Alkenes from vinyl iodides

Alkenes from vinyl iodides and Grignard reagents. Cross coupling of vinyl iodides with Grignard reagents to form alkenes is possible with catalysis by this palladium complex. Yields are 80-877o (six examples). Of more interest, the reaction occurs almost exclusively (>97%) with retention of configuration (equation I). 

The adducts derived from catechol borane are hydrolyzed by water to vinylboronic acids. These materials are useful intermediates for the preparation of terminal vinyl iodides. Since the hydroboration is a syn addition and the iodinolysis occurs with retention of the alkene geometry, the iodides have the -configuration.214... 

It is more difficult to conduct the addition reactions of nucleophilic radicals to electron poor alkenes because the resulting atom transfer steps are often endothermic and are too slow to propagate chains, even with iodides. An exception is illustrated in Scheme 57 resonance-stabilized vinyl radicals (especially if they are secondary or tertiary) are reactive enough to abstract iodine from alkyl iodides.178... 

Reactions which are apparently stereospecific occur in the nucleophilic displacement of vinylic iodide [31] in the electron-deficient alkenes E- and Z-24 shown in Scheme 9.14. With ethanolic toluenethiolate, the sole detectable product from the reaction of -24 is -25. However, -25 is also the sole detectable product from the reaction of Z-24. This stereoconvergence demands that the stereoisomers react through a common intermediate, and it was reasonably suggested that initial nucleophilic addition of the thiolate anion yields a resonance-stabilised carbanion (26) whose stereoisomerisation, again by rotation about a carbon-carbon single bond, is much faster than the loss of iodide to yield the substitution product ( fy). 

Vinyl halides represent yet another important class of intermediates in the conversion of ketones to alkenes. The most widely applied conditions for the conversion of ketones into vinyl halides are those developed by Barton et a/. ° for the conversion of 3p-acetoxyandrost-5-ene-17-one into 3P-hydroxyandrosta-5,16-diene (Scheme 44). These conditions of vinyl halide formation and subsequent reduction have been useful in a number of steroid systems for the introduction of a A -carbon-carbon double bond and have been shown to be compatible with such functional groups as alcohols, isolated double bonds and acetals. The scope of vinyl iodide formation from hydrazones has been studied by Pross and Stemhell, and recently the original reaction conditions were improved by using sterically hindered guanidine bases rather than triethylamine. Haloalkenes have also been prepared from the corresponding ketones by treatment with iodoform and chromium chloride or with phosphorous penta-halides. ... 

Although it probably did not involve a Heck reaction per se, Balme and co-workers employed an interesting tandem reaction in their construction of A 2) capnellene (147) (Scheme 6-26) [54J. Presumably vinyl iodide 144 undergoes initial oxidative addition with the palladium(O) catalyst to furnish a cr-alkenylpalladium(n) intermediate that is complexed to the pendant alkene. Intramolecular addition of the soft malonate nucleophile to this complex, from the opposite face, followed by reductive elimination, then provides tricycle... 

In more complex reaction cascades an additional alkyne-insertion step can occur. Thus starting with intramolecular carbopalladation of a vinyl iodide to a carbon-carbon triple bond, followed by two intramolecular alkene-insertion steps and termination with dehydropalladation, a palladium-catalyzed synthesis of l-(5 -methylbicyclo[3.1.0]hex-T-yl)-5,5-bis(carboethoxy)cyclo-hexadiene (52) starting from l-iodo-4,4-bis(carboethoxy)-ll-methyldodeca-l,ll-dien-6-yne (51) is achieved. ... 

These problems may be avoided by making an organometallic compound [often of Cu(I) or Mg(II)] from the halide intended to become the palladium a-complex and to use another vinyl halide as the electrophile. Palladium prefers to take out a halide rather than a hydrogen atom in the P-elimination step and all three problems disappear. In the synthesis of this T, Z-dicnc 134, we prefer to use a Pd a-complex for the Z-alkene part 136 and a vinyl iodide 135 for the E-alkene. 

