The asymmetric [2 + 2] cycloaddition reactions of alkenes with alkynes are interesting as it has provided a powerful method for the construction of fused and strained cyclobutenes with multiple chiral centers. In this paper, we report the establishment of a dual catalysts system comprising nickel and zinc, which allowed the asymmetric [2 + 2] cycloaddition reactions of azabenzonorbornadienes with terminal alkynes in good yields and excellent enantioselectivities.Alkynes and alkenes are versatile building blocks in organic synthesis, and the transitional metal catalyzed reactions of alkynes and alkenes represent the diversity of organic reactions. To the reactions of bicyclic alkenes, the hydroalkynylation, [1] nucleophilic ringopening, [2] cycloaddition, [3] and some other reactions were well documented ( Figure 1). [4][5][6][7][8] Clearly, the development of new transitional metal catalyst system that with good chemoselectivity for the above mentioned reactions is of highly desirable and significant challenge. Among these reactions, the asymmetric [2 + 2] cycloaddition reaction seemed to be most intriguing as fused and strained cyclobutenes are generated with multiple chiral centers. The group of Cheng has taken the lead in the [2 + 2] cycloaddition reaction of bicyclic alkenes, [3a,c] and has first demonstrated the cycloaddition reaction of azabenzonorbornadiene with terminal alkyne, which featured the using of zinc powder to reduce the corresponding nickel or cobalt precursor, the synthetic application of the products were explored by ring-expansion to give cyclooctatetraene derivatives. By employing ruthenium catalyst, the group of Tam has further studied the scope of alkynes by using internal electron-deficient alkynes including alkynyl halides, alkynyl esters, and alkynyl phosphonates. [3b,9] In order to develop an asymmetric fashion, our group has used an iridium catalyst assisted by (R)-xylyl-Phanephos as chiral ligand, which has demonstrated excellent chiral control ability, but the reaction yields were generally moderate. [10] Recently, we have proved that using of Lewis acids were extremely effective to the activation of the aza-and oxa-bicyclic alkenes. [11] We envisioned that the similar co-catalyst system comprising a chiral nickel catalyst and Lewis acid could have a good performance in the asymmetric [2 + 2] cycloaddition reactions of azaben-Figure 1. Divergent reactions of heterobicyclic alkenes with alkynes (X=O or N-alkyl, R 1,2 = alkyl).
The asymmetric [2 + 2 + 2] cycloaddition reactions of 1,6-enynes and oxabenzonorbornadienes was accomplished by using the complex of [Rh(COD) 2 ]BF 4 and (R)-Xyl-P-Phos as chiral catalyst. A range of 1,6-enynes and oxabenzonorbornadienes were well tolerated in the cycloaddition reaction, which afforded various polycyclic products with asymmetric quaternary carbon centers generally in excellent enantioselectivities.
The asymmetric ring opening reactions of bicyclic alkenes with boronic acids were accomplished by using a highly active palladium/zinc co-catalytic system that was suitable for both azabenzonorbornadienes and oxabenzonorbornadienes, which were transformed to the corresponding chiral hydronaphthalene products in high yields (up to 99%) and high optical purities (up to 98% ee). The reaction protocol is general and mild and displays good functional group tolerance.
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