Stereodefined synthesis of cyclic amidines by domino 1,7-H shift and 6π electrocyclisation.

Unsaturated N2-sulfonyl amidines are transformed into valuable N-heterocyclic products when heated with BF2OTf. Mechanism studies suggest a domino 1,7-H shift, activating a C-H bond, followed by electrocylisation that results in stereodefined cyclic amidines.

Synthesis and reactivity of 1-sulfonylcyclooctatriazoles.

Strained eight-membered cyclic alkynes undergo rapid inverse electron demand cycloaddition with sulfonyl azides to give the corresponding 1-sulfonylcyclooctatriazoles in excellent yield. Treatment of these sulfonyltriazoles with a chiral rhodium(II) carboxylate catalyst prompted transannular C-H bond insertion in good yield and with excellent ee, or 1,2-H shift.

A Self-Assembling Flavin for Visible Photooxidation.

A new flavin-based gelator is reported which forms micellar structures at high pH and gels at low pH. This flavin can be used for the photooxidation of thiols under visible light, with the catalytic efficiency being linked to the self-assembled structures present.

Modular Synthesis of Highly Substituted 3-Azapyrroles by Rh(II)-Catalyzed N-H Bond Insertion and Cyclodehydration.

A modular synthesis of highly substituted 3-azapyrroles has been developed using a three-step sequence comprising copper-catalyzed alkyne-azide cycloaddition (CuAAC), N-H bond insertion, and cyclodehydration. 1-Sulfonyl-1,2,3-triazoles (1-STs) can be accessed from common alkyne and sulfonyl azide building blocks by CuAAC using CuTC. Rhodium(II)-acetate-promoted 1-ST denitrogenation results in highly electrophilic rhodium azavinyl carbenes that, here, underwent insertion into the N-H bond of secondary α-aminoketones to form 1,2-aminoalkenes. These products were cyclized and dehydrated using BF3·OEt2 into highly substituted 3-azapyrroles. The three steps (CuAAC, N-H bond insertion, and cyclodehydration) could be telescoped into a one-pot process. The method proved to be highly efficient and tolerated a wide range of substituents.

High-performance liquid chromatography quantification of enantiomers of a Dihydroxylated tetrahydrofuran natural product.

Both enantiomers of petromyroxol are putative pheromones in sea lamprey (Petromyzon marinus). Here, we describe the separation and quantification of the petromyroxol enantiomers using high-performance liquid chromatography tandem mass spectrometry. The separation was tested on a wide range of chiral columns with normal phases, and effects of the chromatographic parameters such as mobile phase and temperature on the separation were optimized. The AD-H column showed the best separation of enantiomers with n-hexane and ethanol as the mobile phase. The enantiomers were detected by multiple reaction monitoring with a positive atmospheric-pressure chemical ionization on triple quadrupole mass spectrometer. Validation revealed that the method was specific, accurate, and precise. The validated method was applied to measure the amount of petromyroxol enantiomers in water conditioned with sea lamprey larvae, the source of the putative pheromone. This method will be applied in quantifying the natural scalemic petromyroxol mixture, enabling further investigations of a rare non-racemic enantiomeric pheromone mixture in a vertebrate species.

Enantioselective synthesis of (+)-petromyroxol, enabled by rhodium-catalyzed denitrogenation and rearrangement of a 1-sulfonyl-1,2,3-triazole.

Petromyroxol is a nonracemic mixture of enantiomeric oxylipids isolated from water conditioned with larval sea lamprey. The (+)-antipode exhibits interesting biological properties, but only 1 mg was isolated from >100 000 L of water. Recently, transition-metal-catalyzed denitrogenation of 1-sulfonyl-1,2,3-triazoles has emerged as a powerful strategy for the synthesis of value-added products, including efficient diastereocontrolled construction of tetrahydrofurans. This methodology enabled the rapid development of the first synthesis of (+)-petromyroxol in 9 steps and 20% overall yield from a readily accessible starting material.

Synthesis of cyclopropyl-substituted furans by brønsted Acid promoted cascade reactions.

