Steven A. Raw

Facile and general synthesis of quaternary 3-aminooxindoles.

A novel approach to the valuable quaternary 3-aminooxindole skeleton is reported on the basis of intramolecular arylation of enolates of substituted amino acids. The reaction tolerates dialkyl- and arylalkylamines as well as a range of carbon substituents (primary and secondary alkyl, aryl). The cyclization of N-indolyl-substituted substrates is accompanied by direct C-H arylation of the indole, leading to indolo-fused benzodiazepines.

Rhodium(III)-Catalyzed C–H Activation/Annulation with Vinyl Esters as an Acetylene Equivalent

The behavior of electron-rich alkenes in rhodium-catalyzed C-H activation/annulation reactions is investigated. Vinyl acetate emerges as a convenient acetylene equivalent, facilitating the synthesis of sixteen 3,4-unsubstituted isoquinolones, as well as select heteroaryl-fused pyridones. The complementary regiochemical preferences of enol ethers versus enol esters/enamides is discussed.

Synthesis of the Louisianin Alkaloid Family via a 1,2,4-Triazine Inverse-Electron-Demand Diels—Alder Approach

Isolated in 1995, the four members of the louisianin family (A, B, C and D) are simple pyridine and 2-pyridone alkaloids that display both antibacterial and anticancer activity. Herein we describe the synthesis of all four members of the louisianin family, from a conveniently prepared 1,2,4-triazine and via a common tetrasubstituted pyridine intermediate. This study includes the synthesis of louisianin B in both racemic form and as the (-)-enantiomer.

Highly substituted pyridines via tethered imine-enamine (TIE) methodology

A tethered imine-enamine methodology has been developed for the direct conversion of 1,2,4-triazines into highly substituted pyridines via the inverse electron demand Diels-Alder reaction which avoids the need for a discrete aromatisation step. This TIE methodology has also been applied in one pot reaction cascades involving 1,2,4-triazines and utilising MnO(2)-mediated tandem oxidation processes (TOPs).

Preparation of quinoxalines, dihydropyrazines, pyrazines and piperazines using tandem oxidation processes.

Alpha-hydroxyketones undergo MnO2-mediated oxidation followed by in situ trapping with aromatic or aliphatic 1,2-diamines to give quinoxalines or dihydropyrazines, respectively, in a one pot procedure which avoids the need to isolate the highly reactive 1,2-dicarbonyl intermediates. Modifications of the procedure allow the formation of pyrazines and piperazines.

In situ oxidative diol cleavage–Wittig processes

Abstract 1,2-Diol cleavage followed by in situ trapping of the resulting aldehyde with a stabilised phosphorane is described; both manganese dioxide and silica-supported sodium periodate can be used as the heterogeneous oxidant, but the latter reagent is generally the most efficient.

Approaches to oximidines, lobatamides and related natural products: the coupling reactions of 3-iodoacrolein O-methyl oximes

Abstract Both 2 E - and 2 Z -3-iodoacrolein O -methyl oximes are prepared in two steps from ethyl propiolate. Lithium–iodine exchange is effected and the resulting organolithium reagents added to several electrophiles, including styryl isocyanate which gives a conjugated O -methyl oxime enamide of the type found in the side chains of the oximidine, lobatamide and CJ-12950 natural products. The Pd(0) catalysed cross-coupling of these iodoalkenes is also explored.

The first synthesis of the epoxide-containing macrolactone nucleus of oximidine I

Abstract A synthesis of the epoxydiene-containing macrolide nucleus of oximidine I is reported, starting from commercially available 3-butyn-1-ol. The key macrocyclisation step is achieved using Horner–Wadsworth–Emmons methodology in the presence of an epoxide.

CHAPTER 3 - Recent Advances in the Chemistry of 1,2,4-Triazines

Publisher Summary This chapter outlines the recent advancement made in the chemistry of 1,2,4-triazines from a purely synthetic chemistry standpoint, focusing on specific reactions of 1,2,4-triazine system. It describes four ways of syntheses of 1,2,4-triazine such as condensations of 1,2-dicarbonyls and equivalents, oxidative approaches, 1,2,4-triazine-n-oxides and their derivitisation, and reaction of two equivalents of acyl-hydrazone with an α-haloketone using both thermal and microwave-mediated variants. The 1,2,4-triazines are very π-deficient heterocycles and, consequently, every carbon atom in the ring is susceptible to nucleophilic attack. The chapter summarizes some of the recent advancement in the functionalization of 1,2,4-triazine scaffold such as dimerization, substitution chemistry of 1,2,4-triazines, and substituent activation. One of the most valuable transformation of 1,2,4-triazine ring system is the inverse electron demand aza -Diels–Alder reaction with enamines to produce substituted pyridines. In addition to enamines, several other classes of electron-rich dienophile have been exploited in aza -Diels–Alder reactions with 1,2,4-triazines. The most common is norbornadiene, which, via an aza -Diels–Alder/ retro -Diels–Alder sequence, converts 1,2,4-triazine into the corresponding pyridine with no additional functionality. All the aza -Diels–Alder transformations of 1,2,4-triazine ring results in an aromatic product, usually the corresponding pyridine, as a consequence of aromatization by elimination from the dihydropyridine precursor. Although 1,2,4-triazines have been extensively utilized in the synthesis of ligands, liquid crystals, and cyclophanes, they have not often been exploited in natural product total synthesis.

Diastereoselective alkylation reactions of 1-methylcyclohexa-2,5-diene-1-carboxylic acid

The deprotonation and alkylation of 1-methylcyclohexa-2,5-diene-1-carboxylic acid has been investigated under a range of conditions. In all cases, the formation of compounds 14 was found to be completely stereoselective, although compound 14c was formed as an impurity when alkyl iodides were used as electrophiles, and doubly-alkylated compounds 17 were formed in some cases when alkyl bromides were used.