Enantioselective Total Synthesis of Dysiherbols A, C, and D

Herein, we report the enantioselective total synthesis of dysiherbols A, C, and D, a unique group of 6/6/5/6/6 pentacyclic quinone/hydroquinone sesquiterpenes, featuring a photo-induced quinone–alkene [2 + 2] cycloaddition and a tandem [1,2]-anionic rearrangement/cyclopropane fragmentation as key elements. Based on our total synthesis, the originally proposed structures of dysiherbols C and D have been revised. Detailed computational studies were carried out to gain deep insight into the unprecedented [1,2]-anionic rearrangement, which revealed that the transformation, albeit a symmetry-forbidden process, proceeded through a concerted manner owing to the release of high ring-strain energy and the evolution of local aromaticity in the transition state. Taking all, the present work offers a mechanistically interesting and synthetically useful approach to accessing dysiherbols and related congeners

Asymmetric Total Synthesis of Dragonbloodins A1 and A2

The first asymmetric total synthesis of dragonbloodins A1 and A2, a pair of unprecedented chalcone-flavan heterotrimmers, has been achieved through a series of rationally designed or bioinspired transformations. Key elements of the synthesis include a highly efficient heterotrimerization reaction to assemble the two chalcone units and one flavan unit in one pot and a tandem oxidative dearomatization/cyclization/oxygenation reaction to forge the polycyclic core of dragonbloodins A1 and A2. The present synthesis unambiguously confirms the biogenetic relationship and absolute stereochemistry of dragonbloodins A1 and A2

Rh(II)-Catalyzed Transannulation of <i>N</i>‑Sulfonyl-1,2,3-Triazoles with 2,1-Benzisoxazoles or 1,2-Benzisoxazoles

A Rh­(II)-catalyzed transannulation of <i>N</i>-sulfonyl-1,2,3-triazoles with 2,1-benzisoxazoles has been developed, which affords an efficient method for the synthesis of quinazoline derivatives. The transformation represents an unprecedented example which utilizes <i>N</i>-sulfonyl-1,2,3-triazole as an aza-[2C]-component in cycloadditions. Meanwhile, a Rh­(II)-catalyzed formal [3 + 2] cycloaddition of <i>N</i>-sulfonyl-1,2,3-triazoles with 1,2-benzisoxazoles is also presented, which enables the rapid synthesis of functionalized imidazole derivatives

Rapid Biomimetic Total Synthesis of (±)-Rossinone B

A biomimetic total synthesis of (±)-rossinone B has been achieved through a highly efficient strategy featuring a series of rationally designed reactions, including a one-pot allylic rearrangement/oxidation reaction to generate the vinyl quinone 27, an intramolecular vinyl quinone Diels−Alder reaction to construct the linear 6−6−5 tricyclic core of 28, and a double conjugate addition/β-elimination cascade to complete the total synthesis of 1

Total Synthesis of Sporolide B and 9-<i>epi</i>-Sporolide B

The total synthesis of the structurally unique secondary metabolite sporolide B (1b) is described. The total synthesis of 1b was developed on the basis of preliminary studies that revealed the reactivity of an appropriate o-quinone as a diene system toward a number of indene derivatives as dienophiles, first in intermolecular and thence intramolecular settings. Thus, substrates were devised (37 and 75) that underwent exquisite intramolecular [4+2] cycloaddition reactions under thermal conditions to provide primitive sporolide-type structures that were subsequently elaborated to a sporolide model system, 9-epi-sporolide B, and 1b. The requisite indene o-quinone precursor 75 was synthesized through a ruthenium-catalyzed [2+2+2] cycloaddition reaction between a propargylic alcohol and a chloroacetylenic cyclopentenyne, followed by elaboration and silver-promoted oxidation of the resulting chloroindene derivative. In addition to the total synthesis of 1b, this work demonstrated, for the first time, the power of the intramolecular hetero [4+2] cycloaddition reaction in the total synthesis of complex molecules and the application of the ruthenium-catalyzed [2+2+2] cycloaddition reaction to highly substituted indene systems possessing a chlorine residue on the aromatic nucleus

