4- derivatives Johnson-Claisen rearrangement

Scheme 13.12 Johnson-Claisen rearrangement of an ortholactone-derived substrate.

Scheme 13.18 Stereoselective Johnson-Claisen rearrangement of a cyclopentenol derivative.

The orthoester Johnson-Claisen rearrangement" describes the thermal rearrangement of the ketene acetal 338, which is derived by refluxing allylic... 

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],... 

In the particular case in which the carbonyl group belongs to a carboxylic acid derivative, such as an ester (17) or an amide (18) (or other functional groups which may be converted into it by a FGI), then they may be disconnected according to the "orthoacetate-modification" of the retro-Claisen rearrangement (Schemes 7.7 and 7.8) developed mainly by Eschenmoser [7] and Ziegler [8], independently, in the synthesis of alkaloids, and Johnson in a very simple and yet highly stereoselective synthesis of squalene [9]. 

The eighth volume of this serial publication comprises eight contributions from international authors. Four of these deal with well-defined groups of compounds thiopyrones (R. Zahradnik, R. Mayer, and W. Broy), phenoxazines and phenothiazines (M. Ionescu and H. Mantsch), diazepines (F. D. Popp and A. Catala Noble), and benz-isoxazoles (anthranils and indoxazenes) (K.-H. Wiinsch and A. J. Boulton). J. M. Tedder has surveyed the field of the heteroaromatic diazo compounds which are derived from a variety of heterocyclic ring systems, and M. Schulz and K. Kirschke discuss heterocyclic peroxides. The remaining two chapters survey well-known reactions the Hilbert-Johnson reaction is covered by J. Pliml and M. PrystaS, and heterocyclic Claisen rearrangements by B. S. Thyagarajan. 

In their short synthesis of ( - )-162, Pearson and Hembre also began with the protected D-erythronolactone derivative 197, which was converted in three steps into a mixture (97 3) of diastereomeric allylic alcohols 203 (Scheme 29) 127). Separation of the epimers, although possible, was not necessary as both alcohols yielded the same product 204 after Johnson orthoester Claisen rearrangement. Subsequent Sharpless asymmetric dihydroxylation with AD-Mix-p gave as major... 

Tetraethynylmethane (39), a potential monomer for a three-dimensional superdiamonoid carbon network [1], was elusive for many years [51, 52], until its synthesis was accomplished in 1993 by Feldman and co-workers [53]. The key step in the synthesis was the acid-mediated Johnson orthoester variant of the Claisen rearrangement, which provided the central quaternary methane C-atom with suitable functional groups for the ultimate transformation into 39 [Scheme 13-9(b)]. Solid 39, like tetraethynylethene (20), decomposes rapidly at room temperature in either the presence or absence of oxygen. The earlier efforts to prepare tetraethynylmethane had yielded the peralkynylated derivatives 40-42 [Scheme 13-9(c, d)] [51, 52]. Tetraethy-nylallene represents another potential precursor for a three-dimensional carbon network [1], but remains elusive of the perethynylated [K]cumulenes, so far only the silyl-protected [3]cumulenes 43a and 43b [Scheme 13-9 (e)] have been prepared [54]. With 44 [Scheme 13-9 (f)], the first transition metal complex of a perethynylated ligand is now available [55]. 

In 1988 Heathcock reported the Johnson, Eschenmoser and Ireland-Claisen rearrangements of ketene acetals derived from chiral non-racemic allyUc alcohols (Scheme 4.23) [25]. The alcohols were themselves derived from Evans aldol additions. While the Johnson and Eschenmoser rearrangements were used to iUus-... 

Claisen rearrangement of 3,4-unsaturated glycosides to C4-branched derivatives provided useful intermediates for the total synthesis of thromboxanes (Scheme 20). First reported independently by Corey et al. [41] and Hernandez [42],both the Eschenmoser amide acetal and the Johnson orthoester procedure afforded good results for the conversion of allylic alcohol 99 (R = Me, R = H) to the respective amide or ester 100. Corey et al. further transformed the former compound to lactone 101, previously described as a precursor for the total synthesis of thromboxane B2 (102). A number of further derivatives 100 (R = allyl, R = H or TBDMS, R = NMe2 or OEt) and its C2-epimer were prepared in a similar manner during later thromboxane synthetic studies [43,44]. 

The control of the configuration of the side chain at C-8 in a synthesis of C-gly-coside antibiotic pseudonomic acid 212 described by DeShong [46] resulted from a Claisen-Johnson rearrangement Dihydropyrane derivatives 213-214 after treatment with triethyl orthoacetate afforded an inseparable mixture of diastereomers. The anomeric center was then reduced and the side chain secondary alcohol oxidized. Diastereomeric ketones 215 and 216 were isolated at this stage in a 2 1 ratio (Scheme 6.33). 

Various codeine 399 derivatives were prepared for structure activity studies via a sequence of reactions that began with a Claisen-Eschenmoser rearrangement affording amide 401 from codeine 399 [96]. Unexpectedly, with the same alkaloid under the Claisen-Johnson conditions the orthoesters 402 and 403 were the only products isolated (Scheme 6.66). 

In a recent study [105], the same group applied the Claisen-Johnson rearrangement to D-glucose derived spirocyclic substrate 437. This reaction afforded a mixture of stereoisomers. It is worthy of note that the selectivity of the rearrangement is highly dependant upon the substitution of the orthoester (Scheme 6.72). The Claisen-Ireland rearrangement was inoperative with these glucose derivatives. 

A combination of enzymatic resolution and orthoester rearrangement has been used by Brenna in a short synthesis of (R)-(-)-baclofen 503 (Scheme 6.79) [123a]. R) or (S)-3-Methyl-2-phenylbutylamine 506 were recently obtained using the same strategy (Scheme 6.79) [123bj. A Claisen-Johnson rearrangement of a benzyl vinyl ether studied by Raucher provided substituted arenes 510. Better results were observed with electron donating substituted arenes. This reaction has been extended to indole derivatives 511 (Scheme 6.79) [124]. 

The quaternary center of a dendritic tetramines 522 and 523 described by Feldman [128] was established through a Claisen-Johnson rearrangement of aUylic alcohol 524 (Scheme 6.81). One of the main steps in the synthesis of the protease inhibitor 526 [129] was achieved through a high-yield diastereoselective Claisen-Johnson rearrangement as described in Scheme 6.81. A stereoselective synthesis of the alkyUdene dipeptide isosteres 530 and 532 proceeded via a Claisen-Johnson rearrangement. It is worthy of note that yields with anti- or syn-configured ami-noalcohol derivatives 529 and 531 were quite different (Scheme 6.81) [130]. 

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