Preparation of thiochromans via thermal cyclization

Formation of the thiochroman ring system is achieved by a two step synthesis that involves heating 3‐thiophenyl‐1‐propanols or 4‐thiophenyl‐2‐butanols in toluene with catalytic amounts of p‐toluenesulfonic acid. The propanols are made by the addition of sulfur stabilized carbanions to styrene oxide, ethylene oxide, propylene oxide, and isobutylene oxide. The carbanions are generated by treatment of either benzyl phenyl sulfide or thioanisole with butyllithium. The effect of substitution at the 1 and 3 positions of the propanols on the reaction yields is discussed. The mechanism of the reaction apparently involves intramolecular electrophilic aromatic substitution rather than a Claisen or thio‐Claisen rearrangement.     

Stereoselective syntheses of epothilones A and B via nitrile oxide cycloadditions and related studies

The expedient and fully stereocontrolled synthesis of epothilones A and B are described. The routes described make extensive study of nitrile oxide cycloadditions as surrogates for aldol addition reactions and have led to the realization of a highly convergent synthesis based on the Kanemasa hydroxyl-directed nitrile oxide cycloaddition. As well, our synthetic efforts have led to the development of new reaction methodologies and served as the proving ground for several modern methods for asymmetric carbon-carbon bond formation.     

Efficient syntheses of 2,3-disubstituted natural quinazolinones via iridium catalysis

Natural products sclerotigenin, pegamine, deoxyvasicinone, mackinazolinone, and rutaecarpine were synthesized. Core quinazolinone structures were constructed via Ir catalysis.     

Efficient stereoselective syntheses of cyclic amino acids via Michael-induced ring-closing reactions

[reaction: see text] Zn-chelated glycine ester enolates are highly efficient nucleophiles for the synthesis of trans-methoxycarbonylcyclopropyl- and cyclobutylglycines by domino sequences of Michael additions and subsequent ring closures. They react to give the anti isomers with high yields and excellent diastereoselectivities.     

Peptidomimetics via copper-catalyzed azide-alkyne cycloadditions

This critical review concerns the impact of copper-mediated alkyne-azide cycloadditions on peptidomimetic studies. It discusses how this reaction has been used to insert triazoles into peptide chains, to link peptides to other functionalities (e.g. carbohydrates, polymers, and labels), and as a basis for evolution of less peptidic compounds as pharmaceutical leads. It will be of interest to those studying this click reaction, peptidomimetic secondary structure and function, and to medicinal chemists.     

Efficient syntheses of rugulosin analogues

Oxidation of 3b or 14c,d with Pb(OAc)4 in AcOH for 20 min at 25 degrees C and 1 h at 75 degrees C gave flavoskyrin-type dimers 6b and 15c,d in 53-86% yield. Heating a solution of 6b or 15c,d in pyridine under air for 1 h at 75-80 degrees C and then for 1-2 h at 110 degrees C afforded rugulosin-type dimers 10b and 17c,d in 61-88% yield. This two-step sequence provides a practical route to this unusual natural product skeleton.     

Efficient syntheses of oncinotine and neooncinotine

We have synthesized two natural alkaloids, oncinotine (1) and neooncinotine (2), by means of efficient ring-closing metathesis (RCM) reactions. The required dienes for RCM were assembled from three basic components: 2-allylpiperidine (5), 9-decenoic acid (6), and diamines 7. We developed two different methods to achieve the linkage: the Michael addition of acrylamide and two amidations of succinic anhydride. The Grubbs catalyst was used to form the 17- and 18-membered lactams in 50% and 68% yields, respectively.     

Efficient synthesis of isoxazolidine-tethered monolayer-protected gold nanoparticles (MPGNs) via 1,3-dipolar cycloadditions under high-pressure conditions

A maleimide-modified 2.5 +/- 0.5 nm mixed monolayer protected gold nanoparticle (2-C(12)MPGN) containing approximately 30% maleimide-terminated dodecanethiolate/dodecanethiolate ligands was prepared. The 2-C(12)MPGN was reacted with a series of nitrones (a-i) at both atmospheric and hyperbaric (11 000 atm) conditions to form the corresponding isoxazolidine-modified nanoparticles (3-C(12)MPGN) via an interfacial 1,3-dipolar cycloaddition. At atmospheric pressures, the reaction proceeds slowly (if at all) and makes this reaction impractical for the synthetic modification of the nanoparticles. However, by performing the reaction under the high-pressure conditions, the reaction proceeds efficiently and quantitatively. TEM shows that the use of high pressure does not affect the size of the gold nanoparticle core. The 3-C(12)MPGNs were characterized by (1)H NMR spectroscopy by comparing the spectra obtained with those of model reactions utilizing N-dodecylmaleimide (4) with the same nitrones (a-i) to form 5. Additionally, the cycloaddition reaction also occurs more readily with 4 than with 2-C(12)MPGN with all nitrones, indicating that the environment of the latter affects the cycloaddition reaction.     