Total Synthesis of Sporolide B and 9-<i>epi</i>-Sporolide B

The total synthesis of the structurally unique secondary metabolite sporolide B (1b) is described. The total synthesis of 1b was developed on the basis of preliminary studies that revealed the reactivity of an appropriate o-quinone as a diene system toward a number of indene derivatives as dienophiles, first in intermolecular and thence intramolecular settings. Thus, substrates were devised (37 and 75) that underwent exquisite intramolecular [4+2] cycloaddition reactions under thermal conditions to provide primitive sporolide-type structures that were subsequently elaborated to a sporolide model system, 9-epi-sporolide B, and 1b. The requisite indene o-quinone precursor 75 was synthesized through a ruthenium-catalyzed [2+2+2] cycloaddition reaction between a propargylic alcohol and a chloroacetylenic cyclopentenyne, followed by elaboration and silver-promoted oxidation of the resulting chloroindene derivative. In addition to the total synthesis of 1b, this work demonstrated, for the first time, the power of the intramolecular hetero [4+2] cycloaddition reaction in the total synthesis of complex molecules and the application of the ruthenium-catalyzed [2+2+2] cycloaddition reaction to highly substituted indene systems possessing a chlorine residue on the aromatic nucleus

Unified Biomimetic Approach to (+)-Hippolachnin A: In-Depth Insights into Its Biosynthetic Origin

A formal biomimetic synthesis of (+)-hippolachnin A has been achieved under the guidance of its plausible biosynthetic pathway. Pivotal transformations include an intriguing 1O2-mediated [4 + 2] cycloaddition and a tandem Kornblum–DeLaMare rearrangement/hemiketalization/dehydration reaction. The current work not only offers a unified approach to access skeletally diverse plakortin-type polyketides but also provides convincing evidence to elucidate their underlying biosynthetic network

Rhodium(II)-Catalyzed Formal [3 + 2] Cycloaddition of <i>N</i>‑Sulfonyl-1,2,3-triazoles with Isoxazoles: Entry to Polysubstituted 3‑Aminopyrroles

A novel rhodium­(II)-catalyzed formal [3 + 2] cycloaddition of <i>N</i>-sulfonyl-1,2,3-triazoles with isoxazoles has been achieved that provides an efficient method for the synthesis of polysubstituted 3-aminopyrrole derivatives. An operationally simple one-pot synthesis of the titled compounds from terminal alkynes, tosyl azide, and isoxazoles was also developed. The presented reaction affords an illustrative example of employing 1,2,3-triazoles as the [2C]-component in relevant cycloaddition reactions

Total Synthesis of Sporolide B and 9-<i>epi</i>-Sporolide B

The total synthesis of the structurally unique secondary metabolite sporolide B (1b) is described. The total synthesis of 1b was developed on the basis of preliminary studies that revealed the reactivity of an appropriate o-quinone as a diene system toward a number of indene derivatives as dienophiles, first in intermolecular and thence intramolecular settings. Thus, substrates were devised (37 and 75) that underwent exquisite intramolecular [4+2] cycloaddition reactions under thermal conditions to provide primitive sporolide-type structures that were subsequently elaborated to a sporolide model system, 9-epi-sporolide B, and 1b. The requisite indene o-quinone precursor 75 was synthesized through a ruthenium-catalyzed [2+2+2] cycloaddition reaction between a propargylic alcohol and a chloroacetylenic cyclopentenyne, followed by elaboration and silver-promoted oxidation of the resulting chloroindene derivative. In addition to the total synthesis of 1b, this work demonstrated, for the first time, the power of the intramolecular hetero [4+2] cycloaddition reaction in the total synthesis of complex molecules and the application of the ruthenium-catalyzed [2+2+2] cycloaddition reaction to highly substituted indene systems possessing a chlorine residue on the aromatic nucleus

Biomimetic Syntheses of Rubialatins A, B and Related Congeners

The first total syntheses of rubialatins A and B, two newly discovered naphtho­hydro­quinone dimers, were achieved with high efficiency and elegancy through rationally designed biomimetic approaches. The tandem ring contraction/Michael addition/aldol reaction followed by oxidation enabled the rapid access of prerubialatin from readily available precursors, which then diverted into rubialatins A and B via epoxidation and photoinduced skeletal rearrangement, respectively. Moreover, several new rubialatin congeners were also obtained along the synthetic tour, some of which were proved to be authentic natural products