Gold‐Catalyzed Formal Dehydro‐Diels–Alder Reactions of Ene‐Ynamide Derivatives Bearing Terminal Alkyne Chains: Scope and Mechanistic Studies

A new protocol for the synthesis of a variety of N‐containing aromatic heterocycles by a formal gold‐catalyzed dehydro‐Diels–Alder reaction of ynamide derivatives has been developed. Deuterium‐labeling experiments and kinetic studies support the involvement of a dual gold catalysis mechanism in which a gold acetylide moiety adds onto an aurated keteneiminium.     

A Criterion for Finite Topological Determinacy of Map-Germs

Let f, g: (Rⁿ, 0) (R^p, 0) be two C map-germs. Then f and gare C⁰-equivalent if there exist homeomorphism-germs h and lof (Rⁿ, 0) and (R^p, 0) respectively such that g = l f h^–1.Let k be a positive integer. A germ f is k-C⁰-determined ifevery germ g with j^k g(0) = j^k f(0) is C⁰-equivalent to f. Moreover,we say that f is finitely topologically determined if f is k-C⁰-determinedfor some finite k. We prove a theorem giving a sufficient conditionfor a germ to be finitely topologically determined. We explainthis condition below. Let N and P be two C manifolds. Consider the jet bundle J^k(N,P) with fiber J^k(n, p). Let z in J^k(n, p) and let f be suchthat z = j^kf(0). Define Whether (f) < k depends only on z, not on f. We can thereforedefine the set Let W^k(N, P) be the subbundle of J^k(N, P) with fiber W^k(n, p).Mather has constructed a finite Whitney (b)-regular stratificationS^k(n, p) of J^k(n, p) – W^k(n, p) such that all strata aresemialgebraic and K-invariant, having the property that if S^k(N,P) denotes the corresponding stratification of J^k(N, P) –W^k(N, P) and f C(N, P) is a C map such that j^kf is multitransverseto S^k(N, P), j^kf(N) W^k(N, P) = and N is compact (or f is proper),then f is topologically stable. For a map-germ f: (Rⁿ, 0) (R^p, 0), we define a certain ojasiewiczinequality. The inequality implies that there exists a representativef: U R^p such that j^kf(U – 0) W^k (Rⁿ, R^p = and suchthat j^kf is multitransverse to S^k (Rⁿ, R^p) at any finite setof points S U – 0. Moreover, the inequality controlsthe rate j^kf becomes non-transverse as we approach 0. We showthat if f satisfies this inequality, then f is finitely topologicallydetermined. 1991 Mathematics Subject Classification: 58C27.     

Palladium-catalyzed direct arylation of simple arenes in synthesis of biaryl molecules

Significant progress has been made in the direct arylation of simple arenes. A number of catalyst systems have been developed which enable the intramolecular direct arylation of aryl chlorides, bromides and iodides in high yield as well as conditions capable of achieving intermolecular direct arylation with simple arenes. This account describes recent progress by our group and others in the development of these reactions.     

Efficient preparation of 3‐substituted quinazolinediones directly from anthranilic acids and isocyanates

An efficient and practical synthesis of 3‐substituted quinazolinediones is described. The protocol uses readily available isocyanates and anthranilic acids as precursors in a one‐pot operation and has been demonstrated on >50 g scale. Isolation of the products via filtration directly from the reaction media is facile, affording high‐purity material. This procedure was then applied to the synthesis of Zenarestat. J. Heterocyclic Chem., (2011).     

Applications of and alternatives to pi-electron-deficient azine organometallics in metal catalyzed cross-coupling reactions

While the use of pi-deficient azine halides in palladium catalyzed cross-coupling reactions is common, the use of pi-electron deficient azine organometallics has been less intensively examined. In recent years, important advances have been made that are beginning to address this deficiency and need. The purpose of this tutorial review is to highlight and discuss the innovations that facilitate the synthesis of azine-containing biaryls with a focus on the pyridine structural motif. Given the number of important compounds which exhibit azine-heterobiaryls and the wide use of cross-coupling methods in their synthesis, this review should be of interest among synthetic organic chemists and organometallic chemists alike.     

Efficient synthesis of antiviral agent uprifosbuvir enabled by new synthetic methods

An efficient route to the HCV antiviral agent uprifosbuvir was developed in 5 steps from readily available uridine in 50% overall yield. This concise synthesis was achieved by development of several synthetic methods: (1) complexation-driven selective acyl migration/oxidation; (2) BSA-mediated cyclization to anhydrouridine; (3) hydrochlorination using FeCl₃/TMDSO; (4) dynamic stereoselective phosphoramidation using a chiral nucleophilic catalyst. The new route improves the yield of uprifosbuvir 50-fold over the previous manufacturing process and expands the tool set available for synthesis of antiviral nucleotides.

An efficient route to the HCV antiviral agent uprifosbuvir was developed in 5 steps from readily available uridine in 50% overall yield.     

Biaryl synthesis via direct arylation: establishment of an efficient catalyst for intramolecular processes

In this Communication, we describe direct arylation reactions with improved scope and catalyst activity for the intramolecular formation of biaryl compounds. This was achieved through the establishment of a highly active and robust catalyst system and the subsequent development of a novel phosphine ligand 27. The enhanced catalytic activity extends these transformations to include previously unreactive and poorly reactive substrates, and allows for very low catalyst loadings to be employed-as little as 0.1 mol %.     

High-yielding intramolecular direct arylation reactions with aryl chlorides

[reaction: see text] An N-heterocyclic carbene palladium catalyst system is used to promote direct arylation of a broad range of aryl chlorides to form six- and five-membered ring biaryls. An influence of the halide on the palladium precatalyst on catalyst activation has been revealed, as has a beneficial effect of NHC salts that allows the turnover numbers to be increased by simple addition of imidazolium salts to the reaction mixture.     

Palladium-catalyzed direct arylation of nitro-substituted aromatics with aryl halides

Direct arylation reactions of nitrobenzenes and aryl halides occur in good yield and high ortho regioselectivity. These reactions can be performed on gram scale with as few as 3 equiv of the nitro arene relative to the aryl halide. The synthetic utility of this method is demonstrated via rapid synthesis of a Boscalid intermediate.