Rearrangements, Claisen Johnson-ester variant

A salient structural feature of intermediate 18 (Scheme 2b), the retrosynthetic precursor of aldehyde 13, is its y,r5-unsaturated ester moiety. As it turns out, the Johnson ortho ester variant of the Clai-sen rearrangement is an excellent method for the synthesis of y,<5-unsaturated esters.11 In fact, the Claisen rearrangement, its many variants included, is particularly valuable in organic synthesis as a method for the stereocontrolled construction of trans di- and tri-substituted carbon-carbon double bonds.12,13 Thus, it is conceivable that intermediate 18 could be fashioned in one step from allylic alcohol 20 through a Johnson ortho ester Claisen rearrangement. In... 

Scheme 1. Parent Claisen rearrangement (a) and the Johnson ortho ester variant (b).

P-citronellene 605 f 612 (/Q-citronellic acid 232, 235 (/ )-citronellol 360 Claisen rearrangement 17, 87, 90, 137 f., 140, 142, 194 -, Johnson ortho ester variant see Johnson ortho ester Claisen rearrangement cobalt-mediated cyclization... 

The Johnson ortho-ester variant of the Claisen rearrangement provides access to y,5-unsaturated esters.The reaction entails heating the allylic alcohol with an ort/io-ester in the presence of a carboxylic acid to form a ketene acetal, which then rearranges to the trans-unsatmated ester.An elevated reaction temperature is necessary for the in situ formation of the ketene acetal but not for the rearrangement. 

This reaction was first reported by Johnson et al. in 1970. It is a highly stereoselective synthesis of y,5-unsaturated esters from the reaction between allylic alcohols and an orthoester in the presence of a trace amount of weak acid, such as propionic acid. Because this reaction is the modification or variant of the Claisen Rearrangement, it is often referred to as the Johnson orthoester Claisen rearrangement. Occasionally, this reaction is also known as the Claisen-Johnson orthoester rearrangement, " or Johnson orthoester protocol. This reaction involves the formation of mixed orthoester from allyl alcohol and the added orthoester, which loses an alcoholic component to form a ketene acetal then migrates to unsaturated carbonyl compounds via the Claisen Rearmagement with high syn selectivity. Posner further extended this reaction to use sulfonyl orthoester. Overall, this reaction has been applied to the synthesis of a variety of complicated natural products, such as squalenes. ... 

Extremely useful ramifications of the Claisen rearrangement emerged with Johnson s discovery of the orthoester variant of this transformation. His approach (Scheme 2.156) involved the following sequence of steps, which were carried out in one reaction vessel (i) transesterification of the orthoester with an allylic alcohol to give 490 (ii) elimination to form the intermediate ketene acetal 491 and (iii) [3,3] sigmatropic rearrangement to yield the y, -unsaturated ester 492. The Johnson-Claisen procedure is properly considered to be one of the most efficient methods available to prepare y,(5-unsaturated esters such as 492. ° ... 

Most [3,3]-sigmatropic rearrangements take place thermally, and the Cope, oxy-Cope and Claisen rearrangements are among the most important rearrangements in this class. Important variants of the Claisen rearrangement include the Johnson modification via orthoesters, the Eschenmoser modification via ketene N,O-acetals, the Ireland modification via ketene silylacetals and the Corey modification via boron ester enolates [696], The aza-Claisen rearrangement has also seen... 

The Claisen rearrangement of bis-allyl vinyl ethers and related systems has been studied by several groups [98]. Modest to high levels of regioselectivity were obtained in the parent Claisen as well as Johnson, Eschenmoser and Ireland variants of the reaction. Parker and Farmar applied the ester enolate variant of the Ireland-Claisen rearrangement of a bis-aUylic ester to the synthesis of biflora-4,10(19),15-triene, using the rearrangement to install the 1,3-diene component for a subsequent intramolecular Diels-Alder reaction [99]. 

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