Cycloaddition/rearrangement synthesis

In the overall cycloaddition-rearrangement process [64], the C-3 - C-8a relative stereochemistry of the indolizidinone obtained by rearrangement of the isoxazolidine derives from the cycloaddition step and is not affected during the rearrangement. This allowed the control of two out of three chiral centers in a synthetic protocol for a synthesis of the amphibian alkaloid ( + )-Gephyro-toxin 223AB (Scheme 46) [65c]. 

Cycloaddition reactions of furans are still widely used as key steps in the construction of complex molecules including natural products. As an example, the intramolecular Diels-Alder cycloaddition of 2-amido substituted furans provides a useful tool for the synthesis of fused, nitrogen-containing poly-heterocycles. Thus, thermolysis of 3-substituted amidofuran produces tricyclic indolinone 39 as a 2 1 mixture of diastereomers via amidofuran cycloaddition-rearrangement methodology, which serves as a key intermediate in the total synthesis of ( )-dendrobine, a major component of the Chinese ornamental orchid Dendrobium nobile . 

Padwa A, Dimitroff M, Liu B (2000) Formal Synthesis of ( )-Dendrobine Use of the Amidofuran Cycloaddition/Rearrangement Sequence. Org Lett 2 3233... 

In a preliminary chapter, entitled Introduction, the underlying principles of physical organic chemistry, as applied to stereoselective reactions, are succintly recalled. The three subsequent chapters describe the chiral auxiliaries, reagents, catalysts and ligands that are most commonly used in asymmetric synthesis. The remaining chapters are devoted to the description and delineation of the scope of the main classes of asymmetric organic reactions. These indude protonations and deprotonations alkylations and related reactions additions to C=0, C=N and C=C double bonds cycloadditions rearrangements and transition metal-catalyzed reactions. 

Namitharan, K. and Pitchumani, K. 2011. Copper(l)-catalyzed three component reaction of sulfonyl azide, alkyne, and nitrone cycloaddition/rearrangement cascades A novel one-step synthesis of imidazolidin-4-ones. Org. Lett. 13(21) 5728-5731. 

The cycloaddition/rearrangement IMDAF cascade of 2-amidofurans such as 319 was remarkably efficient given that two heteroaromatic systems are compromised in the reaction. Closure of 321 to the remaining D-ring of the Strychnos skeleton (i.e., 322) was carried out from the aza-tetracyclic intermediate 321 by an intramolecular palladium-catalyzed enolate-driven cross-coupling between the A-tethered vinyl iodide and the keto functionality. The cycloaddition/rearrangement approach was successfully applied to a synthesis of the heptacyclic fi-amework of ( )-strychnine 323 (Scheme 13.72) [114], which required only 13 steps from furanyl indole 319 and proceeded in an overall yield of 4.4%. 

SCHEME 21.36. [4-1-2]-Cycloaddition/rearrangement cascade for the total synthesis of strychnine. 

Within the cubane synthesis the initially produced cyclobutadiene moiety (see p. 329) is only stable as an iron(O) complex (M. Avram, 1964 G.F. Emerson, 1965 M.P. Cava, 1967). When this complex is destroyed by oxidation with cerium(lV) in the presence of a dienophilic quinone derivative, the cycloaddition takes place immediately. Irradiation leads to a further cyclobutane ring closure. The cubane synthesis also exemplifies another general approach to cyclobutane derivatives. This starts with cyclopentanone or cyclohexane-dione derivatives which are brominated and treated with strong base. A Favorskii rearrangement then leads to ring contraction (J.C. Barborak, 1966). 

H-Azepine, 2-methyl-1-methoxycarbonyl-rearrangement, 7, 504 1 //-Azepine, 3-methyl-1 -methoxycarbonyl-cycloaddition reactions, 7, 520 IH-Azepine, 1-phenyl-synthesis, 7, 542 1 H-Azepine, N-phthalimido-formation, 7, 508 IH-Azepine, N-sulfonyl-UV spectra, 7, 501 1 H-Azepine, tetrahydromethylene-synthesis, 7, 540 IH-Azepine, N-p-tosyl-protonation, 7, 509 synthesis, 7, 537 3H-Azepine, 3-acyl-2-alkoxy-synthesis, 7, 542-543 3H-Azepine, 3-acyl-2-methoxy-rearrangements, 7, 505 3H-Azepine, 2-alkoxy-hydrolysis, 7, 510... 

