Pd-Catalyzed Aerobic Oxidative Heck Cross-Coupling for the Straightforward Construction of Indole δ-Lactams

摘要

class="head no_bottom_margin" id="sec1title">IntroductionThe leuconoxine subfamily of aspidosperma-derived monoterpene indole alkaloids (e.g., >1–>8 in ) was isolated from the plants of the genus Leuconotis (Apocynaceae) (, , ). These natural products possess a unique diaza-[5.5.6.6]-fenestrane structural motif that is extremely rare in indole natural products. The latex of the plants was used traditionally to treat worm infections and yaws diseases. Owing to their high structural complexity and interesting biological properties, these and the related natural products have attracted much attention in the synthetic community. The efficient construction of the δ-lactam-containing (, highlighted in red) ring-fused system has been the key issue of intensive synthetic efforts. The reported methods include free radical-induced cyclization (, , , , , ), Heck cross-coupling (, ), and Friedel-Crafts reactions (, , href="#bib53" rid="bib53" class=" bibr popnode">Zhong et al., 2012, href="#bib55" rid="bib55" class=" bibr popnode">Zhong et al., 2014, href="#bib54" rid="bib54" class=" bibr popnode">Zhong et al., 2015, href="#bib24" rid="bib24" class=" bibr popnode">Liang et al., 2016, href="#bib52" rid="bib52" class=" bibr popnode">Zheng et al., 2018) at C20−C21; the amidation of ester (href="#bib46" rid="bib46" class=" bibr popnode">Xu et al., 2013, href="#bib47" rid="bib47" class=" bibr popnode">Xu et al., 2015, href="#bib34" rid="bib34" class=" bibr popnode">Nakajima et al., 2010, href="#bib14" rid="bib14" class=" bibr popnode">Higuchi et al., 2015, href="#bib23" rid="bib23" class=" bibr popnode">Li et al., 2015) or oxidative amidation of alcohol (href="#bib35" rid="bib35" class=" bibr popnode">Pfaffenbach and Gaich, 2015) at N1−C2; and the transannular cyclization (href="#bib48" rid="bib48" class=" bibr popnode">Yang et al., 2014a, href="#bib49" rid="bib49" class=" bibr popnode">Yang et al., 2014b, href="#bib6" rid="bib6" class=" bibr popnode">Dagoneau et al., 2016) of an aryl amide with ketone functionality via N1−C21.href="/pmc/articles/PMC6637253/figure/fig1/" target="figure" rid-figpopup="fig1" rid-ob="ob-fig1">class="inline_block ts_canvas" href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=6637253_gr1.jpg" target="tileshopwindow">target="object" href="/pmc/articles/PMC6637253/figure/fig1/?report=objectonly">Open in a separate windowclass="figpopup" href="/pmc/articles/PMC6637253/figure/fig1/" target="figure" rid-figpopup="fig1" rid-ob="ob-fig1">Figure 1Selected Structures of Leuconoxine Subfamily