Michael addition rearrangement

Dramatic rate accelerations of [4 + 2]cycloadditions were observed in an inert, extremely polar solvent, namely in5 M solutions oflithium perchlorate in diethyl ether(s 532 g LiC104 per litre ). Diels-Alder additions requiring several days, 10—20 kbar of pressure, and/ or elevated temperatures in apolar solvents are achieved in high yields in some hours at ambient pressure and temperature in this solvent (P.A. Grieco, 1990). Also several other reactions, e.g, allylic rearrangements and Michael additions, can be drastically accelerated by this magic solvent. The diastereoselectivities of the reactions in apolar solvents and in LiClO EtjO are often different or even complementary and become thus steerable. 

Purines, N-alkyl-N-phenyl-synthesis, 5, 576 Purines, alkylthio-hydrolysis, 5, 560 Mannich reaction, 5, 536 Michael addition reactions, 5, 536 Purines, S-alkylthio-hydrolysis, 5, 560 Purines, amino-alkylation, 5, 530, 551 IR spectra, 5, 518 reactions, 5, 551-553 with diazonium ions, 5, 538 reduction, 5, 541 UV spectra, 5, 517 Purines, N-amino-synthesis, 5, 595 Purines, aminohydroxy-hydrogenation, 5, 555 reactions, 5, 555 Purines, aminooxo-reactions, 5, 557 thiation, 5, 557 Purines, bromo-synthesis, 5, 557 Purines, chloro-synthesis, 5, 573 Purines, cyano-reactions, 5, 550 Purines, dialkoxy-rearrangement, 5, 558 Purines, diazoreactions, 5, 96 Purines, dioxo-alkylation, 5, 532 Purines, N-glycosyl-, 5, 536 Purines, halo-N-alkylation, 5, 529 hydrogenolysis, 5, 562 reactions, 5, 561-562, 564 with alkoxides, 5, 563 synthesis, 5, 556 Purines, hydrazino-reactions, 5, 553 Purines, hydroxyamino-reactions, 5, 556 Purines, 8-lithiotrimethylsilyl-nucleosides alkylation, 5, 537 Purines, N-methyl-magnetic circular dichroism, 5, 523 Purines, methylthio-bromination, 5, 559 Purines, nitro-reactions, 5, 550, 551 Purines, oxo-alkylation, 5, 532 amination, 5, 557 dipole moments, 5, 522 H NMR, 5, 512 pJfa, 5, 524 reactions, 5, 556-557 with diazonium ions, 5, 538 reduction, 5, 541 thiation, 5, 557 Purines, oxohydro-IR spectra, 5, 518 Purines, selenoxo-synthesis, 5, 597 Purines, thio-acylation, 5, 559 alkylation, 5, 559 Purines, thioxo-acetylation, 5, 559... 

There are a number of powerful synthetic reactions which join two trigonal carbons to form a CC single bond in a stereocontrolled way under proper reaction conditions. Included in this group are the aldol, Michael, Claisen rearrangement, ene and metalloallyl-carbonyl addition reactions. The corresponding transforms are powerfully stereosimplifying, especially when rendered enantioselective as well as diastereoselective by the use of chiral controller groups. Some examples are listed in Chart 20. 

Fusion of an all cyclic ring onto the piperidine so as to form a perhydroisoquinoline is apparently consistent with analgesic activity. Synthesis of this agent, ciprefadol (68), starts with the Michael addition of the anion from cyclohexanone 56 onto acrylonitrile (57). Saponification of the nitrile to the corresponding acid ( ) followed by Curtius rearrangement leads to isocyanate Acid... 

An intramolecular version of enolate Michael addition to enantiomerically pure vinylic sulfoxides is represented by reaction of a cyclopentenone sulfoxide with dichloroketene (Scheme 5)90 this type of additive Pummerer rearrangement has been developed by Marino and coworkers91 into a highly effective way of constructing variously substituted lactones in very high enantiomeric purity (equation 43). 

