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(−)-Cylindrocyclophane A is a 22-membered C2-symmetric [7.7]paracyclophane that bears bis-resorcinol functionality and six stereocenters. We report a synthetic strategy for (−)-cylindrocyclophane A that uses 10 C−H functionalization reactions, resulting in a streamlined route with high enantioselectivity and efficiency (17 steps). The use of chiral dirhodium tetracarboxylate catalysis enabled the C–H functionalization of primary and secondary positions, which was complemented by palladium-catalyzed C(sp2)–C(sp2) cross-couplings, resulting in the rapid formation of the macrocyclic core and all stereocenters with high regio-, diastereo-, and enantioselectivity. The use of a late-stage palladium-catalyzed fourfold C(sp2)–H acetoxylation installed the bis-resorcinol moieties. This research exemplifies how multilaboratory collaborations can produce substantial modernizations of complex total synthesis endeavors.more » « lessFree, publicly-accessible full text available November 8, 2025
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Wright, Austin C.; Stoltz, Brian M. (, Chemical Science)Herein we report our recent progress toward the enantioselective total synthesis of the diterpenoid natural products curcusones A–D by means of complementary Stetter annulation or ring-closing metathesis (RCM) disconnections. Using the latter approach, we have achieved the concise construction of the 5–7–6 carbocyclic core embedded in each member of the curcusone family. Essential to this route is the use of a cross-electrophile coupling strategy, which has not previously been harnessed in the context of natural product synthesis.more » « less
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Wright, Austin C.; Lee, Chung Whan; Stoltz, Brian M. (, Organic Letters)
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Wright, Austin C.; Du, Yun Emily; Stoltz, Brian M. (, The Journal of Organic Chemistry)
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