Search

A metal- and oxidant-free, practical and efficient method for the synthesis of highly versatile and synthetically useful ortho-trifluoromethanesulfonylated anilines from arylhydroxylamines and trifluoromethanesulfinic chloride was developed. This rapid transformation proceeded smoothly with good yields and excellent ortho-selectivity in the absence of any metals or ligands. Mechanistically, the reaction comprised a noncanonical O-trifluoromethanesulfinylation of the arylhydroxylamine, and the subsequent [2,3]-sigmatropic rearrangement to afford ortho-trifluoromethanesulfonylated aniline derivatives. The practical application of this reaction was demonstrated by further conversion into a series of functional molecules under different reaction conditions.

An organic acid catalyzed direct arylation of aromatic C(sp(2))-H bonds in phenols and naphthols for the preparation of 1,1'-linked functionalized biaryls was developed. The products are non-C2-symmetrical, atropoisomeric, and represent previously untapped chemical space. Overall this transformation is operationally simple, does not require an external oxidant, is readily scaled up (up to 98 mmol), and the structurally diverse 2,2'-dihydroxy biaryl (i.e., BINOL-type), as well as 2-amino-2'-hydroxy products (i.e., NOBIN-type) are formed with complete regioselectivity. Density-functional calculations suggest that the quinone and imino-quinone monoacetal coupling partners are exclusively arylated at their α-position by an asynchronous [3,3]-sigmatropic rearrangement of a mixed acetal species which is formed in situ under the reaction conditions.

A broad spectrum of O-aryloximes is readily available on treatment of inexpensive oximes with symmetrical diaryliodonium salts in the absence of a transition metal.

The synthesis of fused N-heterocycles starting from readily available 2-nitrobiaryls and phenylmagnesium bromide is disclosed.

Normal phase chiral HPLC methods are presented for the enantiomeric separation of 30 biaryl atropisomers including 18 new compounds recently produced via a novel synthetic approach. Three new cyclofructan based chiral stationary phases were evaluated. Separations were achieved for all but six analytes and the LARIHC™ CF6-P alone provided 15 baseline separations. Effects of polar modifiers and temperature effects also were studied. Apparent thermodynamic parameters were determined by van't Hoff plots. Preparative scale methods were developed and employed resulting in the first ever isolation of these novel atropisomers in their pure enantiomeric form. Insights into the mechanism of retention and chiral discrimination are presented.

We disclose an efficient and operationally simple protocol for the preparation of fused N-heterocycles starting from readily available 2-nitrobiaryls and PhMgBr under mild conditions. More than two dozen N-heterocycles, including two bioactive natural products, have been synthesized using this method. A stepwise electrophilic aromatic cyclization mechanism was proposed by DFT calculations.

The reaction proceeds with complete regioselectivity to afford the target compounds, which are difficult to prepare using other methods.

The present new method to synthesize highly substituted cyclopenta[c]furans is applicable to different alkenylalkenones and a wide range of alkynes (III).

Title compounds are synthesized in one step by new gold-catalyzed tandem bicyclization from alkynylalkenones and styrylindoles under mild conditions.

The exo/endo-selectivity in the tandem heterocyclization/formal [4 + 3] cycloaddition of alkynes (I) with furan (II) is shown to be switchable by subtle choice of a gold(I) or silver(I) catalyst, in general.

A dramatic substituent effect was found in the silver(I)-catalyzed cyclization reaction of ortho-alkynylaryl aldehyde oxime derivatives. When R is an alkyl group, the Ag(I)-catalyzed reaction in dimethylacetamide at 110 °C (conditions A) affords isoquinolines in good to excellent yields, in contrast, isoquinolin-1(2 H)-ones were produced in moderate to high yields under conditions B (dimethylformamide, room temperature) when R is an acetyl group. A plausible mechanism was proposed for this product selectivity control reaction (PSCR) by subtle structure modification.