Unsaturated carbonyl compounds iodide

A mixture of 1,4-dioxane and water is often used as the solvent for the conversion of aldehydes and ketones by H2Se03 to a-dicarbonyl compounds in one step (Eq. 8.117).331 Dehydrogenation of carbonyl compounds with selenium dioxide generates the a, (i-unsaturated carbonyl compounds in aqueous acetic acid.332 Using water as the reaction medium, ketones can be transformed into a-iodo ketones upon treatment with sodium iodide, hydrogen peroxide, and an acid.333 Interestingly, a-iodo ketones can be also obtained from secondary alcohol through a metal-free tandem oxidation-iodination approach. 

This protocol could be extended to a range of different ,/i-unsaturated carbonyl compounds and either activated or deactivated aryl iodides [22], An application of related Heck chemistry to the synthesis of methylated resveratrol (3,4, 5-trihydroxy-( )-stilbene) is shown in Scheme 6.4 [23]. The phytoalexin resveratrol exhibits a variety of interesting biological and therapeutic properties, among them activity against several human cancer cell lines. Botella and Najera have shown that the trimethyl ether of resveratrol (Scheme 6.4) can be rapidly prepared by microwave-assisted Heck reaction of the appropriate aryl iodide and styrene derivatives, using the same oxime-derived palladacycle as indicated in Scheme 6.3. 

In order to modulate the reactivity of intermediate 331, it was transformed into its copper derivative by treatment with copper(I) bromide or iodide in THF at —78 °C, and then was allowed to react with a,/3-unsaturated carbonyl compounds (to give compounds 343 resulting from a conjugated addition), acyl chlorides (to give ketones 344) and copper(II) chloride (to dimerize giving compounds 345) (Scheme 100)"° ". ... 

Isoxazoles have been used to transpose functionality within a,/3-unsaturated carbonyl compounds (72JA9128). Thus, on exposing either (E)- or (Z)-/3-ionone oxime (449) to a mixture of iodine-potassium iodide in hot aqueous THF containing sodium bicarbonate, the isoxazole (450) was formed in high yield. Catalytic reduction of this isoxazole led... 

In an indirect electrochemical process, vitamin B,2 has been used as catalyst for the cathodic alkylation of a,p-unsaturated carbonyl compounds by alkyl iodides as exemplified in the formation of (+)- X0-brevicomine [30] ... 

Conversion of a Mannich base hydrochloride into an a,/ -unsaturated carbonyl compound, is illustrated by the formation of phenyl vinyl ketone, which is obtained directly by steam distillation (Expt 6.147). Alternatively the Mannich base may be treated with methyl iodide to form the quaternary salt, which then gives the a,/ -unsaturated carbonyl compound by a base-catalysed elimination reaction. 

Selenium-stabilized carbanions can be also generated by 1,4-addition of nucleophilic reagents to a-selanyl a,[3-unsaturated carbonyl compounds. The conjugate addition of trialkylsilyllithium compounds to 133, followed by reaction with allyl iodide, afforded the addition products 134 with good m-stereoselectivity (R = Me dr 86 14 R = Ph dr 94 6) (Scheme 34).214 The addition of lithium dialkylcuprates to 2-phenylselanylcycloalk-2-enones has also been used for the synthesis of natural products.215,216... 

The 1,2-addition of allyl iodide to cyclic and acyclic a,/ -unsaturated carbonyl compounds has been achieved by using indium and indium trichloride. The reactivities of a,/3-unsaturated carbonyl compounds depend upon their structure. The reaction of ketones smoothly undergoes in THF or DMF. In the case of cyclic ketones, however, the solvent plays a crucial role, where much improved yields have been obtained in DMF than in THF (Equation (49)).236 Indium-mediated 1,2-allylation of /3-bromoacrolein produces homoallylic alcohol derivatives (Equation (50)), which can be transformed to cyclopentanones by a Pd-catalyzed cyclization.237,238... 

