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A general method for the N-arylation of indoles using catalysts derived from CuI and trans-1,2-cyclohexanediamine (1a), trans-N,N'-dimethyl-1,2-cyclohexanediamine (2a), or N,N'-dimethyl-ethylenediamine (3) is reported. N-Arylindoles can be produced in high yield from the coupling of an aryl iodide or aryl bromide with a variety of indoles.

This paper details the copper-catalyzed N-arylation of pi-excessive nitrogen heterocycles. The coupling of either aryl iodides or aryl bromides with common nitrogen heterocycles (pyrroles, pyrazoles, indazoles, imidazoles, and triazoles) was successfully performed in good yield with catalysts derived from diamine ligands and CuI. General conditions were found that tolerate functional groups such as aldehydes, ketones, alcohols, primary amines, and nitriles on the aryl halide or heterocycle. Hindered aryl halides or heterocycles were also found to be suitable substrates using the conditions reported herein.

The catalytic enantioselective allylation of aldehydes is a long-standing problem with considerable interest to the chemical community. We wish to disclose a new high yielding and highly enantioselective chiral Brønsted acid-catalyzed allylboration of aldehydes. The reaction is shown to be highly general, with broad substrate scope that covers aryl, heteroaryl, α,β-unsaturated, and aliphatic aldehydes. The reaction conditions were also shown to be effective for the catalytic enantioselective crotylation of aldehydes. We believe that the high reactivity of the allyl boronate is due to protonation of the boronate oxygen by the chiral phosphoric acid catalyst.The asymmetric allylboration of aldehydes has been an invaluable tool for the formation of carbon-carbon bonds with control over relative and absolute stereochemistry. 1 The foundation to this reaction was provided by Hoffmann's recognition of the diastereospecificity of the reaction when using both E-and Z-crotylboronates 2a-c and Brown's highly stereoselective allylborations using pinene-derived chiral reagents. 2d-f Over the past three decades additional methodology that has relied upon stoichiometric chiral reagents or mediators have included work by Roush, Binaphthyl derived chiral phosphoric acids (PA) have been shown to be versatile and efficient catalysts that promote a variety of enantioselective transformations. Chiral PA catalysts have found success in a large number of carbon-carbon and carbon-heteroatom bond forming processes along with a variety of oxidation and reduction reactions. 6 Although chiral PAcatalyzed reactions involving aldehydes are very rare 7,8 we investigated the enantioselective synthesis of homoallylic alcohols by reacting aldehydes with allylboronic acid pinacol ester 2 using chiral acid-catalyzed conditions. Boronate 2 is a relatively stable, nontoxic, commercially available reagent so it was an ideal choice for our evaluation of the chemistry.During the initial investigations leading to a catalytic reaction between benzaldehyde and 2, (R)-TRIP-PA (4) was found to be a very effective promoter. 9 Upon solvent screening we found that toluene, m-xylene, benzene and methylene chloride were effective for the asymmetric synthesis of alcohol 3a (Table 1). It was determined that toluene was the most suitable solvent, allowing for a 93% ee of 3a at room temperature in a 1 hour reaction time (entry 8). The enantioselectivity was further improved by reducing the temperature to 0 °C (96% ee, entry 9) and −30 °C (98% ee, entry 10) in presence of 5 mol % of the catalyst. It was fascinating to find that lowering the catalyst loading to 2.5 mol % allowed for a 97% ee (entry 11) and further lowering to 1 mol % (entry 12) still allowed for an impressive 95% enantioselectivity.The optimized reaction conditions were effective in promoting the asymmetric allylboration of a wide range of aldehydes, allowing for an extremely efficient reaction ( Table 2). The substrate scope extended to electron-rich and electron-poor aromatic aldehydes (e...

A new method for the Brønsted acid-catalyzed addition of amide nucleophiles to imines to produce protected aminal products is described. Simple Brønsted acids (phenyl phosphinic acid and trifluoromethanesulfonimide) were shown to be excellent catalysts, providing high yields of the aminal product. A catalytic asymmetric imine amidation using sulfonamides as nucleophiles was successful when a hindered biaryl phosphoric acid catalyst derived from 2,2'-diphenyl-[3,3'-biphenanthrene]-4,4'-diol (VAPOL) was used. Excellent yields and enantioselectivities were found in these additions (up to 99% ee).

[reaction: see text] A general catalytic coupling of arylboronic acids and amines is reported. This room-temperature coupling was realized through the use of catalytic copper(II) acetate, 2,6-lutidine as base, and myristic acid as an additive. Functionalized aniline substrates provided the diarylamine coupling products in good yield (58-91%). A variety of alkylamines were also successfully coupled to give N-alkyl anilines in moderate yield (50-64%).

The enantioselective addition of alcohols to imine electrophiles has been shown to proceed in the presence of a catalytic amount of a chiral phosphoric acid catalyst. The reaction allows for the formation of the respective chiral N,O-aminals in excellent yield and enantioselectivity. A total of 11 different alcohols and 11 different imines were successfully used as a clear demonstration of the reaction generality.

Chiral amino acids are some of the most important small molecules found in biological systems. Natural and unnatural R-amino acids are also highly utilized in academia and in the pharmaceutical, biotech, and chemical industries. Therefore, the discovery of general methodology that can produce chiral R-amino acid derivatives in high yield and with useful levels of enantioselectivity is of considerable importance. 1