Simple iron salts such as FeCl(n), Fe(acac)(n) (n = 2,3) or the salen complex 4 turned out to be highly efficient, cheap, toxicologically benign, and environmentally friendly precatalysts for a host of cross-coupling reactions of alkyl or aryl Grignard reagents, zincates, or organomanganese species with aryl and heteroaryl chlorides, triflates, and even tosylates. An "inorganic Grignard reagent" of the formal composition [Fe(MgX)(2)] prepared in situ likely constitutes the propagating species responsible for the catalytic turnover, which occurs in many cases at an unprecedented rate even at or below room temperature. Because of the exceptionally mild reaction conditions, a series of functional groups such as esters, ethers, nitriles, sulfonates, sulfonamides, thioethers, acetals, alkynes, and -CF(3) groups are compatible. The method also allows for consecutive cross-coupling processes in one pot, as exemplified by the efficient preparation of compound 12, and has been applied to the first synthesis of the cytotoxic marine natural product montipyridine 8. In contrast to the clean reaction of (hetero)aryl chlorides, the corresponding bromides and iodides are prone to a reduction of their C-X bonds in the presence of the iron catalyst.

Progress in testing requires that we evaluate the effectiveness of testing strategies on the basis of hard experimental evidence, not just intuition or a priori arguments. Random testing, the use of randomly generated test data, is an example of a strategy that the literature often deprecates because of such preconceptions. This view is worth revisiting since random testing otherwise offers several attractive properties: simplicity of implementation, speed of execution, absence of human bias.We performed an intensive experimental analysis of the efficiency of random testing on an existing industrial-grade code base. The use of a large-scale cluster of computers, for a total of 1500 hours of CPU time, allowed a fine-grain analysis of the individual effect of the various parameters involved in the random testing strategy, such as the choice of seed for a random number generator. The results provide insights into the effectiveness of random testing and a number of lessons for testing researchers and practitioners.

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The integration of various metal‐catalyzed reactions into a one‐pot processes opens an unprecedentedly short and efficient route to the odoriferous alkaloid (R)‐(+)‐muscopyridine. Importantly, it is shown how metathesis can be used for a most convenient “self‐clearance” of a product mixture (see scheme; OTf=CF3SO3).

Aromatic amines with a stereocenter a to the nitrogen atom are important structural motifs in a number of biologically active compounds.[1] Many of approaches to such structures have been investigated, but each method has limitations. Thus, a highly enantioselective procedure to prepare optically active aromatic amines would be valuable, and an enantioselective route to N-aryl allylic amines would be particularly useful because of the dual functionality in these compounds.Allylic substitution catalyzed by transition metals has emerged as a powerful tool for enantioselective formation of CÀC, CÀN, and CÀO bonds. [2][3][4] However, aromatic amines have not been used commonly in allylic amination, [5][6][7] presumably because they are less nucleophilic than the more commonly used benzylamine or stabilized anionic nitrogen nucleophiles. A general and highly enantioselective reaction between an aromatic amine without an activating group on the nitrogen atom and an achiral allylic ester or a racemic branched allylic electrophile has not been reported.Catalysts based on metals other than palladium [8][9][10][11][12][13][14][15][16] and its congeners often form the more hindered, branched product from nucleophilic substitution with unsymmetrical monosubstituted allylic esters. [17][18][19][20] This reactivity complements the regioselectivity of palladium catalysts, which tend to form the linear products. We previously reported asymmetric allylic substitution of achiral allylic carbonates with aliphatic amines and phenoxides to form branched allylic amines and ethers with high regio-and enantioselectivities in the presence of an iridium complex with a phosphoramidite ligand. [21,22] Reactions of aromatic amines did not occur under the conditions developed originally.Our mechanistic studies have shown that the cyclometalated complex 1, generated in situ by treatment of [{Ir(cod)Cl} 2 ] (cod = cycloocta-1,5-diene) and the ligand L 1 with an alkylamine base (Scheme 1), is likely to be the true catalyst in the allylic amination.[23] Reactions conducted with the isolated complex 1 as catalyst occurred faster and with broader scope than those with the combination of [{Ir(cod)Cl} 2 ] and L 1 .We proposed that the initial system failed to catalyze reactions of anilines because aromatic amines are not basic enough to induce cyclometalation, not because aromatic amines are too weakly nucleophilic to react with the iridium allyl intermediate. [23] If so, then the reactions of aniline should occur with a catalyst generated in situ by the action of a separate additive. Herein we report two convenient methods to generate the active catalyst in situ and the use of this catalyst to develop a general reaction of allylic carbonates with aromatic amines.[24] These reactions occur with a broad range of achiral, linear allylic carbonates to give branched chiral allyl aryl amines in excellent yields and with high regioand enantioselectivities (Scheme 2).The cyclometalated complex 1 was generated in pure form by reaction of [{Ir(cod)Cl} 2 ] and...