Iodine-catalyzed isomerization

The elution order of the CLA isomers is t,t> dt> c,c CLA. The observed elution order within each group of geometric CLA isomers increases as the A values decrease. For the same positional isomer with double bonds closer to the carboxyl group than 10,12-18 2, the c,t isomer elutes before the t,c isomer, and with double bonds further from the carboxyl group than 10,12-18 2 the elution order is reversed. The elution order of the 7,9- and 6,8-CLA was established by analyzing synthetic isomers (22,23,111). A typical separation of the commercial CLA mixture containing four positional isomers that was further increased to eight positional isomers by iodine catalyzed isomerization (88) is shown in Fig. 4.13. 

Fig. 4.13. Partial Ag -HPLC separation of a commercial CLA mixture (Nu ChekPrep) and its isomerized product after iodine catalyzed isomerization. Reproduced with permission of the journal and author Eulitzetal. (88).

Iodine catalyzes the isomerization of a variety of A.A -dichloropolyfluoroanilines to A, 4-di-chlorocyclohexadienimines,43-45 as illustrated by the rearrangement of jV.A-dichloropenta-fluoroaniline (51) to A. 4-dich]oropentafluorocyclohexa-2,5-dien-1-imine (52).43... 

Carotenoids can be converted into mixtures of geometrical isomers under appropriate conditions, the most common being iodine catalyzed photoisomerization. This produces an equilibrium mixture of isomers, in general the all-trans isomers predominates. These isomers in an isomeric mixture cannot be measured separately by simple spectrophotometric determination. The usual method of subsequent measurement would be chromatographic separation, diode-array detection, and spectral analysis. In the absence of any definitive data on extinction coefficients for cfv-isomcrs, they are quantified against the all-trans isomer. Modem procedures involve the direct synthesis of c/.v-carotcnoids. 

Although scheme (138) is the standard mechanism for the radical-catalyzed isomerization of isomeric alkenes, kinetic data for both substitution and isomerization are sparse. Using cis- or frcms-diiodo-ethene and labeled iodine atoms, Noyes et al. (1945) demonstrated that iodine atoms exchanged with predominant retention isomerization was the slower process, the barrier being <4 kcal/mole. Corresponding studies with dibromoethene and bromine atoms indicate a barrier of ca. 3 kcal/mole (Steinmetz and Noyes, 1952) in which bromine-atom departure from and isomerization of the intermediate were competitive. Qualitative selective or stereospecific radical-initiated additions to alkenes have since indicated that radical intermediates probably have stereostability, but the studies cited are definitive. The kinetic analysis provided the essential model for SS in mechanistic schemes such as (138), whether for SE, SH or SN processes. 

Clauson-Kaas) are perhaps the most utilized methods for the de novo synthesis of pyrroles. Recent advances include the following novel approaches to 1,4-diketones Stetter addition of aldehydes to chalcones <07SC1109> ruthenium-catalyzed isomerization of 1,4-alkynediols <07TL5115> and Zn/iodine-mediated dimerization of a-bromoketones <07TL7215>. 

Yamashita, S. (1961). Iodine-catalyzed cis-trans isomerization of azobenzene. Bull. Chem. Soc. Japan 24, 842-845. 

Cu-Bisoxazoline-catalyzed asymmetric cyclopropanation of methyl 2-furoate with ethyl diazoacetate was a key step in the synthesis of the cw-fused 5-oxofuro[23-fc]furan core of spongiane diterpenoids <05OL5353>. An interesting example of rtiodium-catalyzed intramolecular addition of a diazoketone to furan affording a strained cyclobutenone, is illustrated below. Iodine-induced isomerization of the product provided the fused tricyclic dihydrofuran compound <05HCA33Q>. 

Recent publications concern the qualitative and the quantitative determination of 3-carotene by TLC. Isomerization of a- and 3-carotene was catalyzed by iodine according to the method of Zechmeister. Fig. 2A illustrates typically developed TLC plates for a mixture of a- and 3-carotene isomers.Two-dimensional TLC was done on calcium hydroxide plates with 1.2% acetone in petroleum ether as mobile phase. Expected isomers from the iodine-catalyzed reaction are neoisomers U and B for P-carotene and neoisomers U, W, and B for a-carotene. Photoisomerization of aW-trans-a- and p-carotene solutions was also conducted by Nyambaka and Ryley. This photoisomerization of individual a3 -trans-a- and P-carotene solutions produced several isomers each. Nyambaka and Ryley apphed the separation TLC method, which was done by Schwartz and... 

D of 0.2 100. The quantitative method consisted of subtracting the extinction at 270 mjx of solutions treated with iodine from that at 270 mji of the corresponding untreated solutions, and computing from values established with known quantities of a standard. This method, however, was not applicable to low-potency preparations or to those containing vitamin A. At best the cisjtrans isomerization gives the irons form in 75% yield (Verloop et al., 1959) althou in this authors laboratory only 40-50% yields (Nair and deLeon, 1965) were obtained under die same conditions. However, on employing the trifluoroacetates of the cis form in the iodine-catalyzed reaction, we were able to obtain quantitative yields of the trans vitamins D (see Section V). 

