Synthesis of Tanshinone IIA and Related Terpenes via a C-H Functionalization Strategy.

The total synthesis of tanshinone IIA and related bioactive diterpenes isolated from the Chinese plant Salvia miltiorrhiza was completed from a common tetralin building block. The synthetic route highlights a 3,4-disubstituted furan synthesis and various regioselective C-H functionalization reactions, including a Pd catalyzed iodination and an Ir catalyzed borylation, along with an intramolecular stanna-Brook type reaction to construct the ortho-quninone ring of the target molecule.

Biomimetic Domino Knoevenagel/Cycloisomerization Strategy for the Synthesis of Citridone A and Derivatives.

Studies on Knoevenagel condensations between conjugated dienals and 4-hydroxy-2-pyridone/quinolone-type 1,3-dicarbonyl equivalents led to the development of a simple one-pot strategy to access citridone A and related synthetic cyclopenta[b]furopyridones/quinolones. The present work highlights the power of domino cascades in the synthesis of natural product frameworks and may help promote future studies on this promising new class of pyridone alkaloids.

Copper-Catalyzed Annulation of Indolyl α-Diazocarbonyl Compounds Leads to Structurally Rearranged Carbazoles.

Indolyl α-diazocarbonyl compounds have proven to be effective starting materials for the construction of various 2,3-ring fused indole frameworks. Activation of the diazo functional group under metal catalysis generates a spiro-cyclic indolenine-type intermediate which rearranges to provide two distinct carbazoles upon oxidation. The current study investigates the effects of the catalyst as well as the substituents on the migratory group involved in controlling the selectivity of the rearrangement.

Total Synthesis of (+)-6-epi-Ophiobolin†A.

The ophiobolin sesterterpenes are notable plant pathogens which have recently elicited significant chemical and biological attention because of their intriguing carbogenic frameworks, reactive functionalities, and emerging anticancer profiles. Reported herein is a total synthesis of (+)-6-epi-ophiobolin A in 14 steps, a task which addresses construction of the synthetically challenging spirocyclic tetrahydrofuran motif as well as several other key stereochemical problems. This work demonstrates a streamlined synthetic platform to complex ophiobolins leveraging disparate termination modes of a radical polycyclization cascade for divergent elaboration and functionalization.

Tandem Carbenoid C-H Functionalization/Conia-ene Cyclization of N-Propargyl Indoles Generates Pyrroloindoles under Cooperative Rh(II)/Zn(II) Catalysis.

The decomposition of diazodicarbonyl compounds in the presence of various metal catalysts has become a reliable method for the functionalization of indoles via carbenoid intermediates. Exploiting the nucleophilic reactivity of the in situ generated malonic ester product formed, we herein report a tandem C-H functionalization/Conia-ene cyclization of N-alkyne tethered indoles. This double functionalization of diazodicarbonyls generates a range of pyrrolo[1,2-a]-, pyrido[1,2-a]-, and azepino[1,2-a]indole products with good synthetic efficiency.

Enantioselective synthesis of an ophiobolin sesterterpene via a programmed radical cascade.

Cyclase enzymes weave simple polyprenyl chains into the elaborate polycyclic ring systems of terpenes, a sequence that is often difficult to emulate under abiotic conditions. Here we report a disparate synthetic approach to complex terpenes whereby simple prenyl-derived chains are cyclized using radical, rather than cationic, reaction pathways. This strategy allowed us to efficiently forge the intricate 5-8-5 fused ring systems found in numerous complex natural product classes and also enabled a nine-step total synthesis of (-)-6-epi-ophiobolin N, a member of the large family of cytotoxic ophiobolin sesterterpenes. A small-molecule thiol catalyst was found to override the inherent diastereoselectivity observed during a reductive radical cascade cyclization process. This work lays the foundation for efficient synthesis of terpenoid ring systems of interest in medicinal research, particularly those that have been historically challenging to access.

Carbocycles from donor-acceptor cyclopropanes.

This review summarizes research directed towards the formation of carbocyclic adducts from donor-acceptor cyclopropanes. The focus of the review is on annulation and cycloaddition reactions (both inter- and intramolecularly) mediated by Lewis or protic acid, bases, or thermal conditions. Rearrangements resulting in carbocycles and those reactions mediated by transition metal catalysis have been excluded.

Scandium triflate-catalyzed nucleophilic additions to indolylmethyl Meldrum's acid derivatives via a gramine-type fragmentation: synthesis of substituted indolemethanes.

Treatment of indolylmethyl Meldrum's acids with catalytic scandium triflate and a variety of nucleophiles results in the nucleophilic displacement of the Meldrum's acid moiety via a gramine-type fragmentation. The reaction is useful for the generation of heterocyclic compounds of significant molecular complexity.

γ-Substituted butanolides from cyclopropane hemimalonates: an expedient synthesis of natural (R)-dodecan-4-olide.

Exploration into the reactivity of donor-acceptor cyclopropane hemimalonates has led to the facile synthesis of γ-substituted butanolides. Under microwave irradiation, cyclopropane hemimalonates undergo rapid conversion to butanolides in the presence of inorganic salts with an unprecedented retention of stereochemistry. This unique process has been applied to the total synthesis of the naturally occurring (R)-dodecan-4-olide.

Tandem ring-opening decarboxylation of cyclopropane hemimalonates with sodium azide: a short route to γ-aminobutyric acid esters.

Cyclopropane hemimalonates, when treated with sodium azide, undergo a tandem ring-opening decarboxylation to produce γ-azidobutyric acids in good yields. These adducts were hydrogenated to form γ-aminobutyric acid (GABA) methyl esters.

Tandem cyclopropane ring-opening/Conia-ene reactions of 2-alkynyl indoles: a [3 + 3] annulative route to tetrahydrocarbazoles.

A Zn(NTf(2))(2) catalyzed tandem reaction consisting of a nucelophilic ring opening of 1,1-cyclopropanediesters by 2-alkynyl indoles followed by a Conia-ene ring closure results in the efficient one-step synthesis of tetrahydrocarbazoles. The adducts may be further elaborated to carbazoles.