ABSTRACT
A general method for the synthesis of 2,4,5-trisubstituted oxazoles has been developed. Starting from commercially available oxazole, successive metalations using TMPMgCl·LiCl or TMPZnCl·LiCl led to the corresponding magnesiated or zincated species which were stable toward ring fragmentation. Furthermore, they readily reacted with various electrophiles, such as aryl and allylic halides, acid chlorides, TMSCl, and TMS-CN, providing highly functionalized oxazoles.
Subject(s)
Magnesium/chemistry , Organometallic Compounds/chemistry , Oxazoles/chemical synthesis , Piperidines/chemistry , Zinc/chemistry , Lithium/chemistry , Molecular Structure , Oxazoles/chemistry , StereoisomerismABSTRACT
In this review we summarize the most important procedures for the preparation of functionalized organzinc and organomagnesium reagents. In addition, new methods for the preparation of polyfunctional aryl- and heteroaryl zinc- and magnesium compounds, as well as new Pd-catalyzed cross-coupling reactions, are reported herein. Experimental details are given for the most important reactions in the Supporting Information File 1 of this article.
ABSTRACT
The preparation of highly functionalized organometallic compounds can be achieved by direct C-H activation of a broad range of unsaturated substrates using lithium chloride solubilized 2,2,6,6-tetramethylpiperidide bases (TMP(n)MX(m)â p LiCl). These are excellent reagents for converting a wide range of aromatic and heterocyclic substrates into valuable organometallic reagents with broad applications in organic synthesis.
Subject(s)
Amides/chemistry , Lithium Chloride/chemistry , Organometallic Compounds/chemistry , Piperidines/chemistry , Molecular Structure , Organometallic Compounds/chemical synthesis , StereoisomerismABSTRACT
A broad range of functionalized aryl- and heteroarylzinc reagents were prepared via directed zincation of sensitive and moderately activated aromatics and heteroaromatics using TMPZnCl.LiCl under various reaction conditions. Diverse sensitive functional groups such as a nitro group, an aldehyde, an ester, and a nitrile are readily tolerated and are compatible with high metalation temperatures. Furthermore, the resulting zinc organometallics display an excellent reactivity toward various classes of electrophiles providing functionalized aromatics and heteroaromatics in high yields.
ABSTRACT
Successive regio- and chemoselective metalations of chloropyrazines using TMPMgCl x LiCl and TMPZnCl x LiCl furnish, after trapping with electrophiles, highly functionalized pyrazines in high yields. Application to a synthesis of coelenterazine, a bioluminescent natural product in jellyfish Aequorea victoria, in nine steps (9% overall yield) is reported.
Subject(s)
Imidazoles/chemical synthesis , Organometallic Compounds/chemistry , Pyrazines/chemistry , Pyruvaldehyde/chemical synthesis , Animals , Imidazoles/chemistry , Pyrazines/chemical synthesis , Pyruvaldehyde/chemistry , Scyphozoa/chemistryABSTRACT
A wide range of functional aryl and heteroaryl zinc reagents have been efficiently prepared via regio- and chemoselective zincation using TMPZnCl.LiCl and microwave irradiation. Sensitive functional groups like esters are compatible with the high temperatures of the reactions. The resulting zinc species undergo a number of subsequent reactions, providing highly functionalized aromatics and heteroaromatics in high yields.
Subject(s)
Lithium Chloride/chemistry , Microwaves , Zinc/chemistry , Hot Temperature , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , JNK Mitogen-Activated Protein Kinases/metabolism , Protein Kinase Inhibitors/chemistryABSTRACT
A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF via direct zincation using TMPZnCl.LiCl, a new exceptionally mild and efficient base. Activated arenes and heteroarenes are metalated at room temperature. Remarkably, sensitive functions such as an aldehyde as well as a nitro group are tolerated, expanding significantly the scope of directed metalations.
ABSTRACT
Efficient zincation and magnesiation of chlorinated pyrimidines can be performed at convenient temperatures (e.g., 25 and 55 degrees C) by using TMPMgCl x LiCl and TMP(2)Zn x 2 MgCl(2) x 2 LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) as effective bases. Quenching of the resulting zincated or magnesiated pyrimidines with various electrophiles furnishes highly functionalized pyrimidines in 51-93% yield. Oxidative aminations were carried out, thus leading to aminated pyrimidines. By using this methodology, we have also prepared pharmaceutically relevant pyrazolopyrimidines and the fungicide Mepanipyrim.
Subject(s)
Lithium/chemistry , Magnesium/chemistry , Organometallic Compounds/chemical synthesis , Pyrimidines/chemical synthesis , Zinc/chemistry , Amination , Chlorine/chemistry , Organometallic Compounds/chemistry , Pyrazoles/chemical synthesis , Pyridines/chemical synthesis , Pyrimidines/chemistry , TemperatureABSTRACT
Two successive regio- and chemoselective magnesiations using TMPMgCl x LiCl and TMP(2)Mg x 2 LiCl enable the full functionalization of protected uracils and thiouracils in good to excellent yields.
Subject(s)
Magnesium/chemistry , Organometallic Compounds/chemistry , Sulfhydryl Compounds/chemistry , Thiouracil/chemistry , Uracil/chemistry , Molecular Structure , StereoisomerismABSTRACT
Successive regio- and chemoselective magnesiations of pyrimidines using TMPMgCl.LiCl furnish, after trapping with various electrophiles, highly functionalized derivatives in good to excellent yields. Applications to the synthesis of antiviral and anti-inflammatory agents such as p38 and sPLA2 kinase inhibitors are reported.
Subject(s)
Combinatorial Chemistry Techniques , Magnesium/chemistry , Organometallic Compounds/chemistry , Pyrimidines/chemistry , Alkalies/chemistry , Indicators and Reagents , Molecular Structure , StereoisomerismABSTRACT
The cobalt-catalyzed [6+2] cycloaddition of cyclooctatetraene 1 with alkynes 3 affords monosubstituted bicyclo[4.2.2]deca-2,4,7,9-tetraenes 4 in fair to good yields. Due to the valence tautomerism, 1,3,5-cyclooctatriene 2, in equilibrium with bicyclo[4.2.0]octa-2,4-diene A, and alkynes 3 are converted to 10 and 11 according to [6+2] and [4+2] cycloadditions, respectively.