Iodonium enolates

Recent progress on the use of hypervalent iodine reagents for the construction of carbon-het-eroatom (N, O, P, S, Se, Te, X) bonds is reviewed. Reactions of aryl-A3-iodanes with organic substrates are considered first and are loosely organized by functional group, separate sections being devoted to carbon-azide and carbon-fluorine bond formation. Arylations and alkenyla-tions of nucleophilic species with diaryliodonium and alkenyl(aryl)iodonium salts, and a variety of transformations of alkynyl(aryl)iodonium salts with heteroatom nucleophiles are then detailed. Finally, the use of sulfonyliminoiodanes as aziridination and amidation reagents, and reactions of iodonium enolates formally derived from monoketones are summarized. 

One of the most notable recent advances in iodonium ylide chemistry is the first demonstrable generation of iodonium enolates 44 formally derived from unactivated monocarbonyl compounds [197]. This was accomplished by the treatment of (Z)-jS-acetoxyvinyliodonium salts with lithium ethoxide, either in THF or in THF-DMSO (12 1) (Scheme 72). 

N-Phenylbenzaldimine is similarly unreactive with the decenolate ylide. However, when the iodonium enolates are employed with N-acyl- and N-sul-fonylimines of aromatic aldehydes, aziridinyl ketones are obtained (Scheme 74) [198,199]. 

Iodonium ylides of type 6 cannot be isolated, unless the carbanion center is substantially stabilized (83MI1, 92MI1, 97MI1, 02MI1). For example, although iodonium enolates 22 can be prepared by base-catalyzed condensations of DAIB or iodosylbenzene with /J-dicarbonyl compounds, they are not similarly available from unactivated ketones and esters. Indeed, cyclic and acyclic mono-ketones are converted to a-hydroxy dimethylketals 23 with DAIB (or 13) in KOH/MeOH (86ACR244, 99QR273). Other... 

Thermal reactions of the iodonium enolate 279 with acetonitrile and carbon disulfide in the presence of Cu(acac)2 lead to the heterobicyclic ketones 285 and 286, respectively (98TL9073), while similar treatment of the hybrid sulfonyl-carbonyl ylide 287 with CS2 or phenylacetylene affords the tricyclic sulfones 288 and 289 (97T9365). 

Iodonium enolates 293, formally derived from unactivated monoketones, can be generated in situ by the action of lithium ethoxide on (Z)-/3-acetoxyvinyhodonium salts 292 (97JA11598, 98TL5569, 99JOC3181). When aliphatic or aromatic aldehydes are present in the reaction... 

The iodosobenzene HBF4 complex 2022 adds to the enol silyl ether 653 of acetophenone to give the labile iodonium salt 2023, which reacts with cyclohexene or tetramethylethylene to give the adducts 2024 and 2025 [188] (Scheme 12.55). 

Michael-type addition of an enolate anion to an alkynyliodonium salt probably produces the unstable iodonium ylide 34 34a. Loss of Phi from... 

Another important variant of the preceding approach is the cycloaddition reaction between monocarbonyl iodonium salt 47 and an alkene to give dihydrofuran 48 (88TL3703 89JOC2605). The iodonium salt 47 is generated by the oxidation of acetophenone silyl enol ether (46) with iodosobenzene in the presence of fluoboric acid. 

It has been shown that selective a-vinylation of enolate anions derived from 1,3-dicarbonyl compounds can be achieved by reaction with 4-/-butyl-1 -cyclohexenyl-(aryl)iodonium and 1-cyclopentenyl(aryl)iodonium tehafluoroborates without competing a-arylation, provided that the alkenyliodonium salt used bears a / -mcthoxyphcnyl, rather than phenyl, group.24... 

The relatively unstable / -oxoalkyl(aryl)iodonium salts 46 can be generated by a low temperature reaction of silyl enol ethers with reagent 45 (Scheme 21) [40]. 

Iodonium salts 46 have been proposed as the reactive intermediates in several synthetically useful carbon-carbon bond forming reactions [1,40]. Reactions of adducts 46 with various silyl enol ethers selectively afford 1,4-diones, while the reactions with alkenes lead to the products of alkylation at the allylic position (Scheme 22) [40]. 

