Marc C. Kimber

A Facile and Mild Synthesis of Enamides using a Gold Catalyzed Nucleophilic Addition to Allenamides

A mild and facile synthesis of enamides has been developed, based on nucleophilic addition of electron-rich aromatic and heteroaromatics to an allenamide unit catalyzed by a gold salt. Yields for the transformation were 29-98%.

An Intermolecular Hydroamination of Allenamides with Arylamines Catalyzed by Cationic Au(I) Salts

An intermolecular hydroamination of allenamides with arylamines has been achieved under mild Au(I) catalysis conditions delivering allylamino E-enamides stereoselectively and in high yield. The reaction is made possible via a convenient method for conjugated N-acyliminium formation.

A one-pot synthesis of thiophene and pyrrole derivatives from readily accessible 3,5-dihydro-1,2-dioxines

Abstract A one-pot synthesis of 2,5-disubstituted thiophene, 1,2,5-tri- and 2,5-disubstituted pyrrole derivatives from readily available 3,5-dihydro-1,2-dioxines is described. The reaction proceeds by an initial Kornblum–de la Mare rearrangement of the 3,5-dihydro-1,2-dioxine to its isomeric 1,4-diketone followed by condensation of the in situ 1,4-diketone with sulfur, ammonia or a primary amine.

Synthesis of ABC Analogues of the Antitumour Antibiotic Streptonigrin

Abstract ABC analogues of the antitumour antibiotic streptonigrin, that contain the key metal chelation site and redox-active quinone unit that are essential for biological activity, were prepared via palladium catalysed cross-coupling of 2-iodo-8-nitroquinoline or 2-iodo-6-methoxy-5-nitroquinoline with 2-trimethylstannio-6-methylpyridine. Mild oxidation of the pyridyl methyl group introduced the acid functional group on ring C and Fremys salt oxidation afforded the quinone unit which was elaborated to give the 5-amino-6-methoxy substitution pattern present in streptonigrin.

A Preparative and Preliminary Spectroscopic Study of Analogues of a Zinquin-Related Fluorophore

The syntheses of the 4- and 5-methoxy isomers of 4-N-(6-methoxy-2-methyl-8-quinolyl)-4-methylbenzenesulfon-amide and of N-(2-methoxy-8-quinolyl)-4-methylbenzenesulfonamide are described. The 6-methoxy compound is a precursor of Zinquin ester, a specific fluorophore for Zn(II). The 2-methoxy analogue was synthesized by nitration of 2-chloroquinoline and subsequent functional group manipulation. The 4-methoxy isomer was synthesized from a 4-quinolone derivative, and the 5-methoxy isomer was synthesized by a standard Skraup quinoline synthesis. The structures of the 4- and 5-methoxy isomers were determined by single-crystal X-ray analysis. All of these compounds showed a bathochromic shift in their ultraviolet/visible spectra upon addition of Zn(II) to the solution. These compounds are all weakly or non-fluorescent in solution. All form fluorescent complexes with Zn(II) except the 5-methoxy compound. The 4-methoxy compound forms a significantly more fluorescent complex than those of the 6-methoxy compound and Zinquin ester and has a higher quantum yield than the others.

The Au(I) catalyzed activation of allenamides and their subsequent transformation into chromanes: a method for the regiocontrolled addition to the α- and γ-positions of the allene unit.

Au(I) activation of allenamides in the presence of phenols leads to the formation of chromanes in moderate to good yields. This catalytic process is dependent on the counterion which facilitates the activation of the in situ formed imine. Furthermore, this iminium can be intercepted by trimethylallyl silane, via the Hosomi-Sakurai reaction, giving a formal procedure for the regioselective intermolecular addition of two carbon nucleophiles to an allenamide at the α- and γ-positions.

A Preparative and Spectroscopic Study of Fluorophores for Zinc(II) Detection

Zinc(II) specific fluorophores are of substantial importance in the study of intracellular Zn 2+ . Two such widely used fluorophores are 2-methyl-8-(4-toluenesulfonamido)-6-quinolyloxyacetic acid, Zinquin (1), and its ethyl ester, Zinquin ester (2), which fluoresce strongly when bound by Zn 2+ . To gain insight into the factors affecting the fluorescence of such fluorophores the closely related 4-methyl-N-(6-methoxy-2-methyl-8-quinolyl)-benzenesulfonamide (3), and nine analogues (4–12), substituted at sulfur by nine different substituents have been prepared and their fluorescing characteristics and those of their Zn 2+ complexes have been examined. The nine substituents are: 2,2,2-trifluoroethyl (4), 4-methoxyphenyl (5), 4-acetamidophenyl (6), 4-bromophenyl (7), 4-nitrophenyl (8), 3-trifluoromethylphenyl (9), naphth-1-yl (10), naphth-2-yl (11) and 5-dimethylaminonaphth-1-yl (12). Under neutral conditions in 75/25% v/v ethanol/water solutions, (3)–(7) and (9)–(11) fluoresce weakly in the free state, (8) does not fluoresce and (12) fluoresces strongly. Ultraviolet (UV)-visible spectroscopy shows that (3)–(12) complex to Zn 2+ , but unlike the remainder, the complexes of (8) and (12) do not fluoresce, with those possessing electron-withdrawing substituents, (4) and (9), being the most fluorescent. On this basis ethyl-2-(2-methyl-quinolyloxy-8-(2,2,2-trifluoroethylsulfonamido))acetate (19) was prepared and its Zn 2+ complex was found to be substantially more fluorescent than that of (2).

An asymmetric synthesis of trans-fused butyrolactones from endoperoxides

The intermolecular addition of 1,3-dicarbonyl equivalents to endoperoxides in the presence of an organocatalyst yields trans-fused butyrolactones in high yield and enantioselectivities. This methodology expands the synthetic utility of endoperoxides and further underlines their potential as sources of oxygen functionality for natural and non-natural product target synthesis.

Synthesis of 1,3-Dienes via a Sequential Suzuki–Miyaura Coupling/Palladium-Mediated Allene Isomerization Sequence

We report a facile method for the synthesis of 1,3-dienes by a sequential process consisting of a palladium-catalyzed, base-free, Suzuki-Miyaura coupling/isomerization sequence. This sequence couples boronic acids with propargyl alcohols, generating the requisite allene in situ, followed by conversion of the unactivated allene to its 1,3-diene via a hydro-palladation/dehydro-palladation process. This process is general for a range of boronic acids, including boronic acids with electron-donating and -withdrawing groups, as well as heteroarylboronic acids. Key to this process is the boric acid byproduct of the base-free Suzuki-Miyauru coupling, which generates the required palladium-hydrido complex [H-Pd(II)-OB(OH)2] required for the isomerization.

The stereochemical outcome of allyl magnesium and indium additions to 5-substituted norbornen-7-ones and its application to cis fused carbocycle formation via ring rearrangement metathesis

The addition of allyl magnesium and allyl indium reagents to a key TBS protected norbornenyl building block, synthesised in 6-steps from commercially available 1,1-dimethoxy-2,3,4,5-tetrachlorocyclopentadiene, has been achieved providing the syn addition products with high diastereoselectivity. The subsequent exposure of the addition products to metathesis conditions, in the presence of ethene, then provided cis fused[3.0.3]-carbocycles with very high regioselectivity, via a Ring Rearrangement Metathesis (RRM) transformation.