Key Laboratory of Drug-Targeting and Drug Delivery System of the Ministry of Education and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
College of Pharmacy, Third Military Medical University, Chongqing, 400038, China.
Angew Chem Int Ed Engl. 2021 Jun 14;60(25):13913-13917. doi: 10.1002/anie.202102842. Epub 2021 May 11.
Here we report that the chemoselective activation of Tsuji's 2-(cyanomethyl)allyl carbonates to generate the palladium-trimethylenemethane 1,3-dipoles via a deprotonation strategy can be realized in the presence of Morita-Baylis-Hillman carbonates from substantial activated ketones. The following S 2'-addition enables the formation of new 1,3-dipole species having an activated alkene moiety through a second deprotonation process, which then undergo cascade [1+2]/[3+2] annulations to furnish complex bicyclic [3.1.0]hexane frameworks having three contiguous quaternary stereogenic centers with good to excellent enantioselectivity. Moreover, by using benzoyl aldehyde-derived substrates, a [1+4]/[3+2] annulation sequence is similarly developed to produce fused cyclopenta[b]furan architectures.
在这里，我们报告了在 Morita-Baylis-Hillman 碳酸酯存在下，通过脱质子策略，可以实现 Tsuji 的 2-(氰甲基)烯丙基碳酸酯的化学选择性活化，生成钯-三甲烯甲烷 1,3-二极体，该碳酸酯来自大量活化的酮。随后的 S 2'-加成通过第二次脱质子过程形成具有活化烯键部分的新的 1,3-二极体物种，然后通过级联 [1+2]/[3+2]环加成反应生成具有三个连续的季立体中心的复杂双环[3.1.0]己烷骨架，具有良好到优异的对映选择性。此外，通过使用苯甲酰基衍生的底物，同样可以开发出[1+4]/[3+2]环加成序列，以产生稠合的环戊[b]呋喃结构。
