Asymmetric chlorolactonization reaction of alkenes is one most important reactions in organic chemistry due to the resulting chiral3,4-Disubstituted is ocoumar in is the fundamental unit of many compounds that possess a wide spectrum of biological activity.We have developed a more practical and efficient catalytic asymmetric chlorolactonization of styrene-type carboxylic acids with DCDMH using C3-symmetrical cinchonine-squaramide(CSCS) as organocatalyst.Series of chiralchloro substituted isochroman-1-ones were obtained in excellent yields(up to 99%)and enantioselectivities(up to 99% ee).To the best of our knowledge,the results are the best ever achieved.Moreover,in our case,the asymmetric hctonization is stereospecific,with use of terminal alkenes forming 5-exo products,while 6-endo chloro substituted isochroman-1-ones were obtained in higheree values when internal alkenes was used in the reaction.Furthermore,the nature ofcarboxylic acid has significant influence on the enantioselectivity.The reaction of carboxylic acids bearing an electron-withdrawing group on the phenyl ring afforded the corresponding products in higher ee.Gratefully,in this asymmetric transformation,our easily available C3-symmetrical CSCS organocatalyst can berecovered and reused for six cycles without losing the activity and enantioselectivity.The methodology has provided a convenient approach for the synthesis of optical pure isochro man-1-one derivatives.In addition,further studies indicated that the optical pure isochroman-1-one products exhibit potent anti-HIV activity.
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