Directed metalation of tertiary benzamides.: Short syntheses of hydrangenol and phyllodulcin

Brief syntheses of isocoumarin natural products hydrangenol ($\text{2}$) and phyllodulcin ($\text{3}$) via ortho-lithiated benzamide intermediates are described.     

Directed metalation of tertiary benzamides. Abbreviated syntheses of phenanthro-quinolizidine and -indolizidine alkaloids

Short synthesis of the alkaloids cryptopleurine ($\text{1}$) and antofine ($\text{2}$) via directed metalation of the common phenanthrene amide $\text{3}$ are described.     

Directed ortho metalation reactions. Synthesis of the naturally-occurring benz[a]anthraquinones X-14881 C and ochromycinone

The synthesis of the benz[a]anthraquinone natural products X-14881 C (1c) and ochromycinone (1a) via an aromatic directed metalation strategy (Scheme 1) is described.     

Synthesis and metalation of trifluoromethylpyrimidines. Metalation of diazines. XVI

A new route to trifluoromethylpyrimidines is described. Lithiation of trifluoromethylpyrimidines was successfully achieved and was used to synthesize new pyrimidine derivatives. A new synthetic route to a biologically active molecule with antimycotic activities is reported.     

Directed ortho metalation methodology. The N,N-dialkyl aryl O-sulfamate as a new directed metalation group and cross-coupling partner for Grignard reagents

[reaction: see text] The ortho metalation (RLi/THF/-93 degrees C) of 3 followed by quench with a variety of electrophiles constitutes a new general route to substituted aryl O-sulfamates 4a-k. The Kumada-Corriu cross-coupling of O-sulfamates 4e, 4n-s, and 6a with Grignard reagents gives biaryls 9a-m, and the use of 2-halo and boron derivatives 4h, 4i, and 4k for Suzuki-Miyaura cross-coupling and generation of benzynes leads to naphthols 7a and 7b. A relative metalation ranking of the OSONEt(2) is reported.     

Reductive metalation of 1,2-diaryl-substituted ethenes: synthetic applications

Reduction of 1,2-diaryl-substituted ethenes with Na metal in dry THF allowed easy access to a variety of 1,2-diaryl-1,2-disodiumethanes. These diorganometallic intermediates were elaborated into the corresponding 1,2-diarylethanes (aqueous work up), or cycloalkylated with 1,3-dichloropropanes. The last reaction led to a highly diastereoselective synthesis of trans-1,2-diaryl-substituted cyclopentanes.     

Directed metalation and regioselective functionalization of 3-bromofuran and related heterocycles with NaHMDS

A mild and regioselective functionalization protocol for 3-bromofuran and analogs has been developed. Selective metalation and functionalization of C2 can be achieved as a result of the directing effect of the adjacent electron-withdrawing bromo group. In addition, the C5 position can also be selectively functionalized by blocking the C2 position via silylation or by simply controlling the reaction temperature. These functionalized compounds bearing a C3 bromo substituent may be further elaborated by utilizing a Suzuki–Miyaura cross-coupling procedure.     

Synthesis and metalation of novel fluorescent conjugated macrocycles

[reaction: see text] Large shape-persistent conjugated macrocycles with tunable pore diameters in the nanometer regime were prepared by a simple, one-pot procedure. These new self-assembled macrocycles contain rings of 48-66 covalently bonded atoms and can bind multiple metal ions, forming soluble luminescent complexes.     

Transformation of pyrazolo[4,3-c]isothiazoles into 3,4-disubstituted 1,2-isothiazoles

Pyrazolo[4,3-c]isothiazoles 4 and 5 were synthesized by the reaction of 4-aminoantipyrine 1 with thionyl chloride. Treatment of 4 or 5 with alkylamines underwent pyrazole ring opening to afford 3,4-disubstituted 1,2-isothiazoles 8a-f .     

Directed ortho metalation approach to C-7-substituted indoles. Suzuki-Miyaura cross coupling and the synthesis of pyrrolophenanthridone alkaloids

[reaction: see text] Although the indole N-phosphinoyl derivative 4 undergoes n-BuLi deprotonation/electrophile quench to afford C-7-substituted products, its deprotection requires harsh conditions. On the other hand, the N-amide 12, upon sequential or one-pot C-2 metalation, silylation, C-7 metalation, and electrophile treatment, furnishes indoles 7 in good overall yields. In combination with the Suzuki-Miyaura protocol, C-7 aryl (heteroaryl)-substituted indoles 14 and 16 are obtained, including hippadine and pratosine, members of the pyrrolophenanthridone alkaloid family.     

