The palladium-catalyzed α-arylation of ketones has become a useful and general synthetic method. In this process, an enolate is generated from a ketone and base in the presence of an aryl halide, and a palladium catalyst couples this enolate with the aryl halide. With the advent of new catalysts composed of sterically hindered, electron-rich alkylphosphine and N-heterocyclic carbene ligands, this process now encompasses a broad range of enolates and related anions, including those derived from amides, esters, aldehydes, nitriles, malonates, cyanoesters, nitroalkanes, sulfones, and lactones. In the proposed mechanism for this reaction, the carbon−carbon bond of the product is formed by reductive elimination from an arylpalladium enolate intermediate. The structures and reactions of arylpalladium complexes of enolate, cyanoalkyl, and malonate ions have been studied to determine how the binding mode and electronic and steric parameters influence the rate and mechanism of reductive elimination.

Palladium-Catalyzed α-Arylation of Carbonyl Compounds and Nitriles

2A palladium-catalyzed α-arylation of amides is reported. Intermolecular arylation of N,N-dimethylamides and lactams occurs using aryl halides, silylamide base, and a palladium catalyst. Intramolecular arylation of N-(2-halophenyl)amides occurs using alkoxide base and a palladium catalyst. The palladium catalyst was formed in situ from Pd(dba)2 (dba = trans,trans-dibenzylidene acetone) and BINAP (2,2‘-bis(diphenylphosphino)-1,1‘-binaphthalene). Although the intermolecular arylation of amides is less general than that reported previously for ketones, unfunctionalized and electron-rich aryl halides gave α-arylamides in 48−75% yield and N-methyl-α-phenylpyrrolidinone in 49% yield. These reactions provided the highest yields yet reported for regioselective amide arylations. Intramolecular amide arylation of 2-bromoanilides gave oxindoles in 52−82% yield. Mono- and disubstituted acetanilides gave 1,3-di- and 1,3,3-trisubstituted oxindoles. The use of dioxane, rather than THF, solvent was important for some of ...

Palladium-Catalyzed Inter- and Intramolecular α-Arylation of Amides. Application of Intramolecular Amide Arylation to the Synthesis of Oxindoles

Medium ring nitrogen heterocyles

The mitomycins (Figure 1) are a unique family of natural products with a rich history. Hata and coworkers at Kwoya Hakko Kogyo Company in Japan first isolated mitomycins A and B from Streptomyces caespitosus found in soil samples in 1956.[1-3] Although the mitomycins were isolated by researchers at Kwoya Hakko Kogyo, the absolute structure of the mitomycins was determined by Webb and Coworkers at American Cyanamid Company.[4,5] X-ray crystal structures of the mitomycins by Tulinsky also proved critical in determination of the structures of the mitomycins.[6,7] Since that time a number of other members of this family of natural products have been isolated, including FR-900482 and FR-66979 from Streptomyces sandaensis in 1988 (Figure 1).[8, 9]



Figure 1

Members of the mitomycin family of natural products.



The biological activity attributed to this family of natural products is a manifestation of their ability to form both inter- and intra-strand DNA cross-links in the minor groove with a specificity favoring 5′-CG-3′ steps.[10,11] At the time of this discovery, no previous examples of natural products acting as DNA cross-linking agents were known. It was after this initial finding that several other natural products were found to also form cross-links with DNA.[12-14] Recent studies have shown that in addition to the formation of DNA cross-links, this family of compounds is also capable of forming cross-links with minor groove-binding nuclear proteins, such as high mobility group I/Y (HMG I/Y now named HMG A1) proteins.[15,16] Additionally, it was shown that monoalkylation and not cross-linking was the major adduct found when an FR-900482 derivative was incubated with nucleosomes. This result could suggest alternate modes of action of this family of natural products in the context of cellular chromatin.

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Mitomycinoid Alkaloids: Mechanism of Action, Biosynthesis, Total Syntheses, and Synthetic Approaches

The oxidative conversion of alicyclic ketones into lactones with permonosulfuric acid was discovered by Baeyer and Villiger in 1899, and in their honor the general process by which ketones are converted into esters or lactones is now known as the Baeyer–Villiger reaction. The literature on this synthetically useful process has been reviewed comprehensively through 1953 in Volume 9 of Organic Reactions, and less comprehensive reviews of the reaction have appeared since then. More recent investigations have led to the development of new synthetic reagents, to improvements in experimental reaction conditions, and to a better understanding of regiochemical and stereochemical aspects of the reaction. Baeyer–Villiger reactions now often can be carried out with functional group chemoselectivity and regiochemical control. Although the recent removal from commerce of 90% hydrogen peroxide and reagents based upon this oxidant are a setback to Baeyer–Villiger reaction methodology, alternative reagents, catalysts, and methods described in this review are available to fill the gaps.



The definition of the Baeyer–Villiger reaction is somewhat fuzzy, and can be considered to include both ketones and aldehydes. In addition to the traditional use of organic and inorganic peracids as oxidants, examples of oxygen insertion reactions using hydrogen peroxide, alkyl peroxides, and several metal ion oxidants are considered to fall within the scope of this chapter and are included in the tabular survey.


Keywords:

Baeyer-Villiger oxidation;
ketones;
aldehydes;
Criegee mechanism;
migrating step;
rate determining addition;
straight chain ketones;
monocyclic ketones;
polycyclic ketones;
α,β-unsaturated ketones;
1,2 dicarbonyls;
reagents;
fused ring ketones;
peracid reactions;
α,β-unsaturated aldehydes;
ketals;
acetals;
side reactions;
alternative methods;
experimental procedures;
scope;
limitations;
spirocyclic ketones;
bridged compounds;
nitrogen derivatives

The Baeyer–Villiger Oxidation of Ketones and Aldehydes

Rossi and J. F. Bunnett, ibid., 38, 3020 (1973); (c) J. V. Hay, T. Hudlicky, and J. F. Wolfe, J. Am. Chem. Soc., 97, 374 (1975): (d) M. F. Semmelhack, B. P. Chong, R. D. Stauffer, T. D. Rogerson, A. Chong, and L. D. Jones, ibid., 97, 2507 (1975). (3) The 'H NMR spectra of 3 and 4 are consistent with the assigned stereochemistry: 3 (CCI4, TMS), 6 7.1 (br s, 5 H), 6.3 (d, J = 12, 1 H), 5.5 (d, J =

D E Keeley

Papers

Synthetic studies toward mitomycins. 1. Total synthesis of deiminomitomycin A.