Application of directed metallation in synthesis. Part 3: Studies in the synthesis of (±)-semivioxanthin and its analogues

The synthesis of several analogues of (±)-semivioxanthin including five thiophene analogues, using directed metalation are reported. The strategy consisted of the synthesis of functionalized naphthalene or benzo[b]thiophene as building blocks followed by annelation of the pyrone.     

Reactivity of some “ladder” type complexes under conditions of metallation

The behavior of binuclear “ladder” type complexes FpL, where Fp=Cp(CO)₂Fe, L=p-MeC₆H₄Cr(CO)₃ (4), CH₂C₆H₅Cr(CO)₃ (5), andp-FpC₆H₄Cr(CO)₃ (6), under conditions of metallation was studied. Unlike compounds5 and6, the σ-bound ligand L in compound4 migrates from the iron atom to the cyclopentadienyl ring to give complexes Me(CO)₂FeC₅H₄−C₆H₄(p-Me)Cr(CO)₃. The electrochemical reduction potentials of the complexes4–6 and the rearrangement products were measured. The migration activity of L is determined by the ease of reductive cleavage of the Fe−L bond and the susceptibility of the system to undergo intramolecular electron transfer from the Cp ligand to the aromatic ring. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1832–1835, September, 1998.     

Synthesis of mono-, di-, tri-, and tetraethyl-o-carboranes by electrophilic alkylation ofo-carborane with ethyl bromide in the presence of AICl3 and their transformations

Optimal conditions for the preparation of 9-ethyl-, 9,12-diethyl, 8,9,12-triethyl-, and 8,9,10,12-tetraethyl-o-carboranes under the action of EtBr on o-carborane in the presence of AICl₃ were determined. The behavior of these o-carborane derivatives towards electrophilic and nucleophilic reagents was studied. The presence of four ethyl groups in positions 8, 9, 10, and 12 of the carborane polyhedron increases the electron density on the boron atoms in positions 4, 5, 7, and II to the point where they are able to enter into reactions of electrophilic substitution, and in positions 3 and 6 to the point that they become resistant to the action of nucleophilic reagents. Reactions of 1,2-dilithium-8,9,10,12-tetraethyl-o-carborane with various electrophilic reagents were studied.Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp 2755–2763, November, 1996.     

A Simple Strategy for the Preparation of 6-Substituted 3H-Benzoxazol-2-ones and 3H-Benzothiazol-2-ones

The double metallation of 6-bromo-3H-benzothiazol-2-one and 6-bromo-3H-benzoxazol-2-one with methyl magnesium bromide and alkyllithium bases is described. Alkylation with a variety of electrophiles occurs at the 6-position of the heterocycles in good yields.      

Assessing Alkali-Metal Effects in the Structures and Reactivity of Mixed-Ligand Alkyl/Alkoxide Alkali-Metal Magnesiates

Advancing the understanding of using alkali-metal alkoxides as additives to organomagnesium reagents in Mg−Br exchange reactions, a homologous series of mixed-ligand alkyl/alkoxide alkali-metal magnesiates [MMg(CH₂SiMe₃)₂(dmem)]₂ [dmem=2-{[2-(dimethylamino)ethyl]methylamino} ethoxide; M=Li, 1 ; Na, 2 ; (THF)K, 3 ] has been prepared. Structural and spectroscopic studies have established the constitutions of these heteroleptic/heterometallic species, which are retained in arene solution. Evaluation of their reactivity towards 2-bromoanisole has uncovered a marked alkali-metal effect with potassium magnesiate 3 being the most efficient of the three ate reagents. Studies probing the constitution of the exchange product from this reaction suggest that the putative [KMgAr₂(dmem)]₂ (Ar=o-OMe−C₆H₄) intermediate undergoes redistribution into its single metal components [KAr]_n and [MgAr(dmem)]₂ ( 5 ). This process can be circumvented by using a different potassium alkoxide containing an aliphatic chain such as KOR’ (R’=2-ethylhexyl) which undergoes co-complexation with Mg(CH₂SiMe₃) to give [KMg(CH₂SiMe₃)₂(OR’)]₂ ( 7 ). This ate, in turn, reacts quantitatively with 2-bromoanisole furnishing [KMgAr₂(OR’)]₂ ( 9 ) which is stable in solution as a bimetallic compound. Collectively this work highlights the complexity of these alkali-metal mediated Mg−Br exchange reactions, where each reaction component can have a profound effect not only on the success of the reaction; but also the stability of the final metalated intermediates prior to their electrophilic interception.     

