Total Synthesis of Lyconesidine B, a Lycopodium Alkaloid with an Oxygenated, Amine-Type Fawcettimine Core

This report describes the total synthesis of the complex, oxygenated tetracyclic alkaloid, lyconesidine B. The key synthetic challenge involves diastereoselective generation of a decahydroquinoline ring with a quaternary carbon at the angular position via domino cyclopropanation, ring-opening, and reduction. Another crucial step is the domino ene-yne metathesis involving a quaternary ammonium ion, leading to the construction of a decahydroazaazulen framework

Construction of the ACDE Ring System of Calyciphylline A-type Alkaloids via Intramolecular Diels-Alder Reaction of a Tetrasubstituted Olefin

A concise synthesis of the ACDE tetracyclic ring system of calyciphylline A-type alkaloids was investigated. The intramolecular Diels–Alder reaction of a tetrasubstituted olefin with furan enabled the construction of the ACD ring system bearing two contiguous quaternary carbons in one step, and subsequent intramolecular [3+2] cycloaddition successfully gave the E ring

Synthesis of 8β-hydroxy-9(11),13-abietadien-12-one from (+)-dehydroabietylamine and its AhR ligand activity

8β-Hydroxy-9(11), 13-abietadien-12-one (1), an abietane diterpenoid and an aryl hydrocarbon receptor (AhR) ligand, was synthesized in six steps from commercially available (+)-dehydroabietylamine (2). We used the hypervalent iodine catalyst phenyliodine dicarboxylate, a safer alternative to toxic organoselenide reagents, for the oxidative dearomatization of ferruginol (7) to compound 1. Compounds 1 and 2, as well as the synthetic intermediates (compounds 3–7), were evaluated for AhR ligand activity. Only compounds 1 and 7 were active, which suggests that AhR affinity is influenced by the steric environment around the C-18 position of these compounds

An Enantioselective Synthesis of 2-Imidazolidinones through Bifunctional Thiourea-Catalyzed Tandem Mannich/Cyclization of Isocyanatomalonate Diester

A chiral bifunctional thiourea-catalyzed Mannich reaction of diethyl 2-isocyanatomalonate with N-sulfonylimines was described. The tandem cyclization proceeded smoothly after Mannch reaction, directly furnishing chiral 2-imidazolidinones in 72‒99% yields with 83‒98% ees. Sterically demanding sulfonyl group was crucial for aliphatic imines to afford the corresponding product in high enantioselectivity

Enantioselective Acetalization by Dynamic Kinetic Resolution for the Synthesis of γ‐Alkoxybutenolides by Thiourea/Quaternary Ammonium Salt Catalysts: Application to Strigolactones

Although acetalization is a fundamental transformation in organic synthesis, intermolecular asymmetric acetalization remains an unsolved problem. In this study, a thiourea‐ammonium hybrid catalyst was shown to promote the O‐alkylation of enols with a racemic γ‐chlorobutenolide through dynamic kinetic resolution to give chiral acetals with good enantioselectivity. The catalyst simultaneously activates both the nucleophile and electrophile in a multifunctional manner. This method was applied to the asymmetric synthesis of several strigolactones. DFT calculations suggest that hydrogen‐bonding interactions between the chlorine atom of the γ‐chlorobutenolide and the tosylamide hydrogen atom of the catalyst, as well as other types of noncovalent catalyst–substrate interactions, are crucial for achieving high stereoselectivity

Palladium(0)-catalyzed benzylic C(sp³)-H functionalization for the concise synthesis of heterocycles and its applications

C-H functionalization reactions involve the activation of otherwise unreactive C-H bonds, and represent atom economical methods for the direct transformation of simple substrates to complex molecules. While transition metal-catalyzed C(sp²)-H functionalization reactions are regularly used in synthesis, C(sp³)-H functionalization is rarely applied to the synthesis of complex natural products because of the difficulties associated with controlling selectivity. With this in mind, we focused on the development of new palladium (Pd)(0)-catalyzed C(sp³)-H functionalization reactions for the synthesis of complex molecules, resulting in several new methods capable of solving these problems. We initially developed a concise synthetic method for the facile construction of oxindoles and spirooxindoles via a Pd-catalyzed benzylic C(sp³)-H functionalization reaction. This method was subsequently extended to the synthesis of various heterocycles, including 2-arylindoles, benzocarbazole, indolocarbazole, indoloquinazolinone, and indoloquinazolinedione, as well as the total synthesis of several pyrrolophenanthridine alkaloids without the need for any protecting groups. This method was also successfully applied to the synthesis of the right-hand fragment of benzohopane from tetrahydro-2H-fluorene, which was constructed by a Pd-catalyzed benzylic C(sp³)-H functionalization. In this review, we provide a detailed discussion of our most recent investigations pertaining to Pd(0)-catalyzed benzylic C(sp³)-H functionalization

Synthesis of 3,3-Disubstituted 2-Aminoindolenines by Palladium-Catalyzed Allylic Amidination with Isocyanide

Synthesis of 3, 3-disubstituted 2-aminoindolenines was achieved by palladium-catalyzed allylic amidination with an isocyanide. It was found that isocyanides are effective building blocks in palladium-catalyzed allylic functionalizations, analogous to carbon monoxide. This approach enables the direct construction of the indolenine ring along with the formation of a quaternary carbon and the introduction of an amino substituent in one step under mild conditions

Synthetic Study of Matrine-Type Alkaloids: Stereoselective Construction of the AB Rings of the Quinolizidine Skeleton

A new method has been developed for the stereoselective construction of the AB rings of the quinolizidine skeleton of ­matrine-type alkaloids with a cis-cis stereochemistry. The key features of this method involve: (i) construction of the quinolizidine by reduction of an acylpyridinium cation; and (ii) late-stage introduction of methoxypyridine by sequential Stille coupling and diastereo­selective hydrogenation reactions

Synthesis of 3,3-disubstituted indoline-2-thiones catalysed by an N-heterocyclic carbene.

A catalytic method has been developed for construction of indoline-2-thiones containing an all-carbon quaternary centre at the C-3 position. Successive treatment of α, β-unsaturated aldehydes bearing an isothiocyanato moiety with an in situ generated N-heterocyclic carbene and an appropriate heteroatomic nucleophile provided the 3, 3-disubstituted indoline derivatives in moderate to good yields

Synthesis of the ABCDG ring skeleton of communesin F based on carboborylation of 1,3-diene and Bi(OTf)₃-catalyzed cyclizations

Communesins, isolated from the mycelium of a strain of Penicillium sp., are cytotoxic heptacyclic indole alkaloids bearing a bis-aminal structure and two contiguous quaternary carbon centers. Toward a total synthesis of communesin F, we synthesized a pentacyclic ABCDG ring skeleton via carboborylation of 1, 3-diene and a Friedel–Crafts-type cyclization, resulting in the formation of an azepine ring through a Bi(OTf)₃-catalyzed SN2’ reaction