Iodo olefin

Viprostol (81) also incorporates a hydroxy group moved to C-16 and protects this from facile metabolic oxidation by vinylation. It is a potent hypotensive and vasodilatory agent both orally and transdermally. The methyl ester moiety is rapidly hydrolyzed in skin and in the liver so it is essentially a prodrug. It is synthesized from protected E-iodo olefin 78 (compare with 75) by conversion to the mixed organocuprate and this added in a 1,4-sense to olefin 79 to produce protected intermediate 80. The synthesis of viprostol concludes by deblocking with acetic acid and then reesterification with diazomethane to give 81 [19]. 

Jin, H., Uenishi, J., Christ, W. J., Kishi, Y. Catalytic effect of nickel(ll) chloride and palladium(ll) acetate on chromium(ll)-mediated coupling reaction of iodo olefins with aldehydes. J. Am. Chem. Soc. 1986, 108, 5644-5646. 

Jin, H. Uenishi,J. Christ,W.J. Kishi,Y., Catalytic Effect of Nickel(II) Chloride and Palladium(II) Acetate on Chromium(III)-Mediated Coupling Reaction of Iodo Olefins with Aldehydes. / Am. 

For the first (6 g) and the second (60 g) campaign, utilizing the Zhao olefination procedure, also used by Smith and Marshall, we obtained the desired cis-vinyl iodide 4 in 20 to 31 % yield after chromatographic purification on silica gel. Only a small amount of the undesired trans isomer was detected cis trans - 10 1 to 15 1) and this could not be separated from the desired cis compound. This is fortunately not a problem as they can be separated after the next step in the sequence. We did not observe any rfes-iodo olefin 23, suggesting that the formation of the iodo ylide from ethyltriphenylphosphonium iodide, via ylide iodination (Scheme 4), was complete before it was added to aldehyde 18. 

It was found, as reported, that the reaction of 2-iodo ethyltriphenylphosphonium iodide 20 with 18 afforded epoxide 25 as a mixture of isomers in addition to the desired 4 in a 1 1 ratio. Alternative approaches were investigated in an attempt to minimize this major byproduct, but they were unsuccessful. For example, employing a method described by Shen (where the initially formed betaine intermediate was deprotonated with a second equivalent of base and then iodinated) produced des-iodo olefin 23. Utilizing Hanessian s phosphonates in this process also resulted in only des-iodo olefin 23. 

In order to promote selective deprotonation at C-1 in 109, an electron attracting substituent is required at the para position, C-S. The nitrile group was chosen— also because it permitted ready conversion to phenolic hydroxyl at the end of the synthesis (Scheme 15). lodination of sulfone 109 followed by iodide-cyanide exchange gave the C-5 nitrile 115. The optically active acid (-f) 103 (Scheme 14), via its methyl ester (4-) 102, was converted in good yield into iodo olefin 116. 

C-19 methyl functionality in the tetracyclic ketone 164, the Nt-H group was alkylated with the optically active i .-tosylate 224 (which was in turn obtained from the R propargylic alcohol via a two-step sequence) in aceto-nitrile/K2C03, followed by treatment with tetrabutylammonium fluoride hydrate to obtain the acetylenic ketone 225 in 96% yield. The terminal alkyne in 225 was converted into the iodoolefm functionality by treating with dicyclohexyhodoborane [I-B(Cy)2], followed by protonolysis. The iodo-olefin 226 was obtained in 74% yield. It was subjected to a Pd-catalyzed a-vinylation to obtain the key C-19 methyl-substituted pentacy-clic system 227. This was followed by a Wittig/hydrolysis/epimerization... 

Carbonylation,—The substituted butenolides (20) are synthesized in good yield (70—100%) by carbonylation of the iodo-olefin (19) in the presence of catalytic amounts of [PdCl2(PPh3)2] under mild conditions (30 °C, 1—3 atm CO). ... 

The anomalous iodoacetamide-fluoride reaction violates this rule, in that a less stable -halonium complex (18) must be involved, which then opens to (19) in the Markownikoff sense. This has been rationalized in the following way estimates of nonbonded destabilizing interactions in the possible products suggest that the actual product (16) is more stable than the alternative 6)5-fluoro-5a-iodo compound, so the reaction may be subject to a measure of thermodynamic control in the final attack of fluoride ion on the iodonium intermediate. To permit this, the a- and -iodonium complexes would have to exist in equilibrium with the original olefin, product formation being determined by a relatively high rate of attack upon the minor proportion of the less stable )9-iodonium ion. 