The coupling of two enantiomerically pure fragments to form an alkene of fixed geometry in the centre of ebelactone allows a convergent synthesis.50 One fragment, the vinyl iodide 285 is ultimately derived from a coupling between a chiral aldehyde and a chiral allyl boronate but more immediately by silyl-cupration of an alkyne 284 and iodination. 

Both these products were used in the synthesis of epothilone A 173. The disconnection of the lactone is simple but the other is less obvious. The epoxide must come from a cis alkene and that can be made by a Suzuki coupling of a borane derived from 174 and the Z-vinyl iodide 175. As you will see, 174 was made from 169 and 175 from 172, unlikely as it seems. 

The pronounced sensitivity of alkynes to cyclization in the presence of external nucleophiles is illustrated in studies of formaldiminium ion (99) in which an alkyne and alkene compete as intramolecular ir-nucleophiles. While cyclization of (99) in water afforded 4-hydroxypiperidine (98) in 73% yield, cyclization in the presence of 10 equiv. of Nal gave vinyl iodide (100) in 76% yield (Scheme 34). It has been suggested that the mechanism of these nucleophile-promoted iminium ion-alkyne cyclizations probably involves rate-determining attack of the nucleophile on a ir-complex or bridged cation produced from reversible interaction of the iminium ion and alkyne groups. ... 

Radical reactions. The nickel boride adsorbed on the resin induces the formation of radicals from alkyl iodides, which can be intercepted in situ by alkenes such as acrylic esters and vinyl ethers. ... 

The enantiomer 366 of fungal metabolite YM-47522 has been prepared (thereby characterizing the natural product) in 13 steps from 365. The key alkene stereochemistries were installed by substitution of a terminal iodide with E-l,2-ditributylstannylethene, conversion to the vinyl iodide and PdCl2(MeCN)2-catalysed coupling with another organotin reagent (Scheme 37). ... 

Based on a transformation described by Catellani and coworkers [80], Lautens s group [81] developed a series of syntheses of carbocycles and heterocycles from aryl iodide, alkyl halides and Mizoroki-Heck acceptors. In an early example, the authors described a three-component domino reaction catalysed by palladium for the synthesis of benzo-annulated oxacycles 144 (Scheme 8.37). To do so, they used an m-iodoaryl iodoalkyl ether 143, an alkene substimted with an electron-withdrawing group, such as t-butyl acrylate and an iodoalkane such as -BuI in the presence of norbomene. It is proposed that, after the oxidative addition of the aryliodide, a Mizoroki-Heck-type reaction with nor-bornene and a C—H activation first takes place to form a palladacycle PdCl, which is then alkylated with the iodoalkane (Scheme 8.37). A second C—H activation occurs and then, via the formation of the oxacycle OCl, norbomene is eliminated. Finally, the aryl-palladium species obtained reacts with the acrylate. The alkylation step of palladacycles of the type PdCl and PdCl was studied in more detail by Echavarren and coworkers [82] using computational methods. They concluded that, after a C—H activation, the formation of a C(sp )—C(sp ) bond between the palladacycle PdCl and an iodoalkane presumably proceeds by oxidative addition to form a palladium(IV) species to give PdC2. This stays, in contrast with the reaction between a C(sp )—X electrophile (vinyl or aromatic halide) and PdCl, to form a new C(sp )—C(sp ) bond which takes place through a transmetallation. 

Several papers have appeared describing the synthesis of alkyl halides from organoboranes. Alkyl chlorides are obtained by the reaction of trialkylboranes with dichloramine-T, and in somewhat lower yield with iV,N-dichlorourethane/ whereas alkyl bromides are produced in excellent yield when the boranes derived from terminal alkenes and dicyclohexylborane are treated with either Bt2 or BrCl. Alkyl iodides are obtained from the same boranes by the use of ICl-NaQAc " or iodide ion-chloramine-T/ and this latter method has been applied to the radioiodination of olefins (with Vinyl iodides result from... 

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