1,2-苯基异噁唑为氮源的铜催化苯乙烯不对称硼胺化

Copper-Catalyzed Enantioselective Aminoboration of Styrenes with 1,2-Benzisoxazole as Nitrogen Source

报道了一种以手性亚砜膦配体/铜络合物为催化剂的苯乙烯不对称硼胺化反应.该方法以联硼酸频哪醇酯(B2pin2)为硼源,以商业可得的1,2-苯基异噁唑为亲电氮源,合成了一类β-氨基硼酸酯类化合物,目标产物可以方便地转化为β-硼酯伯胺化合物,为结构多样的手性氨基化合物合成提供了一条技术途径.

Organoboron compounds are important intermediates in organic synthesis because of their high utilities for C—C and C—X bond formations.Transition metal-catalyzed borylative difunctionalization of alkenes,which can simultaneously introduce C—B,C—C or C—X bonds,could directly construct highly functionalized organoboron in one step.Among these reactions,copper catalyzed enantioselective aminoboration of styrenes is an efficient approach to generate enantiorichedβ-aminoboronate which is a class of useful chiral compounds.In this work,employing styrenes as substrates,1,2-benzisoxazole as an electrophilic primary amine source,bis(pinacolato)diboron(B2pin2)as boron source and LiOCH3 as base,an enantioselective Cu-catalyzed aminoboration of styrenes by using a chiral sulfoxide-phosphine(SOP)ligand was developed,and a board range of chiralβ-aminoalkylboranes,which could be readily converted to a class of valuableβ-hydroxylalkylamines,were accessed with high yields and ee values.A general procedure for this aminoboration of styrenes is described in the following:in a glove box,CuI(0.05 mmol),chiral sulfoxide phosphine ligand L1(0.06 mmol),and 2 mL of anhydrous tetrahydrofuran were added into a flame-dried tube.The resulting mixture was stirred at room temperature for 30 min.Then bis(pinacolato)diboron(B2pin2)(0.75 mmol),LiOCH3(1.25 mmol),styrene 1(0.5 mmol),1,2-benzisoxazole(0.75 mmol)and another 2 mL of THF were added into the reaction system in sequence.The reaction tube was removed out from the glove box and stirred at 20℃for 12 h.After the reaction was finished,the NMR yield was firstly determined with dimethyl terephthalate(9.7 mg,0.05 mmol)as internal standard,then,the crude product was recovered and purified with a preparative TLC which was alkalized with triethylamine to give the desiredβ-aminoboronates in moderate to good yields(47%~84%)and enantioselectivities(81%~99%).To demonstrate the utility of this reaction,β-boronate primary amine could be easily obtained by removing the Schiff base group ofβ-aminoboronate 3 under the methanol solution of hydroxylamine hydrochloride,which could be further oxidized to give corresponding chiralβ-amino alcohol in moderate yield(48%).