Published papers

An iridium-catalyzed reductive olefination of N-methoxyamides in a one-pot process is reported. The method begins with hydrosilylation of an amide carbonyl. The O-Si bond in the resulting N,O-silylacetal is then cleaved under mild conditions with TBACl to give an aldehyde, which undergoes various types of Wittig reactions in a highly stereoselective manner. The method is successfully applied to the construction of dienoates, which are widely observed in biologically active polyketides.

The control of the selectivity is a central issue in the total synthesis of complex natural products. In this paper, we report the total synthesis of (±)-keramaphidin B and (±)-ingenamine. The key reaction is a DMAP-catalyzed Diels-Alder reaction in which the regioselectivity is completely controlled by dynamic crystallization. Our synthesis successfully demonstrates that dynamic crystallization can be an alternative when the selectivity is not controlled by either kinetic or thermodynamic approaches in solution.

Natural linear polyamines play diverse roles in physiological processes by interacting with receptors at the cellular level. Herein, we describe the stereodivergent synthesis of oligopyrrolidines, which are conformationally constrained polyamines. We synthesized dimeric and trimeric 2-oxo-oligopyrrolidines using an iterative coupling strategy. The key to our success is an iridium-catalyzed trans/cis-selective nucleophilic addition and subsequent threo/erythro-stereoselective reduction. The synthesized pyrrolidines show varying cytotoxicities against a human cancer cell line depending on the number of rings and their stereochemistry.

The total synthesis of lobatamides A (1 a) and C (1 c) via a common bislactone intermediate is reported. The allylic aryl moiety including a trisubstituted Z-olefin was constructed by hydroboration of a 1,1-disubstituted allene and subsequent Migita-Kosugi-Stille coupling. Although the seco acid proved to be highly unstable even in the presence of weak bases, Zhao macrolactonization under acidic conditions via the α-acyloxyenamide successfully provided the common bislactone intermediate. Hydrozirconation-iodination of the terminal alkyne and subsequent copper-mediated coupling with primary amides proceeded successfully in the presence of the sensitive bislactone framework. The developed synthetic route enables the late-stage installation of enamide side chains, which are crucial structures for V-ATPase inhibition.

An iterative approach to the synthesis of polyol fragments of polyketides is developed based on an iridium-catalyzed hydrosilylation of morpholine amides. Each round includes an aldol reaction using either morpholine amide or morpholine ketoamide and iridium-catalyzed hydrosilylation of the morpholine amide to give the new aldehyde, which is used for the next round. This strategy is successfully applied to the concise synthesis of the C11 to C21 polyol fragment of sekothrixide.