Rearrangement protocols

Further variations of the Claisen rearrangement protocol were also utilized for the synthesis of allenic amino acid derivatives. Whereas the Ireland-Claisen rearrangement led to unsatisfactory results [133b], a number of variously substituted a-allenic a-amino acids were prepared by Kazmaier [135] by chelate-controlled Claisen rearrangement of ester enolates (Scheme 18.47). For example, deprotonation of the propargylic ester 147 with 2 equiv. of lithium diisopropylamide and transmetallation with zinc chloride furnished the chelate complex 148, which underwent a highly syn-stereoselective rearrangement to the amino acid derivative 149. 

The acetal [1,2]-Wittig rearrangement protocol is also applicable to the synthesis of medium-sized cyclic ethers. For example, a reaction of the 9-membered cyclic acetal 37 with lithium piperidide provides the 8-membered ring ether 38 in good yield along with high diastereoselectivity (equation 20) . 

K. Tadano, Natural product synthesis starting with carbohydrates based on the Claisen rearrangement protocol, in Studies in Natural Products Chemistry, Atta-ur Rahman, ed., Elsevier Science, New York, 1992, pp. 405-455. 

Pearson and Hembre synthesized a key intermediate (19) using the Johnson-Claisen rearrangement protocol in the total synthesis of the indolizidine... 

Preparation of J/V-Ac-Glu-VP[CF=CH]-Ala was also reported using the imidate rearrangement protocol [20]. 

With the preparation of racemic drhydroisocodeine (79), Chida reported a formal synthesis of morphine [52], The synthesis is based on a cascade of sequential Claisen rearrangements of an allylic vicinal diol derivative as key steps. The Claisen rearrangement protocol, as an efficient strategy for the installation of the C13 quaternary carbon, was successfully employed in the preparation of the Amaryllidaceae alkaloid galanthamine, published 1 year before the synthesis of dihydroisocodeinone [64],... 

Similarly, Paquette s stereoselective synthesis of a marine sesquiterpene from the capnellene family utilizes this addition/rearrangement protocol/ Alcohol 50, produced by lithium acetylide addition to 49, underwent smooth rearrangement to provide 51 in excellent yield. 

An application toward the synthesis of alloyohimbane required reacting the protected tryptamine derivative 42 with cyclohexadiene and formalin to obtain the requisite [2.2.2] bicyclic adduct 43 [17]. Under the standard aqueous aza Diels-Alder conditions, a modest 22% yield of 43 is obtained, which upon further elaboration involving Mariano s [18] aza Claisen rearrangement protocol yields alloyohimbane 44 (Scheme 2.5). 

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