During 1989-93 lithium perchlorate iethyl ether (LiC104 EtiO, LP-DE) was studied as a reaction medium in organic synthesis when it was observed that cycloadditions, sigmatropic rearrangements, Michael additions and aldol condensations carried out in LP-DE occurred quickly and selectively under mild reaction conditions [33]. In addition, LP-DE allowed the reaction and subsequent work-up to be carried out under essentially neutral conditions. 

As indicated, many of the more highly fimctionalized building blocks did not result in 2-pyridones. However, a thorough structure elucidation of by-products and intermediates was used to propose a mechanism for the formation of the 2-pyridone core based on a Michael addition followed by a Dimroth-type rearrangement (Fig. 3). 

Fig. 30 Asymmetric aza-Claisen rearrangement of (Z)-configured trifluoroacetimidates 44 3.1.2 Bispalladium-Catalyzed Michael-Addition of a-Cyanoacetates...

The synthesis was carried out as shown in Scheme 13.24. A diol was formed and selectively tosylated at the secondary hydroxy group (Step A-4). Base then promoted the skeletal rearrangement in Step B-l by a pinacol rearrangement corresponding to 23-11 => 23-III in the retrosynthesis. The key intramolecular Michael addition was accomplished using triethylamine under high-temperature conditions. 

Michael addition of amidoxime 7 to DMAD, followed by thermal rearrangement. 

The ratio of 8Z to HE is slightly better in the presence of DABCO in THF (Table 6.2 entry 9) than in pure methanol (Table 6.2 entry 7). Since the DABCO must be removed prior to the thermal rearrangement and the minimal impact on overall yield, we decided to run the Michael addition in methanol to afford a mixture of Z- and -adducts 8 in quantitative yield. The resulting solution of adducts 8 was solvent-switched to xylenes and heated at 125 °C for 2h, and at 135 °C for 4h to give a 62% assay yield of desired product 3. The reaction mixture was concentrated and hydroxypyrimidinone 3 was directly crystallized in 54% isolated yield as a white crystalline solid. 

In a related example, reaction of N-hydroxy-N-methylthiophene-2-carboximidamide 56 with DMAD gave a double Michael addition product 57, which when heated at reflux in xylenes, afforded hydroxypyrimidinone 60 in 57% overall yield (Scheme 6.21) [9f]. The mechanism invoked was opening of the oxa-diazole 57 to 58, followed by a [3,3]-Claisen-type rearrangement to 59, which, after tautomerization and cyclization, afforded 60. 

The reaction starts with the formation of a mixed anhydride and an acetate on treatment with an excess of acetic anhydride at 80 °C. There follows a Dieckmann condensation to give 2-590 and an intramolecular rearrangement/Michael addi-hon/retro Michael addition to afford the desired tetracyclic compound 2-592 via 2-591 in an overall yield of remarkable 92%. 

Majumdar and coworkers used a combination of a 3,3-sigmatropic rearrangement followed by an intramolecular [1,6]-Michael addition for the synthesis of py-rimidine-annulated heterocycfes as 4-308 from 4-307 (Scheme 4.66) [103]. 

Allylic nitro compounds undergo [2.3]sigmatropic rearrangement to afford rearranged alcohols, as shown in Eq. 7.4346 and Eq. 7.44 47 Because the allylic nitro compounds used in these reactions are readily prepared either by the Henry reaction or the Michael addition, these reactions may be useful in organic synthesis. 

A diverse group of organic reactions catalyzed by montmorillonite has been described and some reviews on this subject have been published.19 Examples of those transformations include addition reactions, such as Michael addition of thiols to y./bunsatu rated carbonyl compounds 20 electrophilic aromatic substitutions,19c nucleophilic substitution of alcohols,21 acetal synthesis196 22 and deprotection,23 cyclizations,19b c isomerizations, and rearrangements.196 24... 

---