Schmidt reaction of ketones, 7, 530 from thienylnitrenes, 4, 820 tautomers, 7, 492 thermal reactions, 7, 503 transition metal complexes reactivity, 7, 28 tungsten complexes, 7, 523 UV spectra, 7, 501 X-ray analysis, 7, 494 1 H-Azepines conformation, 7, 492 cycloaddition reactions, 7, 520, 522 dimerization, 7, 508 H NMR, 7, 495 isomerization, 7, 519 metal complexes, 7, 512 photoaddition reactions with oxygen, 7, 523 protonation, 7, 509 ring contractions, 7, 506 sigmatropic rearrangements, 7, 506 stability, 7, 492 N-substituted mass spectra, 7, 501 rearrangements, 7, 504 synthesis, 7, 536-537... 

Azirine, trans-2-methyl-3-phenyl-racemization, 7, 33, 34 1-Azirine, 2-phenyl-reactions, 7, 69 with carbon disulfide, S, 153 1-Azirine, 3-vinyl-rearrangements, 7, 67 Azirines, 7, 47-93 cycloaddition reactions, 7, 26 fused ring derivatives, 7, 47-93 imidazole synthesis from, 5, 487-488 photochemical addition reactions to carbonyl compounds, 7, 56 photolysis, 5, 780, 7, 28 protonated... 

Diaziridine, 3-benzyl-1,3-dimethyl-inversion, 7, 7 Diaziridine, 1,2-dialkyl-reaction with iodides, 7, 217 thermal decomposition, 7, 217 Diaziridine, dibenzoyl-rearrangement, 7, 214 Diaziridine, 3,3-dimethyl-Raman spectra, 7, 202 Diaziridine, fluoro-synthesis, 7, 232 Diaziridines acylation, 7, 213 from azomethines, 7, 231 calculations, 7, 198 from chloramine, 7, 230 cycloaddition reactions, 7, 28 electron diffraction, 7, 19 199 c/s-fused NMR, 7, 201 hydrolysis, 7, 216 inversion stability, 7, 200... 

Thiophene, 3-pentadeuterophenyl-chemical shifts, 4, 730 Thiophene, 2-phenyl-oxidation, 4, 800 phototranspositions, 4, 743 rearrangement, 4, 42 reduction, 4, 775 synthesis, 4, 865, 914 UV spectrum, 4, 735 Thiophene, 3-phenyl-photochemical rearrangements, 4, 735 phototranspositions, 4, 743 lsmeier formylation, 4, 759 Thiophene, 2-pivaloyl-Birch reduction, 4, 775 Thiophene, polybromo-reactivity, 4, 829 Thiophene, polylithio-synthesis, 4, 831 Thiophene, (propargylthio)-rearrangement, 4, 746 Thiophene, 2-(3-pyridinyl)-synthesis, 4, 781 Thiophene, 2-(5-pyrimidinyl)-synthesis, 4, 781 Thiophene, 3-pyrrolidinyl-cycloaddition reactions, 4, 68 with dimethyl acetylenedicarboxylate, 4, 788-789... 

Adducts derived from cyclopropyl-TMM reactions are versatile synthetic intermediates. Alkylidenecyclopropanes have been proven useful in further Pd-cata-lyzed transformations [4], On the other hand, vinylcyclopropanes can undergo smooth thermal ring-expansion to cyclopentenes. Thus, a total synthesis of 11-hy-droxyjasionone (27) was achieved with the cyclopropyl-TMM cycloaddition as the crucial step, and the thermal rearrangement of the initial adduct (28) as an entry to the bicyclo[6.3.0]undecyl compound (29), a key intermediate in the synthetic sequence (Scheme 2.9) [19]. 

This methodology has been used for the synthesis of the C3-C14 segment 24 of the antitumor agent laulimalide 23 (Scheme 4.22) [35]. The constrained chiral BOX ligand 21c in combination with Cu(OTf)2 afforded dihydropyrane 6f by a cycloaddition reaction in good yield and ee this was converted to the C3-C14 segment 24 via a Ferrier-type rearrangement in several steps. 

Scheme 79 Snapper s total synthesis of asteriscanolide (116) by sequential intramolecular cyclobutadiene cycloaddition, ring-opening CM (ROCM), and Cope rearrangement [167]...

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