Iodo-ester alkenes

Iodocarbonyls are excellent substrates for atom transfer cyclization, as shown by examples from our recent work in Scheme 29.19-129 When two carbonyl (or cyano) groups are present, bromides can also serve as radical precursors. Photolysis with 10% ditin usually provides excellent yields of kinetic products at high concentration, and alkene substituents often dictate the regioselectivity. The y-iodo ester products are particularly versatile for subsequent transformations, which can often be conducted in situ. Although tertiary iodine products sometimes go on to give lactones or alkenes, primary and secondary iodides can often be isolated if desired. The last example is particularly noteworthy the kinetic product from the cyclization presented in Scheme 27 is trapped, because bromine atom transfer is much more rapid that reverse cyclization. 

The radical intermediates from Cr(II) reduction of alkyl halides can in principle be used synthetically, but have only seen limited attention to this point. co-Haloalkynes (bromides, iodides), in the presence of excess Cr(C104)2, undergo cyclization reactions to form exo-alkylidene cycloalkanes (equation 176)347. These reactions proceed by the radical cyclization of intermediate 42 onto the alkyne unit, which undergoes subsequent reduction by Cr(II) to give a hydrolytically unstable vinylchromium(III). Rings of four, five and six members can be formed. Alternatively, a-iodo esters undergo intramolecular atom transfer radical cyclizations onto alkynes or alkenes with catalytic or stoichiometric amounts of... 

The addition of bromine or iodine to ( )-alkenylboronic acids or esters afforded intermediates, which were converted by base into (Z)-l-halo-l-alkenes.543 On the other hand, ( )-iodo-l-alkenes of high stereochemical purity were prepared by treatment of ( )-l-alkenylboronic acids or esters with sodium hydroxide followed by 1 molar equiv. of iodine.544 Iodine monochloride was used in place of iodine for such a base-induced iodination with retention or inversion of the stereochemistry (Equation (110)).545 Chloramine-T/Nal (Equation (111)),546,547 CuX2 (X = Cl, Br) (Equation (112)),548 and iV-halosuccinimides (Equation (113))549 halogenated the C-B bond with retention of stereochemistry. 

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)). 

Et3B-induced additions of perfluoroalkyl iodides,7 a-iodo esters (Scheme 6.4), iodoamides,8 a-iodonitriles9 and simple alkyl iodides to alkenes and alkynes have been reported. Interestingly, these reactions were also performed with success in aqueous media,10 demonstrating the ability of Et3B to act as an initiator in water. 

With an acceptor-substituted alkene moiety tethered to the molecule, the intermediate silyl enol ether may undergo an intramolecular [2-I-2] cycloaddition.The silyl-assisted addition of hydrogen halides to cyclopropanes is not restricted to ketones with carbonyl groups as activating function or iodide as nucleophile. Esters and other acid derivatives underwent similar reactions when treated with iodotrimethylsilane alone or in the presence of an additional catalyst such as mercury(II) or zinc(II) chloride.Subsequent treatment of the y-iodo ester with potassium carbonate in tetrahydrofuran gave the respective y-butyrolactones in good yield. 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

The mechanism of oxidation probably involves in most cases the initial formation of a glycol (15-35) or cyclic ester,and then further oxidation as in 19-7. In line with the electrophilic attack on the alkene, triple-bonds are more resistant to oxidation than double bonds. Terminal triple-bond compounds can be cleaved to carboxylic acids (RC=CHRCOOH) with thallium(III) nitrate or with [bis(trifluoroacetoxy)iodo]pentafluorobenzene, that is, C6F5l(OCOCF3)2, among other reagents. 