Bidentate Lewis Acids Derived from o-Diethynylbenzene with Group 13 and 14 Functions

Starting from 1,2-diethynylbenzene, a series of bidentate Lewis acids was prepared by means of hydrometalations, in particular hydrosilylation, hydroboration, hydroalumination and terminal metalation based on group 13 and 14 elements. In the case of terminal alkyne metalation, the Lewis-acidic gallium function was introduced using triethylgallium under alkane elimination. A total of six different Lewis acids based on a semiflexible organic scaffold were prepared, bearing −SiClMe₂, −SiCl₂Me, −SiCl₃, −B(C₆F₅)₂, −AlBis₂ (Bis=bis(trimethylsilyl)methyl) and −GaEt₂ as the corresponding functional units. In all cases, the Lewis acid functionalisation was carried out twice and the products were obtained in good to excellent yields. In the case of the twofold gallium Lewis acid, a different structural motif in the form of a polymer-like chain was observed in the solid state. All new bidentate Lewis acids were characterised by multinuclear NMR spectroscopy, CHN analysis and X-ray diffraction experiments.     

Lateral Metallation and Redistribution Reactions of Sodium Ferrates Containing Bulky 2,6-Diisopropyl-N-(trimethylsilyl)anilide Ligands

Alkali-metal ferrates containing amide groups have emerged as regioselective bases capable of promoting Fe−H exchanges of aromatic substrates. Advancing this area of heterobimetallic chemistry, a new series of sodium ferrates is introduced incorporating the bulky arylsilyl amido ligand N(SiMe₃)(Dipp) (Dipp=2,6-iPr₂-C₆H₃). Influenced by the large steric demands imposed by this amide, transamination of [NaFe(HMDS)₃] (HMDS=N(SiMe₃)₂) with an excess of HN(SiMe₃)(Dipp) led to the isolation of heteroleptic [Na(HMDS)₂Fe{N(SiMe₃)Dipp}]_∞ ( 1 ) resulting from the exchange of just one HMDS group. An alternative co-complexation approach, combining the homometallic metal amides [NaN(SiMe₃)Dipp] and [Fe{N(SiMe₃)Dipp}₂] induces lateral metallation of one Me arm from the SiMe₃ group in the iron amide furnishing tetrameric [NaFe{N(SiCH₂Me₂)Dipp}{N(SiMe₃)Dipp}]₄ ( 2 ). Reactivity studies support that this deprotonation is driven by the steric incompatibility of the single metal amides rather than the basic capability of the sodium reagent. Displaying synergistic reactivity, heteroleptic sodium ferrate 1 can selectively promote ferration of pentafluorobenzene using one of its HMDS arms to give heterotrileptic [Na{N(SiMe₃)Dipp}(HMDS)Fe(C₆F₅)]_∞ ( 4 ). Attempts to deprotonate less activated pyridine led to the isolation of NaHMDS and heteroleptic Fe(II) amide [(py)Fe{N(SiMe₃)Dipp}(HMDS)] ( 5 ), resulting from an alternative redistribution process which is favoured by the Lewis donor ability of this substrate.     

甲基吡啶侧链金属化和烷基化反应的研究

甲基吡啶侧链上的氢易于质子化被碱金属所取代,但传统的侧链金属化的方法,其实验操作都比较繁复。前文报道,吡啶与金属钠在乙醚回流中可形成吡啶自由基负离子钠络合物(C_5H_5N~-Na~ ),它是一种有效的金属     

Synthesis and metallation of 2-(pyridyl)benzoic acids and ethyl 2-(pyridyl)benzoates: a new route to azafluorenones

The ring deprotonation of 2-(2- and 4-pyridyl)benzoic acids using lithium dialkylamides in THF at rt, and the in situ cyclization afforded 4- and 2-azafluorenones, respectively. 1-Azafluorenone was obtained from ethyl 2-(3-pyridyl)benzoate using a similar protocol.