Tandem reactions rearrangement

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

Tandem reactions of heterocycles combining Diels-Alder reactions with sig-matropic rearrangements 98S227. 

Tandem reactions combining Diels-Alder reactions with sigmatropic rearrangements in syntheses of heterocycles 98S227. 

Neuschuetz K., Velker J., Neier R. Tandem Reactions Combining Diels-Alder Reactions With Sigmatropic Rearrangement Processes and Their Use in Synthesis Synthesis 1998 227-255... 

For preparation of allyl coumarins and dihydrofuranocoumarins by tandem Claisen rearrangement-cyclization the usual procedures required vigorous reaction conditions, workup procedures were tedious, and long reaction times led to low yields. The rearrangement of allyloxycoumarins 48 to dihydrofuranocoumarins 49 has been optimized in good yields in a sealed Teflon containers with BF3-ether in N-methyl-... 

Keyword Carbocycles a Cascade Reactions a Cycloadditions a Combinatorial Chemistry a Domino Reactions a Enantioselective Transformations a Ene Reactions a Eieterocydes a Natural products a Preservation of Resources and Environment a Sigmatropic Rearrangements a Tandem Reactions a Transition Metal-Catalyzed Transformations... 

Among all tandem hydroformylation sequences the ones involving additional C,C-bond formations are the most synthetically valuable tandem hydroformylation sequences. These C,C-bonds can be formed by adding nucleophiles, which attack the carbonyl carbon, or by adding electrophiles, which attack the a-position. Furthermore, tandem reactions in which the aldehyde or an aldehyde derivative is involved in sigmatropic rearrangement are described. 

The domino cycloaddition-iV-acyliminium ion cyclization cascade has been extensively reviewed. Tandem reactions combining Diels-Alder reactions and sigma-tropic rearrangement reactions in organic synthesis have been extensively reviewed. The tandem Diels-Alder reaction between acetylenedicarboxaldehyde and N,N -dipyrrolylmethane has been extensively studied at the RHT/3-21G and RHF/6-31G levels.The molecular mechanism of the domino Diels-Alder reaction between hexafluorobut-2-yne and A,A -dipyrrolylmethane has been studied using density functional theory. 

Detailed time-dependent NMR studies were also performed in order to evaluate the kinetic profile of the tandem reaction (Fig. 6.17). Experimental data was coherent with a reversibly-irreversihly-coupled model, suggesting the proposed rearrangement step to he faster compared to the iminolactone cycfizafion. The studies also revealed the forward nitroaldol formation to he of comparable rate to tandem cycfizafion, while the reverse nitroaldol reaction was slower and thereby rate determining for the overall DCR process. 

Neuschiitz, K. Velker, J. Neier, R. (1998) Tandem reactions combining Diels-Alder reactions with sigmatropic rearrangement processes and their use in synthesis. Synthesis, 3, 227-55. 

Cycloadditions of dienes with oxyallyl offer the opportunity to prepare seven-membeted ring systems. This reaction has also proved to be of importance in Ae furan series. A few examples may illustrate the value of this methodology. A tandem Pummerer rearrangement and intramolecular [4-i3]-cycloaddition with a fiiran derivative has been reported <99TL545>. For a similar reaction see <99T13999>. 

A tandem Wolff rearrangement reaction followed by cyclization leads to the formation of thieno[3,2-f]pyrans in moderate yields as shown in Scheme 26 <1998T6457>. A key step of the reaction involves thermolysis of diazoketophosphonate 97. 

Substituted benzo[ ]thiophene derivatives have been prepared in excellent yields by a tandem Pummer rearrange-ment/Diels-Alder reaction of the intermediate furan with maleic anhydride or A -phenylmaleimide (Equation 87) <1996JOC6166>. 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone applies a tandem Claisen rearrangement and intramolecular ene-reaction. Most 19-nonsteroid contraceptive agents are produced by total synthesis from nonsteroidal starting materials. 

Dihydroxy-l,3-dioxepins readily undergo vinylacetal rearrangement in the presence of a Lewis acid to give tetrahydrofuran-3-carbaldehydes (CHEC-II(1996)). This methodology was applied in a tandem Heck reaction -rearrangement process for the synthesis of a variety of 2,4-substituted tetrahydrofuran-3-carbaldehydes (Scheme 19) <2006CC3119>. 

Claisen condensation equivalent, 10, 174 Claisen rearrangement equivalent, 10, 176 combined G—H activation-Cope rearrangement, 10, 177 as strategic reaction, 10, 178 tandem Claisen rearrangement-Cope equivalent,... 

Fig. 7.9 Electrocyclic tandem reaction as generated by RAIN. Rearrangement of a benzocyclobutane 8 into a isochromanone lTvia intermediate compounds 9 and 10.

Fig. 44 Ruthenium-catalyzed tandem Overman rearrangement/RCM/ATRC reactions...

As shown in Equation (179), a tandem Claisen rearrangement-lactonization involving the C-3 side chain of furan 292 was employed for a concise synthesis of hyperolactone C <2003JNP1039>. Although the product yield was low, the reaction created two contiguous quaternary carhon centers in one step. 

In 1971, Yamada et al. published their preliminary smdies toward dendrobine (82) 173). Their starting material was the cheap, commercially available arene thymol, and the key step was an intramolecular Robinson annulation also known as Johnson s tandem reaction. After unexpected rearrangements within an ozoifization, their protocol was modified and in 1972 Yamada et al. were able to present the first S3mthesis of ( )-dendrobine (82) 146). 

Chuard et al. used allylsulfoxides as precursors of oxygen-centered radicals (Scheme 83) [229]. The Evans-Mislow rearrangement of allylsulfoxides leads to allyl sulfonyl ethers. The authors decided to use those as source of oxygen radicals. In addition, when the allyl sulfoxide was branched on a cyclobutene, the tandem reaction delivered a cyclobutyloxy radical that collapsed and underwent ring expansion in good overall yield. Thus, starting from sulfoxide 283,... 

Combination of a Diels-Alder reaction and a [3,3] sigmatropic rearrangement provides access to 1,4-substituted 2-cyclohexenyl derivatives75- 76,11 . Thus, Diels-Alder reaction of ( )-l,3-bu-tadienyl thiocyanate with methyl acrylate is followed by a [3,3] sigmatropic rearrangement to the isothiocyanate. The isothiocyanate is trapped by the solvent to give racemic 0-cthyl-/V-(4-methoxycarbonyl-2-cyclohexcnyl)thiocarbamate in a 66 33 diastereomeric ratio (cisjtram). A Lewis acid catalyzed variant of this tandem reaction showed better diastereoselectivity (90 10)111. 

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