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A facile method for the oxidative ortho-cyclization of 1- and 2-naphtholic sulfonamides as well as a new method for the preparation of N-unsubstituted spirolactam derivative (X) of 1-naphthol is given.

In contrast to the effective arylation of diarylsulfides and diphenylselenide, the conversion of diphenyltelluride is insufficiently slow.

A route to a racemic diene intermediate for the synthesis of tetrodotoxin is described. Key steps of the sequence leading to such a compound include the oxidative amidation of a phenol, a Cu(II)-catalyzed cyclocondensation of a nitroketone with an olefin (Machetti–DeSarlo reaction), and a nucleophilic fragmentation of the resulting isoxazoline. Several unusual reactions encountered in the course of this study are thoroughly discussed.

The presented procedure gives access to a broad scope of arylated enones and crotonic systems with reasonable yields by employment of a relative simple catalytic system compared to common protocols.

A catalyst consisting of the 1:2 complex of Pd(OAc)2 (1 mol %) with N-(4-carbethoxy)-phenylurea promotes the Heck arylation of a range of crotonic and cinnamic substrates, including aldehydes, ketones, esters, and nitriles, with electron-rich—but not electron-deficient—aryl iodides.

This is a review of our efforts toward the synthesis of a group of natural products that display noteworthy biological activity: Fredericamycin A, nothapodytine B, and topopyrones B and D. In each case, directed aromatic functionalization methodology greatly facilitated the assembly of the key molecular subunits.

An overview of the para- [ (II), (IV), (VI), (VIII), (X)] and ortho-oxidative cyclizations [ (XII), (XIV)] of phenolic sulfonamides is given.

The use of an acetylenic alane, generated in situ from (IIa), permits the conversion of chloroglycinates into the title compounds with moderate yields.

Condensation of α-chloroglycinates with isonitriles (II) or Et2AlCN gives 5-amino-oxazoles in moderate yields.

Catalyst screening reveals that N-phenylurea in combination with Pd(O-Ac)2 is superior, even when compared to “Phos”-type ligands.

The oxidative amidation of phenols effects the conversion of appropriately substituted phenols into 4-amidodienones (‘ para -oxidative amidation’) or 2-amidodienones (‘ ortho -oxidative amidation’) by the action of hypervalent iodine reagents. The reagent, (diacetoxyiodo)benzene (‘DIB’) is especially effective in these transformations. This paper focuses on techniques for the desymmetrization of the dienoes thus obtained, leading to the stereocontrolled creation of N -substituted spiro carbons. The methodology creates new opportunities in alkaloid synthesis, as apparent from a number of examples.

Catalytic amounts of Yb(fod) 3 catalyze a bimolecular ene-like reaction between ordinary aldehydes and vinyl ethers, in which the oxygen functionality is located at the central carbon of an allylic system. These reactions proceed at room temperature in high yield.

[(2-Alkynyl)-benzoyl]-acetate esters undergo cycloaromatization in good yield upon treatment with CSA in refluxing chloroform.

We describe a practical five-step synthesis of the unusual hydrazonoacid found in luzopeptins, together with observations concerning its chemical behaviour.

Reaction of various enones and enals with cyanoacetamide in DMSO-tBuOK under an oxygen atmosphere furnishes 3-cyanopyridones directly and in good yield.

N-acetyl oxazolone derivatives of serine and threonine are readily converted into reactive acid chlorides that condense efficiently with various C-protected aminoacids, even poorly nucleophilic ones.

The reaction proceeds via an initial oxidation with PhI(OAc)2 in pure TFA as a solvent followed by heating in toluene.

A double conjugate addition sequence anneals heterocyclic rings onto a 2-alkyl quinone monoketal intermediate. This operation, reminiscent of a Barco annulation, proceeds in excellent overall yield. The new chemistry offers interesting opportunities in alkaloid synthesis.