Chloroacetic acid promotes an efficient and diastereoselective intramolecular cascade reaction of electron-deficient ynenones to deliver products featuring a 2,3,5-trisubstituted furan bearing a fused cyclopropyl substituent at the 5-position. Synthetically relevant polycyclic building blocks featuring rings of various sizes and heteroatoms have been synthesized in high yield using this mild acid-catalyzed reaction.

Rhodium(II)-catalyzed stereocontrolled synthesis of 2-tetrasubstituted saturated heterocycles from 1-sulfonyl-1,2,3-triazoles.

Rhodium(II) acetate catalyzes the denitrogenative transformation of 4-substituted 1-sulfonyl-1,2,3-triazoles with pendent allyl and propargyl ethers and thioethers to onium ylides that undergo [2,3]-sigmatropic rearrangement to give 2-tetrasubstituted heterocycles with high yield and diastereoselectivity.

Rhodium(II)-catalyzed stereocontrolled synthesis of dihydrofuran-3-imines from 1-tosyl-1,2,3-triazoles.

Rhodium(II) acetate catalyzes the denitrogenative transformation of 5-substituted and 4,5-disubstituted 1-sulfonyl-1,2,3-triazoles with pendent allyl and propargyl ether motifs to oxonium ylides that undergo [2,3]-sigmatropic rearrangement to give substituted dihydrofuran-3-imines in high yield and diastereoselectivity.

Practical asymmetric synthesis of bioactive aminotetralins from a racemic precursor using a regiodivergent resolution.

Catalyst-controlled asymmetric ring opening of a racemic oxabicyclic alkene leads to two readily separable regioisomeric products both in excellent ee. A cationic Rh catalyst, with added NH(4)BF(4) to modulate reactivity, was required to obtain synthetically useful yields. The utility of each substituted aminotetralin product has been demonstrated by their conversion to different biologically relevant molecules in a highly efficient and practical manner.

Second-generation synthesis of azadirachtin: a concise preparation of the propargylic mesylate fragment.

A second bite of the apple: A new and highly efficient synthesis of the propargylic mesylate fragment of azadirachtin has been accomplished (see scheme; Bn = benzyl, Ms = methanesulfonyl, PMB = para-methoxybenzyl, TBDPS = tert-butyldiphenylsilyl). An enantioselective catalytic hetero Diels-Alder reaction sets up the stereocenter at C15, which then controls the installation of the remaining functionality in a total of only 17 steps.

The azadirachtin story.

Azadirachtin has been the subject of intensive research within the scientific community ever since its isolation from the neem tree in 1968. There are now over 1000 publications relating to this natural product which cover all aspects of structural, biological and synthetic studies. Herein, we describe the worldwide synthesis efforts towards this fascinating molecule.

The synthesis of azadirachtin: a potent insect antifeedant.

We describe in full the first synthesis of the potent insect antifeedant azadirachtin through a highly convergent approach. An O-alkylation reaction is used to unite decalin ketone and propargylic mesylate fragments, after which a Claisen rearrangement constructs the central C8-C14 bond in a stereoselective fashion. The allene which results from this sequence then enables a second critical carbon-carbon bond forming event whereby the [3.2.1] bicyclic system, present in the natural product, is generated via a 5-exo-radical cyclisation process. Finally, using knowledge gained through our early studies into the reactivity of the natural product, a series of carefully designed steps completes the synthesis of this challenging molecule.

Clean and efficient synthesis of O-silylcarbamates and ureas in supercritical carbon dioxide.

The synthesis of a family of O-silylcarbamates from the corresponding silylamines has been achieved simply by heating the silylamine in supercritical carbon dioxide (scCO2), and these O-silylcarbamates have been shown to be effective precursors for the synthesis of a range of symmetrical and unsymmetrical ureas.

Synthesis of natural products from the Indian neem tree Azadirachta indica.

The synthesis of five natural products (3, 6, 7, 10, and 14), isolated from the Indian neem tree Azadirachta indica, is reported from a common intermediate (2). The judicious choice of transacetalization conditions allows efficient access to both the azadirachtinin (9 and 10) and the azadirachtin (3, 6, 7, and 14) skeletons.