Studies On Selective Acetoxylation And Arylation Of O-carboranes Via B-H Activation

Carboranes are a class of polyhedral boron hydride clusters with 3D aromaticity.Owing to their unique photoelectric and biochemical activities,o-carborane derivatives have significant applied prospects in boron neutron capture therapy?luminescent materials and coordination chemistry.Therefore,exploring the methodologies of functionalized o-carborane that was in great importance to promote the development of carborane chemistry.However,o-carborane have ten B-H bonds with similar chemical reactivity.Therefore,how to achieve specific selective functionalization of B-H vertices that has been one of the goals pursued by boron chemists.Based on the calcd results that the electrophilic reactivity of 10 B-H bonds in o-carborane is reduced in the following order:B?8,9,10,12?>B?4,5,7,11?>B?3,6?.In recent years,the chemists have been achieved related functionalization of B?8,9,10,12?-H,B?4,5,7,11?-H and B?3,6?-H via diverse strategies successively.The detailed results were as shown bellow:?a?The selective functionalization of B?8,9,10,12?-H was well developed by trasition metal catalyzed electrophilic B-H activation;?b?By introducing a directing group?DG?on cage carbon,the selective functionalization of B?4,5,7,11?-H with weak electrophilic activity had been achieved;?c?The electron-deficient B?3,6?-H vertices could be easily activated by electron-rich metal center.For the three types of B-H vertices in o-carborane,there remained much difficulty although researchers have successively achieved some related reports.Therefore,it is of great significance to develop efficient method to achieve direct functionalization of specific B-H vertices of o-carborane to promote the development of o-carborane chemistry.Based on this point,this paper carried out research on“the selective acetoxylation and arylation of o-carborane via B-H activation”,the main contents include the following four parts:?1?The selective acetoxylation of o-carboraneA selective mono-/tetraacetoxylation of o-carboranes with acetic acid via cross dehydrogenative coupling of cage B-H/O-H bonds has been developed,and a series of mono-and tetra-acetoxylated o-carboranes have been synthesized with moderate to good yields as well as good selectivity.Mechanism studies indicated that the acetoxyl originates from acetic acid directly,and kinetic isotope experiments demonstrated that the cleavage of the O-H bond is not involved in the rate-determining step.On the basis of the mono-acetoxylation,the coordination effect of copper with the B-H bond would suppress multi-acetoxylation.In the presence of acetic anhydride,the acetoxyl would react with Pd?OAc?₂ to form palladacyclic intermediate.Subsequently,after three more cycles,the tetraacetoxylation product would be acquired.This is the first example to utilize electronic effect to form the B-O bond via cross dehydrogenative coupling of B-H and O-H bonds.?2?The selective B?4?Suzuki-type arylation of o-carboraneBy changing the charge distribution of boron vertices via introducing an amide bearing the strong withdrawing effect on cage B?9?,the B?4?-H and B?5?-H bonds were polarized.9-benzamide-o-carborane and phenylboronic acid were selected as model substrates,the selective B?4?arylation of o-carboranes via Suzuki-Miyaura coupling has been developed with the help of the induction and position effect of the amide.The Suzuki product had been proved to be further transformed to a novel kind of tri-substituted nido-carborane fused oxazole with potential application in boron neutron capture therapy,organometallic as well as coordination chemistry.?3?The selective B?3,6?arylation of o-carboraneBased on the fact that the electron-deficient B?3,6?-H vertices could be easily activated by electron-rich metal centers,we introduced the strong?-donating ability of NHCs to mediate the density of the center of Pd and to activate B?3,6?-H.We have achieved B?3,6?-arylation in o-carborane by using the in formed Pd-NHC catalytic system with iodobenzene.The Pd-NHC complex could be formed in situ and thus prevent the deprotonation and deboronation of o-carborane.The reduced electrophilicity of Pd-NHC would inhibite the electrophilic palladation with B?8,9,10,12?-H bonds.The B?3,6?-H was activated and a series of o-carboranes derivatives anchored with active groups have been synthesized under mild conditions.This work offers an efficient protocol for selective activation of B?3,6?-H bonds and has an important effect on promoting the application of o-carborane derivatives in related disciplines.?4?The selective B?3/6?alkenylation of o-carboraneDiphenylacetylene and o-carborane as the model substrate,the strong?-donating ability of NHCs to mediate the density of the center of Pd and to activate B?3/6?-H.An efficient in situ Pd-NHC catalytic system for regioselective alkenylation of B?3/6?-H bonds of o-carborane under the air has been developed for the first time.Under stepwise method,a series of unsymmetric o-carboranes anchored with active groups have been synthesized with moderate to good yields.The reaction has good universality and provide theoretical guidance for its application in medicinal chemistry and luminescent materials.