Unlike ordinary aryl chlorides, the title hererocycles participate readily in Castro-Stephens, Stille, Suzuki, and carbonylation reactions under the catalytic influence of Pd(0).

Total syntheses of the representative phenanthroizidine alkaloids, tylophorine and antofine, and of their seco congeners, septicine and julandine, have been completed from sterically congested 3,4-diarylpyridines prepared by a modified Knoevenagel−Stobbe synthesis. Central to the success of this effort was the ability of α-dicarbonyl enones to combine in a formal [4 + 2]-cycloaddition with sterically demanding vinyl ethers.

Benzazocenone intermediates for mitomycinoids are now available in only six steps. Key phases of this sequence include the ene-like reaction of 2-methoxypropene with a 2-azidophenyacetaldehyde and a novel heterocyclic ring formation/expansion reaction.

The abnormal reluctance of piperazic acids to undergo N-2 acylation seems to be due to an electronic effect, not a steric / conformational problem. A system suitable for probing these issues was assembled by methods that have produced a versatile building block for β-hydroxy-α-aminoacids of either relative stereochemistry and of either (L) or (D) configuration.

The evolution of our strategy for the synthesis of (+)-Camptothecin and related substances is presented in detail.

A catalytic ene-like reaction of aldehydes with those vinyl ethers that display the oxygen functionality at the central carbon of an allylic system, e.g., 2-methoxypropene, is discussed in detail. The reaction is promoted by 0.05 equiv. of the 1:1 complex of Yb(fod)3 and acetic acid, and it is forms the centerpiece of our synthesis of chlorovulone II, mitomycinoids and phyllanthocin.

N-Acyl derivatives of piperazic acids display an unusual degree of conformational rigidity. As a consequence, α-N-coupling of a piperazic acid of given configuration (d or l) with an α-aminoacyl unit of opposite configuration (l or d) produces a “heterochiral” dipeptide that exists in a conformation conducive to the formation of a peptide turn. Piperazic acids and related compounds may thus be regarded as conformationally rigid analogues of proline, and because they are readily available in either antipodal form by synthesis, they should become of great interest in the study of peptide turns.

We describe a total synthesis of (±)-chlorovulone II that is 10 steps shorter than the best alternative currently available (nine vs 19 steps). The key event of the synthesis is an aldol addition of the enolate of ethyl acetate into 4-cyclopentene-1,3-dione, a substance that has received little attention as an educt for prostanoid synthesis and for which little is known about carbonyl 1,2-addition with enolates. In addition, we provide chemical and stereochemical details of a route to a key intermediate toward the title compound that involves a carbonyl−ene reaction and a radical addition to an aldehyde carbonyl.

Micrococcin P1, 1, is an antibiotic that exhibits noteworthy antibacterial, antiprotozoal, antimalarial,cytotoxic, and gene-modulating activities. This notwithstanding, its precise structure remained undefined until mid-2009, when our group carried out the total synthesis of a substance that proved to be spectroscopically and polarimetrically identical to the natural product. This work lifted all structural and stereochemical ambiguities that have surrounded micrococcin since its discovery. Of course,knowledge of the precise structure of the molecule is essential in understanding intimate details of its mode of action and in charting possible medicinal chemistry activity. This review summarizes present knowledge about the sources, properties, and chemical synthesis of micrococcin P1.

A novel oxidation of indolic 2-oxazolines with iodobenzene diacetate leads to unusual spiroheterocycles of potential interest in synthetic and medicinal chemistry. In several instances, addition of 2,2,2-trifluoroethanol (the solvent for such oxidations) to the substrates was observed.

We describe the chemical synthesis of the accepted structure of micrococcin P1, a member of the thiostrepton group of antibiotics, and we show that this architecture does not correspond to that of the natural product. Methods developed during the present study should greatly facilitate ongoing efforts centering on the determination of the actual structure of microccin P1, in addition to being applicable to the synthesis of more complex thiostrepton congeners.