sulfides, which can be run slightly above room temperature, result in chirality transfer from a C-S bond to a C-C bond. Due to the mild reaction conditions, the yields often prove to be superior to the oxygen counterparts and result in nearly complete chiral transmission. No loss of optical purity is observed during the dechlorination step, e.g., rearrangement of 1 and 2 and subsequent dechlorination to give 3 and 4429. 

The ketene-Claisen rearrangement of allyl sulfides with the less reactive chloromethylketene results in a decrease in the selectivity of formation of 27 (de as 50%)627. 

Chiral allylthioether 137 has been prepared in order to study stereoselectivity in the ketene Claisen rearrangement [51]. It is accessible from 120a in 5 steps. The first step, 8 2 displacement of the tosylate, occurs with nearly complete inversion of the asymmetric center (98% ee). Reduction, Wittig reaction, and subsequent protection furnishes 137 with an ee of... 

Ester 775a has been used as an intermediate in synthesizing substrates that produce 1,2-asymmetric induction in the ketene Claisen rearrangement of allylic sulfides [220] (Scheme 104). Reduction of 775a with diisobutylaluminum hydride gives allylic alcohol 776 (> 94% de). Conversion to thioether 111 is accomplished with thiolacetic acid under Mitsunobu conditions this is followed by saponification of the resulting S-acetyl intermediate and alkylation with isopropyl bromide. 

Treatment of allyl sulfide 111 with dichloroketene, generated in situ by reductive elimination of chlorine from trichloroacetyl chloride, results in an intramolecular ketene Claisen rearrangement giving 779 with high, 2-syn selectivity (94% de). Reductive dechlorination and subsequent lactonization affords chiral butyrolactone 780, with an optical purity that exceeds 95%. 

Originally, ketene Claisen rearrangements were described by Bellus and Malherbe in the reaction of allyl sulfides and dichloro ketene a) R. Malherbe, D. Bellus, Helv. Chim. Acta. 1978, 61, 3096-3099. 

The ketene-Claisen rearrangement of a 1,3-dipolar allyl vinyl ether 124 is known as the Bellus-Claisen rearrangement [86]. 

Two novel, potentially general, rearrangement procedures have been reported for the synthesis of phoracantholide J (117). The first employs an internal acetal formation followed by a Claisen rearrangement, while the alternative involves a Keten-Claisen rearrangement (Scheme 25). ... 

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