Iodoalkenes

The reaction of perfluoroalkyl iodides with alkenes affords the perfluoro-alkylated alkyl iodides 931. Q.a-Difluoro-functionalized phosphonates are prepared by the addition of the iododifluoromethylphosphonate (932) at room temperature[778], A one-electron transfer-initiated radical mechanism has been proposed for the addition reaction. Addition to alkynes affords 1-perfluoro-alkyl-2-iodoalkenes (933)[779-781]. The fluorine-containing oxirane 934 is obtained by the reaction of allyl aicohol[782]. Under a CO atmosphere, the carbocarbonylation of the alkenol 935 and the alkynol 937 takes place with perfluoroalkyl iodides to give the fluorine-containing lactones 936 and 938[783]. 

Iodine cleavage of 2,2-difluoroalkenylboranes provides a general route to l-difluoro-2-iodoalkenes [49] (equation 32)... 

To date, only one example of a combination of a photochemically induced transformation with a transition metal-catalyzed reaction has been found in the literature. This hv/Pd°-promoted process allows the synthesis of five-membered cyclic y-keto esters 5-119 from 5-iodoalkenes 5-117 in the presence of CO and an alcohol 5-118 as a nucleophile (Scheme 5.24) [41]. The yields are high, and differently substituted iodoalkenes can be employed. 

Palladium-catalyzed coupling of the borane derived from A with 1-bromo-1-pentyne to give B as well as the coupling of iodoalkene C with alkyne D were the two key-steps. 

The method enables conversion of substituted alkynes to (fc)-2-methyl-1 -alkenylalumi-num species, and, by subsequent iodinolysis, to the corresponding iodoalkenes with retention of the double-bond configuration. Depending on the substitution pattern of the starting alkyne, many useful products emerge from this reaction, which themselves can serve as building blocks for transition metal-mediated or -catalyzed coupling reactions [59—62]. 

A 1,2-metalate rearrangement of a higher order cuprate, known as a Kodenski rearrangement [64], was used as a key step in the synthesis of the marine antiinflammatory sesterterpenoid manoalide 95 (Scheme 9.20) [65]. Treatment of the alkenyl lithium 89 (prepared from the alkenylstannane 88 with s-BuLi in a diethyl ether-pentane mixture) with the homocuprate 91 (produced from iodoalkane 90) gave the iodoalkene 94 in 72% overall yield from 88. The reaction proceeds as fol-... 

Electrophiles also react at C-5 of 1,3-dioxin-4-ones. Two ways of activation have been reported (1) magnesiation of 5-iodo-l,3-dioxin-4-ones afforded the Grignard reagents which can be cross-coupled with allyl halides in the presence of copper cyanide <2001TL6847> or with iodoalkenes under Pd(0) catalysis <2002T4787> and (2) Sc(OTf)3-catalyzed reaction of a side-chain-hydroxylated l,3-dioxin-4-one with aldehydes provided the bicyclic dioxinone in 60-85% yield (Scheme 27) <20050L1113>. 

Third, chromium-based reagents prepared by reduction of 1,1-dihalo compounds with CrCl2 are suitable for the transformation of aldehydes to (i4)-iodoalkenes, (it)-alkenylsilanes, " and ( )-alkenylboronic esters with one-carbon homologation (Equation (8)). The amount of CrCl2 can be reduced to a catalytic amount by using manganese (or zinc) and MesSiCl. " ... 

Similar cyclizations can be performed using iodoalkenes bearing a malonate or similar GH-acidic pendant, though in this case l,3-bis-(diphenylphosphino)propane (dppp) is required as a ligand (Equation (45)). ... 

Reduction to ether 16 To iodoalkene 87 To methylene 87 Kulinkovich cyclization 197... 

Sonogashira coupling [18] (copper (I) acetylenes with iodoalkenes)... were described. 

