Yefeng Tang

The Divergent Synthesis of Nitrogen Heterocycles by Rhodium(II)-Catalyzed Cycloadditions of 1-Sulfonyl 1,2,3-Triazoles with 1,3-Dienes†

The first rhodium(II)-catalyzed aza-[4+3] cycloadditions of 1-sulfonyl 1,2,3-triazoles with 1,3-dienes have been developed, and enable the efficient synthesis of highly functionalized 2,5-dihydroazepines from readily available precursors. In some cases, the reaction pathway could divert to formal aza-[3+2] cycloadditions, thus leading to 2,3-dihydropyrroles. In this context, the titled reaction represents a capable tool for the divergent synthesis of two types of synthetically valuable aza-heterocycles from common rhodium(II) iminocarbene intermediates.

Diastereoselective Total Synthesis of (±)‐Schindilactone A

Schindilactone A (1) and structures 2–4 (Scheme 1a) are representative members of a novel group of nortriterpenoids isolated by Sun and co-workers from the plants of Schisandraceae, which have been used in China for the treatment of rheumatic lumbago and related diseases. Preliminary biological assays indicated that some of them possess biological activities for inhibiting hepatitis, tumors, and HIV-1. The synthetic challenge posed by 1 stems from the complexity of its molecular structure: a highly oxygenated framework bearing 12 stereogenic centers, eight of which are contiguous chiral centers located in the FGH tricyclic ring system, and an oxa-bridged ketal that lies within an unprecedented 7–8 fused carbocyclic core. The structural complexity together with the attractive biological activities has rendered 1 a target for synthetic studies. Herein we report our efforts on the development of synthetic methods and a strategy centered on the construction of the polycyclic ring system that allowed the first total synthesis of ( )-schindilactone A. This concise strategy opens a pathway for the syntheses of other compounds related to schindilactone A (2–4, Scheme 1a), as well as their derivatives and analogues.

Total Synthesis of Sporolide B

An ocean of discovery: The first total synthesis of the highly oxygenated, marine-derived, natural product sporolide B has been achieved through a convergent strategy. The key steps involve a ruthenium-catalyzed [2+2+2] cycloaddition to assemble the indene structural motif and a thermally induced Diels-Alder-type reaction to forge the macrocycle (see scheme).

Total Synthesis of Crisamicin A

Stereoselective total synthesis of natural product crisamicin A (1) was accomplished for the first time via the Pd/TMTU-catalyzed alkoxycarbonylative annulation to generate a unique cis-pyran-fused lactone, an intermolecular Diels-Alder reaction to construct the pyranonaphthoquinone unit, and a novel Pd-thiourea pincer complex-catalyzed homocoupling of functionalized naphthoquinones.

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

A novel rhodium(II)-catalyzed formal [3 + 2] cycloaddition of N-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.

Insight into the high reactivity of commercial Fe–Si–B amorphous zero-valent iron in degrading azo dye solutions

Improving intrinsic reactivity is one of the key requirements in applying zero-valent iron in the field. As a new kind of zero-valent iron, iron based amorphous alloys were recently found to be capable of rapidly remediating wastewater. However, the mechanisms for the rapid degradation have not yet been fully understood. In this study, commercial Fe–Si–B amorphous alloy ribbons (Fe–Si–BAR) were used to degrade azo dyes (Direct Blue 6 and Orange II) to study the reaction kinetics, pathway and mechanism behind the high reactivity of these iron based amorphous alloys. The results show that, under the same conditions, the surface normalized reaction rate constants for the decomposition of Orange II and Direct Blue 6 by Fe–Si–BAR could be 1300 and 60 times larger respectively than those obtained by using 300 mesh iron powders. Through UV-vis spectrophotometry and mass spectrometry, it is found that the intermediate products of the azo dyes degraded by Fe–Si–BAR are similar to those produced in degradation by iron powders. However, the controlling step of the degradation reaction by Fe–Si–BAR turns out to be the diffusion process rather than the surface chemical reaction found in the reaction by iron powders. Further analysis indicates that the high degradation efficiency of Fe–Si–BAR results from its amorphous structure and the metalloid additions, which could enhance the catalytic effect and promote the formation of a non-compact and easily detached oxide layer on the surface. The experiments under different environmental conditions show that the factors that influence the degradation efficiency of crystalline iron powders affect that of Fe–Si–BAR in a similar way, but Fe–Si–BAR is capable of efficiently degrading wastewater under broader conditions than the crystalline iron powders. The results indicate that Fe–Si–BAR is a promising environmental catalyst for wastewater treatment.

Total Synthesis of Sporolide B and 9-epi-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.

Diastereoselective Total Synthesis of (±)‐Schindilactone A, Part 3: The Final Phase and Completion

The final phase for the total synthesis of (±)-schindilactone A (1) is described herein. Two independent synthetic approaches were developed that featured Pd-thiourea-catalyzed cascade carbonylative annulation reactions to construct intermediate 3 and a RCM reaction to make intermediate 4. Other important steps that enabled the completion of the synthesis included: 1) A Ag-mediated ring-expansion reaction to form vinyl bromide 17 from dibromocyclopropane 30; 2) a Pd-catalyzed coupling reaction of vinyl bromide 17 with a copper enolate to synthesize ketoester 16; 3) a RCM reaction to generate oxabicyclononenol 10 from diene 11; 4) a cyclopentenone fragment in substrate 8 was constructed through a Co-thiourea-catalyzed Pauson-Khand reaction (PKR); 5) a Dieckmann-type condensation to successfully form the A ring of schindilactone A (1). The chemistry developed for the total synthesis of schindilactone A (1) will shed light on the synthesis of other family members of schindilactone A.

Diastereoselective Total Synthesis of (+/-)-Schindilactone A, Part 1: Construction of the ABC and FGH Ring Systems and Initial Attempts to Construct the CDEF Ring System

First-generation synthetic strategies for the diastereoselective total synthesis of schindilactone A (1) are presented and methods for the synthesis of the ABC, FGH, and CDEF moieties are explored. We have established a method for the synthesis of the ABC moiety, which included both a Diels-Alder reaction and a ring-closing metathesis as the key steps. We have also developed a method for the synthesis of the FGH moiety, which involved the use of a Pauson-Khand reaction and a carbonylative annulation reaction as the key steps. Furthermore, we have achieved the construction of the central 7-8 bicyclic ring system by using a [3,3]-rearrangement as the key step. However, unfortunately, when this rearrangement reaction was applied to the construction of the more advanced CDEF moiety, the anticipated annulation reaction did not occur and the development of an alternative synthetic strategy would be required for the construction of this central core.

Enantioselective and Collective Syntheses of Xanthanolides Involving a Controllable Dyotropic Rearrangement of cis-β-Lactones†

Lets swap: a scalable, atom-economic, enantio-, and diastereoselective synthetic route to trisubstituted γ-butyrolactones based on a Wagner-Meerwein-type dyotropic rearrangement of cis-β-lactones is described. This methodology was applied in efficient and protecting-group-free formal syntheses and total syntheses of various xanthanolide natural products.