Isoxazole to oxazole: a mild and unexpected transformation.

3-Aryltetrahydrobenzisoxazoles prepared en route to the coleophomone natural products and analogues, were found to undergo a remarkable base-mediated rearrangement to 2-aryltetrahydrobenzoxazoles. The scope of this unprecedented, facile transformation was probed: a range of analogues was produced, a mechanism proposed, and an application demonstrated by synthesis of a known herbicidal compound.

In(OTf)3-catalysed one-pot versatile pyrrole synthesis through domino annulation of α-oxoketene-N,S-acetals with nitroolefins.

In(OTf)3-catalyzed robust and sustainable one-pot access to previously unknown and synthetically demanding polysubstituted pyrroles via [3 + 2] annulation of α-oxoketene-N,S-acetals with ß-nitrostyrenes has been achieved under solvent-free conditions. The merit of this domino Michael addition/cyclization sequence is highlighted by its operational simplicity, short reaction time (5-10 min), good to excellent yields, tolerance of a large variety of functional groups, and efficiency of producing two new (C-C and C-N) bonds and one highly functionalized pyrrole ring in a single operation, which make it an ideal alternative to existing methods.

New routes towards reutericyclin analogues.

A range of N-acylpyrrolo[3,4-c]isoxazoles and derived N-acyltetramides has been prepared via a nitrile oxide dipolar cycloaddition approach, as analogues of the acyltetramic acid metabolite reutericyclin, of interest for its antibiotic potential against Gram-positive bacteria including hospital-acquired infections of resistant Clostridium difficile.

Palladium catalyzed oxidative coupling of α-enolic dithioesters: a new entry to 3,4,5-trisubstituted 1,2-dithioles via a double activation strategy.

An operationally simple, facile, and convenient one-pot straightforward method for the construction of 3,4,5-trisubstituted 1,2-dithioles has been explored and developed via palladium catalyzed self-coupling of α-enolic dithioesters for the first time. Pd(0) efficiently catalyzes the activation and cleavage of S-H and C-S bonds to achieve cascade coupling, which results in the concomitant formation of new S-S and C-C bonds. Optimization data, substrate scope, and mechanistic insights are discussed.

Coenzyme-inspired chemistry 2: 4,5-dihydroimidazolium ylides (NHCs) and the reactions of 2-(1-hydroxyalkyl)-4,5-dihydroimidazoles.

Ketones are prepared from aldehydes via 1-benzyl-2-(1-hydroxyalkyl)-4,5-dihydroimidazoles (adducts of the aldehydes with 1-benzyl-2-lithio-4,5-dihydroimidazoles) whereas 1-benzyl-2-(1-oxoalkyl)-4,5-dihydroimidazoles are shown to act as acyl transfer reagents via C-C bond cleavage. 4,5-Dihydroimidazolium ylides (NHCs) are intermediates in both processes, which constitute thiamine-inspired C-C bond formation and cleavage protocols.

Aldol elaboration of 4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridin-4-ones, masked precursors to acylpyridones.

A core 4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridine-4-one scaffold is elaborated at C-3(Me) by base-mediated aldol condensation to give new 3-alkenyl-4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridine-4-ones, which are masked forms related to the acylpyridone natural products.

Imidazolium ylides from a conjugate addition-proton transfer route and their cycloaddition reactions.

4,5-Dihydroimidazolium ylides formed by conjugate addition-proton transfer from dihydroimidazoles and doubly-activated electron-deficient alkenes afford 2:1 cycloadducts in a one-pot process wherein the alkene also acts as a dipolarophile.

Cycloaddition of homochiral dihydroimidazoles: a 1,3-dipolar cycloaddition route to optically active pyrrolo[1,2-a]imidazoles.

N-Alkylation of optically active 1-benzyl-4-phenyl-4,5-dihydroimidazole with active alkyl halides and treatment of the so-formed 4,5-dihydroimidazolium ions with DBU in the presence of a range of electron-deficient alkene dipolarophiles, constitutes a 'one-pot' cascade terminating in a 1,3-dipolar cycloaddition reaction that affords optically active pyrrolo[1,2-a]imidazoles. Three bonds of the so-formed pyrrolidine moiety are constructed in this cascade. The cycloaddition follows an endo approach of dipole and dipolarophile with anti geometry of the dipole and facial selectivity derived from the phenyl substituent. Inter- and intramolecular cycloaddition modes are observed.

Synthesis of the pyoverdin chromophore by a biomimetic oxidative cyclization.

The fluorescent dihydropyrimido[1,2-a]quinoline chromophore of the pyoverdin siderophores has been synthesized by a biomimetic oxidative cyclization using an iodine(III) reagent, followed by elimination and dehydrogenation.

Intramolecular 1,3-dipolar cycloadditions of dihydroimidazolium ylides: synthesis of pyrrolo[1,2,3-de]quinoxalines and imidazo[1,2-a]indoles.

N-Alkylation of 4,5-dihydroimidazoles with alkene-containing bromomethyl ketones and treatment of the so-formed 4,5-dihydroimidazolium ions with DBU gives rise to an intramolecular 1,3-dipolar cycloaddition reaction that affords (via a reaction cascade involving eliminative ring-opening, recyclisation and prototropic tautomerism) unexpected hexahydropyrrolo[1,2,3-de]quinoxaline products. Steric bulk in both the dihydroimidazole and the dipolarophile allows isolation of an imidazo[1,2-a]indole, the initial product of cycloaddition. When the bromomethyl ketone contains no other functionality, or when cycloaddition is inhibited due to steric constraints, the dihydroimidazolium ion undergoes ring-opening hydrolysis followed by recyclization of the exposed amino ketone to afford either 3-alkyl-1-formylpiperazine-2-ones or 3-aryl-1-formyl-1,4,5,6-tetrahydropyrazines.

Preparation of highly substituted pyrrolidines via an organometallic dipole.

Highly substituted pyrrolidines are prepared by formal cycloaddition of imines to a metal-stabilised 'Nicholas' dipole derived from an alkyne-cyclopropane dicobalt complex.

Novel formation and use of a Nicholas carbocation in the synthesis of highly substituted tetrahydrofurans.

The first formation of a Nicholas carbocation through cleavage of a carbon-carbon sigma bond has allowed the preparation of highly substituted tetrahydrofurans in a formal dipolar cycloaddition reaction.