Most organic free radicals are nucleophilic and will react with electrophilic centers. Lewis acids have been used to activate aj3-unsaturated carbonyl compounds towards addition of free radicals and also to stabilize a-keto radicals [67]. The first report of the use of a chiral Lewis acid to effect an asymmetric free-radical reaction was that of Urabe, Yamashita, Suzuki, Kobayashi, and Sato in 1995 [68]. They found that if the BINOL aluminum catalyst 313 is stoichiometrically complexed with lactone 323 and then treated with butyl iodide and tributylstannane in the presence of triethylborane the alkylated lactone 324 can be isolated in 47 % yield with 23 % ee (Sch. 40). 

Unlike the carbanions from 1,3-dithians (see Chapter 3, p. 31 and Chapter 6, p. 90), the sulfinyl carbanions have the ability to undergo Michael additions (conjugate or 1,4-additions) with a,p-unsaturated carbonyl compounds. For instance, the secondary carbanion (44) from the ethyl ethylthiomethyl sulfoxide (45) may be sucessively reacted with ethyl iodide and 3-butene-2-one to give heptan-2,5-dione (46) via the tertiary carbanion (47), as shown in Scheme 23. The carbanion (47) may also be condensed with propyl bromide, and hydrolysis of the product yields ethyl propyl ketone (48) (Scheme 23). 

P-Aryl-ai,fi-unsaturated carbonyl compounds,2 In the presence of Pd(OAc)2-LiCl (1 5) aryl iodides react with allyl trimethylsilyl ethers in DMF to form (E)-/ -aryl-a,/ -unsaturated aldehydes and ketones. A similar reaction has been reported for allyl alcohols (7, 274). 

Organometallic reagents exhibit their expected typical reaction pattern towards a, S-unsaturated carbonyl compounds. Whereas methyllithium reacted cleanly at — 10°C with 3-cyclo-propylidenebutan-2-one (3) to give 3-cyclopropylidene-2-methylbutan-2-ol (4) in 80% yield via 1,2-addition, methylmagnesium iodide converted the ketone 3 to a 60 40 mixture of the 1,2- and 1,4-addition products 4 and 5 in 55% yield. The ratio depended on the substrate structure and was totally reversed when a phenyl substituent was present on the double bond. Soft methylcuprates only gave the 1,4-adducts 2l-o upon reaction with 1 in diethyl ether for 20 minutes at — 10°C to — 30 °C and subsequent warming to 20 °C (Table 1). 

A(, -Dimethyl(methylene)iminium salts have been the most widely used class of preformed iminium salts, mainly due to their applications in the synthesis of a,p-unsaturated carbonyl compounds, normally accomplished by subjecting the /V, -dimethyl Mannich base to quatemarization followed by base-induced elimination. Table 3 outlines various counterion forms of /V, -dimethyl(methylene)iminium salts that have been used in Mannich reactions as well as their synthetic precursors. The crystalline iodide (30), known also as Eschenmoser s salt , has seen the most widespread use and is prepared by thermal fragmentation of (iodomethyl)trimethylammonium iodide or, more conveniently, by a variant of the... 

The 2,3-quinodimethane (298) of 1-benzoylindole has been generated from the 2,3-di(bromo-methyl) indole (297) by treatment with sodium iodide and can be trapped by a range of electrophilic dienophiles, such as maleimides, DMAD, benzoquinone, and a,/J-unsaturated carbonyl compounds and sulfones (Scheme 87) <89TL7289,91T1925>. 

The addition of an allylic group was reported in the synthesis of heneicos-6-en-ll-one, the sex pheromone of the Douglas fir tussock moth (Fig. 55)P Short syntheses of frontalin and endo and exo-brevicomin are based on this principle.292 Several authors compared this method to the classical process using the toxic tin hydrides. Thus, adamantane derivatives were prepared from 1-adamantyl iodide and a,p-unsaturated carbonyl compounds in better yields than by the tin hydride method.293... 

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