Vinyl iodide

In organic chemistry, a vinyl iodide functional group (also known as iodoalkenes) is any alkene with an iodide substituent directly bonded to one of the alkene carbons (sp2). Vinyl iodides are versatile molecules that serve as important building blocks and precursors in organic synthesis. They are commonly used in carbon-carbon forming reactions in transition-metal catalyzed cross-coupling reactions, such as Heck reaction, Sonogashira coupling, and Suzuki coupling. Synthesis of well-defined geometry or complexity vinyl iodide is important in stereoselective synthesis of natural products and drugs. In organic chemistry, a vinyl iodide functional group (also known as iodoalkenes) is any alkene with an iodide substituent directly bonded to one of the alkene carbons (sp2). Vinyl iodides are versatile molecules that serve as important building blocks and precursors in organic synthesis. They are commonly used in carbon-carbon forming reactions in transition-metal catalyzed cross-coupling reactions, such as Heck reaction, Sonogashira coupling, and Suzuki coupling. Synthesis of well-defined geometry or complexity vinyl iodide is important in stereoselective synthesis of natural products and drugs. Vinyl iodides are generally stable under nucleophilic conditions. In SN2 reactions, back-attack is difficult because of steric clash of R groups on carbon adjacent to electrophilic center (see figure 1a). In addition, the lone pair on iodide donates into the ╥* of the alkene, which reduces electrophilic character on the carbon as a result of decreased positive charge. Also, this stereoelectronic effect strengthens the C-I bond, thus making removal of the iodide difficult (see figure 1b). In SN1 case, dissociation is difficult because of the strengthened C-I bond and loss of the iodide will generate an unstable carbocation(see figure 1c) In cross-coupling reactions, typically vinyl iodides react faster and under more mild conditions than vinyl chloride and vinyl bromide. The order of reactivity is based on the strength of carbon-halogen bond. C-I bond is the weakest of the halogens, the bond dissociation energies of C-I is 57.6kcal/mol, while fluoride, chloride and bromide are 115, 83.7, 72.1 kcal/mol respectively. As a result of having weaker bond, vinyl iodide does not polymerize as easily as its vinyl halide counterparts, but rather decompose and release iodide.It is generally believed that vinyl iodide cannot survive common reduction conditions, which reduces the vinyl iodide to an olefin or unsaturated alkane. However, there is evidence in literature, in which a propargyl alcohol's alkyne was reduced in presence of a vinyl iodide using hydrogen over Pd/CaCO3 or Crabtree's catalyst. Besides using vinyl iodides as useful substrates in transition metal cross-coupling reaction, they can also undergo elimination with a strong base to give corresponding alkyne, and they can be converted to suitable vinyl Grignard reagents. Vinyl iodides are converted to Grignard reagents by magnesium-halogen exchange (see Scheme 1a). The scope of this synthetic method is limited since it requires higher temperatures and longer reaction time, which affects functional group tolerance. However, vinyl iodide with electron withdrawing group can enhance rate of exchange(see Scheme 1b). Also addition of lithium chloride helps enhance magnesium-halogen exchange (see Scheme 1c). It is predicted lithium chloride breaks up aggregates in organomagnesium reagents. Vinyl iodides are synthesized by methods such as iodination and substitution reaction. Vinyl iodides with well-defined geometry (regiochemistry and stereochemistry) are important in synthesis since many natural products and drugs that have specific structure and dimension. Example of regiochemistry is whether the iodide is positioned in either alpha or beta position on the olefin. Stereochemistry such as E-Z notation or cis-trans alkene geometry is important since some transition metal cross-coupling reactions, such as the Suzuki coupling, can retain olefin geometry. In synthesis, it is useful to introduce vinyl iodide at various positions to be set up for a coupling reaction at the next synthetic step. Below are various means and methods in introducing and synthesizing vinyl iodides. The common and simplest approach to make vinyl iodide is addition of one equivalent HI to alkyne. This generally makes 2-iodo-1-alkenes or α-vinyl iodide by Markovnikov's rule. However, this reaction does not happen at good rates or very high stereoselectively. As a result, most synthetic methods often involve a hydrometalation step before addition of I+ source. Introducing an α-vinyl iodide from a terminal position of an alkyne is a difficult step. in addition, the vinyl metal intermediate can be mildly nucleophilic, for example vinyl aluminum, can form C-C bonds under catalytic conditions. However, Hoveyda group have demonstrated using nickel-based catalyst (Ni(dppp)Cl2), DIBAL-H with N-iodosuccinimide (NIS), selectively favor α-vinyl iodide with little to no byproducts. Also they observed reverse selectivity for β with Ni(PPh3)2Cl2 in their hydroalumination reactions under same conditions with little or no byproducts. The advantage of this method is that is inexpensive (and commercially available), scalable and one-pot reaction. Another method doesn't involve hydrometalation but hydroiodation with I2/hydrophosphine binary system, which was developed by Ogawa's group.