Iodo ketones, cyclization

The crude iodo ketone usually contains up to 10% benzene, which does not interfere with the cyclization step (Part B). Complete removal of the benzene takes time, during which a considerable proportion of the iodo ketone may decompose. 

Barhier cyclization The Barbier reaction has been used for cyclopentenone annclation.5 Thus a-allylcycloalkanones are converted into the iodo ketones 1, which on treatment in THF with magnesium activated by HgCl2 are converted into bicycloalkanols (2) in moderate to good yield. Formation of cw-fused products is greatly favored. The reaction gives poor yields when extended to annelation of six-und scvcn-mcmbcred rings. 

Fig. 18 Ni(0)-catalyzed Et2Zn mediated cyclizations of 5-iodo ketones to cyclopentanols...

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... 

Vinylogous Barbier reaction,4 Smlj (2 equiv.) can effect cyclization of the unsaturated iodo ketone 1 in THF containing DMPU (or HMPA) to give a bicyclic samarium enolatc (a) that can be trapped by an aldol reaction. 

Cyclization and expansion of dichlorocyclobutanonesf Reaction of BujSnH/ AIBN with the adduct (1) of the reaction of enfree radical addition to the free double bond and reduction of the remaining chloride to provide 2. Reaction of 2 with lSi(CH3)3/Znl2 results in transformation to a seven-membered cyclic cr-iodo ketone, which is converted to cnone 3 by DBU. 

Sole and co-workers found the smooth carbonyl addition reaction of amino-tetheied aryl iodides and ketones [29], Treatment of the 2-iodoanilino ketone 119 with PPhs, Et3N and CS2CO3 in toluene afforded the alcohol 120. The cyclized product 122 was obtained from 2-iodobenzylamino ketone 121. The cyclized product 124 of the iodo ketone 123 was converted to the indole derivative 125 in high yield by acid-catalyzed dehydration. In these reactions, no or-arylation was observed. 

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). 

This hypoiodite reaction can also be used for ring expansion of cyclic ketones.2 Thus Barbier cyclization of a-(w-iodopropyl)cyclododecanone (3) furnishes the bicyclic alcohol 4, which undergoes regioselective cleavage to a 15-membered iodo... 

The photostimulated reaction of benzylamines with an o-iodo (bromo) substituent (281) and ketone enolate ions gave the product 282 that cyclized spontaneously to give 283 (equation 174)327. 

Simple double aza-Michael reaction of divinyl ketones with primary amines was utilized to generate TV-substituted 3-phenyl-4-piperidones in good yields <07EJO4376>. In a somewhat similar mode, the diastereoselective synthesis of cyclic (3-amino esters by an Sn2 substitution-cyclization of an iodo-a,(3-unsaturated ester with (.Sj-u-mcthy 1 benzylamine was described <07OBC3614>. A combination intramolecular Michael-type addition followed by retro-Michael elimination was exploited in the generation of a phosphoryl dihydropyridone intermediate in the synthesis of /m .v-2,6-disubstitutcd 1,2,5,6-tetrahydropyridines <07JOC2046>. 

Michael acceptor groups other than a,p-unsaturated esters give only traces of cyclized products under similar conditions. The major products result from 1,2- and 1,4-additions of n-butyllithium in the case of co-iodo-a,(3-unsamrated ketones or amides. 

As a sequel to the elegant and highly efficient synthesis of camphor by an intramolecular cyclization. Money et have successfully applied this method to the synthesis of the naturally-occurring sesquiterpenoids campherenone (110) and campherenol (111) whose structures and absolute stereochemistries have recently been deduced.In this sequence, dihydrocarvone (112) was readily converted into the keto-ketal (113) from which the homologated chloro-ketone (114) was obtained. Treatment of the corresponding enol acetate (115) with boron trifluoride in wet methylene chloride afforded the two bicyclic chloro-ketones (116) and (117) in 55-60% yield. Conversion of the corresponding iodo-ketals... 

In 1989 Curran and co-workers reported on a photocatalytically induced free-radical cyclization leading to various cyclic, bi-, or polycyclic carbocycles (fused and spiro) via isomerization of unsaturated iodides (alkenes, alkynes) [63]. This corresponds to the nonreductive variant of the tin hydride method. Under sunlight irradiation and in the presence of 10 mol% hexabutylditin, a-iodo esters, ketones, and malonates are efficiently transformed via an iodide atom transfer chain mechanism (eq. (4)). 

A mixture of THF and DMPU has been used as a solvent for Sml2 in various reactions such as cyclization of alkynyl halides [90,91], tandem iodo-enone cy-clization/samarium enolate aldol reaction [92], coupling of (3-silylacrylic esters [93], deprotection of arenesulfonamides [94] and pyridine-2-sulfonamides [95], radical ring-opening reactions of cyclopropyl ketones and the trapping of the resulting samarium(III) enolates by a variety of electrophiles [96] (Scheme 41). 

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