Iridium-Catalyzed Enantioselective C(sp~3)-H Borization Of Cyclobutanes

Optically active cyclobutanes are widespread subunits in numerous natural products and pharmaceuticals.In addition,the significance of these frameworks has also been demonstrated by their frequent use in synthetic chemistry.Therefore,it has high practical and economic value,which provides a powerful impetus for efficient and highly stereoselective synthesis methods.Traditionally,the use[2+2]cycloaddition,ring expansion of cyclopropanes,cyclic extension of propylene oxide,ring shrinkage of a five-or six-member ring,C-H bond activation and intramolecular ring closure of linear compounds provides efficient methods to prepare these frameworks.However,these methods require pre-functionalization of the substrates.The atom-and step-economic approaches in these area remains sporadic..Cycloalkyl boronic acid and its derivatives are versatile synthons owing to their flexibility,stability widely application in C-O,C-N,C-C,C-X bonds forming reaction.We herein present the first example of Ir-catalyzed C?sp³?-H borization of cyclobutanes using chiral bidentate boryl ligands,providing a vast array of chiral cyclobutyl boronates in good to excellent enantioselectivities.In the current work,we have developed a highly enantioselective C?sp³?-H borization of cyclobutene by using this[Ir?COD?Cl]₂ as a catalyst to achieve the chiral cyclobutane.We have screened a series of conditions such as catalyst,ligand,solvent,temperature,catalyst dosage,B₂pin₂dosage,and reaction time.Finally,the optimum conditions for Iridium-catalyzed enantioselective C?sp³?-H borization of cyclobutanes are determined:1.0 equiv.substrate 1aa,1.5 equiv.B₂pin₂,1mol%[Ir?COD?Cl]₂,0.5 mol%CBL,hexane as solvent,reacted at 80 ^oC for 12 h.84%yield and 95:5 e.r.value are obtained.We have developed a series of reaserch for 21different substrates.Its yield was 54-88%,e.r.value was 86:14-96:4.We have developed a series of derivatization of products including potassium trifluoroborate,furanization,ethylene,hydroxymethylation and gram-scale reactions.yield of reactions was 40-95%and the absolute configuration of the product was?1S,2R?.we proposed a reasonable catalytic cycle mechanism to explain the stereoselectivity of cyclobutane products.Substrates and products was subjected to a series of tests and characterization,including borate product optical rotation test,hydrogen spectrum?¹H NMR?,carbon spectrum(¹³C NMR),boron spectroscopy(¹¹B NMR)and high resolution mass spectrometry.