Dummy groups

Alkenylboronic acids and esters have been prepared by thermal or catalyzed hydroboration of 1-alkynes with catecholborane (HBcat), pinacolborane (HBpin), or dihaloboranes 41-43, followed by hydrolysis to boronic acids or alcoholysis to boronic esters. A convenient alternative to improve chemo- and regioselectivity is the hydroboration of alkynes with dialkylboranes. For selective removal of dummy groups, the oxidation of two cyclohexyl groups was conduced by treatment of l-alkenyl(dicyclohexyl)borane intermediates with Me3N-0 (Equation (7)).116 The... 

Scheme 2 (a) Chemoselectivity in arylations with unsymmetric salts, (b) Common/advanced dummy groups... 

In metal-catalyzed reactions, steric factors usually control the selectivity, and hindered groups such as 2,4,6-trimethylphenyl (mesityl) and 2,4,6-triisopropylphenyl (TRIP) are very useful dummy groups [40, 49-51]. In the absence of steric effects, the most electron-donating aryl group is generally transferred with moderate selectivity. Common dummy groups, as well as more advanced alternatives such as cyclophane- and uracil-derived dummies [44, 52], are depicted in Scheme 2b. 

Carroll and coworkers developed a metal-free phenylation of anilines with diphenyUodonium trifluoroacetates in DMF at 130 °C [91]. A thorough chemoselectivity study with anilines and diaryliodonium triflates was later performed by the Olofsson group, revealing that electronics are more important than sterics in this transformation, and hence that both the mesityl and the trimethoxyphenyl groups are suitable dummy groups [27]. Carbazoles were efficiently aiylated in toluene at 50 °C in the presence of BuOK [92], and anilines could be obtained in aqueous ammonia at 80 °C (Scheme 5a) [93]. 

In 2011, Olofsson s group developed an efficient synthesis of diaiyl ethers that was applicable to a large substrate scope (Scheme 8a). The reactions were performed in THF or toluene at room temperature or 40 °C, and the mild conditions proved compatible with racemization-prone a-amino acid derivatives, which could be arylated without erosion of the enantiomeric excess [119]. The chemoselectivity in phenoxide arylation with unsymmetric diaiyUodonium salts was subsequently investigated, and the 4-methoxyphenyl moiety was found to be a suitable dummy group, resulting in completely chemoselective transfer of the other aryl group [27, 53]. A similar transformation was reported later, in which diaiyUodonium salts with a 2,4-dimethoxyphenyl dummy group were utilized in acetonitrile with potassium carbonate as base [120]. 

Oh and coworkers reported a room temperature arylation of a-substituted malonates with NaH in DMF in 1999 [183]. These conditions were recently applied in the chemoselective arylation of a cychc p-ketoester with an unsymmetric, boron-substituted diaryliodonium salt, leading to a product with a suitable handle for further functionalizations [82]. Olofsson and coworkers performed a detailed chemoselectivity investigation with unsymmetric iodonium salts in the a-arylation of malonates, which resulted in the discovery of an anti ort/io-effect and the conclusion that both mesityl and anisyl moieties are suitable dummy groups in these reactions [27]. This fact was utilized by the group of Shibata, who developed a pentafluorophenylation of cyclic p-ketoesters with unsymmetric TRIP salts under mild conditions (Scheme 14a) [81]. 

Asymmetric a-functionalization of carbonyl compounds with iodine(lll) reagents is discussed in Chap. 639 and in a recent review [178], and is only briefly covered here. Asymmetric a-arylations with chiral diaryliodonium salts have proven to be difficult to achieve, both because of complicated synthetic routes to chiral, unsymmetric salts with suitable dummy groups, and because of the modest enantioselectivities observed in the arylations [188, 189]. Ochiai and coworkers reported the only successful example to date, where 1,1 -binaphthyl-derived iodonium salts gave chemo- and enantioselective arylation of p-ketoesters in up to 53% ee (see Scheme 7 in Chap. X) [190]. 

To get around this problem, we nse a clever trick. We use a starting amine that already has two dummy groups on it ... 

And we choose onr dummy groups so that they are easily removable after we alkylate. So, we first alkylate, and then we remove the dummy groups ... 

In this step, the dummy groups are removed, generating the desired product. 

Using a QM method, optimize the central fragment, QMi, with the appropriate dummy groups. 

Optimize the whole system using a MM potential but keeping the geometry of the central fragment (minus dummy groups) fixed at its previously optimized value. 

Figure 3 A schematic diagram of the dummy group method of Bersuker et al [27] applied to an alkane chain. QMi and QM2 are the central QM and the ligand QM fragments, respectively.

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