The iodine-catalyzed photoisomerization of the D vitamins, as such, afforded the trans isomers only in 45% yield (Nair and deLeon, 1965) compared with a 75% yield reported by Verloop et al. (1959). Hence cis,trans isomerization of the parent compounds appeared to offer little promise as a quantitative technique. Fortunately we discovered later that, by replacing the free vitamin D vdth their trifluoroacetates (made in hexane solution), cis,trans isomerization in hexane resulted in a... 

It was envisioned that hydrindanone 83 and cyclopentene 85 could be used as intermediates in the synthesis of e f-retigeranic acid A (1) and e f-retigeranic acid B (2), respectively. To prepare the building block 90, cyclopentene 85 was reduced with diimide (93 %) in order to prevent isomerization and subsequently deprotected with PPTS to yield hydrindanone 90 (quant.), which could provide access to <77/-retigeranic acid B (2) (Scheme 10.7). Hydrindanone 83 was reduced via an enol triflate and then subjected to Pd-catalyzed reduction to provide cyclopentene 91 (87 % from 83). Upon hydrogenation of 91 with Pd/C and cleavage of the acetal with iodine, protected hydrindanone 92 (95 % from 91) was obtained. The deprotection of 92 provided ent-60, whose enantiomer was used in previous syntheses of retigeranic acid A (1) by Corey [14] and Hudlicky [46, 47]. 

The enormous amount of overactivation in photochemistry is not always required for solid-state cis-trans isomerizations. There are also some thermal E/Z isomerizations of crystalline olefins that are catalyzed by iodine. For example, crystalline czs-stilbenes 91 can be isomerized to give frans-stilbenes 92 without intervening liquid phases (Scheme 8). The isomerizations follow first-order kinetics with various rate constants for 4-MeO, two modifications of 2-MeO, 2-EtO, 2-n-PrO, and 2-i-PrO substitution. The activation energies vary from 20 to 32 kcal mol but could not be interpreted [54]. Similarly, cfs-l,2-diben-... 

A series of pyrido[2,3-rf pyrimidine-2,4-diones bearing substituents at C-5 and/or C-6 were synthesized using palladium-catalyzed coupling of uracil derivative 417 with vinyl substrates or allyl ethers to give the regioisomeric mixtures of 418/419 and 420/421, respectively. The ratio of the isomeric structures was dependent on the substituent R. In the case of the reaction with -butyl vinyl ether, only the product 419 was obtained. However, the reactions with acrylonitrile, ethyl acrylate, 2-trifluoromethylstyrene, and 3-nitrostyrene afforded only 418. Also, reaction with allyl phenyl ether gave only 420. The key intermediate 417 was prepared by the reaction of 6-amino-l-methyluracil with DMF-DMA (DMA = dimethylacetamide), followed by N-benzylation with benzyl chloride and vinyl iodination with iV-iodosuccinimide (NIS) (Scheme 15) <2001BML611>. 

One of the best known reactions of 1-azirines is the acid/catalyzed hydrolysis to aminoketones. Since the Neber reaction also accomplishes this same synthetic end, this reaction may appear to have little practical value. This is not the situation because with the Neber reaction there is no control over the aminoketone that will be obtained from a given ketone. For example, when oxime (127) derived from benzyl methyl ketone (126) is subjected to the Neber reaction aminoketone 128 is obtained.59 The amino function is substituted for the most acidic a-hydrogen. The isomeric aminoketone (132) that could not be prepared by the Neber reaction can be formed by the hydrolysis of 1-azirine (131). The synthesis of this 1-azirine has been accomplished from allyl benzene (129) through vinyl azide (130) using iodine azide.22... 

When the hydrogenation function is embedded in the crystal voids of an MFI topology, the formation of trans-isomers is strongly reduced. After partial reduction of soy bean oil with such catalyst from an iodine value of 140 to 80, virtually no trans-isomers are obtained (56). This is the result of pore mouth catalysis combined with zeolite shape selectivity. Due to the bent character of the cts-isomer chains in triglycerides, trans-configured chains preferentially enter the pore mouths for hydrogenation. In this environment, metal-catalyzed cis-trans isomerization is restricted for steric reasons as multiple readsorption is minimal. 

In this synthesis (Scheme 6), the C2-symmetri-cal triacetonide of D-mannitol (32) is converted via the epoxide 33 and its nucleophilic addition product 34 to the propargylic alcohol derivative 35. From this intermediate, the Z-configured vinyl iodide 36 is stereoselectively obtained by hydroalumination/iodination. The Pd-catalyzed Heck cyclization then affords the isomerically pure product 37, which represents a potential building block for the synthesis of la,2y5,25-trihy-droxy-vitamin D, following the classical Wittig strategy of Lythgoe. 

Oxidative cyclization of benzyl and other 2-hydroxyethyl ethers to afford dioxolanes (Equation 46) can be achieved using A -iodosuccinimide in nitromethane for R = Ph <1998AGE3177> or photochemical reaction with iodine and polymer-supported iodobenzene diacetate in acetonitrile <2005SL923>. In a related process, RuCl2(Ph3P)2 catalyzes the isomerization of allyl 2-hydroxyethyl ether to form 2-ethyl-l,3-dioxolane <2004SL1203>. 

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