0-Iodo ketones, synthesis

Ito s regio- and stereoselective total synthesis relied on dicyclopentadiene as starting material The derived ketone 755 was cleaved to provide 756 which was crafted into 757 (Scheme LXXXV). FoUowing reduction of the carbomethoxy group, conversion to iodo ketone 758 was realked with trimethylsilyl iodide. Reaction of 758 with DBU resulted chiefly in conversion to 752 which was transformed into silphinene essentially as described above. 

Highly ry//-selective aldol synthesis from cr-iodo ketones is promoted under aqueous conditions by a distannane system, (BujSnb, Bu2SnF2, and HMPA. Aqueous solutions of acetaldehyde or formaldehyde provide /3-hydroxy ketones.272 The ate complex Li+[//-Bu2Snl ( generated from Lil and -Bu2SnI2 leads to the highest class of syn-diastereoselectivity in the Reformatsky-type reaction (Equation (106)).273... 

ShaCK, Jean TS, Wang DC (1990) Intramolecular Radical Cyclization of Silylacetylenic or Olefinic a-Iodo Ketones Application to the Total Synthesis of ( )-Modhephene. Tetrahedron Lett 31 3745... 

Iodo 20-oxo steroids are important intermediates for synthesis of 21-hydroxy 20-oxo steroids, e.g., dehydrocorticosterone and cortisone,711 also deoxycorticosterone 712 so the preparation of these a>iodo ketones by the following very interesting reaction with iodine should be noted ... 

Most of the synthetic efforts during the past year have appertained to the preparation of the ester portion of harringtonine (13a) and analogues related to it. As far as the synthesis of the basic alkaloid skeleton is concerned, an improvement in the transformation of the iodo-ketone (21) into cephalotaxinone (18) (see Vol. 4 of these Reports) has been achieved. Three sets of conditions were explored for this transformation, of which by far the best (94% yield) was irradiation of (21) in refluxing liquid ammonia in the presence of excess of potassium t-butoxide. 

In combination with protic acid, NIS has been used for the preparation of a-iodo enones and j8, -dihalo enones (eqs 4 and 5 HTIB = [Hydroxy(tosyloxy)iodojbenzene). More reactive alkenes such as enol acetates react with NIS to afford a-iodo ketones. The reaction of enol ethers with NIS in the presence of an alcohol, affording iodoacetals, allows the synthesis of acetals by dehalogenation or mixed ketene acetals by elimination. ... 

Iodosylbenzoic acid (85) is also a convenient recyclable hypervalent iodine oxidant for the synthesis of a-iodo ketones by oxidative iodination of ketones [88], Various ketones and p-dicarbonyl compounds can be iodinated by this reagent system under mild conditions to afford the respective a-iodo substituted carbonyl compounds in excellent yields. The final products of iodination are conveniently separated from by-products by simple treatment with anionic exchange resin Amberlite IRA 900 HCOs" and are isolated with good purity after evaporation of the solvent. The reduced form of the hypervalent iodine oxidant, 3-iodobenzoic acid (59), can be recovered in 91-95% yield from the Amberlite resin by treatment with aqueous hydrochloric acid followed by extraction with ethyl acetate [88]. 

The first iodine-catalyzed synthesis of 2-alkyl substituted oxazoles 130 by a decarboxylative domino reaction was reported. Aryl methyl ketones 128 were transformed in situ into a-iodo ketones and then, by the Kornblum oxidation, into 1,2-diketones. After the addition of the a-amino acid 129, an l2-mediated cyclization/decarboxylation gave oxazoles 130. The reaction proceeds better if the Ar has electron-donating substituents and if the R group is a branched alkyl chain or phenyl residue. The reaction used oxone to regenerate iodine (13JOC6065). 

Cinchona alkaloids can be used to effect an asymmetric synthesis of /3-selenoaryl-ketones from cyclic enones and j8-iodo-ketones are smoothly obtained from the conjugate addition of trimethylsilyl iodide to enones, followed by hydrolysis of the intermediate trimethylsilyl ether. ... 

The regioselective synthesis of of-iodo ketones is achieved in good yields by CAN in presence of iodine. The more highly substituted of-iodo ketones are preferentially formed (scheme 34) (Horiuchi and Kiji, 1988). In a study of the iodination of 1,3,5-trimethylbenzene (mesitylene) and 1,2,3,4,5-tetramethylbenzene (durene) by CAN/I2, it was shown that the reactive intermediate is most likely the I ion and that the reaction can be considered as an electrophilic aromatic substitution reaction (Galli, 1991). 

A new facile synthesis of a-iodo-ketones involves oxidation of alkenes using silver chromate and iodine [equation (48)], while thallium(iii) acetate and iodine are effective for the conversion of enol acetates into a-iodo-ketones. 

A one pot procedure for the preparation of 1,3-sclenazoles has been reported. The method, a variation on the Hantzsch synthesis, involves the a-tosylation of ketones 90 with [hydroxy(tosyloxy)iodo]benzene followed by treatment with selenoamides to give 1,3-selenazoles 91 in moderate to high yields <00S1219>. 

Using other hypervalent iodine compounds or different reagent combinations, various functional groups can be introduced in the a-position of ketones. a-Tosylations of ketones can be achieved directly using [hydroxy(tosyloxy)-iodo]benzene 6. The major drawback is the low regioselectivity observed in these reactions, although the a-tosylation of silyl enol ethers circumvents this problem. In the last few years some efforts have been done in the synthesis of chiral hypervalent iodine compounds [48, 53-55,113-117], but only a few of them have been used successfully in stereoselective synthesis. With chiral derivatives of type 59 it is possible to a-tosylate propiophenone with about 40% ee [56,118,119]. 

Oxidative methanolysis of azetidinone 176 followed by hydrogenolysis of compound 177 afforded /3-lactam 178, which was protected to obtain the protected amine 179. The best conditions for rearrangement of 179 were found using TFA. Conversion of compound 180 to carbacephem 183 was accomplished by ketone reduction, alcohol protection, and elimination of methanol. Synthesis of carbacephem derivative 186 has been performed by rhodium(n)-catalyzed cycliza-tion of iodonium ylide 185 <1997TL6981> (Scheme 33). The iodonium ylide 185 was easily prepared from the corresponding /3-keto ester 184 and [(diacetoxy)iodo]benzene in good yield. 

This approach was used for the synthesis of furo[3,2-/z]quinolines (277). The reaction of 5-chloro-7-iodo-8-methoxyquinoline (229) with several ketone enolate ions gave the substitution product 276 (70-80 % yield, R = Me, t-Bu, 2-furyl,/>-anisyl) which, when treated with HBr at 100 °C, quantitatively led to 277 (equation 111)326. 

Numerous linkers have been developed with the aim of immobilizing substrates on a solid support. Commercially available (+)-a-lipoic acid has been employed as a novel, chemically stable linker for the immobilization of ketones. The utility of this thioacetal-based linker in solid-phase synthesis has been demonstrated by the synthesis of several 4-acetylbiphenyls by means of the Suzuki reaction. The products were readily cleaved from the solid support by treatment with [bis(trifluoroacetoxy)iodo]benzene [PhI(OCOCF3)2] [107]. 

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