Positional selectivity electrophilic oxygenation

The 3-pyridyl O-carbamate affords, under the sec-BuLi/TMEDA conditions, only 4-substituted products. A reinvestigation of LDA metalation (85JOC5436) has shown that high-yield conversion of 320 into the 4-TMS (319) and 2,4-bis-TMS (321) derivatives can be effected (Scheme 97) [90UP1]. Furthermore, LiTMP metalation of 319 followed by electrophile quench leads to derivatives 322, thus demonstrating the TMS protection route to 2-substituted 3-oxygenated pyridines. Another, potentially useful result is the 2-position selective ipso carbodesilylation of 321 with benzoyl chloride, yielding 323. 

The position of electrophilic substitution of quinolones and isoquinolones depends upon the pH of the reaction medium. Each type protonates on carbonyl oxygen so reactions in strongly acidic media involve attack on this cation the contrast can be illustrated by the nitration of 4-quinolone at different acid strengths. The balance between benzene ring and unprotonated heterocyclic ring selectivity is small, for example 2-quinolone chlorinates preferentially, as a neutral molecule, at C-6, and only secondly at C-3. 

Treatment of the potentially electrophilic Z-xfi-unsaturated iron-acyl complexes, such as 1, with alkyllithium species or lithium amides generates extended enolate species such as 2 products arising from 1,2- or 1,4-addition to the enone functionality are rarely observed. Subsequent reaction of 2 with electrophiles results in regiocontrolled stereoselective alkylation at the a-position to provide j8,y-unsaturated products 3. The origin of this selective y-deproto-nation is suggested to be precoordination of the base to the acyl carbonyl oxygen (see structures A), followed by proton abstraction while the enone moiety exists in the s-cis conformation23536. 

From this point on, the regioselectivity of substituted allyl anions is much less regular, and somewhat less explicable. For a start, X-substituted allyl anions react with carbonyl electrophiles with a selectivity. This is explicable, but it is determined by the site of coordination by the metal, not by the frontier orbitals. We can contrast the reaction of the oxygen-substituted lithium anion 4.57 with an alkyl halide, which is y selective, as usual, and the reaction of the zinc anion 4.58 with a ketone, which is a selective.304 The oxygen substituent coordinates to the zinc cr-bound at the y position, and the aldehyde is then delivered to the a position in a six-membered cyclic transition structure 4.59. The same reaction with the lithium reagent 4.57 gives a 50 50 mixture of a and y products, and so lithium is not so obviously coordinated in the way that the zinc is. This type of reaction is often brought under control in the sense 4.59 for synthetic purposes by... 

There is no satisfactory method for heteroatom arylation of oxygenated pyrimidines. (9-Alkylation of hydroxypyrimidines competes with the favored 7V-alkylation hard electrophiles may move the selectivity in favor of O-alkylation. Therefore, both (9-arylation and 0-alkylation are best effected in the electrophilic positions by substitution reactions on the chlorides, sulfides, and oxidized sulfides using a metal salt of the phenol or alcohol. In the 5-position, the options are vigorous reaction conditions for substitution of a bromine substituent, and (9-alkylation in competition with A-alkylation. 

Notes and discussion. In this method a c/5-l,2-stannylene acetal, derived from mannose, nucleophilically displaces a triflate from the C-4 position of a galactopyranoside, with inversion of stereochemistry. The example reported below allows entry to a Man-P-(1,4)-Glu derivative. It has been found that the reactivity of the electrophile and the nucleophilicity of the oxygens within the cis-1,2-stannylene acetal greatly affect the overall outcome of the reaction. The nucleophilicity of the oxygens within the stannylene complex decreases in the order equatorial anomeric > equatorial non-anomeric > axial anomeric. Moreover, the yield and ratio of products are found to be highly solvent dependent as the solvent polarity increases, the reactivity of the reactants and the yield of the desired 8 2 reactions increase. Thus when the reaction described herein was performed at 25 °C, in DMF, for 5 days, the disaccharide 46 formed in 40%, when it was performed at 25 °C in DMA for 3 days, 53% of the required disaccharide formed, but best yields and selectivities (59%) were obtained by performing the reaction at 25 °C, in DMSO, for 2 days. 

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