The sequential Overman/Claisen rearrangement: Development and application to total synthesis of (+)-neostenine

Nakayama Yasuaki, Maeda Yuichiro, Kotatsu Masayuki, Sekiya Ruriko, Ichiki Masato, Sato Takaaki, Chida Noritaka

doi:10.24496/tennenyuki.57.0_oral1

<p>Our research group has been exploring practical strategies to obtain biologically active natural products by combination of chirality transfer reactions and sigmatropic rearrangements. In this talk, we will report development of sequential Overman/Claisen rearrangement of cyclic orthoamide 7, which derived from easily available tartaric acid. A solution of 7 and tert-butylbenzene in the presence of BHT (2,6-di-tert-butylhydroxy- toluene) was heated to 180 °C in a sealed tube, giving rearranged product 10 through α-hydroxyimidate 8 (orthoamide-type Overman rearrangement). The resulting allylic alcohol 10 was then subjected to the Johnson–Claisen rearrangement in one-pot sequence (Scheme 2). It is noteworthy that the orthoamide-type Overman rearrangement successfully differentiated the two hydroxyl groups derived from L-tartaric acid without use of protecting group manipulations. In addition, all of the performed rearrangements proceeded in a completely diastereoselective fashion through a chair-like transition state to give 11 as a single diastereomer.</p><p> To demonstrate the practical utility of the Overman/Claisen rearrangement, we applied this methodology to the total synthesis of (+)-neostenine (6, Scheme 5). The Overman/Claisen rearrangement of cyclic orthoamide 25 afforded 26 in complete diastereoselectivity. The first enantioselective total synthesis of (+)-neostenine (6) was successfully accomplished from 26(Scheme 6, 7).</p>

The sequential Overman/Claisen rearrangement: Development and application to total synthesis of (+)-neostenine

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