Copper-catalyzed Addition Of Arylboronic Esters To （Boc）₂O

Organocopper reagents have developed rapidly in the field of transition metal catalysis.Because of its cheap and easy to abtain,and the formation of C-Cu bond has low polarity.It can be better combined with nucleophile when participating in the formation of C-C bond reaction,to achieve the purpose of transferring carbon-containing nucleophile.This makes it stand out among many organometallic reagents,and is gradually replacing precious metals such as Ru,Rh and Pd to be the new favorite of catalytic reaction.Compared with conventional organometallic reagents（Grignard reagents,magnesium reagents,lithium reagents,zinc reagents,etc.）,organoboron reagents are convenient to synthesize,lower toxic,handy to store and with more stable physical properties,supernal functional groups tolerance.Based on the various merits of organoboron reagents,they become good substrates for the synthesis of ideal compound skeletons.In recent years,researches about copper catalysis had mainly focused on the use of organoboron reagents as substrates to complete the formation of C-C bonds.In this context,we report our findings that copper could promote the addition of arylboronic esters to（Boc）₂O under mild conditions.Moderate to high yields of methyl aryl carboxylates could be obtained after simple post-processing.Preliminary mechanistic studies revealed that an addition-elimination mechanism might be involved in this transformation.Thus this methodology provided a powerful supplement for the synthesis of aryl carboxylic acid derivatives and expanded both the concept and scope of organoboron-based copper catalysis.The main experimental conclusions are as follows:（1）The optimal reaction conditions for the esterification of arylboronic ester and（Boc）₂O were obtained.Cheap and available Cu Cl（10 mmol%）was used as the catalyst,4,4’-dimethyl-2,2’-bipyridyl（13 mmol%）as the ligand,lithium methoxide（2.5 equiv）as the base,and N,N-dimethylacetamide（DMA,0.5 m L）was the solvent,under argon atmosphere,arylboronic ester compound（0.375 mmol）and（Boc）₂O（0.25 mmol）reacted at 30℃for 6 h.After that,methyl iodide（5 equiv）was added directly and continued stirring for 2 h.The reaction yield was up to 96%.（2）It has been proved that the reaction system of arylboronic ester with（Boc）₂O had a wide range of functional group tolerance.A total of 31 arylboronic ester substrates were expanded under the optimal experimental conditions.The experimental results showed that the arylboronic esters with electron-withdrawing or electron-donating groups and even heterocyclic groups had been could react smoothly to obtain the corresponding target products.At the same time,the experimental results showed that the yield of the gram-scale reaction was up to 89%.（3）Explored the reaction mechanism.After obtaining good yields,some controlled experiments were conducted to explore the reaction mechanism,at the same time provided a theoretical basis for other researches.（4）The H,C and F spectra of the target product and the active intermediate were characterized by NMR and their structures were confirmed.