Rearrangement Johnson

Thus, the (R)-glycidol (R)-897 was transformed to ethyl (S)-6-benzyloxy-3-methyl-4(E)-hexenoate (S)-899 via addition of acetylide followed by spontaneous isomerization, stereoselective reduction, and Claisen-Johnson rearrangement. The chiral ester (S)-899 was converted to (R)-4-methyl-6-phenylthiohexanol (R)-902. The primary alcohol (R)-902 was then transformed to the terminal acetylene (R)-904, a common intermediate for the synthesis of carbazoquinocins A (272) and D (275). Chain elongation of (R)-904 by two carbon atoms led to (R)-905, the chiral precursor for carbazoquinocin D (275) (639) (Scheme 5.116). 

Alkyl-4-ketoglutaric acids 265, potential substrates of transaminases that are important for the nervous system, can be synthesized (from an enol ether 263 that was not isolated) by a Claisen-Johnson rearrangement affording a 2-ethylidene-4-methylglutarate 264 whose ozonolysis in CH2Cl2 at — 78 °G followed by reduction with dimethyl sulfide provided the final product (Scheme 81) <1999TL6577>. 

Johnson rearrangement of allylic alccdiols (274) and (277) led to the enantiomeric 7,8-unsaturated esters (276) and (279), respectively (Scheme 48). Both transition states (275) and (278) favor a pseudo-equatorial position of the benzyloxymethylene substituent the newly formed chiral center is obtained in very hi optical purity throu the chirality transfer process. As a consequence of this geometrical preference, secondary allylic alcohols invariably provide predominantly ( )-configured double bonds upon thermal Gaisen rearrangement The ( -selectivity usually increases with the steric bulk of the C-2 substituent, an effect which was rationalized by a pseudo-1,3-diaxial interaction in the transition state leading to the (Z)-alkene (280 Figure S). ... 

The Johnson rearrangement involves reaction of an allylic alcohol with ethyl orthoacetate to give a mixed ortho ester that loses ethanol and then undergoes... 

Among the various versions of the sigmatropic rearrangements, [3,3]-sigmatropic rearrangements became, in the past 20 years, a powerful tool for C-C bond formation. In synthesis, they are particularly the method of choice for 1,3-chiraUty transfer, for the stereoselective formation of di- and especially trisubstituted double bonds and for the constmction of quaternary centers. The aim of this chapter is to emphasize the scope and limitation of the orthoester Claisen-Johnson rearrangement by comparison with the related rearrangements and to illustrate the utility of this reaction in synthesis [1]. 

The Claisen-Johnson rearrangement [7] is closely related to both Saucy vinyl allyl ether rearrangement and Eschenmoser rearrangement. The reaction proceeds via a ketene acetal, which results from the condensation between an ortho-ester and an aUylic alcohol giving rise to a mixed orthoester followed by the elimination of the low-boihng-point alcohol. This ketene intermediate forms after rearrangement of a y,d-unsaturated ester (Scheme 6.1). 

Many charge-accelerated reactions have been observed in [3,3] sigmatropic rearrangements [10], In the Claisen-Johnson rearrangement, a combination of micro-wave irradiation and acidic catalysis (KSF day) has been used successfully by Jones with several cyclic allylic alcohols [1 Ij. Rate acceleration (9 min versus 12.5 h for conventional heating) and better yields were observed (Scheme 6.3). 

An other example of particular stereoselectivity observed during a Claisen-Johnson rearrangement has been described by Yadav [18]. In this study, the observed stereoselection is both the result of stereoelectronic effects [19] and of anti selectivity by reference to the sulfur atom (Scheme 6.9). Axial attack is favored in aU cases. Steric interactions in compound 69 induced a half-chair flipping (70) and consequently an attack syn to the sulfur atom. In compounds 66 and 72 both axial attack and anti sulfur selectivity afforded compounds 68 and 74, respectively (Scheme 6.9). 

In open chain series the Claisen-Johnson rearrangement is known to give rise to E-configuration for the resulting double bond [20]. An unprecedented stereochemical reversal from alkyl to aryl substituents has been described by Basavaiah... 

As pointed out earlier, ketene acetal involved in the Qaisen-Johnson rearrangements is obtained after alcohol exchange in the starting orthoester and elimination of the low-boihng-point alcohol. The whole process requires generally acid catalysis, propionic acid being the most common catalyst, and heating or even distillation to shift the equihbrium to the formation of the ketene acetal. Obviously, these reaction conditions are not always compatible with sensitive compounds. 

The same group [26], in a new synthesis of tocopheryl acetate 115, appUed a stereoconvergent Claisen-Johnson rearrangement to compounds 116 and 117, ester 118 was isolated in good yields in both cases (Scheme 6.15). 

The Claisen-Johnson rearrangement is also a reaction of choice for the construction of quaternary centers in the synthesis of triquinanes and related ter-penes. Accordingly, transposition of aUyUc alcohol 125 is a cornerstone reaction in the synthesis of tricyclic compound 124, a key intermediate for the access to several triquinanes described by Iwata [28] (Scheme 6.17). Acid 126 was obtained in 57% yield after transposition and saponification. Claisen allyl vinyl ether rearrangement was also applied to allylic alcohol 125. Oxidation of the aldehyde inter-... 

In a stereoselective synthesis of (-)-chokol A 130, Suzuki and Kametani [30] introduced the side chain by Claisen-Johnson rearrangement with a modest stereoselectivity. However the stereogenic center in / -position to the ester group in compound 132 is suppressed later in the synthesis (Scheme 6.18). 

In the synthesis of ( )-cycIoIaurene 136 and ( )-j8-cuparenone 137, the same author [32] used a Claisen-Johnson rearrangement affording ester 139 for the construction of one of the two quaternary centers as depicted in Scheme 6.20. 

In syntheses of two marine sesquiterpenes, africanol 172 and dactylol 173, Paquette [39] prepared the bicydic aUylic alcohol 175 in nine steps from 4,4-di-methyl cyclohexanone 174. The Claisen-Johnson rearrangement was highly stereoselective and gave rise to ester 176 with the proper configuration of the side chain methyl in relation to dactylol 173 (Scheme 6.26). 

A Claisen-Johnson rearrangement with transfer of chirahty has been used by Pearson in a stereoselective synthesis of A-factor 199, an autoregulator of the production of streptomycin in Streptomyces griseus [42]. Allylic alcohol 200 is prepared in 80% yield and 84% ee by oxazaboroUdine reduction of the corresjxjnding ketone. Orthoester rearrangement afforded ester 201 in 75% yield. Ozonolysis of unsaturated ester 201 is then followed by lactonization (Scheme 6.29). 

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