Photoaddition of ketones to imidazoles,thiazoles, isothiazoles and isoxazoles. Synthesis of their oxetanes

Imidazole itself did not undergo photoaddition reactions with ketones. However, irradiation of 1-acetyl and 1-benzoylimidazole, and 1,1-carbonyldiimidazole with benzophenone yielded oxetanes. On irradiation with carbonyl compounds, 1,2-dimethylimidazole and 1-benzylimidazole did not give oxetanes but a hydroxyaryl or hydroxyalkyl derivative. Thiazole itself did not yield any photoaddition product, but 2,4-dimethylthiazole afforded oxetanes on irradiation with benzophenone and with 3-benzoylpyridine. Irradiation of 2,4-dimethylthiazole with acetophenone led to the formation of a dimeric material. On irradiation with benzophenone, 4-methylisothiazole did not yield an oxetane but rather a hydroxyphenyl derivative. 3,5-Dimethylisoxazole on irradiation with benzophenone and with 3-benzoylpyridine gave oxetanes. Irradiation of 4,5-dimethylisoxazole yielded similarly an oxetane with benzophenone     

3-芳基磺酰氧基(取代)异噻唑的合成及除草活性

通过3-羟基异噻唑和4-氰基-5-甲硫基-3-羟基异噻唑与芳基磺酰氯在碱性条件下缩合,合成了3-芳基磺酰氧基异噻唑和3-芳基磺酰氧基-4-氰基-5-甲硫基-异噻唑.对所合成的化合物进行了除草活性的测定.     

Synthesis of functionalized 1,5-cyclooctadienes by LICKOR metalation

1,5-Cyclooctadiene was lithiated under LICKOR superbase conditions followed by reaction with alkyl halides or ethylene oxide to yield 3-substituted 1,5-cyclooctadienes in high yield and purity. This procedure is suitable for preparation of 1,5-cyclooctadienes carrying pendant functional groups for immobilization on solid-phase resins.     

Fused 1,2-dithioles. IV. Synthesis and reactions of 1,2-dithiole s-oxides

1,2-Dithiolopyrrolones and their heterologues of type 1 are resonance stabilized systems displaying a high dipole moment. Upon oxidation with organic peracids compounds 2 , 5 , 15a, 16a, 20a and 25a gave the corresponding S(2)-oxides and, depending on substituents, in some cases the S(2)- and S(1)-dioxides. The S(2)-monoxides showed a proclivity to disproportionation and were easily reduced to dithioles with symme trical dimethylhydrazine. From S(2)-oxides and several primary amines bicyclic isothiazole-S-oxides were obtained (S/N-exchange reaction). From the N-unsubstituted isothiazole S-oxide 10e the N-hydroxyisothiazole 9d was synthesized by an aza-Pummerer-type rearrangement. The assumption is made that S(2)-oxides may be biologically important as active metabolites of pyrrothines and analogues of type 1 in their action as antibacterials and antimycobacterials.     

Directed metalation/ligand coupling approach to the enantioselective synthesis of 1,1′-binaphthyls

Introduction of a 2-isopropoxycarbonyl or 2-NN-dimethylcarbamoyl group into homochiral 1-p-tolyl- or 1-t-butyl-sulfinylnaphthalenes, via directed metalation reaction, followed by ligand coupling reaction with 1-naphthylmagnesium bromide, furnished atropisomeric 1,1′-binaphthyls in 82–95% enantiomeric excess (e.e.).     

Synthesis with 1,2-Oxazines. II. Synthesis and Properties of 2,3-dimethyl-5,6-dihydro-4H-1,2-oxaziniumiodide

Preparation of 2,3-Dimethyl-5,6-dihydro-4H-1,2-oxaziniumiodide was achieved by N-alkylation of 3-methyl-5,6-dihydro-4H-1,2-oxazine. Reactions with C-nucleophiles led to the corresponding N-methyl-perhydro-1,2-oxazine derivatives. Reaction with sodium hydride in triglyme led to 3-methyl-4-aza-1,3-pentadiene.