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Boric acid reactivity control system
The Suzuki-Miyaura reaction is a palladium or nickel-catalyzed cross-coupling between boric acid or borate and an organic halide or organic pseudohalide. (Miyaura, A. Chem. Rev., 1995) This cross-coupling transformation is an effective method to form C-C bonds in the synthesis of complex molecules. This reaction is tolerant to functional groups and has become increasingly common and widespread in coupling organic compounds (Barder, 2005; Billingsley, 2007; Littke, 2000; Nicolaou, 2005).
It is well known that boric acid is sensitive to many common reagents. (Hall, 2005; Tyreit, 2003) Therefore, boric acid functional groups are usually introduced in the last step of the synthesis of structural units. However, many methods for doing so (boron hydride, capturing organometallic reagents with trimethyl borate, etc.) are not resistant to various common functional groups such as alcohols, aldehydes, ketones, alkynes and olefins. This makes the synthesis of complex boric acid structural units very challenging. In contrast, organotoxanone is significantly tolerant to a variety of reaction conditions, and is often carried into complex coupling partners through multiple steps. As a result, despite well-known disadvantages including toxicity and high molecular weight, organotin has been widely used in the synthesis of complex molecules (De Souza, MVN, 2006; Pattenden, G., 2002; Hong, B.-C., 2006). And by-products that are difficult to remove. The ability to similarly carry protected boric acid through multi-step synthetic sequences can greatly increase its utility and expand its scope of application.
One of the research areas of Suzuki-Miyaura reaction is the development of protecting groups for boric acid functional groups. A compound comprising a protected boric acid and another functional group can undergo chemical conversion of another functional group without chemically converting boron. The protecting group is then removed (deprotected) to give free boric acid, which can be subjected to a Suzuki-Miyaura reaction to crosslink the compound with an organic halide or organic pseudohalide.
In one example of a boric acid protecting group, each of the two B-OH groups is converted to a borate group (> 6-0-R) or a boramide group (> 6-NH-R) Where R is an organic group. Organic groups can be removed by hydrolysis to provide free boric acid. Current data indicate that metal transfer between boric acid and Pd (II) requires the formation of an electronically activated anionic borate complex and / or a hydroxyl p2-bridged organoborate-Pd (II) intermediate. Both mechanisms require Lewis acidic empty boron orbitals. It is known that a bidentate ligand containing a strong electron donor heteroatom may inhibit cross-coupling of organoboron compounds by reducing the Lewis acidity of the sp2-hybridized boron center. Using this effect, some selective cross-couplings with halogen-containing boron-protected organoborane have been reported recently. (Deng, 2002; Hohn, 2004; Holmes, 2006; Noguchi, 2007). Examples of the protecting group used in these selective reactions include pinacol esters (borates) and 1,8-diaminonaphthalene (boramides). However, the heteroatom-boron bonds in these protected compounds tend to be strong. The relatively harsh conditions required to cleave these ligands are often incompatible with complex molecular synthesis.
In another example of protected boric acid, a boron-containing compound is converted to a tetracoordinate anion, such as [R-BF3], where R represents an organic group. Compounds containing these protecting groups exist in the form of a salt with a counterion, such as K + or Na. These anionic compounds have been reported to effectively inhibit boron reactions during chemical transformations such as nucleophilic substitution, 1,3-dipolar cycloaddition, metal-halogen exchange, oxidation, epoxidation, dihydroxylation, carbonylation and Alkenylation (Wittig or Horner-Wadsworth-expression response). (Molander, 2007) Boron itself is not protected by the Suzuki-Miyaura reaction, but can be used directly in coupling transformations. In the purification of boric acid used in the Suzuki-Miyaura reaction, another class of tetracoordinate boron anions [R-B (OH) 3T] has been reported. (Cammidge, 2006) Like trifluoroborate anions, trihydroxyborate anions are reactive in the Suzuki-Miyaura reaction.
Each of these typical boric acid protection strategies has some disadvantages. Borates and boron amides protect boron from a variety of reaction conditions, including Suzuki-Miyaura reaction conditions.
However, the harsh conditions required for deprotection
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