Iodonium salts 49 and 50 are efficient electrophilic alkylating reagents towards a variety of organic nucleophiles, including silyl enol ethers. The reaction with silyl enol ether 51 proceeds under mild conditions and selectively affords the appropriate product of alkylation 52 along with iodobenzene as the by-product (Scheme 24) [41]. 

Enolate anions derived from various 1,3-dicarbonyl compounds can be viny-lated with cyclohexenyl- and cyclopentenyl- iodonium salts (Scheme 27) [50]. The vinylation of enolate anions 58 in these reactions is frequently accompanied by the formation of the phenylated dicarbonyl compounds however, the selectivity of these vinylations can be improved by using alkenyl(p-methoxyphenyl)-iodonium salts instead of 57. 

Asymmetric phenylation of carbanions with chiral iodonium salts has recently been reported [70]. The chiral diiodonium salt 93 selectively reacts with potassium enolate of l-oxo-2-indancarboxylate 92 to give the a-phenylated indanone 94 with moderate enantioselectivity (Scheme 42). 

Alkynyl(phenyl)iodonium salts can be used for the preparation of substituted alkynes by the reaction with carbon nucleophiles. The parent ethynyliodonium tetrafluoroborate 124 reacts with various enolates of /J-dicarbonyl compounds 123 to give the respective alkynylated products 125 in a high yield (Scheme 51) [109]. The anion of nitrocyclohexane can also be ethynylated under these conditions. A similar alkynylation of 2-methyl-1,3-cyclopentanedione by ethynyliodonium salt 124 was applied in the key step of the synthesis of chiral methylene lactones [110]. 

Likewise, the reaction of the lithium enolate of aminomalonate 126 with alkynyliodonium triflates 127 affords alkynylmalonates 128 in good yields (Scheme 52) [111]. The best yields in this reaction are observed when a freshly prepared solution of the lithium enolate in THF is added to a stirred cold solution of the iodonium salt. The use of potassium enolate instead of lithium, or addition of the reagents in a different order, results in lower yields of products 128. 

After florisil (magnesium-silicate) filtration and concentration, crude 18 was treated with a THF solution of a 1 1 mixture of sodium iodide and mcte-chloroperoxybenzoic acid (MCPBA) yielding in 67 % (from 5) the a-iodo ketones 6.8 The ratio of diastereomers in this mixture was not described further. Mechanistically MCPBA oxidizes the iodide ion to an iodoniumion-species, which reacts with the double bond, generating intermediate 21. After TMS is removed the tricyclic iodonium ion collapses to desired 6. In contrast to this transformation the researchers observed no useful yields by direct treatment of the silyl enol ether with molecular iodine. 

Silyl enol ethers are quite reactive towards IOB-boron trifluoride (or tetrafluoroboric acid) and can be considered as valuable starting materials for several reactions of synthetic importance. Of special interest is their use for carbon-carbon bond formation 1,4-diketones and unsaturated ketones are the products of such reactions further, they can be transformed to oc-hydroxy, methoxy or trifyloxy ketones. With tetrafluoroboric acid IOB forms a yellow solution containing the highly electrophilic Phi+ OH BF4 , stable up to 0°C. This species reacts readily with silyl ethers of several ketones, notably acetophenones, at —78°C, forming an unstable iodonium ion (ArCOCH2I+ Ph) which with another silyl ether affords 1,4-diketones. 

An interesting reaction between the bis phenyl iodonium triflate of acetylene and the silyl enol ether of acetophenone afforded an allene (PhCOCH=C=C=CHCOPh, 84%) [6], Also, alkynyl iodonium tosylates and carbon monoxide in methanol or ethanol, with palladium catalysis, furnished alkyne carboxylates [53]. 

The treatment of alkynyliodonium salts not amenable to cyclopentene formation with sodium azide in methanol affords vinyliodonium salts and/or enol ethers (equation 107)". Enol ether formation also occurs when glyme is employed as the solvent (equation 108)". Finally, regeneration of the vinylidene-iodonium ylide, PhC (N3)=C—IPh, from (Z)-(/ -azido-/ -phenylvinyl)phenyliodonium tosylate with potassium J-butoxide in glyme likewise affords an enol ether (equation 109). 