Iodine azide, on the other hand, forms pure adducts with A -, A - and A -steroids by a mechanism analogous to that proposed for iodine isocyanate additions. Reduction of such adducts can lead to aziridines. However, most reducing agents effect elimination of the elements of iodine azide from the /mwj -diaxial adducts of the A - and A -olefins rather than reduction of the azide function to the iodo amine. Thus, this sequence appears to be of little value for the synthesis of A-, B- or C-ring aziridines. It is worthy to note that based on experience with nonsteroidal systems the application of electrophilic reducing agents such as diborane or lithium aluminum hydride-aluminum chloride may yet prove effective for the desired reduction. Lithium aluminum hydride accomplishes aziridine formation from the A -adducts, Le., 16 -azido-17a-iodoandrostanes (97) in a one-step reaction. The scope of this addition has been considerably enhanced by the recent... 

There are several available terminal oxidants for the transition metal-catalyzed epoxidation of olefins (Table 6.1). Typical oxidants compatible with most metal-based epoxidation systems are various alkyl hydroperoxides, hypochlorite, or iodo-sylbenzene. A problem associated with these oxidants is their low active oxygen content (Table 6.1), while there are further drawbacks with these oxidants from the point of view of the nature of the waste produced. Thus, from an environmental and economical perspective, molecular oxygen should be the preferred oxidant, because of its high active oxygen content and since no waste (or only water) is formed as a byproduct. One of the major limitations of the use of molecular oxygen as terminal oxidant for the formation of epoxides, however, is the poor product selectivity obtained in these processes [6]. Aerobic oxidations are often difficult to control and can sometimes result in combustion or in substrate overoxidation. In... 

In another example of a radical process at the pyrrole C-2 position, it has been reported that reductive radical cycloaddition of l-(2-iodoethyl)pyrrole and activated olefins, or l-(oj-iodo-alkyl)pyrroles 34 lead to cycloalkano[a]pyrroles 35 via electroreduction of the iodides using a nickel(II) complex as an electron transfer catalyst <96CPB2020>. Thus, it appears the radical chemistry of pyrroles portends to be a fertile area of research in the immediate or near future. 

Vicinal iodo carboxylates may also be prepared from the reaction of olefins either with iodine and potassium iodate in acetic acid/ or with N-iodosuccinimide and a carboxylic acid in chloroform. " A number of new procedures for effecting the hydroxylation or acyloxylation of olefins in a manner similar to the Prevost or Woodward-Prevost reactions include the following iodo acetoxylation with iodine and potassium chlorate in acetic acid followed by acetolysis with potassium acetate reaction with iV-bromoacetamide and silver acetate in acetic acid reaction with thallium(III) acetate in acetic acid and reaction with iodine tris(trifluoroacetate) in pentane. ... 

No j3-bromo- or iodoalkyl complexes have yet been isolated. The reaction of vicinal dibromides or diiodides with [Co (CN)j] , [Co(CN)5H], or a Co(I)-DMG complex merely gives the olefin 32, 75,105,109,161), though kinetic evidence was obtained for the intermediate formation of the j8-bromo complex in the reaction of [Co"(CN)5] with a,j8-dibromopropionate and a,/3-dibromosuccinate (75). It is interesting that the pentacyanide produced is the bromo or iodo, and not the aquo, complex 32, 75), which suggests that the decomposition may involve a cis rather than a trans elimination of Co—X. The /3-chloroethyl complex can be prepared by tbe reaction of [Co(CN)5H]3- with CICH2CH2I 105). 

The 5,6-disubstituted dihydropyran 2049 is converted by iodosobenzene diacetate and Me3SiBr 16 or Mc3Sil 17 in pyridine to the 3-bromo (or 3-iodo) compounds 2050 in 79 or 84% yield, respectively [198] (Scheme 12.59). Reaction of olefins such as cyclohexene (or enol ethers) with iodosobenzene diacetate, tetra-... 

