Alan Ford,† Hugues Miel, Aoife Ring,† Catherine N. Slattery,† Anita R. Maguire,*,†,‡ and M. Anthony McKervey* †Department of Chemistry and ‡School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland Almac Discovery Ltd., David Keir Building, Stranmillis Road, Belfast BT9 5AG, United Kingdom Almac Sciences Ltd., Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, United Kingdom

Modern Organic Synthesis with α-Diazocarbonyl Compounds

Transition-metal-catalyzed carbene transformations and cross-couplings represent two major reaction types in organometallic chemistry and organic synthesis. However, for a long period of time, these two important areas have evolved separately, with essentially no overlap or integration. Thus, an intriguing question has emerged: can cross-coupling and metal carbene transformations be merged into a single reaction cycle? Such a combination could facilitate the development of novel carbon–carbon bond-forming methodologies.Although this concept was first explored about 10 years ago, rapid developments inthis area have been achieved recently. Palladium catalysts can be used to couple diazo compounds with a wide variety of organic halides. Under oxidative coupling conditions, diazo compounds can also react with arylboronic acids and terminal alkynes. Both of these coupling reactions form carbon–carbon double bonds. As the key step in these catalytic processes, Pd carbene migratory insertion plays a vital role i...

Diazo compounds and N-tosylhydrazones: novel cross-coupling partners in transition-metal-catalyzed reactions.

New synthetic procedures for intramolecular oxidative C-N bond formation have been developed for the preparation of carbazoles starting from N-substituted amidobiphenyls under either Cu-catalyzed or metal-free conditions using hypervalent iodine(III) as an oxidant. Whereas iodobenzene diacetate or bis(trifluoroacetoxy)iodobenzene alone undergoes the reaction to provide carbazole products in moderate to low yields, combined use of copper(II) triflate and the iodine(III) species significantly improves the reaction efficiency, giving a more diverse range of products in good to excellent yields. On the basis of mechanistic studies including kinetic profile, isotope effects, and radical inhibition experiments, the copper species is proposed to catalytically activate the hypervalent iodine(III) oxidants. The synthetic utility of the present approach was nicely demonstrated in a direct synthesis of indolo[3,2-b]carbazole utilizing a double C-N bond formation.

Intramolecular Oxidative C−N Bond Formation for the Synthesis of Carbazoles: Comparison of Reactivity between the Copper-Catalyzed and Metal-Free Conditions

Recent developments in copper-catalyzed reactions of diazo compounds

An unprecedented protocol for cyanation at arene C-H bonds has been developed by employing N,N-dimethylformamide and ammonia as a combined source for the cyano "CN" unit. Isotopic incorporation experiments revealed that the carbon and nitrogen of the "CN" originate from the N,N-dimethyl moiety of DMF and ammonia, respectively. The present cyanation reaction shows an excellent degree of regioselectivity, producing only monosubstituted nitriles at the less hindered C-H position, and it allows for the preparation of doubly labeled nitrile compounds for the first time.

A new combined source of "CN" from N,N-dimethylformamide and ammonia in the palladium-catalyzed cyanation of aryl C-H bonds.

It was discovered that Cu(IPr)Cl-catalyzed reaction of terminal alkynes with α-aryldiazoacetates provides indene derivatives, formal [3 + 2] cycloaddition adducts. Excellent regio- and chemoselectivity were observed to afford either 3H- or 1H-indene esters depending on the reaction conditions employed. The reaction is proposed to proceed via tandem processes: alkyne insertion into copper-carbenoid, intramolecular electrophilic attack on the aromatic ring, and then isomerization.

Copper-catalyzed reaction of alpha-aryldiazoesters with terminal alkynes: a formal [3 + 2] cycloaddition route leading to indene derivatives.

A procedure for the Cu-catalyzed hydrocyanation of alpha-aryl diazoesters has been developed using acetone cyanohydrin as a source of hydrogen cyanide (HCN). It was found that the addition of trimethylsilyl cyanide (TMSCN) significantly accelerates the conversion presumably by delivering free cyanide ion in situ, thus producing various types of alpha-aryl cyanoacetates in high yields under mild conditions.

Eun Ju Park

Papers

Copper-catalyzed reaction of alpha-aryldiazoesters with terminal alkynes: a formal [3 + 2] cycloaddition route leading to indene derivatives.

Acetone cyanohydrin as a source of HCN in the Cu-catalyzed hydrocyanation of alpha-aryl diazoacetates.