Uetake Yuta, Uwamori Masahiro, Nakada Masahisa
Department of Chemistry and Biochemistry, Faculty of Science and Engineering, Waseda University , 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan.
J Org Chem. 2015 Feb 6;80(3):1735-45. doi: 10.1021/jo5026699. Epub 2015 Jan 26.
The formal enantioselective total synthesis of nemorosone, garsubellin A, clusianone, and hyperforin is described. The catalytic asymmetric intramolecular cyclopropanation (CAIMCP) of an α-diazo ketone, a common synthetic intermediate for the above four polycyclic polyprenylated acylphloroglucinols previously reported by us, exhibited low enantioselectivity. However, CAIMCP of the corresponding α-diazo β-keto sulfone afforded the desired product in 79% yield with 84% ee. Investigation of the CAIMCP of the α-diazo β-keto sulfone demonstrated the formation of a rearrangement product in the presence of molecular sieves 4 Å, whereas, in the presence of H2O, the byproduct derived from ring-opening of the desired cyclopropane was observed. X-ray crystallographic analysis suggested that the above two products are derived from the same chiral intermediate. The product derived from ring-opening of the cyclopropane was successfully transformed to the respective synthetic intermediates for the total syntheses of nemorosone, garsubellin A, clusianone, and hyperforin, which had previously been reported by us.
本文描述了降香萜酮、加苏贝林A、clusianone和贯叶连翘素的形式对映选择性全合成。α-重氮酮的催化不对称分子内环丙烷化反应（CAIMCP）是我们之前报道的上述四种多环多异戊烯基酰基间苯三酚的常见合成中间体，该反应表现出低对映选择性。然而，相应的α-重氮β-酮砜的CAIMCP以79%的产率和84%的对映体过量（ee）得到了所需产物。对α-重氮β-酮砜的CAIMCP研究表明，在4Å分子筛存在下会形成重排产物，而在水存在下，会观察到由所需环丙烷开环产生的副产物。X射线晶体学分析表明，上述两种产物源自相同的手性中间体。由环丙烷开环产生的产物成功转化为我们之前报道的降香萜酮、加苏贝林A、clusianone和贯叶连翘素全合成的各自合成中间体。