When / -dicarbonyl enolates are allowed to react with alkynyliodonium salts, typically in ter/-butyl alcohol or THF, alkynyl- and/or cyclopentenyl- -dicarbonyl compounds are obtained. The product compositions are largely regulated by the migratory aptitude of R in the alkynyl moiety and the availability of alkyl side chains for the MC-insertion (MCI) pathway (equation 45). These divergent modes of reactivity are nicely illustrated by the reactions of the 2-phenyl-1,3-indandionate ion with ethynylfphenyl)- and 4-methyl-1-hexynyl(phenyl)iodonium tetrafluoroborates (equation 1 15)27 2. 

MCI reactions of alkynyliodonium salts with enolates derived from active methylene compounds containing two acidic CH bonds follow a divergent course that leads to furans, presumably via carbenic insertion into enolic OH bonds (equation 122)28. In the reaction of acetylacetonate ion with the l-decynyl(phenyl)iodonium ion, CH insertion is competitive with OH insertion (equation 123)28. 

Because the hydrogen atom and phenyl group migrate so readily, the reactions of / -dicarbonyl enolates with ethynyl- and (phenylethynyl)iodonium salts can be expected to result in alkynylation. It has already been noted that the 2- -hexyl-l,3-indandionate ion undergoes alkynylation with (phenylethynyl)phenyliodonium tetrafluoroborate (equation 43), despite the availability of the -hexyl group for [2 + 3] annulation. Ethynylations of six / -dicarbonyl enolates and the anion of 2-nitrocyclohexane with ethynyl(phenyl)-iodonium tetrafluoroborate in THF have also been reported27. For example, admixture of the ethynyliodonium salt and the anion of ethyl 2-cyclopentanone-l-carboxylate in THF affords the 1-ethynyl derivative in 71% isolated yield (equation 124)27. 

The reactions of the lithium enolate of diethyl 2-[(diphenylmethylene)amino]malonate with several alkynyliodonium triflates are rare examples of enolate alkynylations with iodonium species other than the ethynyl(phenyl)- and (phenylethynyl)phenyliodonium ions (equation 125)16. Two experimental protocols were followed, i.e. addition of the enolates to the iodonium salts and vice versa, the former procedure giving higher yields of alkynylmalonates. As with other enolate alkynylations, these reactions are thought to involve alkylidenecarbene intermediates. It has been proposed, however, that the carbenes rearrange with migration of the diethyl 2-[(diphenyl) amino] malonate anion 16. 

Why the thienyl- and furyllithium compounds attack the iodine atom instead of the p-carbon atom of alkynyliodonium ions is not entirely clear. However, they are much harder nucleophiles than the enolate salts of /Ldicarbonyl compounds and might prefer the harder iodonium center3. The much higher basicity of the heteroaryllithium reagents might also facilitate the formation of iodate ions and the displacement of alkynyllithiums from such intermediates. 

Apart from copper(I)-mediated reactions, few studies of the treatment of vinyliodonium salts with carbanions have appeared. The vinylations of the 2-phenyl- and 2- -hexyl-l,3-indandionate ions shown in equations 222 and 223 are the only reported examples of vinyliodonium-enolate reactions known to this author26,126. ( ,)-l-Dichloroiodo-2-chloroethene has been employed with aryl- and heteroarvllithium reagents for the synthesis of symmetrical diaryliodonium salts (equation 224)149,150. These transformations are thought to occur via the sequential displacement of both chloride ions with ArLi to give diaryl (/ -chlorovinyl)iodanes which then decompose with loss of acetylene (equation 225). That aryl(/ -chlorovinyl)iodonium chlorides are viable intermediates in such reactions has been shown by the conversion of ( )-(/ chlorovinyl)phenyliodonium chloride to diaryliodonium salts with 2-naphthyl- and 2-thienyllithium (equation 226)149,150. 

The treatment of the thermodynamic enolate of 2-methylcyclohexanone with ethynyl(phenyl)iodonium tetrafluoroborate in tetrahydrofuran affords 2-ethynyl-2-methylcyclohexanone (equation 267). This is the only example known to this author of the alkynylation of an unactivated monocarbonyl compound with an alkynyliodonium salt. However, the earlier conclusion that simple enolates do not undergo alkynylation with alkynyliodonium salts (section II.D.7 and II.G) needs to be revvised. 

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