Total syntheses via cyclopropanols

Cyclopropanols are readily available via the Kulinkovich cyclopropanation, the Simmons-Smith reaction, and other synthetic methods. Due to their intrinsic ring stains, cyclopropanols and their derivatives are highly reactive and can be converted to different structural scaffolds which are frequently found in many natural products. In this review, we highlight the applications of various cyclopropanol ring opening/expansion/fragmentation reactions in the total syntheses of natural products.     

Exceptional molecular architectures via cycloadditions to pyrenequinones

The thermal reaction of phencyclone (2) with a 1:1 mixture of 1,8-pyrenequinone (4) and 1,6-pyrenequinone (5) yields 2:1 adducts only of compounds 2 and 4. The observed polycyclic aromatic hydrocarbon 8 is formed via double Diels-Alder addition of 2 to 4, and the polycyclic ketone 9 arises from a combination of Diels-Alder and hetero-Diels-Alder reactions of 2 and 4. In contrast, Lewis acid-catalyzed reactions of 2, 4, and 5 give 2:1 adducts only of 2 and 5. The chief product, polycyclic diketone 10, is derived from a double hetero-Diels-Alder addition of 2 to 5. X-ray analysis of compound 8 shows it to be an exceptionally large polycyclic aromatic arch, and the X-ray structure of 10 reveals it to be a chiral molecular tweezer.     

Oppolzer-type intramolecular Diels-Alder cycloadditions via isomerizations of allenamides

A new approach to Oppolzer's intramolecular Diels-Alder cycloaddition (IMDA) through γ-isomerization of readily available N-tethered allenamides is described. These IMDA reactions are carried out in tandem with the allenamide isomerization or 1,3-H shift, leading to complex nitrogen heterocycles in a highly stereoselective manner.     

Efficient eco-friendly syntheses of dithiocarbazates and thiosemicarbazones

ABSTRACT

Eight Schiff bases have been synthesized by conventional and three different eco-friendly methods, whereby two aromatic carbonyl compounds viz. 2-thiophenecarboxaldehyde and salicylaldehyde were reacted with S-methyl, S-benzyl, and S-n-octyl-dithiocarbazates and thiosemicarbazide. In order to evaluate the efficiency of the synthesis methods, the time to complete the reaction and the yield of the Schiff base synthezised by eco-friendly methods, such as solvent-free grinding, water as a solvent, and lemon juice as catalyst, were compared with those synthesized by the conventional method. The chemical structures of all the synthesized Schiff bases, where two of them are novel and reported for the first time, were fully characterized by a variety of physico-chemical, analytical, and spectroscopic techniques. The molecular and crystal structures of the Schiff bases especially those having 2-thiophene moiety were further elucidated by single crystal X-ray diffraction analyzes.     

Efficient total syntheses and structural verification of both diospongins A and B via a common delta-lactone intermediate

The total syntheses of the two aryl C-glycoside natural products diospongins A and B are described. The key reactions involved stereoselective reductions of the appropriate oxocarbenium cations that were derived from a common delta-lactone intermediate.     

Synthesis of an asymmetric fullerene dimer via sequential cycloadditions

A single isomer of a monofunctionalised C₇₀ fullerene is isolated and characterised using variable temperature NMR spectroscopy. Pendant methylene bromide groups allow for further cycloaddition reactions and a C₆₀-C₇₀ asymmetric fullerene dimer is thus prepared.     

Efficient total syntheses of polygodial and drimenin.

A short and stereoselective total synthesis of (±) polygodial and drimenin is presented. The efficiency of the synthesis is due to the easy access to intermediate diol $\text{4}$ and its successful direct oxidation into polygodial.     

Efficient total syntheses of louisianins C and D

An efficient synthetic route for the preparation of louisianins C and D was developed starting with the commercially available 4-cyanopyridine. Louisianins C and D were synthesized in seven steps and with overall yields 22% and 20%, respectively, following a novel cyclization-decarboxylation sequence involving 4-bromo-6,7-dihydrocyclopenta[c]pyridin-5-one as the key intermediate.     

Stereocontrolled syntheses of the nemorensic acids using 6-diazoheptane-2,5-dione in carbonyl ylide cycloadditions

Levulinic acid-derived 6-diazoheptane-2,5-dione (9) serves as a common precursor in a formal synthesis of frontalin 19, and in syntheses of cis-nemorensic acid 1, 4-hydroxy-cis-nemorensic acid 2, 3-hydroxy-cis-nemorensic acid 3, and nemorensic acid 4. The key step in these syntheses is the Rh(2)(OAc)(4)-catalyzed tandem carbonyl ylide formation-intermolecular 1,3-dipolar cycloadditions of diazodione 9 with formaldehyde, alkynes or allene, which occur with high regioselectivity. Subsequent oxidative cleavage of the ring originally derived from the cyclic carbonyl ylide intermediate provides a straightforward access to polysubstituted tetrahydrofurans, and in particular an efficient entry to the nemorensic acids. Enantioselective cycloadditions with diazodione 9, using chiral rhodium catalysts, gave cycloadducts in up to 51% ee.