Cyanogen Iodide (ICN) has been used extensively for the cyanation of alkenes and aromatic compounds [12], iodination of aromatic compounds [13], formation of disulfide bonds in peptides [14], conversion of dithioacetals to cyanothioacetals [15], formation of trans-olefins from dialkylvinylboranes [16], lactonization of alkene esters [17], formation of guanidines [18], lactamization [19], formation of a-thioethter nitriles [20], iodocyanation of alkenes [21], conversion of alkynes to alkyl-iodo alkenes [22], cyanation/iodination of P-diketones [23], and formation of alkynyl iodides [24]. The products obtained from the reaction of ICN with MFA in refluxing chloroform were rrans-16-iodo-17-cyanomarcfortine A (14)... 

Fig. 16.20. Alkenylation of isomeric alkenylboronic acid esters with isomeric iodo-alkenes stereoselective synthesis of isomeric 1,3-dienes.

A similar reaction has been adopted for the preparation of amides from alkenes by the photoaddition of "CONH2 radicals generated from formamide by benzophe-none [7], or via a TBADT [25] photocatalyzed hydrogen abstraction. Solar light has been used in the first case. Furthermore, the introduction of an ester function has been accomplished by generating an alkoxycarbonyl radical by photolysis of [bis(alkoxyoxalyloxy)iodo]benzene at 0-5 °C and ensuing addition to vinyl sulfones in the presence of 1,4-cyclohexadiene [9]. 

In contrast to other methods, functional groups such as esters, amides, nitriles, alkenes, alkynes, etc. were unaffected, under these conditions. In pure methanol, ethanol or ethylene glycol, thioacetals were converted to acetals. The use of [bis(trichloroacetoxy)iodo]benzene gave equally good results [44]. Generally, since trichloroacetic acid is 3 times cheaper than trifluoroacetic acid on a mole basis, [bis(trichloroacetoxy)iodo]benzene may be an alternative to BTI. 

The spectrum of applications of potassium permanganate is very broad. This reagent is used for dehydrogenative coupling [570], hydrox-ylates tertiary carbons to form hydroxy compounds [550,831], hydroxylates double bonds to form vicinal diols [707, 296, 555, 577], oxidizes alkenes to a-diketones [560, 567], cleaves double bonds to form carbonyl compounds [840, 842, 552] or carboxylic acids [765, 841, 843, 845, 852, 869, 872, 873, 874], and converts acetylenes into dicarbonyl compounds [848, 856, 864] or carboxylic acids [843, 864], Aromatic rings are degraded to carboxylic acids [575, 576], and side chains in aromatic compounds are oxidized to ketones [566, 577] or carboxylic acids [503, 878, 879, 880, 881, 882, 555]. Primary alcohols [884] and aldehydes [749, 868, 555] are converted into carboxylic acids, secondary alcohols into ketones [749, 839, 844, 863, 865, 886, 887], ketones into keto acids [555, 559, 590] or acids [559, 597], ethers into esters [555], and amines into amides [854, 555] or imines [557], Aromatic amines are oxidized to nitro compounds [755, 559, 592], aliphatic nitro compounds to ketones [562, 567], sulfides to sulfones [846], selenides to selenones [525], and iodo compounds to iodoso compounds [595]. 

In this connection, intramolecular Michael addition of 0-carbamates to a,3-unsaturated esters (Scheme 60)," iodo cyclization of allylic and homoallylic trichloroacetamidates" or aminomercuration of alkenic carbamates" has been used for the preparation of amino alcohols. 

Styryl derivatives of 2-aminofurans, as well as alkenyl compounds, also undergo intramolecular cycloaddition and the alkene function can be introduced by Stille coupling of a suitably functionalised aryl iodide. This approach is illustrated by the tetrahydroquinoline synthesis summarised in Scheme 26 (99JOC3595). The iodo derivative 143 is readily prepared from the carbamate ester 142 (67% yield) and Stille coupling with vinyltributyltin gives the styrene 144 (72% yield). Intramolecular cycloaddition and dehydration is then achieved simply by heating compound 144 in toluene under reflux (24 h) to give the tetrahydroquinoline 145 in 79% yield. 

---