B. Reactions.—(/) Halides. Whereas ylides are alkylated in the normal way on treatment with a-bromo- or a-iodo-esters, quite different reactions occur with a-fluoro- and a-chloro-acetates. When salt-free ylides were refluxed in benzene with ethyl fluoroacetate or trifluoroacetate normal Wittig olefin synthesis took place with the carbonyls of the ester groups to give vinyl ethers, e.g. (14). On the other hand, methyl chloroacetate with... 

Soon afterwards [123] the bromo- (105) and iodo- (106) analogs of chlorovulone I (100) were also isolated from C. viridis in exceptionally low yield (ca. 0.01% of lipid extract). Their structures were established principally by spectroscopic means in comparison with chlorovulone I. Both of the new compounds possess the same olefin geometries as found in clavulone I and chlorovulone I. R Stereochemistry at Cl 2 was established in 105 by comparisons of CD spectra with those of chlorovulone I (100). These new halogenated clavulones showed levels of antiproliferative activity and cytotoxicity comparable to those of chlorovulone I (100). 

Generally, the intermolecular Heck reaction between 2-iodo-, 4-iodo- and 5-iodo-l-methylimidazoles and olefins suffers from low yields (< 25%). Therefore, these transformations are of limited synthetic utility [29]. In one case, variable yields for adduct 62 (15-58%) were observed for the Heck reaction of 5-bromo-l-methyl-2-phenylthio-lf/-imidazole (61) and a large excess of methyl acrylate [42]. 

Analogous to simple carbocyclic aryl halides, 5-halopyrimidines readily take part in Pd-catalyzed olefinations under standard Heck conditions. In a simple case, Yamanaka et aL synthesized ethyl 2,4-dimethyl-5-pyrimidineacrylate (102) via the Heck reaction of 5-iodo-2,4-dimethylpyrimidine and ethyl acrylate [70]. 

Iodocyclization of the olefinic tetrazole 5-but-3-enyl-l//-tetrazole 79 using Nal ICO ( and I2 in anhydrous acetonitrile at 0 °C under argon atmosphere in the dark affords a 72% isolated yield of a 1 1 mixture of 5-iodomethyl-6,7-dihydro-tetrazolo[l,5-zr] pyrrole 80 and 6-iodo-5,6,7,8-tctrahydro-tetrazolo[1,5-tf]pyridinc 81 (Equation 5) <2003T6759>. 

For comparison, fluorous-phase-soluble Pd complexes are only 74-98% selective towards the trans product [168-170]. The isolated yields of the product approached 70% when a threefold excess of olefin to iodobenzene was used (Table 3) however, the percent yield decreased with the use of bromobenzene as expected since activation of bromine-carbon bonds is less favorable than iodo-carbon bonds. It was also possible to catalyze the reaction in the absence of additional triethylamine base (Table 3). In this case, the tertiary amines of the den-drimer most likely act as the base. The catalysts, in general, were fully recover-... 

The procedure reported here, which is that of Hassner and Heathcock,3 is more convenient than the Wenker synthesis of aziridines4 and appears to be more general.5 It represents a simple route from olefins to aziridines (via 8-iodo carbamates).356 Aziridines are also useful as intermediates in the synthesis of amino alcohols and heterocyclic systems.5,7-9... 

Cyclopropanes 82 can be converted to the corresponding y-bromoalkyl ferf-butyl peroxides 83 employing a method published in 1982 by Bloodworth and Courtneidge, which uses peroxymercuration and subsequent bromodemercuration (Scheme 36). Perox-ymercuration is also useful to prepare a-iodo-/3-terf-butylperoxyethanes 85 from olefins as shown by Bloodworth and coworkers in 1987 (Scheme 37). The fraw -addition of... 

An attempt was also made to produce 0-iodo acyl iodides by the reaction of iodine, carbon monoxide and olefins in the presence of palladium or platinum chloride. This is, in effect, an attempt to make Dr. Tsuji s reaction catalytic rather than stoichiometric. No carbonyl insertion occurred at 1 atm. of carbon monoxide. However, it was found that iodination of the olefin was catalyzed by platinum olefin complexes and that an additional increase in catalytic activity accompanied the presence of carbon monoxide. There has been much speculation at this conference concerning the possibility of affecting catalytic activity by changing the ligands in the coordination sphere of the catalyst. This would appear to be such a case. 

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