Transferring iodine: more than a simple functional group exchange in organic synthesis

Abstract

Some synthetic features of the IPy 2 BF 4 reagent are presented. Among others, its utility to promote unusual 'carbon-carbon' coupling processes will be discussed. Furthermore, the unique iodinating ability of this reagent towards aromatic and other unsaturated systems will be summarized.The rich chemistry of the carbon-iodine bond has made it a particularly rewarding synthetic tool of routine use for the purpose of functional group interconversion. Iodinated compounds are also credited as helpful diagnostic aids when the radioactive isotopes of the element are used [1]. Moreover, the growing presence and impact of hypervalent iodine compounds represents an additional source of interest in iodine containing reagents [2].The bis(pyridinium) iodonium (I) tetrafluoroborate (IPy 2 BF 4 ) is a stable and solid reagent, that acts as a mild source of iodonium ions towards different types of unsaturated compounds, as it will be shown in this article. Initial efforts were devoted to the development of a methodology that can be useful to accomplish vicinal iodofunctionalization of an alkene. Thus, when the reagent is mixed in CH 2 Cl 2 with an alkene and a nucleophile the corresponding products derived from the addition of an iodine atom and the nucleophile across the double bond are formed, for instance MeOH for 1a, in Scheme 1 [3]. Usually, an acid is required to neutralize the supply of pyridine molecules from the iodinating reagent, avoiding the formation of adducts, such as 1b, that incorporate pyridine as a nucleophile through a competition process for the capture of the intermediate iodonium ion. In this regard, tetrafluoroboric acid is very useful due to the low nucleophilic character of the BF 4 ¹ counteranion. When simply the reagent, the acid and the alkene are mixed at low temperature, a clean, regio-and stereoselective iodofluorination takes place [3,4], as also depicted in Scheme 1 for the case of 1c.*Lecture presented at the 5th International Conference on Heteroatom Chemistry (ICHAC-5), London, Ontario, Canada, 5-10 July 1998, pp. 369-512. Scheme 1Addition is the usual outcome of the reaction of IPy 2 BF 4 with alkenes. However, starting from vinylsilanes an easy substitution process occurs, resulting in a very efficient and simple procedure for the iodo-silicon exchange from E 2a, and Z 2b monosubstituted trimethylsilylalkenes, giving rise stereospecifically to the formation of compounds 3a and 3b, respectively (Scheme 2) [5]. Otherwise, this is known to be an elusive transformation.Interestingly, the reagent is also an efficient iodinating agent promoting addition reactions of alcohols to the same alkenylsilanes furnishing compounds 4 (Scheme 3), by simply running the transformation in the presence of the corresponding alcohol as cosolvent [6]. The resulting adducts can be dehydroiodinated with the tertiary base 1,8-diazobicyclo[5.4.0]undec-7-ene (DBU), giving the stereochemically well-defined trisubstituted enol ethers, in a stereospecific manner.The same sequence, but requiring t-butyldimethy...

New Pyrazolopyrimidine Inhibitors of Protein Kinase D as Potent Anticancer Agents for Prostate Cancer Cells

“…Aminolysis with ammonia and methyl amine at room temperature provided the nucleophilic aromatic substitution product 5 [41] which was brominated to give the pyrazolopyrimidine 6 [40]. Attempts at forming the 3-iodo derivative with iodine [41], N -iodosuccinimide [42], or Barluenga's reagent [43] were not successful. A selective Suzuki coupling at the 3-position with aromatic boronic acids R 2 B(OH) 2 led to the chlorinated derivative, and the chlorine group was reduced by a catalytic hydrogen transfer process to give product 1 with R 4  = H ( Fig.…”

Synthesis of 2-N,N-Dimethylaminomethyl-2,3,3a,12b-tetrahydrodibenzo-[b,f]furo[2,3-d]oxepin Derivatives as Potential Anxiolytic Agents

“…When the cyclization step was performed with I 2 under basic reaction conditions the expected tetrahydrofuran derivatives 4a and 5a were obtained in satisfactory yield (80%), although the diastereoselectivity outcome of the cyclization was somewhat lower (4a : 5a; 90 : 10). The use of IPy 2 BF 4 (bis(pyridine)iodonium(I) tetrafluoroborate; Barluenga's reagent) 16) or MCPBA resulted in slightly increased yields (92% for 4c, 5c and 99% for 4a, 5a) but not diastereoselectivity at all. Remarkable is the fact that the cyclization reaction with Barluenga's reagent reached completion in two minutes affording the expected products in nearly quantita- Chart 1 Fig.…”

Halogen Bonding in Solution

“…[Bis(pyridine)iodine] + and [bis(pyridine)bromine] + salts are useful reagents for organic synthesis [90]. As sources of electrophilic halogens, they are applicable for I + or Br + transfer reactions, in, for example, the halogenation of alkenes, alkynes, and aromatics, in oxidations, and in halocyclizations [76,90,91].…”

“…As sources of electrophilic halogens, they are applicable for I + or Br + transfer reactions, in, for example, the halogenation of alkenes, alkynes, and aromatics, in oxidations, and in halocyclizations [76,90,91]. The earliest [bis (pyridine)iodine] + and [bis(pyridine)bromine] + complexes were generated in situ from chloroform solutions of pyridine and AgNO 3 upon addition of Br 2 [92] or INO 3 [93].…”