The development of new palladium catalysts for the arylation of amines and alcohols with aryl halides and sulfonates is reviewed. Initial systems as well as mechanistic issues are discussed briefly, while subsequent generations of catalysts are described in greater detail. For these later generations of catalysts, substrate scope and limitations are also discussed. The review is organized by substrate class. Modifications and improvements in technical aspects of reaction development are described where appropriate. In addition, applications of this technology toward natural product synthesis, new synthetic methodology, and medicinal chemistry are chronicled. This review is organized in a manner that is designed to be useful to the synthetic organic chemist.

Practical Palladium Catalysts for C-N and C-O Bond Formation

The palladium-catalyzed coupling of amines with aryl halides or aryl alcohol derivatives, commonly dubbed Buchwald–Hartwig amination, has matured from a synthetic laboratory procedure to a technique that is widely used in natural product synthesis as well as in other fields of academic interest. Furthermore, due to the versatility and reliability of this reaction, researchers in industrial environments have included this methodology in their toolbox as a standard procedure for the synthesis of amine derivatives. Therefore, it is not surprising that first industrial processes up to ton-scale have been performed using this cross-coupling reaction. The authors who are involved in the application of this reaction to industrial processes on this scale give an overview of the recent developments in this field of chemistry, also including fundamental principles, with a special focus on the industrial approach and issues to be considered relevant in scaling-up this transition metal-catalyzed chemistry. This review differs from the already existing excellent academic reviews by focusing on the practical problems arising during implementing the methodology in an industrial environment as well as giving practical hints to this end.

Palladium‐Catalyzed CN and CO Coupling–A Practical Guide from an Industrial Vantage Point†

This critical review concerns the impact of copper-mediated alkyne–azide cycloadditions on peptidomimetic studies. It discusses how this reaction has been used to insert triazoles into peptide chains, to link peptides to other functionalities (e.g. carbohydrates, polymers, and labels), and as a basis for evolution of less peptidic compounds as pharmaceutical leads. It will be of interest to those studying this click reaction, peptidomimetic secondary structure and function, and to medicinal chemists.

Peptidomimetics via copper-catalyzed azide–alkyne cycloadditions

Palladium-assisted routes to nucleosides.

An attempt is made to survey and categorize selective protection and deprotection reactions, so that practicing chemists/biologists may be able to choose a method for the preparation of protected inositol derivatives, depending on their requirement. In addition to being useful for those who work with inositols, it is hoped that this review will help to widen the scope of using cyclitol derivatives for the synthesis of various classes of natural and unnatural compounds with interesting properties. Emphasis is given to the literature published between 1985 and the end of the year 2002, involving selective protection/deprotection of inositol hydroxyl groups.

Regioselective protection and deprotection of inositol hydroxyl groups.

The first total synthesis of one of the spicamycin congeners, SPM VIII (3), is described. A preliminary model study for construction of the characteristic N-glycoside linkage in spicamycin using tetra-O-benzyl-beta-D-mannopyranosylamine (13) and halopurines 5 revealed that Pd-catalyzed conditions successfully provided the coupling products 14 and 15 in good yields. It was also shown that thermal anomerization of the N-glycosides easily occurred, which resulted in the predominant formation of the beta-anomer as the thermodynamically favored compound, and the activation energy of anomerization of 15 was estimated to be ca. 30 kcal/mol. The novel aminoheptose unit of spicamycin 6 was prepared stereoselectively by carbon elongation of an acyclic aldehyde, prepared by ring cleavage reaction of a highly functionalized cyclohexane derived from naturally abundant myo-inositol. The Pd-catalyzed coupling reaction of the beta-heptopyranosylamine 6 with protected 6-chloropurine 5d, followed by deprotection, provided spicamycin amino nucleoside 2, whose condensation with dodecanoylglycine completed the total synthesis of 3. This study confirmed the proposed unique structure of a novel nucleoside antibiotic.

Total Synthesis of Spicamycin

Total synthesis of spicamycin amino nucleoside.

Pd-catalyzed coupling reaction of glycosylamines with 6-chloropurines: Synthesis of 6-(β-D-mannopyranosylamino)-9H-purine and its β-D-gluco isomer, N-glycoside models for spicamycin and septacidin

The new and efficient synthesis of 7-O-acetyl-4-azido-2,3,6-tri-O-benzyl-4-deoxy-L-glycero-α-L-manno-heptopyranosyl acetate (5), a key intermediate for the synthesis of novel anti-cancer antibiotic, spicamycin (1), starting from D-ribose is described.

Tamotsu Suzuki

Papers

Total Synthesis of Spicamycin

Total synthesis of spicamycin amino nucleoside.

Pd-catalyzed coupling reaction of glycosylamines with 6-chloropurines: Synthesis of 6-(β-D-mannopyranosylamino)-9H-purine and its β-D-gluco isomer, N-glycoside models for spicamycin and septacidin

The new and efficient synthesis of a heptose moiety of spicamycin

Total Synthesis of Spicamycin.