Johnson-Claisen reaction

Jacobi has described an elegant tandem application of the Johnson-Claisen reaction and the Diels-Alder cycloaddition to generate 355. The nature of the nitrogen substituent (R) directly influences the efficiency of the subsequent thermal cyclization of the initial rearrangement product... 

The Johnson Claisen rearrangement,31 also called the ortho ester Claisen rearrangement, involves the reaction of an allylic alcohol with an ortho ester, often triethyl orthoacetate, in the presence of a carboxylic acid such as propionic acid, usually at temperatures between 120 and 140 JC (Scheme 3).1 The intermediate kctcnc acetal rearranges stereoselectively. 

More recently, Kitazume and co-workers found that allylic alcohols 7 undergo the Johnson Claisen rearrangement in higher yields when the reaction is run in a sealed tube at 130 C for 12 hours.35 Under these conditions. (/ )-7 is converted into 8 with high E stereoselectivity and complete 1,3-chiral transfer. 

DFT studies on the facial selectivities of six Johnson-Claisen rearrangements (Scheme 5) analogous to those used in the synthesis of gelsemine have reproduced experimental results in five out of the six cases, but have predicted formation of the same product (21) in all six reactions. The selectivity in these cases has been attributed to a combination of steric repulsions between vinylic proton H(l) and allylic proton H(7) or H(14), and electrostatic attractions between C(l) and the oxetane hydrogens C(5)-H and C(16)-H. Both of these factors, however, apparently predicted the non-observed product in the conversion of (22) into (23)22... 

The increased syn/anti selectivity observed in the Johnson-Claisen rearrangement of the ketene acetal from the trisubstituted alkene is an indication that the reaction goes through a six-membered chairlike transition state4 (Scheme 1.2d). Transition state B is disfavored compared to state A, due to the developing 1,3-diaxial interactions between the two methyl groups in the transition state. 

Johnson et al. used their newly developed orthoester Claisen reaction to achieve a highly stereoselective total synthesis of aM-trans squalene (5)1 (Scheme 1.20. The diene diol 6 underwent Johnson-Claisen rearrangement when it was heated with ethyl orthoacetate in the presence of propionic acid for 3 h at 138 C. The diene dialdehyde 7, obtained by treatment of the resulting ester with lithium aluminum hydride followed by oxidation with Collins reagent, reacted with 2-propenyllithium to give the tetraene diol 8. The tetraene dialdehyde 9, which... 

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. ° ... 

Related reactions Carroll rearrangement, Claisen-lreland rearrangement, Eschenmoser-Claisen rearrangement, Johnson-Claisen rearrangement ... 

The second route (272) is an enantiospecific one that starts from (+)-S-l-benzyloxycarbonyl-3-piperidein-5-ol (426), obtained from the corresponding racemate by preferential lipase-catalyzed esterification of its enantiomer by means of vinyl acetate, as in the preparation of 419. Reaction of 426 with triethyl orthoacetate, followed by Johnson-Claisen rearrangement, gave the tetrahydropyridine ester 427, which was converted by unexceptional means into the ketoamide 428. Reductive removal of the functional groups then provided another synthesis of (-I- )-R-demethoxy-carbonyl-15,16,17,20-tetrahydrosecodine (2), and Dess-Martin oxidation... 

A very elegant stereoselective synthesis of juvenile hormone has been achieved by Johnson and co-workers,who employed the olefinic ketal Claisen reaction to great advantage. Thus, the hydroxy-ester (15), on treatment with the olefin-ketal (16) in acidic medium was converted into the ester (17). Sodium borohydride reduction to the corresponding allylic alcohol and a second Claisen-reduction sequence as described above yielded the trienol-ester (18). Chlorination under Sni conditions and selective reduction of the resultant primary allylic chloride produced the well-known triene-ester (19) which was converted to juvenile hormone (11). 

A soln. of the startg. m. and 4 equivalents ketal heated ca. 8 hrs. at 100° in toluene containing 2,4-dinitrophenol as catalyst, and the intermediate ketone treated at 0° with NaBH4 in methanol > product. Y up to 81% purity 98%. -This olefinic ketal Claisen reaction is useful for preparing trans-disubst as well as trans-trisubst. olefinic bonds. The above producure is the last of a succession of 3 similar steps. F. e. and catalysts s. W. S. Johnson et al., Am. Soc. 92, 4463 (1970) Proc. Natl. Acad. Sci. U.S. 67, 1462, 1465, 1810, 1824 (1970) geospecific synthesis of ethylene derivs., review, s. J. Reucroft and P. G. Sammes, Quart. Rev. 25,135 (1971). 

Scheme 13.30 Sequential Johnson-Claisen and Eschenmoser-Claisen rearrangements. Scheme 13.31 Double Ireland-Claisen rearrangement reactions.

Johnson (see Hilbert-Johnson Reaction) Johnson-Claisen Rearrangement Jones Oxidation... 

Scheme 6.76). Heathcock developed a synthetic strategy wherein the 1,2-stereoselection obtainable from aldol reaction is parlayed by a subsequent Claisen rearrangement into 1,4 and 1,5-stereoselection [118]. Claisen-Johnson, Claisen-Eschenmoser and Claisen-Ireland rearrangements were examined in this study. However the orthoester Claisen-Johnson rearrangement was not the most convenient in this case. The rather harsh reaction conditions often led to dehydration and other byproducts. An example of this rearrangement is given in Scheme 6.76. 

Cook has relied on the Johnson-Claisen rearrangement for the conversion of allylic alcohol 356 to ester 358. The reaction proceeds via a boat-like transition state 357 to jdeld 2 1 diastereoselection of the exocyclic stereogenic center of 358. ... 

Two C-H catalytic activation reactions were employed in a synthesis of rhazinal 3.23 (Scheme 3.20). The starting material was prepared from a readily available aldehyde 3.24, An aldol reaction installed a methylene group a to the carbonyl. This was followed by addition of methyl lithium and a Johnson-Claisen rearrangment... 

Kobayashi et al. have examined the synthetic applications of 7-trifluoromethylated propargyl alcohols." Thus, treatment of various propargyl alcohols with an excess amount of triethyl orthoacetate in the presence of an acid catalyst at heating gives the corresponding Johnson Claisen products in 32-55% yields. On the other hand, they have also examined the Sn2 reaction of the cuprate derived from... 

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],... 

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