The synthesis of cyclic 10-X-3 species usually involves oxidation of an alkyl or aryl iodide which has an appropriate nucleophilic neighboring group. Addition of chlorine to /3-iodoacrylic acid (17) gives cyclic 10-1-3 species (18) (09LA(369)119). The intermediacy of the iodoalkene dichloride is uncertain. 

To boronic acid 84 (184 mg, 0.74 mmol) was added iodoalkene 79 (222 mg, 0.60 mmol), THF (5 mL), and H20 (43 mg, 2.4 mmol). The mixture was cooled to 0 °C and Pd(PPh3)4 (49 mg, 0.07 mmol) in dry THF (1.5 mL) was added by cannula. After 5 min, TIOEt (377 mg, 1.51 mmol) was added over 10 min. After 2 h, this was partitioned (EtOAc/H20). The aqueous phase was extracted with EtOAc (2 x) and the organic phases were washed with H20 (2 x) and brine (1 x), dried (MgS04), filtered, and concentrated to give a dark residue. This was filtered through silica gel (EtOAc/hexanes 1 9) and purified by HPLC (EtOAc/hexanes 4 96) to give the desired ester yield 219 mg (82%). 

Manoalide, a marine anti-inflammatory sesterterpenoid, has been synthesized555 using a 1,2-metallate rearrangement of a higher order cuprate and a Pd(0)-catalysed carbonylation of an iodoalkene to generate the central dihydropyranone ring. 

The equivalent intramolecular Heck-type vinylation of a a>-vinyl-(Z)-iodoalkene has been used as the key step in the synthesis of A-ring synthons for 1 at,25-di hydroxy vitamin D3 and its analogues403. The reaction takes place under reflux in acetonitrile in the presence of one equivalent of triethylamine404 and gives a 81% yield (equation 102). 

Lithium dimethylcuprate transfers a methyl group, which substitutes for iodine on the iodoalkene. Even halogens on. s/r-hybridized carbon are reactive in substitution reactions with lithium dialkylcuprates. 

Palladium catalysed cyclic carbozincation of u>-iodoalkenes and copper promoted conjugate addition of alkylzincs to nitroalkenes preparation of 1-butyl-1-(3-nitro-2-phenylpropyl)cyclopentane60... 

Fig. 16.15. Stereoselective preparations of trans-alkenyl-boronic acid esters (B) and trans-alkenylboronic acids (C) and their stereoselective conversion into c/s-bromoalkenes and trans-iodoalkenes, respectively.

Fig. 16.17. Mechanism of the carbocupration of acetylene (R = H) or terminal alkynes (R H) with a saturated Gilman cuprate. The unsaturated Gilman cuprate I is obtained via the cuprolithiation product E and the resulting carbolithiation product F in several steps—and stereoselectively. Iodolysis of I leads to the formation of the iodoalkenes J with complete retention of configuration. Note The last step but one in this figure does not only afford I, but again the initial Gilman cuprate A B, too. The latter reenters the reaction chain "at the top" so that in the end the entire saturated (and more reactive) initial cuprate is incorporated into the unsaturated (and less reactive) cuprate (I). - Caution The organometallic compounds depicted here contain two-electron, multi-center bonds. Other than in "normal" cases, i.e., those with two-electron, two-center bonds, the lines cannot be automatically equated with the number of electron pairs. This is why only three electron shift arrows can be used to illustrate the reaction process. The fourth red arrow—in boldface— is not an electron shift arrow, but only indicates the site where the lithium atom binds next.

Fig. 16.19. Palladium-cata lyzed, stereoselective alkenylation of an arylboronic acid (preparation according to Figure 5.39) with a variety of iodoalkenes. The boronic acid is converted into the boronate anion A. The ion A reacts with the Pd(II) intermediate B via transmetalation subsequent reductive elimination leads to the coupling products.

Fig. 16.26. Pd(0)-catalyzed atkenylations of the organozinc bromides A and B and the organozinc chloride G with the iodoalkene C and the bro-moalkenes D and E, respectively, as an efficient method for the preparation of trans-configured C=C double bonds.

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